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Shen A, Wu M, Guo Z, Ali F, Wu J, Chen H, Cheng Y, Lian D, Peng J, Yu M, Chen K. Effects and mechanisms of trifolin on attenuating hypertension-induced vascular smooth muscle cell proliferation and collagen deposition in vivo and in vitro. Sci Rep 2025; 15:16145. [PMID: 40341164 PMCID: PMC12062450 DOI: 10.1038/s41598-025-01022-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Accepted: 05/02/2025] [Indexed: 05/10/2025] Open
Abstract
Trifolin exhibits anti-tumor activities; however, its effect on hypertension remains unknown. This study was performed to investigate trifolin's potential therapeutic effects and underlying mechanisms of action on angiotensin II (Ang II)-induced hypertension in mice and Ang II stimulated A7R5 cells. Mice were randomly allocated into six groups: control, Ang II, Ang II + Trifolin (0.1 mg/kg), Ang II + Trifolin (1 mg/kg), Ang II + Trifolin (10 mg/kg), and Ang II + Valsartan (10 mg/kg). The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg/min), and trifolin, valsartan, or double distilled water was administered intragastrically once daily for 4 weeks. Blood pressure, vascular function, pathological morphology, and collagen deposition in Ang II infused mice and cell viability of Ang II stimulated A7R5 cells were assessed. A networking pharmacology analysis was performed to identify potential targets, pathways, and processes. These were verified by determining proliferating cell nuclear antigen (PCNA) expression, cell migration, collagen protein expression and related pathway activation in vivo and in vitro using masson, immunohistochemistry, cell counting Kit-8 assays, phalloidin staining, wound healing assays, and western-blotting. Different concentrations of trifolin effectively mitigated the rise in systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse wave velocity, abdominal aorta wall thickness, and collagen deposition of Ang II infused mice. Notably, higher concentrations of trifolin exhibited greater attenuation which was similar to the effects of valsartan (a positive control). Networking pharmacology analysis identified 105 common targets and various gene ontology processes. The Kyoto Encyclopedia of Genes and Genomes pathways analysis identified multiple enriched signaling pathways, including responses to wounding, phosphatidylinositol 3-kinase complex, oxidoreductase, PI3K/AKT, and FoxO signaling pathways. Consistently, trifolin treatment significantly down-regulated the expression of PCNA and the ratio of p-PI3K/PI3K and p-AKT/AKT in the abdominal aorta tissues. In vitro study indicated that trifolin consistently reduced the cell viability, down-regulated the expression of PCNA, collagen I and collagen III, and reduced the cell migration, as well as reduced the ratio of p-PI3K/PI3K and p-AKT/AKT (similar with the effect of PI3K inhibitor: LY294002) in Ang II stimulated A7R5 cells. Trifolin treatment attenuated the elevation of blood pressure, the proliferation and collagen deposition of VSMCs, and modulated multiple signaling pathways, including PI3K/Akt pathway. These results suggest that trifolin could be a potential therapeutic approach for treating hypertension.
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MESH Headings
- Animals
- Cell Proliferation/drug effects
- Mice
- Collagen/metabolism
- Muscle, Smooth, Vascular/drug effects
- Muscle, Smooth, Vascular/metabolism
- Muscle, Smooth, Vascular/pathology
- Muscle, Smooth, Vascular/cytology
- Hypertension/drug therapy
- Hypertension/metabolism
- Hypertension/pathology
- Hypertension/chemically induced
- Angiotensin II
- Cell Movement/drug effects
- Male
- Signal Transduction/drug effects
- Disease Models, Animal
- Cell Line
- Blood Pressure/drug effects
- Myocytes, Smooth Muscle/drug effects
- Myocytes, Smooth Muscle/metabolism
- Mice, Inbred C57BL
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Affiliation(s)
- Aling Shen
- Postdoctoral Workstation, Tianjiang Pharmaceutical Co., Ltd., Jiangyin, 214400, Jiangsu, China
- Department of Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China
- National Clinical Research Center for Cardiovascular Diseases of Traditional Chinese Medicine, Beijing, 100091, China
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
| | - Meizhu Wu
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
| | - Zhi Guo
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
| | - Farman Ali
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
| | - Jinkong Wu
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
| | - Hong Chen
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
| | - Ying Cheng
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
| | - Dawei Lian
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China
| | - Jun Peng
- Clinical Research Institute, the Second Affiliated Hospital & Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China.
- Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, Fujian, China.
- Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases, Fuzhou, 350122, Fujian, China.
- Fujian University of Traditional Chinese Medicine, 1 Qiuyang Road, MinhouShangjie, Fuzhou, 350122, Fujian, China.
| | - Min Yu
- Postdoctoral Workstation, Tianjiang Pharmaceutical Co., Ltd., Jiangyin, 214400, Jiangsu, China.
| | - Keji Chen
- Postdoctoral Workstation, Tianjiang Pharmaceutical Co., Ltd., Jiangyin, 214400, Jiangsu, China.
- Department of Cardiology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.
- National Clinical Research Center for Cardiovascular Diseases of Traditional Chinese Medicine, Beijing, 100091, China.
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Cho N, Moon H, Shin KM, Kang BK, Leem J, Yang C. Safety and effectiveness of an herbal decoction (modified Saengmaeksan) in hypertensive patients: Protocol for a real-world prospective observational study. PLoS One 2025; 20:e0316276. [PMID: 39823432 PMCID: PMC11741599 DOI: 10.1371/journal.pone.0316276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Accepted: 12/11/2024] [Indexed: 01/19/2025] Open
Abstract
OBJECTIVE Hypertension, a common chronic disease, often leads to serious complications. While conventional management relies on antihypertensive drugs, which can cause side effects and adherence issues, alternative treatments like herbal medicine are gaining attention. This study examines the efficacy and safety of modified Saengmaeksan, an East Asian herbal remedy, in treating hypertension. METHODS This single-arm, prospective, observational study will be conducted at Kyunghee Bichedam Korean Medicine Clinic from October 23, 2023 to August 30, 2024, enrolling 30 hypertensive patients. Over 12 weeks, participants will undergo 4 visits, receiving modified Saengmaeksan twice daily for 8 weeks, with a subsequent 4-week follow-up. Primary outcome is the change in systolic blood pressure from the baseline to week 8. Secondary outcomes include diastolic blood pressure changes, radial artery tonometry, and quality of life evaluations. Safety assessments will include monitoring hematologic parameters and adverse events. Data will be analyzed using an ANCOVA model for adjusting confounders. DISCUSSION Modified Saengmaeksan has shown potential for lowering blood pressure in clinical settings, supported by animal and cell studies. However, human studies are scarce. This research will employ radial artery tonometry to analyze blood pressure comprehensively, exploring Saengmaeksan's hemodynamic effects. The study's goal is to support the approval of modified Saengmaeksan as a hypertension treatment by the South Korean Food and Drug Administration and to promote the industrialization of traditional herbal medicine in managing hypertension. The findings will provide essential data for future clinical research, aiding in feasibility assessments and sample size determinations for randomized controlled trials.
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Affiliation(s)
- Nahyun Cho
- Department of Diagnostics, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea
| | - Hobin Moon
- Kyunghee Bichedam Clinic of Korean Medicine, Seoul, Republic of Korea
| | - Kyung-Min Shin
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Byoung-Kab Kang
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
| | - Jungtae Leem
- Department of Diagnostics, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea
- Research Center of Traditional Korean Medicine, College of Korean Medicine, Wonkwang University, Iksan, Republic of Korea
| | - Changsop Yang
- KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea
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Yang Q, Yuan W, Zhao T, Jiao Y, Tang M, Cong Z, Wu S. Magnetic-Powered Spora Lygodii Microrobots Loaded with Doxorubicin for Active and Targeted Therapy of Bladder Cancer. Drug Des Devel Ther 2024; 18:5841-5851. [PMID: 39679132 PMCID: PMC11638078 DOI: 10.2147/dddt.s490652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2024] [Accepted: 11/29/2024] [Indexed: 12/17/2024] Open
Abstract
Background and Purpose Bladder cancer has high recurrence rates despite standard treatments, necessitating innovative therapeutic approaches. This study introduces magnetically powered microrobots utilizing Traditional Chinese Medicine (TCM) Spora Lygodii (SL) encapsulated with Doxorubicin (DOX) and Fe3O4 nanoparticles (Fe/DOX@SL) for targeted therapy. Methods Fe3O4 nanoparticles were synthesized via co-precipitation and combined with SL spores and DOX through dip-coating to form Fe/DOX@SL microrobots. Their propulsion was controlled by a rotating magnetic field (RMF) for precise delivery. The microrobots' mobility and adherence were assessed in various biological media. Therapeutic efficacy was evaluated using an orthotopic bladder cancer model in mice treated intravesically with Fe/DOX@SL under RMF guidance, compared to controls. Results Fe/DOX@SL microrobots demonstrated efficient movement and stable navigation in biological environments. In vivo experiments showed superior retention in the bladder, prolonged adherence to the mucosa, and significantly enhanced tumor suppression in the RMF-guided group. Bioluminescence imaging confirmed reduced tumor growth, and histological analysis revealed substantial tumor regression compared to other treatments. Discussion and Conclusion This study highlights the potential of integrating TCM with advanced microrobotics. The biocompatible Fe/DOX@SL microrobots leverage SL's therapeutic properties and fuel-free magnetic control to overcome challenges in bladder cancer treatment, such as poor drug retention and off-target toxicity. This novel platform represents a promising advancement in targeted cancer therapy. The innovative fusion of TCM and microrobotics introduces a potent, targeted therapeutic strategy for bladder cancer, paving the way for broader biomedical applications.
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MESH Headings
- Urinary Bladder Neoplasms/drug therapy
- Urinary Bladder Neoplasms/pathology
- Animals
- Doxorubicin/pharmacology
- Doxorubicin/chemistry
- Doxorubicin/administration & dosage
- Mice
- Antibiotics, Antineoplastic/pharmacology
- Antibiotics, Antineoplastic/chemistry
- Antibiotics, Antineoplastic/administration & dosage
- Humans
- Drug Screening Assays, Antitumor
- Drug Delivery Systems
- Neoplasms, Experimental/drug therapy
- Neoplasms, Experimental/pathology
- Cell Proliferation/drug effects
- Female
- Medicine, Chinese Traditional
- Magnetic Fields
- Mice, Inbred BALB C
- Magnetite Nanoparticles/chemistry
- Particle Size
- Cell Line, Tumor
- Mice, Nude
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Affiliation(s)
- Qingxin Yang
- Department of Pharmacy, Mianyang Orthopaedic Hospital, Mianyang, 621000, People’s Republic of China
- Mianyang Key Laboratory of Development and Utilization of Chinese Medicine Resources, Mianyang, 621000, People’s Republic of China
- The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu People’s Hospital, Shenzhen, 518000, People’s Republic of China
| | - Wen Yuan
- Mianyang Key Laboratory of Development and Utilization of Chinese Medicine Resources, Mianyang, 621000, People’s Republic of China
| | - Tinghui Zhao
- Department of Burns and Plastic Surgery, Mianyang Central Hospital, Mianyang, 621000, People’s Republic of China
| | - Yanixao Jiao
- Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, 95817, USA
| | - Menghuan Tang
- Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, 95817, USA
| | - Zhaoqing Cong
- Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, 95817, USA
- South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, People’s Republic of China
| | - Song Wu
- South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, People’s Republic of China
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Jin Z, Lan Y, Li J, Wang P, Xiong X. The role of Chinese herbal medicine in the regulation of oxidative stress in treating hypertension: from therapeutics to mechanisms. Chin Med 2024; 19:150. [PMID: 39468572 PMCID: PMC11520704 DOI: 10.1186/s13020-024-01022-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 10/11/2024] [Indexed: 10/30/2024] Open
Abstract
BACKGROUND Although the pathogenesis of essential hypertension is not clear, a large number of studies have shown that oxidative stress plays an important role in the occurrence and development of hypertension and target organ damage. PURPOSE This paper systematically summarizes the relationship between oxidative stress and hypertension, and explores the potential mechanisms of Chinese herbal medicine (CHM) in the regulation of oxidative stress in hypertension, aiming to establish a scientific basis for the treatment of hypertension with CHM. METHODS To review the efficacy and mechanism by which CHM treat hypertension through targeting oxidative stress, data were searched from PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure, the VIP Information Database, the Chinese Biomedical Literature Database, and the Wanfang Database from their inception up to January 2024. NPs were classified and summarized by their mechanisms of action. RESULTS In hypertension, the oxidative stress pathway of the body is abnormally activated, and the antioxidant system is inhibited, leading to the imbalance between the oxidative and antioxidative capacity. Meanwhile, excessive production of reactive oxygen species can lead to endothelial damage and vascular dysfunction, resulting in inflammation and immune response, thereby promoting the development of hypertension and damaging the heart, brain, kidneys, blood vessels, and other target organs. Numerous studies suggested that inhibiting oxidative stress may be the potential therapeutic target for hypertension. In recent years, the clinical advantages of traditional Chinese medicine (TCM) in the treatment of hypertension have gradually attracted attention. TCM, including active ingredients of CHM, single Chinese herb, TCM classic formula and traditional Chinese patent medicine, can not only reduce blood pressure, improve clinical symptoms, but also improve oxidative stress, thus extensively affect vascular endothelium, renin-angiotensin-aldosterone system, sympathetic nervous system, target organ damage, as well as insulin resistance, hyperlipidemia, hyperhomocysteinemia and other pathological mechanisms and hypertension related risk factors. CONCLUSIONS CHM display a beneficial multi-target, multi-component, overall and comprehensive regulation characteristics, and have potential value for clinical application in the treatment of hypertension by regulating the level of oxidative stress.
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Affiliation(s)
- Zixuan Jin
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixian Ge, Xicheng District, Beijing, 100053, China
| | - Yu Lan
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixian Ge, Xicheng District, Beijing, 100053, China
| | - Junying Li
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixian Ge, Xicheng District, Beijing, 100053, China
| | - Pengqian Wang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Xingjiang Xiong
- Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, No.5 Beixian Ge, Xicheng District, Beijing, 100053, China.
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Wu W, Liu R, Guo S, Song W, Hua Y, Hong M, Zheng J, Zhu Y, Cao P, Duan JA. Mechanism and functional substances of Saiga antelope horn in treating hypertension with liver-yang hyperactivity syndrome explored using network pharmacology and metabolomics. JOURNAL OF ETHNOPHARMACOLOGY 2024; 330:118193. [PMID: 38636578 DOI: 10.1016/j.jep.2024.118193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Revised: 04/07/2024] [Accepted: 04/11/2024] [Indexed: 04/20/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Saiga antelope horn (SAH) is a traditional Chinese medicine for treating hypertension with liver-yang hyperactivity syndrome (Gan-Yang-Shang-Kang, GYSK), that has a long history of clinical application and precise efficacy, but its mechanism and functional substances are still unknown. Based on the demand for alternative research on the rare and endangered SAH, the group designed and carried out the following studies. AIM OF THE STUDY The purpose of this research was to demonstrate the functional substances and mechanisms of SAH in the treatment of GYSK hypertension. MATERIALS AND METHODS The GYSK-SHR model was constructed by administering a decoction of aconite to spontaneously hypertensive rats (SHRs). Blood pressure (BP), behavioural tests related to GYSK, and pathological changes in the kidneys, heart and aorta were measured to investigate the effects of SAH on GYSK-SHRs. Proteomic analysis was used to identify the keratins and peptides of SAH. Moreover, network pharmacology and plasma metabolomics studies were carried out to reveal the mechanisms by which functional peptides in SAH regulate GYSK-hypertension. RESULTS SAH has a significant antihypertensive effect on GYSK hypertensive animals. It has also been proven to be effective in protecting the function and structural integrity of the kidneys, heart and aorta. Moreover, SAH improved the abnormalities of 31 plasma biomarkers in rats. By constructing a "biomarker-target-peptide" network, 10 functional peptides and two key targets were screened for antihypertensive effects of SAH. The results indicated that SAH may exert a therapeutic effect by re-establishing the imbalance of renin-angiotensin (RAS) system. CONCLUSIONS Functional peptides from keratin contained in SAH are the main material basis for the treatment of GYSK-hypertension and exhibited the protective effect on the GYSK-SHR model through the RAS system.
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Affiliation(s)
- Wenxing Wu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Animal-Derived Chinese Medicine and Functional Peptides International Collaboration Joint Laboratory, Nanjing, 210023, China
| | - Rui Liu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Animal-Derived Chinese Medicine and Functional Peptides International Collaboration Joint Laboratory, Nanjing, 210023, China.
| | - Sheng Guo
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Wencong Song
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yongqing Hua
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Min Hong
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Jie Zheng
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yue Zhu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Peng Cao
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Animal-Derived Chinese Medicine and Functional Peptides International Collaboration Joint Laboratory, Nanjing, 210023, China
| | - Jin-Ao Duan
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, 210023, China; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Animal-Derived Chinese Medicine and Functional Peptides International Collaboration Joint Laboratory, Nanjing, 210023, China.
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Yihuna YK, Takele NM, Muluneh EK. Determinants of time-to-recovery from hypertension by application of Weibull-Inverse Gaussian shared frailty model. Pan Afr Med J 2024; 48:107. [PMID: 39525538 PMCID: PMC11543998 DOI: 10.11604/pamj.2024.48.107.43082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 06/07/2024] [Indexed: 11/16/2024] Open
Abstract
Introduction hypertension is a major public health problem that is responsible for mortality. In Ethiopia, hypertension is becoming a double burden due to urbanization. The study aims to identify factors that affect the time to recovery from hypertension. Methods in this study, a retrospective study design was used, and the data was collected in the patient´s chart from September 2016 to January 2018. Weibull-Inverse Gaussian shared frailty model was employed to identify factors associated with the recovery time of hypertension. Results eighty-one percent of the sampled patients were recovered to a normal condition, and nineteen percent of the patients were censored. The median survival time for hypertensive patients to attain a normal condition was 13 months. Weibull-Inverse Gaussian shared frailty model was used for predicting the recovery time of hypertension patients. Unobserved heterogeneity in residences, as estimated by the Weibull-Inverse Gaussian shared frailty model, was θ = 0.385 and p-value = 0.00. Conclusion age, systolic blood pressure, related disease, creatine, blood urea nitrogen, the interaction between blood urea nitrogen and age. Therefore, health-care providers give great attention, prioritize those identified factors and provide frequent counseling about reducing hypertension disease.
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Affiliation(s)
- Yeshambel Kindu Yihuna
- Department of Statistics, College of Natural and Computational Sciences, Debark University, Debark, Ethiopia
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Tessema FB, Gonfa YH, Asfaw TB, Tadesse MG, Bachheti RK. In silico Molecular Docking Approach to Identify Potential Antihypertensive Compounds from Ajuga integrifolia Buch.-Ham. Ex D. Don (Armagusa). Adv Appl Bioinform Chem 2024; 17:47-59. [PMID: 38495362 PMCID: PMC10942012 DOI: 10.2147/aabc.s392878] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 02/29/2024] [Indexed: 03/19/2024] Open
Abstract
Background Ajuga integrifolia (Armagusa) is used as a decoction to treat high blood pressure and diabetes, widely in Ethiopia. Specific compounds for anti-hypertension activity were not identified so far. This study aims to provide a scientific basis for the therapeutic use of A. integrifolia as an antihypertension agent. Methods In silico studies were used to evaluate the antihypertensive components of A. integrifolia. Flavonoids identified using HPLC analysis and iridoid glycosides isolated from A. integrifolia in this study and those isolated from synonyms (A. remota and A. bractosa) were considered in the molecular docking study. Interactions were studied by using Autodock vina (1.2) on PyRx 0.8 and visualizing in 2D and 3D using ligPlot+ and Discovery studio software. Activities like vasoprotection and druglikeness properties were predicted using online servers. Results Flavonoids such as quercetin, myricetin, and rutin were identified and quantified by HPLC analysis from different extracts of A. integrifolia. Reptoside and 8-O-acetylharpgide isolated from the aerial part of A. integrifolia. The binding energies of all 17 candidates considered in this study range from -10.2 kcal/mol to -7.5 kcal/mol and are lower than enalapril (reference drug: -5.9 kcal/mol). The binding energies, in most case, constitute hydrogen bonding. Biological activity predicted using PASS test also showed that the flavonoids have more probability of activity than the iridoid glycosides. Druglikeness properties of the candidate molecules showed that most follow the Lipinski rule of five with few violations. Conclusion Lower binding energies involving hydrogen bonding and predicted activities concerning hypertension confirm the traditional use of the aerial part of the medicinal plant concerned. Flavonoids: rutin, myricetin, quercetin, and kaempferol take the leading role in the antihypertensive activity of the aerial part of A. integrifolia. The iridoid glycosides studied are almost similar in their effect on their antihypertensive activity and still better than the reference drug.
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Affiliation(s)
- Fekade Beshah Tessema
- Department of Chemistry, College of Natural and Computational Science, Woldia University, Woldia, Ethiopia
- Department of Industrial Chemistry, College of Natural and Applied Sciences, Addis Ababa Science and Technology University, Addis Ababa, Ethiopia
| | - Yilma Hunde Gonfa
- Department of Industrial Chemistry, College of Natural and Applied Sciences, Addis Ababa Science and Technology University, Addis Ababa, Ethiopia
- Department of Chemistry, College of Natural and Computational Science, Ambo University, Ambo, Ethiopia
| | - Tilahun Belayneh Asfaw
- Department of Chemistry, College of Natural and Computational Science, Gondar University, Gondar, Ethiopia
| | - Mesfin Getachew Tadesse
- Department of Industrial Chemistry, College of Natural and Applied Sciences, Addis Ababa Science and Technology University, Addis Ababa, Ethiopia
- Centre of Excellence in Biotechnology and Bioprocess, Addis Ababa Science and Technology University, Addis Ababa, Ethiopia
| | - Rakesh Kumar Bachheti
- Department of Industrial Chemistry, College of Natural and Applied Sciences, Addis Ababa Science and Technology University, Addis Ababa, Ethiopia
- Department of Allied Sciences, Graphic Era Hill University, Society Area, Clement Town, Dehradun, 248002, India
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Wang P, Hao D, Xiong X. Anti-hypertension effect of Wuwei Jiangya decoction via ACE2/Ang1-7/MAS signaling pathway in SHR based on network degree-distribution analysis. JOURNAL OF ETHNOPHARMACOLOGY 2024; 319:117121. [PMID: 37660954 DOI: 10.1016/j.jep.2023.117121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Revised: 05/28/2023] [Accepted: 08/30/2023] [Indexed: 09/05/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Wuwei Jiangya decoction (WJD) is a traditional Chinese medicinal formula (Fangji) composed of Gastrodiae Rhizoma, Chuanxiong Rhizoma, Puerariae Lobatae Radix, Cyathulae Radix, and Achyranthis Bidentatae Radix, all of which have been verified to combat hypertension. However, the integrative "shot-gun" mechanism of WJD and its primary active ingredients are still unclear. AIM OF THE STUDY To investigate the anti-hypertensive effects of WJD and its originating ingredients. METHODS Network-based degree distribution analysis combined with in vivo experiments were performed. RESULTS A total of 144 active ingredients in WJD were identified to regulate 84 hypertension-related targets, which are mainly involved in blood pressure and blood vessel diameter regulation. However, for the anti-hypertension effects, "more does not mean better". The majority (76%) of the hubs in the H-network were regulated by no more than four ingredients. We identified 16 primary ingredients that accounted for the therapeutic action against hypertension. For compatibility, the five herbs consistently focused on blood pressure, vascular diameter, and angiogenesis, with the renin-angiotensin system as a primary target. The characteristics of each herb were involved in processes such as lipid localization and oxidative stress, which interact to constitute the regulatory network targeting hypertension, its risk factors, and organ damage. In vivo, WJD significantly reduced systolic blood pressure (SBP), improved left ventricular mass index, and ameliorated cardiac hypertrophy and vascular injury by moderating the renin-angiotensin system via activating the ACE2/Ang-(1-7)/Mas signaling pathway. CONCLUSION WJD can lower SBP and ameliorate cardiac hypertrophy and vascular injury through the ACE2/Ang-(1-7)/Mas pathway, thus providing new insights into the development of traditional Chinese medicine as a therapeutic agent for hypertension.
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Affiliation(s)
- Pengqian Wang
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Danli Hao
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xingjiang Xiong
- Guang'anmen Hospital, Chinese Academy of Chinese Medical Sciences, Beijing, China.
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Khan J, Yadav S, Bhardwaj D, Kumar A, Okanlawon MU. Flavonoids as Potential Natural Compounds for the Prevention and Treatment of Eczema. Antiinflamm Antiallergy Agents Med Chem 2024; 23:71-84. [PMID: 38721791 DOI: 10.2174/0118715230299752240310171954] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2024] [Revised: 02/21/2024] [Accepted: 02/28/2024] [Indexed: 08/21/2024]
Abstract
Eczema is a systemic autoimmune disease characterized by inflammation and skin manifestation with a range of comorbidities that include physical and psychological disorders. Despite recent advancements in understanding the mechanisms involved in atopic dermatitis, current marketed products have shown varying results with more side effects. The present objective of the research studies is to develop new agents for eczema that cut down the cost of the novel drugs available and also improve the efficacy with the least adverse effects. Natural compounds and medicinal plants have been traditionally used since ancient civilizations. Nowadays, research in the herbal field is at its peak. One such natural compound, flavonoid, was found to be beneficial for the treatment of eczema. This review describes the use of certain flavonoid products to prepare preparations suitable for the treatment of prophylaxis or eczema. This is especially true for prophylaxis or atopic eczema treatment. These compounds exhibit anti-inflammatory, anti-inflammatory, anti-inflammatory, and anti-inflammatory properties and are, therefore, used in treatments to prevent allergies, inflammation, and irritation to the skin. We also dock the flavonoid derivatives used with the protein associated with the inhibition of eczema for better lead optimization. These preparations appear to be used for cosmetic, dermatological, or herbal remedies as a local application.
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Affiliation(s)
- Javed Khan
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Shikha Yadav
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Divya Bhardwaj
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Abhishek Kumar
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Moshood Ummuani Okanlawon
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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Lai X, Fang Z, Dong Z, Wu S, Zhou X, Gao Y. A propensity score matched comparison of blood pressure lowering in essential hypertension patients treated with antihypertensive Chinese herbal Medicine: comparing the real-world registry data vs. randomized controlled trial. Clin Exp Hypertens 2023; 45:2249269. [PMID: 37639695 DOI: 10.1080/10641963.2023.2249269] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 08/03/2023] [Accepted: 08/09/2023] [Indexed: 08/31/2023]
Abstract
BACKGROUND Randomized controlled trials have demonstrated that Songling Xuemaikang capsule (SXC) is effective in blood pressure (BP) lowering for essential hypertension. However, the effectiveness of SXC in real-world clinical practice remains unknown. We aimed to investigate whether the BP-lowering effectiveness of SXC in the real-world practice setting is comparable to the efficacy of the intervention in a randomized controlled trial. METHODS We included 1325 patients treated with SXC monotherapy from a real-world registry and 300 from the SXC-BP trial. A propensity score matching (PSM) approach was used to select participants from the two cohorts. The primary outcome was a change in the office of BP from baseline to 8 weeks. RESULTS After PSM, there were 552 patients for the comparative analysis. Clinically meaningful BP reductions were observed both in the real world and in the RCT cohorts after 8-week SXC treatment. The 8-week systolic/diastolic BP was 129.50/81.33 mm Hg vs. 134.97/84.14 mm Hg in the real-world population and the RCT population, respectively. The changes in systolic BP (15.82 ± 10.71 vs. 10.48 ± 10.24; P < .001), and diastolic BP (10.01 ± 7.73 vs. 7.75 ± 8.14; P = .001) from baseline to 8 weeks were significantly greater in the real-world population. CONCLUSION The current comparison demonstrated that SXC monotherapy is at least as effective in real-world settings as within the randomized controlled trial for BP lowering in patients with grade 1 hypertension.
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Affiliation(s)
- Xinxing Lai
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Zhenghao Fang
- Department of Biostatistics, Beijing International Center for Mathematical Research, Peking University, Beijing, China
- Department of Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Zhenyu Dong
- Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Shengxian Wu
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaohua Zhou
- Department of Biostatistics, Beijing International Center for Mathematical Research, Peking University, Beijing, China
- Department of Biostatistics, School of Public Health, Peking University, Beijing, China
| | - Ying Gao
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
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Lin J, Wang Q, Zhong D, Zhang J, Yuan T, Wu H, Li B, Li S, Xie X, An D, Deng Y, Xian S, Xiong X, Yao K. Efficacy and safety of Qiangli Dingxuan tablet combined with amlodipine besylate for essential hypertension: a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. Front Pharmacol 2023; 14:1225529. [PMID: 37492087 PMCID: PMC10363978 DOI: 10.3389/fphar.2023.1225529] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 06/30/2023] [Indexed: 07/27/2023] Open
Abstract
Background: Hypertension, a major cardiovascular risk factor, severely impacts patients' quality of life. Qiangli Dingxuan tablet (QDT) is a formally approved Chinese patent medicine, which has been widely used as an adjunctive treatment for hypertension. This study aimed to investigate the antihypertensive efficacy and safety of QDT combined with amlodipine besylate in patients with essential hypertension. Methods: In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial conducted in China, patients diagnosed with grade 1 to 2 essential hypertension were randomly assigned in a 1:1 to the treatment of QDT or placebo for 12 weeks, alongside their ongoing treatment with amlodipine besylate. The primary outcome was the change in office blood pressure (BP) from baseline to 12 weeks. In addition, safety analysis included the assessment of vital signs and laboratory values. Results: At baseline, 269 patients were randomly assigned to the QDT group (n = 133) or the placebo group (n = 136), and there were no significant differences in baseline characteristics between the two groups. The primary outcome based on the full analysis set from baseline to 12 weeks showed that the mean difference in the change of office systolic BP reduction between the two groups was 6.86 mmHg (95%CI, 4.84 to 8.88, p < 0.0001), for office diastolic BP, the mean difference in the change of office diastolic BP reduction between the two groups was 4.64 mmHg (95%CI, 3.10 to 6.18, p < 0.0001). In addition, traditional Chinese medicine symptom scores were significantly decreased in the QDT group compared with the placebo group. No severe adverse events attributable to QDT were reported. Conclusion: The combination of QDT and amlodipine besylate demonstrates superior efficacy compared to amlodipine besylate monotherapy in the management of essential hypertension. QDT shows potential as an adjunctive treatment for essential hypertension. However, further rigorous clinical trials are warranted to validate these findings. Clinical Trial Registration: [https://clinicaltrials.gov/study/NCT05521282?cond=NCT05521282&rank=1]; Identifier: [NCT05521282].
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Affiliation(s)
- Jianguo Lin
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qingqing Wang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Dongsheng Zhong
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jinju Zhang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Tianhui Yuan
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hui Wu
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bin Li
- First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Shuangdi Li
- Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China
| | - Xiaoliu Xie
- Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Dongqing An
- Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China
| | - Yue Deng
- Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China
| | - Shaoxiang Xian
- First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xingjiang Xiong
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Kuiwu Yao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Eye Hospital China Academy of Chinese Medical Sciences, Beijing, China
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Lin F, Zhang G, Yang X, Wang M, Wang R, Wan M, Wang J, Wu B, Yan T, Jia Y. A network pharmacology approach and experimental validation to investigate the anticancer mechanism and potential active targets of ethanol extract of Wei-Tong-Xin against colorectal cancer through induction of apoptosis via PI3K/AKT signaling pathway. JOURNAL OF ETHNOPHARMACOLOGY 2023; 303:115933. [PMID: 36403742 DOI: 10.1016/j.jep.2022.115933] [Citation(s) in RCA: 34] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 11/04/2022] [Accepted: 11/10/2022] [Indexed: 06/16/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Wei-Tong-Xin (WTX), derives from the Chinese herbal decoction (CHD) of Wan-Ying-Yuan in ancient China, has been shown to be effective therapeutic herbal decoction for treating gastrointestinal diseases. Present studies have demonstrated that WTX had potential to alleviate the symptoms of gastrointestinal inflammation, gastric ulcer and improve gastric motility. AIM OF THE STUDY The study primarily focused on exploring the therapeutic effect and possible pharmacological mechanism of WTX on colorectal cancer (CRC) based on network pharmacology, in vitro and in vivo experiments. MATERIALS AND METHODS Firstly, colorectal cancer and WTX associated with targets were searched from GeneCards database and TCM Systems Pharmacology Database and Analysis Platform (TCMSP) respectively. The protein-protein interaction (PPI) network also was constructed to screening key targets. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to predict the underlying biological function and mechanism involving in the anti-colorectal cancer effect of WTX. Next, CCK-8, colony formation and transwell assays were performed to verify the influence of proliferation and metastasizing ability of HCT116 cells after treated with WTX. Cell cycle, apoptosis and reactive oxygen species (ROS) were analysis by flow cytometry. Hoechst 33258 staining was conducted to observe nuclear morphology changes. Protein expression of apoptosis and PI3K/AKT signaling as well as mRNA expression of ferroptosis and apoptosis were determined by Western Blotting and RT-qPCR. The effects of WTX and LY294002 combination on the PI3K/Akt/mTOR signaling pathway were measured by Western Blotting. Finally, the xenograft tumor mouse model was established by subcutaneous injection of CT26 cells to measure tumors volume and weight. Hematoxylin and eosin (HE) staining and immunohistochemical analysis were used to observe the pathological changes and the protein expression in tumor tissues. RESULTS There were 286 potential treatment targets from 130 bioactive compounds in WTX, 1349 CRC-related targets were identified. Eleven core targets (TP53, AKT1, STAT3, JUN, TNF, HSP90AA1, IL-6, MAPK3, CASP3, EGFR, MYC) were found by PPI network analysis constructed of 142 common targets. The results of KEGG enrichment displayed PI3K/AKT signaling pathway as core pathway. After the treatment of WTX, the inhibitory of viability, metastases and cell cycle arrest at G2/M phase were observed in HCT116 cells. Moreover, WTX induced an increase in the expression of apoptosis proteins (Bak, cytochrome c, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3) and the levels of ROS and MDA, a decrease in the expression of PI3K/AKT signaling related proteins (PI3K, p-PI3K, p-AKT/AKT and p-mTOR/mTOR) and the level of SOD. WTX treatment significantly reduced the tumor weight, increased cleaved caspase-3 positive area and decreased that of ki67 in xenograft mouse model. CONCLUSION Through a network pharmacology approach and in vitro experiments, we predicted and verified the effect of WTX on colorectal cancer cells mainly depended on the regulation of intrinsic apoptosis via PI3K/AKT signaling pathway, and further animal experiments proved that WTX has a good anti-colon cancer effect in vivo.
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Affiliation(s)
- Fei Lin
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Guanglin Zhang
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Xihan Yang
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Mengshi Wang
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Ruixuan Wang
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Meiqi Wan
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Jinyu Wang
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Bo Wu
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Tingxu Yan
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
| | - Ying Jia
- School of Functional Food and Wine, Shenyang Pharmaceutical University, Wenhua Road 103, Shenyang, Liaoning Province, 110016, China.
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Wu R, Zhou Y, Xu H, Zhao W, Zhou L, Zhao Y, Cui Q, Ning J, Chen H, An S. Aqueous extract of Salvia miltiorrhiza Bunge reduces blood pressure through inhibiting oxidative stress, inflammation and fibrosis of adventitia in primary hypertension. Front Pharmacol 2023; 14:1093669. [PMID: 36925635 PMCID: PMC10011461 DOI: 10.3389/fphar.2023.1093669] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 02/17/2023] [Indexed: 03/09/2023] Open
Abstract
Background: Hypertension is a major risk factor for cardiovascular diseases and the leading cause of mortality worldwide. Despite the availability of antihypertensive drugs, alternative treatments are needed due to the adverse events associated with their use. Previous studies have shown that SABP, a combination of aqueous active metabolites of Salvia Miltiorrhiza Bunge DSS, Sal-A, Sal-B and PAL, has a significant antihypertensive effect. However, the underlying mechanisms remain unknown. Objective: This study aimed to determine the effects of SABP on vascular inflammation, oxidative stress, and vascular remodeling in spontaneously hypertensive rats (SHRs). Additionally, the response of adventitial fibroblasts in SHRs to SABP treatment was also studied, including their proliferation, differentiation, and migration. Methods: SABP or perindopril (positive control) were administered intraperitoneally to SHRs, and systolic blood pressure was measured using a tail-cuff approach. The effects of SABP on oxidative stress, inflammation, and vascular remodeling were investigated by transmission electron microscopy, histochemical staining, and Western blot. Adventitial fibroblasts were isolated and cultured from the adventitia of thoracic aorta in SHR and WKY rats. CCK8 assay, wound healing method and immunostaining were used to observe the effect of SABP on fibroblasts proliferation, migration and transformation into myofibroblasts. Moreover, Western blot analysis was also performed to detect the proteins related to oxidative stress, inflammation and fibrosis in adventitial fibroblasts. Results: SHRs displayed higher blood pressure with significant vascular remodeling compared to WKY rats. The thoracic aorta and adventitial fibroblasts of SHRs exhibited significant oxidative stress, inflammation and fibrosis. SABP treatment repressed oxidative stress, inflammatory reaction and vascular remodeling of thoracic aorta in SHR through the ROS/TLR4/NF-κB signaling pathway, and inhibited fibrosis of thoracic aorta. Additionally, SABP inhibited the proliferation and migration of adventitial fibroblasts and their transformation to myofibroblasts in vitro through the TGFβ/Smad3 signaling pathway. Conclusion: These findings suggest that SABP have potential as an alternative treatment for hypertension by ameliorating oxidative stress, inflammation and fibrosis. Further research is needed to fully understand the mechanisms underlying the effects of SABP.
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Affiliation(s)
- Ruoyu Wu
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yongjie Zhou
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Hongjun Xu
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Wei Zhao
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Medical College, Hebei University of Engineering, Handan Economoc and Technological Development Zone, Handan, Hebei, China
| | - Luyang Zhou
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yilin Zhao
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Qingzhuo Cui
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Junda Ning
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Hongxu Chen
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Shengjun An
- Hebei Provincial Engineering Laboratory of Plant Bioreactor Preparation Technology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- College of Integrated Chinese and western medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
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14
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Xu X, Tian W, Duan W, Pan C, Huang M, Wang Q, Yang Q, Wen Z, Tang Y, Xiong Y, Zhu Z, Liu Y, Wei D, Qi W, Ouyang X, Ying S, Wang X, Zhou Z, Li X, Cui Y, Yang S, Xu H. Quanduzhong capsules for the treatment of grade 1 hypertension patients with low-to-moderate risk: A multicenter, randomized, double-blind, placebo-controlled clinical trial. Front Pharmacol 2023; 13:1014410. [PMID: 36703729 PMCID: PMC9871381 DOI: 10.3389/fphar.2022.1014410] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 12/29/2022] [Indexed: 01/11/2023] Open
Abstract
Background: Duzhong [DZ (Eucommia ulmoides Oliv.)] is regarded as a traditional Chinese medicine with a history dating back more than 2000 years. This herb is considered a nourishing herb in China and is commonly used as a tonic to strengthen muscles and bones, nourish the kidneys and liver, and soothe miscarriages. Moreover, there is evidence that DZ is capable of regulating blood pressure (BP), and several compounds isolated from DZ have been shown to have a BP-lowering effect. Quanduzhong capsules contain an extract of DZ [Eucommia ulmoides Oliv. (Eucommiaceae; Eucommiae cortex)] that is effective in treating hypertension. This multicenter, randomized, double-blind, placebo-controlled clinical trial sought to evaluate the clinical efficacy of Quanduzhong capsules in the treatment of low-to-moderate risk grade 1 hypertension patients. Materials and methods: A total of 60 patients from 3 centers with documented low-to-moderate risk grade 1 hypertension were randomly assigned in a 1:1 ratio to the test group or the control group. After a 1 week lead-in period using sham Quanduzhong capsules, all patients who met the entry criteria (29 cases in the test group and 29 cases in the control group) entered the 4 week test period. The test group took Quanduzhong capsules, and the control group continued to take sham Quanduzhong capsules. The primary endpoints [24-h mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) determined via 24-h ambulatory blood pressure monitoring (ABPM); office SBP and DBP] and secondary endpoints [mean arterial pressure; mean pulse; daytime mean SBP and DBP; nocturnal mean SBP and DBP; SBP and DBP load; area under the blood pressure (BP) curve; morning peak BP; early morning SBP and DBP; smoothness index of SBP and DBP; 24 h BP mean coefficient of variation (CV); percentage of patients with circadian restoration in ABPM; home BP; quality of life evaluated by WHO Quality of Life-BREF questionnaire; grading and quantitative evaluation of hypertension symptoms; values of plasmatic renin activity, angiotensin II, aldosterone, β-2 microglobulin and homocysteine] were assessed following the treatment. Drug-related adverse events and adverse drug reactions were also compared. Results: After a 4 week test period, a significant difference in the DBP CV between the two groups was observed (-2.49 ± 4.32 vs. 0.76 ± 4.3; p < .05). Moreover, the mean office SBP change was -7.62 ± 9.32 mmHg, and the mean DBP change was -4.66 ± 6.03 (p < .05). Among the three subjects with abnormal homocysteine levels in the test group, homocysteine levels decreased by 6.23 ± 9.15 μmol/L after treatment. No differences were observed between the two groups in any other indicators. After 4 weeks of treatment, there were no significant differences between the groups in terms of safety indicators (p > .05). No abnormal vital signs (except BP) or severe liver or renal function impairment were observed during the treatment periods; in addition, adverse events and drug reactions were mild. Conclusion: Treatment with Quanduzhong capsules reduced office SBP and DBP as well as DBP CV determined by 24-h ambulatory BP monitoring in patients with grade 1 hypertension at low-to-moderate risk. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=32531, identifier ChiCTR1900021699.
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Affiliation(s)
- Xuan Xu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- The Eighth Hospital of Baotou, Baotou, China
| | - Wende Tian
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wenhui Duan
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chaoxin Pan
- The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China
| | - Mingjian Huang
- The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China
| | - Qinggao Wang
- The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China
| | - Qinghua Yang
- The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China
| | - Zhihao Wen
- The First Affiliated Hospital of Guangxi University of Chinese Medicine, Guangxi, China
| | - Yu Tang
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Yao Xiong
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Zhiyun Zhu
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Yuanyuan Liu
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Dan Wei
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Wenqiang Qi
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Xiaochao Ouyang
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Shaozhen Ying
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Xiaohua Wang
- Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi Province, China
| | - Zhigang Zhou
- Jiangxi Puzheng Pharmaceutical Co, Ltd., Jiangxi, China
| | - Xiaofeng Li
- Jiangxi Puzheng Pharmaceutical Co, Ltd., Jiangxi, China
| | - Yu Cui
- Jiangxi Puzheng Pharmaceutical Co, Ltd., Jiangxi, China
| | - Shuyin Yang
- Jiangxi Puzheng Pharmaceutical Co, Ltd., Jiangxi, China
| | - Hao Xu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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15
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Long LZ, Chu JF, Qu H, Yang QN, Lu Y, Fu CG, Peng J, Chen KJ. Effects of Qingda granule on patients with grade 1 hypertension at low-medium risk: study protocol for a randomized, controlled, double-blind clinical trial. Trials 2023; 24:1. [PMID: 36588157 PMCID: PMC9806902 DOI: 10.1186/s13063-022-07006-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 12/12/2022] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Numerous pre-clinical studies showed that Qingda granule (QDG) was effective in treating hypertension. This study aims to evaluate the efficacy and safety of QDG in reducing blood pressure among patients with grade 1 hypertension at low-medium risk. METHODS The study is designed as a randomized, multi-center, double-blinded, non-inferiority clinical trial. Five hundred fifty-two patients with grade 1 hypertension at low-medium risk from 13 hospitals will be recruited and randomly assigned to the QDG group (n = 276, treated with valsartan capsule simulation agent and QDG) or control group (n = 276, treated with valsartan capsule and QDG simulation agent). The treatment period will be 4 weeks and the follow-up period will last 4 weeks after treatment. Primary outcome will be a decreased value of systolic blood pressure and diastolic blood pressure after treatment. And second outcome will include the decreased value of diastolic blood pressure and systolic blood pressure at the end of follow-up, the percentage of participants achieving normal blood pressure at the end of treatment and follow-up, the Hamilton Anxiety Scale and TCM syndrome scores at the end of treatment and follow-up, and levels of hypertensive hormones at end of treatment and follow-up. DISCUSSION This study will provide initial evidence regarding the clinical efficacy and safety of QDG in treating grade 1 hypertension at low-medium risk. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2000033890 . Registered on 15 June 2020.
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Affiliation(s)
- Lin-zi Long
- grid.411504.50000 0004 1790 1622Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350112 China ,grid.410318.f0000 0004 0632 3409Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091 China
| | - Jian-feng Chu
- grid.411504.50000 0004 1790 1622Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350112 China ,grid.411504.50000 0004 1790 1622Chen Keji Academic Thought Inheritance Studio, Fujian University of Traditional Chinese Medicine, Fu Zhou, China ,grid.411504.50000 0004 1790 1622 Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fu Zhou, China
| | - Hua Qu
- grid.410318.f0000 0004 0632 3409National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China ,grid.410318.f0000 0004 0632 3409Department of Cardiovascular Disease Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091 China
| | - Qiao-ning Yang
- grid.410318.f0000 0004 0632 3409National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China ,grid.410318.f0000 0004 0632 3409Department of Cardiovascular Disease Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091 China
| | - Yan Lu
- grid.411504.50000 0004 1790 1622Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350112 China
| | - Chang-geng Fu
- grid.410318.f0000 0004 0632 3409National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China ,grid.410318.f0000 0004 0632 3409Department of Cardiovascular Disease Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091 China
| | - Jun Peng
- grid.411504.50000 0004 1790 1622Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350112 China
| | - Ke-ji Chen
- grid.410318.f0000 0004 0632 3409National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China ,grid.410318.f0000 0004 0632 3409Department of Cardiovascular Disease Center, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091 China
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16
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Lin J, Wang Q, Xu S, Zhou S, Zhong D, Tan M, Zhang X, Yao K. Banxia baizhu tianma decoction, a Chinese herbal formula, for hypertension: Integrating meta-analysis and network pharmacology. Front Pharmacol 2022; 13:1025104. [PMID: 36534045 PMCID: PMC9755740 DOI: 10.3389/fphar.2022.1025104] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Accepted: 11/22/2022] [Indexed: 03/29/2024] Open
Abstract
Hypertension is a major cardiovascular risk factor, which seriously affects the quality of life of patients. Banxia Baizhu Tianma Decoction (BXD) is a Chinese herbal formula that is widely used to treat hypertension in China. This study aimed to evaluate the efficacy and potential mechanism of BXD for hypertension by meta-analysis and network pharmacology. Meta-analysis was performed to explore the efficacy and safety of BXD combined with conventional treatment for hypertension. Network pharmacology was used to explore the molecular mechanism of BXD in antihypertension. A total of 23 studies involving 2,041 patients were included. Meta-analysis indicated that compared with conventional treatment, combined BXD treatment was beneficial to improve clinical efficacy rate, blood pressure, blood lipids, homocysteine, endothelial function, inflammation, and traditional Chinese medicine symptom score. In addition, meta-analysis indicated that BXD is safe and has no obvious adverse reactions. Network pharmacology showed that the antihypertensive targets of BXD may be AKT1, NOS3, ACE, and PPARG. The antihypertensive active ingredients of BXD may be naringenin, poricoic acid C, eburicoic acid, and licochalcone B. Due to the poor methodological quality of the Chinese studies and the small sample size of most, the analysis of this study may have been affected by bias. Therefore, the efficacy and safety of BXD for hypertension still need to be further verified by high-quality clinical studies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022353666.
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Affiliation(s)
- Jianguo Lin
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Qingqing Wang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Siyu Xu
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Simin Zhou
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Dongsheng Zhong
- Guizhou University of Traditional Chinese Medicine, Guizhou, China
| | - Meng Tan
- Guizhou University of Traditional Chinese Medicine, Guizhou, China
| | - Xiaoxiao Zhang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Kuiwu Yao
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Eye Hospital China Academy of Chinese Medical Sciences, Beijing, China
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17
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GJD Modulates Cardiac/Vascular Inflammation and Decreases Blood Pressure in Hypertensive Rats. Mediators Inflamm 2022; 2022:7345116. [PMID: 36164390 PMCID: PMC9509256 DOI: 10.1155/2022/7345116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/19/2022] [Accepted: 08/12/2022] [Indexed: 11/24/2022] Open
Abstract
Gedan Jiangya decoction (GJD) (aqueous ethanol extract), a traditional Chinese medicine formula which contain six botanical drugs (Uncaria rhynchophylla (Miq.) Miq., Salvia miltiorrhiza Bunge, Pueraria lobata (Willd.) Ohwi, Eucommia ulmoides Oliv., Prunella vulgaris L., and Achyranthes bidentata Blume) was designed to treat hypertension; however, the underlying mechanism of action is unclear. This study aimed to determine the mechanisms of action of GJD in the treatment of hypertension in spontaneously hypertensive rats (SHR). Male SHRs were randomly divided into five groups: GJD doses were low (1.36 g/kg/d), medium (2.72 g/kg/d), and high (5.44 g/kg/d), captopril (13.5 mg/kg/d), and SHR groups, with Wistar-Kyoto rats (WKY) serving as the control. Every rat was gavaged once a day. The ALC-NIBP, a noninvasive blood pressure device, measured systolic (SBP) and diastolic (DBP) blood pressures. Six weeks following treatment, all rats were anesthetized. The blood samples were obtained from the abdominal aorta and then serum isolated to assess endothelin-1 and angiotensin II, interleukin-1beta, interleukin-6, and TNF-alpha. The left ventricular and thoracic aortas were taken for HE staining, immunohistochemistry, RT-qPCR, and western blot examination. Following GJD therapy, SBP and DBP were significantly lowered, as were serum levels of endothelin-1 and angiotensin II. The thickness of the left ventricular and thoracic aorta walls reduced, as did type I collagen, type III collagen, and alpha-SMA expression in the left ventricular and aortic tissues. The GJD treatment significantly reduced serum levels of the inflammatory markers interleukin-1beta, interleukin-6, and TNF-alpha. Furthermore, interleukin-1 beta, interleukin-6, TNF-alpha, TAK1, and NF-κB/p65 levels were significantly reduced in left ventricular and aortic tissues, whereas IkB-alpha levels were significantly elevated. GJD has a dose-dependent effect on all parameters. In conclusion, GJD has been shown to lower blood pressure, improve cardiovascular remodeling, and reduce inflammation via regulating NF-κB in SHRs.
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18
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Network Pharmacology and Molecular Docking-Based Mechanism Study to Reveal Antihypertensive Effect of Gedan Jiangya Decoction. BIOMED RESEARCH INTERNATIONAL 2022; 2022:3353464. [PMID: 36046450 PMCID: PMC9423997 DOI: 10.1155/2022/3353464] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/24/2022] [Accepted: 08/05/2022] [Indexed: 11/17/2022]
Abstract
Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD's pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure.
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19
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Zheng X, Xiong J, Zhang Y, Xu L, Zhou L, Zhao B, Wang Y. Multistate Markov model application for blood pressure transition among the Chinese elderly population: a quantitative longitudinal study. BMJ Open 2022; 12:e059805. [PMID: 35835530 PMCID: PMC9289040 DOI: 10.1136/bmjopen-2021-059805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE To explore the transitions of different blood pressure states based on a multistate Markov model among the Chinese elderly population. SETTING A community health centre in Xiamen, China. PARTICIPANTS 1833 elderly Chinese people. METHODS A multistate Markov model was built based on 5001 blood pressure measurements from 2015 to 2020. Research was conducted to explore the process of hypertension progression, providing information on the transition probability, HR and the mean sojourn time in three blood pressure states, namely normal state, elevated state and hypertensive state. RESULTS Probabilities of moving from the normal state to the hypertensive state in the first year were 16.97% (female) and 21.73% (male); they increased dramatically to 47.31% (female) and 51.70% (male) within a 3-year follow-up period. The sojourn time in the normal state was 1.5±0.08 years. Elderly women in the normal state had a 16.97%, 33.30% and 47.31% chance of progressing to hypertension within 1, 2 and 3 years, respectively. The corresponding probabilities for elderly men were 21.73%, 38.56% and 51.70%, respectively. For elderly women starting in the elevated state, the probabilities of developing hypertension were 25.07%, 43.03% and 56.32% in the next 1, 2 and 3 years, respectively; while the corresponding changes for elderly men were 20.96%, 37.65% and 50.86%. Increasing age, body mass index (BMI) and glucose were associated with the probability of developing hypertension from the normal state or elevated state. CONCLUSIONS Preventive actions against progression to hypertension should be conducted at an early stage. More awareness should be paid to elderly women with elevated state and elderly men with normal state. Increasing age, BMI and glucose were critical risk factors for developing hypertension. The derived transition probabilities and sojourn time can serve as a significant reference for making targeted interventions for hypertension progression among the Chinese elderly population.
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Affiliation(s)
- Xujuan Zheng
- Health Science Center, Shenzhen University, Shenzhen, China
| | - Juan Xiong
- Health Science Center, Shenzhen University, Shenzhen, China
| | - Yiqin Zhang
- Nephrology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, China
| | - Liping Xu
- Nephrology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, China
| | - Lina Zhou
- Nephrology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, China
| | - Bin Zhao
- Department of Medical Laboratory, Affiliated Xiang'an Hospital of Xiamen University, Xiamen, Fujian, China
| | - Yuxin Wang
- Nephrology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, Fujian, China
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20
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Lai X, Dong Z, Wu S, Zhou X, Zhang G, Xiong S, Wu W, Cao R, Wang X, Hua Q, Du J, Fan J, Mao J, Jiang W, Yuan H, Chen Y, Xu Y, Li Z, Zhang J, Dong G, Zhen H, Ding R, Wu Z, Gao Y. Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial. Circ Cardiovasc Qual Outcomes 2022; 15:e007923. [PMID: 35105177 DOI: 10.1161/circoutcomes.121.007923] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)-lowering efficacy and safety of SXC versus losartan in patients with essential hypertension. METHODS In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of -2.5 mm Hg. RESULTS Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (-7.9 [8.0] versus -8.1 [7.9]). The lower boundary of 95% CI (mean difference, -0.24 [95% CI, -1.51 to 1.03]) was above the margin of -2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (-5.7 [4.2] versus -5.0 [4.0]; P=0.020) and total cholesterol (-0.1 [1.0] versus 0.1 [1.2]; P=0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups. CONCLUSIONS SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine. REGISTRATION URL: www.chictr.org.cn; Unique identifier: ChiCTR-IPR-16008108.
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Affiliation(s)
- Xinxing Lai
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China (X.L., Y.G.).,Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China (X.L., S.W., G.Z., Y.G.).,Institute for TCM-X, MOE Key Laboratory of Bioinformatics/Bioinformatics Division, BNRIST, Department of Automation, Tsinghua University, Beijing, China. (X.L.)
| | - Zhenyu Dong
- Department of Traditional Chinese Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China (Z.D., R.C.)
| | - Shengxian Wu
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China (X.L., S.W., G.Z., Y.G.)
| | - Xiaohua Zhou
- Department of Biostatistics, Beijing International Center for Mathematical Research, Peking University, China (X.Z.).,Department of Biostatistics, School of Public Health, Peking University, Beijing, China (X.Z.)
| | - Genming Zhang
- Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China (X.L., S.W., G.Z., Y.G.)
| | - Shangquan Xiong
- Department of Cardiology, People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, China (S.X.)
| | - Wei Wu
- Department of Cardiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China (W.W.)
| | - Rui Cao
- Department of Traditional Chinese Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China (Z.D., R.C.)
| | - Xiaolong Wang
- Department of Cardiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China (X.W.)
| | - Qi Hua
- Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing, China (Qi Hua)
| | - Jinhang Du
- Department of Cardiology of Integrated Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, China (J.D.)
| | - Jinying Fan
- Department of Cardiology, Yantaishan Hospital, Yantai, China (J.F.)
| | - Jingyuan Mao
- Department of Cardiology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China (J.M.)
| | - Weimin Jiang
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China (X.L., Y.G.).,Department of Cardiology, Jiangsu Province Hospital of TCM, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China (W.J.)
| | - Huishu Yuan
- Department of Cardiology, The Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China (H.Y.)
| | - Yushan Chen
- Department of Cardiology, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China (Y.C.)
| | - Yong Xu
- Department of Cardiovascular Medicine, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China (Y.X.)
| | - Zhanquan Li
- Department of Cardiology, People's Hospital of Liaoning Province, Shenyang, China (Z.L.)
| | - Jun Zhang
- Department of Cardiology, Chengdu First People's Hospital, Chengdu, China (J.Z.)
| | - Guiying Dong
- Department of Hypertension, Jinan Hospital of Traditional Chinese Medicine, Jinan, China (Guiying Dong)
| | - Hui Zhen
- Technical Center for Drug Research and Evaluation, China Association of Traditional Chinese Medicine, Beijing, China (H.Z.)
| | - Ru Ding
- Department of Cardiology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China (R.D., Z.W.)
| | - Zonggui Wu
- Department of Cardiology, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, China (R.D., Z.W.)
| | - Ying Gao
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China (X.L., Y.G.).,Department of Neurology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China (X.L., S.W., G.Z., Y.G.)
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21
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Wang Y, Hua Z, Chen W, Zhu Y, Li Y. Efficacy and safety of Tengfu Jiangya tablet combined with valsartan/amlodipine in the treatment of stage 2 hypertension: study protocol for a randomized controlled trial. Trials 2022; 23:171. [PMID: 35193665 PMCID: PMC8864829 DOI: 10.1186/s13063-022-06089-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 02/07/2022] [Indexed: 11/23/2022] Open
Abstract
Background The prevalence rate of hypertension in the Chinese population is on the rise, and the control rate of hypertension is low. International guidelines, including the 2018 Chinese Guidelines for the Management of Hypertension, recommend optimized drug selection and combination therapy for patients with stage 2 hypertension and blood pressure ≥ 160/100 mmHg, including valsartan/amlodipine (Val/Aml). The traditional Chinese medicine (TCM) compound Tengfu Jiangya tablet (TJT; No. Z20110021, Shandong Provincial Food and Drug Administration) is prepared in the medical institution of Affiliated Hospital of Shandong University of Traditional Chinese Medicine. It is an effective compound preparation of TCM for the treatment of hypertension in the national clinical research base of TCM. The aim of this study was to evaluate the efficacy and safety of TJT combined with Val/Aml in the treatment of stage 2 hypertension with hyperactivity of liver yang. Methods This randomized double-blind, placebo-controlled, multicenter trial will be conducted with a total of 288 participants with stage 2 hypertension at seven clinical trial centers. The stratified random method will be used, and the subcenter will be taken as the stratification factor. Eligible patients will be randomly assigned (1:1) into groups receiving either TJT or placebo three times daily for 28 days, both combined with Val/Aml 80/5 mg. The primary efficacy endpoint is the reduction in the mean sitting systolic blood pressure (msSBP) and the mean sitting diastolic blood pressure (msDBP) from baseline to week 4. Adverse events and laboratory test results will be monitored throughout the trial. Discussion This is the first placebo-controlled randomized trial conducted to evaluate the efficacy and safety of a Chinese herbal extract combined with Val/Aml in patients with stage 2 hypertension. Our study may help to provide evidence-based recommendations of a complementary preventive measure for stage 2 hypertension. Trial registration Chinese Clinical Trial Registry ChiCTR2000030611. Registered on 8 March 2020 Supplementary Information The online version contains supplementary material available at 10.1186/s13063-022-06089-z.
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Affiliation(s)
- Yu Wang
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, China
| | - Zhen Hua
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, China
| | - Wenjing Chen
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, China
| | - Yushuo Zhu
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, China
| | - Yunlun Li
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, Shandong, China. .,Shandong University of Traditional Chinese Medicine, Jinan, 250355, Shandong, China.
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22
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Zhang Q, Shao W, Xiao Y, Wang Y, Zhang J, Ao M. Chinese herbal medicine formula combined with calcium antagonist in the treatment of hypertension: a systematic review and meta-analysis. Clin Exp Hypertens 2022; 44:181-190. [PMID: 35000517 DOI: 10.1080/10641963.2021.2013491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Chinese herbal medicine formula and calcium antagonist are commonly used medicines for hypertension in China. This study aims to examine the efficacy and safety of for the treatment of Chinese herbal medicine formula combined calcium antagonist hypertension. METHODS PubMed, the Cochrane library, CNKI, VIP, Sinomed, and Wanfang Database were searched up to January 31, 2021. Data analysis was performed using the Recman 5.3. The source of clinical heterogeneity used stata16.0 for sensitivity analysis. RESULTS 17 RCTs and 1587 cases were finally included. The results shows that the traditional Chinese medicine decoction combined with calcium antagonists is better than calcium antagonists alone in the treatment of hypertension. In addition, it can effectively alleviate the adverse reactions caused by calcium antagonists. However, due to the low quality of methodology and the small-scale research, more high-quality clinical trials are still needed for verification.
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Affiliation(s)
- Qingyuan Zhang
- Evidence-Based Medicine Research Center, School of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Wenxiang Shao
- Evidence-Based Medicine Research Center, School of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Yonghuan Xiao
- Department of Pain Treatment, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, China
| | - Yaling Wang
- Evidence-Based Medicine Research Center, School of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Jingwen Zhang
- Evidence-Based Medicine Research Center, School of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Meiying Ao
- Evidence-Based Medicine Research Center, School of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, China
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23
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Wei W, Li G, Liu Z, Yang H, Liu S, Zou X, Jiao Y. Feibi decoction-medicated serum inhibits lipopolysaccharide-induced inflammation in RAW264.7 cells and BMDMs. Exp Ther Med 2022; 23:110. [PMID: 34976152 DOI: 10.3892/etm.2021.11033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2018] [Accepted: 07/06/2021] [Indexed: 02/05/2023] Open
Abstract
Feibi decoction (FBD) is a traditional Chinese herbal medicine and has been clinically used in the treatment of pulmonary fibrosis (PF), which is characterized by diffuse interstitial inflammation and exaggerated collagen accumulation. However, the potential mechanisms remain to be elucidated. The present study aimed to investigate the effect of FBD-medicated serum (FBDS) on lipopolysaccharide (LPS)-induced inflammation in macrophages. In RAW264.7 macrophages and bone marrow-derived macrophages (BMDMs), FBDS treatment significantly inhibited the production of pro-inflammatory cytokines induced by LPS. In addition, it was indicated that FBDS treatment suppressed the activation of NF-κB and Smad2/Smad3 following LPS treatment. Furthermore, FBDS treatment decreased the expression of transforming growth factor-β1 and chitinase-3-like protein 1. In conclusion, the results demonstrated that treatment with FBDS inhibited LPS-induced inflammation in RAW264.7 and BMDM cells. These data may improve understanding of the effect of FBD on anti-inflammation and help determine the mechanisms underlying the alleviation of PF via FBD.
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Affiliation(s)
- Wan Wei
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.,Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100078, P.R. China
| | - Guodong Li
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Zhaoheng Liu
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Haojie Yang
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Shuo Liu
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Xinxin Zou
- Graduate School, Beijing University of Chinese Medicine, Beijing 100029, P.R. China
| | - Yang Jiao
- Dongfang Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100078, P.R. China
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Wu QJ, Lv WL, Li JM, Zhang TT, Zhou WH, Zhang Q, Wang JC, Wang QN, Yao ZA, Qiang R, Chen ST, Zhao X, Liu S, Cao ZM, Xu L, Li GH, Chen J, Wang L. YinQiSanHuang Jiedu decoction for the treatment of hepatitis B-related compensated liver cirrhosis: study protocol for a multi-center randomized controlled trial. Trials 2021; 22:701. [PMID: 34649610 PMCID: PMC8515328 DOI: 10.1186/s13063-021-05650-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 09/23/2021] [Indexed: 11/10/2022] Open
Abstract
INTRODUCTION Hepatitis B-related compensated liver cirrhosis is related to a higher risk of hepatocellular carcinoma, and antiviral therapy is the preferred method. As the pathological mechanisms of liver fibrosis are complex, drugs developed for a single target are difficult to be effective in clinical practice, so there are no chemical drugs or biological drugs with clear efficacy available for clinical application at present. Traditional Chinese medicine is a kind of medical science that has been gradually formed during thousands of years and continuously enriched by the people of all ethnic groups in China. Traditional Chinese medicine shows curative effects in the treatment of liver diseases, especially in the field of liver fibrosis prevention and treatment. This study aims to test the integrative medicine (Chinese medicine plus antiviral therapy) effective on lowing hepatocellular carcinoma risk among patients with hepatitis-related compensated liver cirrhosis. METHODS AND ANALYSIS This is a multi-center randomized controlled trial, and a total of 5 hospitals and 802 patients will be involved in. All the subjects are randomly allocated to the YinQiSanHuang Jiedu decoction (YQSHD) group (n = 401) or the placebo group (n = 401). The YQSHD group receives YQSHD granule with entecavir (ETV), and the placebo group receives YQSHD placebo with ETV. The treatment period will last for 52 weeks, and the follow-up period for 52 ± 2 weeks. The primary outcome measure is the annual incidence of HCC. Outcomes will be assessed at baseline and after treatment. The objective of this trial is "the integrative of YQSHD with ETV reduce the annual incidence of HCC to 1%." ETHICS AND DISSEMINATION The protocol has been approved by the Medical Ethics Committee of Guang'anmen Hospital, China (No.2019-006-KY), and the other centers in the trial will not begin recruiting until the local ethical approval has been obtained. Trial final results will be disseminated via publication. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR1900021532 . Registered on February 26, 2019.
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Affiliation(s)
- Qing-Juan Wu
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Wen-Liang Lv
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China.
| | - Juan-Mei Li
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Ting-Ting Zhang
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Wen-Hui Zhou
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Qiang Zhang
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Jiu-Chong Wang
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Qing-Nan Wang
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Zi-Ang Yao
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China.,Beijing University of Chinese Medicine, Beijing, China
| | - Rui Qiang
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Si-Tong Chen
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China.,Beijing University of Chinese Medicine, Beijing, China
| | - Xin Zhao
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China.,Beijing University of Chinese Medicine, Beijing, China
| | - Shuang Liu
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Zheng-Min Cao
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China.,Beijing University of Chinese Medicine, Beijing, China
| | - Lei Xu
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China.,Beijing University of Chinese Medicine, Beijing, China
| | - Gao-Hui Li
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Jing Chen
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China
| | - Li Wang
- China Academy of Traditional Chinese Medicine Guanganmen Hospital, Beijing, China.,Beijing University of Chinese Medicine, Beijing, China
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25
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Li Q, Lan T, He S, Chen W, Li X, Zhang W, Liu Y, Zhang Q, Chen X, Han Y, Su Z, Zhu D, Guo H. A network pharmacology-based approach to explore the active ingredients and molecular mechanism of Lei-gong-gen formula granule on a spontaneously hypertensive rat model. Chin Med 2021; 16:99. [PMID: 34627325 PMCID: PMC8501634 DOI: 10.1186/s13020-021-00507-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Accepted: 09/17/2021] [Indexed: 12/28/2022] Open
Abstract
Background Lei-gong-gen formula granule (LFG) is a folk prescription derived from Zhuang nationality, the largest ethnic minority among 56 nationalities in China. It consists of three herbs, namely Eclipta prostrata (L.) L., Smilax glabra Roxb, and Centella asiatica (L.) Urb. It has been widely used as health protection tea for hundreds of years to prevent hypertension in Guangxi Zhuang Autonomous Region. The purpose of this study is to validate the antihypertensive effect of LFG on the spontaneously hypertensive rat (SHR) model, and to further identify the effective components and anti-hypertension mechanism of LFG. Methods The effects of LFG on blood pressure, body weight, and heart rate were investigated in vivo using the SHR model. The levels of NO, ANG II, and ET-1 in the serum were measured, and pathological changes in the heart were examined by H&E staining. The main active components of LFG, their corresponding targets, and hypertension associated pathways were discerned through network pharmacology analysis based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Then the predicted results were further verified by molecular biology experiments such as RT-qPCR and western blot. Additionally, the potential active compounds were predicted by molecular docking technology, and the chemical constituents of LFG were analyzed and identified by UPLC-QTOF/MS technology. Finally, an in vitro assay was performed to investigate the protective effects of potential active compounds against hydrogen peroxide (H2O2) induced oxidative damage in human umbilical vein endothelial cells (HUVEC). Results LFG could effectively reduce blood pressure and increase serum NO content in SHR model. Histological results showed that LFG could ameliorate pathological changes such as cardiac hypertrophy and interstitial inflammation. From network pharmacology analysis, 53 candidate active compounds of LFG were collected, which linked to 765 potential targets, and 828 hypertension associated targets were retrieved, from which 12 overlapped targets both related to candidate active compounds from LFG and hypertension were screened and used as the potential targets of LFG on antihypertensive effect. The molecular biology experiments of the 12 overlapped targets showed that LFG could upregulate the mRNA and protein expressions of NOS3 and proto-oncogene tyrosine-protein kinase SRC (SRC) in the thoracic aorta. Pathway enrichment analysis showed that the PI3K-AKT signaling pathway was closely related to the expression of NOS3 and SRC. Moreover, western blot results showed that LFG significantly increased the protein expression levels of PI3K and phosphorylated AKT in SHR model, suggesting that LFG may active the PI3K-AKT signaling pathway to decrease hypertension. Molecular docking study further supported that p-hydroxybenzoic acid, cedar acid, shikimic acid, salicylic acid, nicotinic acid, linalool, and histidine can be well binding with NOS3, SRC, PI3K, and AKT. UPLC-QTOF/MS analysis confirmed that p-hydroxybenzoic acid, shikimic acid, salicylic acid, and nicotinic acid existed in LFG. Pre-treatment of HUVEC with nicotinic acid could alleviate the effect on cell viability induced by H2O2 and increase the NO level in cell supernatants. Conclusions LFG can reduce the blood pressure in SHR model, which might be attributed to increasing the NO level in serum for promoting vasodilation via upregulating SRC expression level and activating the PI3K-AKT-NOS3 signaling pathway. Nicotinic acid might be the potential compound for LFG antihypertensive effect. Supplementary Information The online version contains supplementary material available at 10.1186/s13020-021-00507-1.
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Affiliation(s)
- Qiaofeng Li
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, China.,Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, School of preclinical medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Taijin Lan
- School of preclinical medicine, Guangxi University of Chinese Medicine, 179 Mingxiu Dong Road, Nanning, 530001, China
| | - Songhua He
- Guangxi Institute for Food and Drug Control, 9 Qinghu Road, Nanning, 530021, China
| | - Weiwei Chen
- Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China.,International Joint Laboratory on Regeneration of Bone and Soft Tissues, Guangxi Medical University, Guangxi, 530021, China
| | - Xiaolan Li
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, China.,Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, School of preclinical medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Weiquan Zhang
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, China.,Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, School of preclinical medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Ying Liu
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, School of preclinical medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China.,College of Pharmacy, Guangxi University of Chinese Medicine, 179 Mingxiu Dong Road, Nanning, 530001, China
| | - Qiuping Zhang
- Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, School of preclinical medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China.,The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, China
| | - Xin Chen
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, China.,Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, School of preclinical medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Yaoyao Han
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, China.,Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, School of preclinical medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Zhiheng Su
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, China.
| | - Dan Zhu
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, China.
| | - Hongwei Guo
- Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation & College of Pharmacy, Guangxi Medical University, 22 Shuangyong Road, Nanning, 530021, China. .,Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education & Center for Translational Medicine, School of preclinical medicine, Guangxi Medical University, Nanning, 530021, Guangxi, China. .,Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, 530021, China.
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Ni J, Yao M, Wang LH, Yu M, Li RH, Zhao LH, Wang JC, Wang YZ, Wang X, Song HQ, Luo BY, Wang JW, Huang YN, Cui LY. Human urinary kallidinogenase in acute ischemic stroke: A single-arm, multicenter, phase IV study (RESK study). CNS Neurosci Ther 2021; 27:1493-1503. [PMID: 34510762 PMCID: PMC8611767 DOI: 10.1111/cns.13724] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/13/2021] [Accepted: 08/17/2021] [Indexed: 12/21/2022] Open
Abstract
Aims Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. Methods RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment‐emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. Results Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment‐emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre‐specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug‐related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post‐treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90‐day assessment. Conclusion HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real‐world large population.
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Affiliation(s)
- Jun Ni
- Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ming Yao
- Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li-Hua Wang
- Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ming Yu
- Department of Neurology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Run-Hui Li
- Department of Neurology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, China
| | - Li-Hong Zhao
- Department of Neurology, Dandong People's Hospital, Dandong, China
| | - Jia-Chun Wang
- Department of Neurology, No. 1 Hospital of Harbin, Harbin, China
| | - Yin-Zhou Wang
- Department of Neurology, Fujian Provincial Hospital, Fuzhou, China
| | - Xin Wang
- Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Hai-Qing Song
- Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China
| | - Ben-Yan Luo
- Department of Neurology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jia-Wei Wang
- Department of Neurology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
| | - Yi-Ning Huang
- Department of Neurology, Peking University First Hospital, Beijing, China
| | - Li-Ying Cui
- Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Du H, Xiao G, Xue Z, Li Z, He S, Du X, Zhou Z, Cao L, Wang Y, Yang J, Wang X, Zhu Y. QiShenYiQi ameliorates salt-induced hypertensive nephropathy by balancing ADRA1D and SIK1 expression in Dahl salt-sensitive rats. Biomed Pharmacother 2021; 141:111941. [PMID: 34328102 DOI: 10.1016/j.biopha.2021.111941] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 07/08/2021] [Accepted: 07/14/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Hypertension is a leading risk factor for developing kidney disease. Current single-target antihypertensive drugs are not effective for hypertensive nephropathy, in part due to its less understood mechanism of pathogenesis. We recently showed that QiShenYiQi (QSYQ), a component-based cardiovascular Chinese medicine, is also effective for ischemic stroke. Given the important role of the brain-heart-kidney axis in blood pressure control, we hypothesized that QSYQ may contribute to blood pressure regulation and kidney protection in Dahl salt-sensitive hypertensive rats. METHODS The therapeutic effects of QSYQ on blood pressure and kidney injury in Dahl salt-sensitive rats fed with high salt for 9 weeks were evaluated by tail-cuff blood pressure monitoring, renal histopathological examination and biochemical indicators in urine and serum. RNA-seq was conducted to identify QSYQ regulated genes in hypertensive kidney, and RT-qPCR, immunohistochemistry, and Western blotting analysis were performed to verify the transcriptomics results and validate the purposed mechanisms. RESULTS QSYQ treatment significantly decreased blood pressure in Dahl salt-sensitive hypertensive rats, alleviated renal tissue damage, reduced renal interstitial fibrosis and collagen deposition, and improved renal physiological function. RNA-seq and subsequent bioinformatic analysis showed that the expression of ADRA1D and SIK1 genes were among the most prominently altered by QSYQ in salt-sensitive hypertensive rat kidney. RT-qPCR, immunohistochemistry and Western blotting results confirmed that the mRNA and protein expression levels of alpha-1D adrenergic receptor (ADRA1D) in the kidney tissue of the QSYQ-treated rats were markedly down-regulated, while the mRNA and protein levels of salt inducible kinase 1 (SIK1) were significantly increased. CONCLUSION QSYQ not only lowered blood pressure, but also alleviated renal damage via reducing the expression of ADRA1D and increasing the expression of SIK1 in the kidney of Dahl salt-sensitive hypertensive rats.
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Affiliation(s)
- Hongxia Du
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Guangxu Xiao
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Zhifeng Xue
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Zhixiong Li
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Shuang He
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Xiaoli Du
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China; Inner Mongolia Medical University, Hohhot 010110, China
| | - Zhengchan Zhou
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Linghua Cao
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Yule Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Jian Yang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China
| | - Xiaoying Wang
- Department of Neurosurgery, Clinical Neuroscience Research Center, Tulane University School of Medicine, New Orleans, LA, USA
| | - Yan Zhu
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Beihua South Road, JingHai District, Tianjin 301617, China; Research and Development Center of TCM, Tianjin International Joint Academy of Biotechnology & Medicine, 220 Dongting Road, TEDA, Tianjin 300457, China.
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Cui Z, Jiamei Y, Yushu Y, Xia F, Haiyan Y, Zhang D, Qiong C, Guangwei Z. Effect of the traditional Chinese medicine Pinggan-Qianyang decoction on SIRT1-PTEN signaling in vascular aging in spontaneously hypertensive rats. Hypertens Res 2021; 44:1087-1098. [PMID: 34188208 PMCID: PMC8418988 DOI: 10.1038/s41440-021-00682-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 04/19/2021] [Accepted: 04/27/2021] [Indexed: 11/09/2022]
Abstract
Age-related functional decline is a physiological phenomenon that occurs in all organ systems. However, the acceleration and early occurrence of this process are observed in cardiovascular pathologies, including hypertension. This study aimed to investigate SIRT1-PTEN signaling in aortic tissue from spontaneously hypertensive rats (SHRs) and changes in SIRT1 and PTEN expression following treatment with Pinggan-Qianyang decoction (PGQYD) and explore the mechanism involved in the treatment of hypertensive vascular aging with traditional Chinese medicine. In this study, we used two rat models: spontaneously hypertensive rats (SHRs) at 14 and 64 weeks of age and WKY rats at 64 weeks of age. The degree of irritability and rotation tolerance time were evaluated to determine the effects of PGQYD on animal behavior. The morphology of the thoracic aorta was examined by hematoxylin-eosin (HE) and Masson staining and electron microscopy. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and superoxide dismutase (SOD) and anti-superoxide anion content were detected. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe the thoracic aorta during vascular aging. RT-qPCR, immunofluorescence, and Western blot analysis were performed to detect changes in the mRNA and protein expression of p53, p21, SIRT1, and PTEN in rat aortic tissues. Behavioral tests and histological and morphological analyses showed the remarkable amelioration of vascular aging after PGQYD treatment compared with that in the older SHRs. Moreover, PGQYD significantly decreased vascular aging in SHRs, as indicated by reduced SA-β-Gal staining, NADPH oxidase activity, and p53 and p21 expression, and increased anti-superoxide anion and SOD content. Furthermore, PGQYD increased SIRT1 and PTEN expression, but the downregulated expression of SIRT1 induced by a SIRT1 inhibitor abolished the PGQYD-induced antiaging effects on gene expression and antioxidant activity and enhanced PTEN expression. PGQYD could ameliorate vascular aging effects in SHRs, which may have been mediated via the regulation of SIRT1-PTEN signaling in aortic tissue.
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Affiliation(s)
- Zhang Cui
- International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China
| | - Yao Jiamei
- International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China
| | - Yang Yushu
- International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China
| | - Fang Xia
- International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China
| | - Yang Haiyan
- International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China
| | - Dan Zhang
- International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China
| | - Chen Qiong
- International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China
| | - Zhong Guangwei
- International Medical Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China. .,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, P.R. China.
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Du X, Tao Q, Du H, Zhao Z, Dong Y, He S, Shao R, Wang Y, Han W, Wang X, Zhu Y. Tengdan Capsule Prevents Hypertensive Kidney Damage in SHR by Inhibiting Periostin-Mediated Renal Fibrosis. Front Pharmacol 2021; 12:638298. [PMID: 34084130 PMCID: PMC8167194 DOI: 10.3389/fphar.2021.638298] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Accepted: 04/08/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND: Hypertension-induced renal damage is a serious and complex condition that has not been effectively treated by conventional blood pressure-lowering drugs. Tengdan capsule (TDC) is a China FDA-approved compound herbal medicine for treating hypertension; however, its chemical basis and pharmacological efficacy have not been fully investigated in a preclinical setting. METHODS: High-performance liquid chromatography (HPLC) was used to identify and quantify the major chemical components of TDC extracted from ultrapure water. Adult spontaneously hypertensive rats (SHR) and age/sex-matched Wistar Kyoto normotensive rats (WKY) were both treated with TDC, losartan, or saline for one month, and their blood pressure (BP) was monitored at the same time by tail-cuff BP system. Biochemical indexes such as urine creatinine (CRE) and blood urea nitrogen (BUN) were determined. Kidney tissue sections were examined with (H&E), and Masson staining to evaluate the pathological effect of TDC on SHR’s kidneys. After TDC treatment, the differentially expressed proteins in the kidneys of SHR were identified by the TMT-based quantitative proteomics analysis, which may provide the targets and possible mechanisms of TDC action. In addition, Western blot analysis, RT-qPCR, and ELISA assays were carried out to further verify the proteomics findings. Finally, two different models involving in vitro renal injuries were established using human kidney HEK293 cells; and the molecular mechanism of TDC kidney protection was demonstrated. RESULTS: Seven chemical compounds, namely Notoginsenoside R1, Ginsenoside RG1, Ginsenoside Re, Ginsenoside Rb1, Sodium Danshensu, Protocatechualdehyde, and Salvianolic acid B, were identified and quantified from the water-soluble extracts of TDC by HPLC. In vivo study using rats showed that TDC effectively reduced BP, BUN, and CRE levels and attenuated renal fibrosis in SHR, and ameliorated damage to the kidneys. Proteomics and subsequent bioinformatics analyses indicated that periostin-mediated inflammatory response and TGFβ/Smad signaling pathway proteins were closely related to the therapeutic effect of TDC in rat kidneys. Western blot analysis and RT-qPCR showed that TDC markedly downregulated the mRNA and protein expression of periostin in renal tissues compared to the untreated SHR. In addition, TGF-β and COL1A1 mRNA levels also decreased in SHR renal tissues following TDC treatment. In vitro studies showed that low to medium doses of TDC down-regulated the expression of periostin in the injury model of HEK293 cell. In addition, medium to high doses of TDC significantly inhibited collagen deposition in TGFβ1-induced HEK293 cell fibrosis. CONCLUSIONS: Major components from the compound herbal medicine Tengdan Capsule are identified and quantified. TDC effectively lowers blood pressure and protects against renal damage caused by hypertension in SHR. Mechanistically, TDC blocks periostin by regulating the TGF-β/Smad signaling pathway in the kidney, both in vivo and in vitro. Preventing periostin-mediated renal fibrosis and inflammation might be a promising strategy for treating a hypertensive renal injury.
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Affiliation(s)
- Xiaoli Du
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Department of pharmacy, Inner Mongolia Medical College, Hohhot, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
| | - Qianqian Tao
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
| | - Hongxia Du
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
| | - Zhenbang Zhao
- Department of pharmacy, Inner Mongolia Medical College, Hohhot, China
| | - Yu Dong
- Department of pharmacy, Inner Mongolia Medical College, Hohhot, China.,Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Shuang He
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
| | - Rui Shao
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
| | - Yule Wang
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
| | - Wenrun Han
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
| | - Xintong Wang
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
| | - Yan Zhu
- Institute of Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.,Tianjin International Joint Academy of Biomedicine, Tianjin, China
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Ye X, Yi Q, Shao J, Zhang Y, Zha M, Yang Q, Xia W, Ye Z, Song P. Trends in Prevalence of Hypertension and Hypertension Phenotypes Among Chinese Children and Adolescents Over Two Decades (1991-2015). Front Cardiovasc Med 2021; 8:627741. [PMID: 34046436 PMCID: PMC8144307 DOI: 10.3389/fcvm.2021.627741] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 04/08/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Hypertension is a leading cause of cardiovascular-related morbidity and mortality. Elevated blood pressure (BP) in children is related to long-term adverse health effects. Until recently, few studies have reported the secular trend and associated factors of hypertension phenotypes in Chinese children and adolescents. Methods: From the China Health and Nutrition Survey (CHNS) 1991-2015, a total of 15,143 records of children aged 7-17 years old were included. Following definitions of hypertension from the Chinese Child Blood Pressure References Collaborative Group, we estimated the prevalence of prehypertension, hypertension, stage 1 hypertension, stage 2 hypertension and its phenotypes (ISH, isolated systolic hypertension; IDH, isolated diastolic hypertension; SDH, combined systolic and diastolic hypertension). General estimation equation was used to analyze the trends in the prevalence of hypertension and hypertension phenotypes, and a multivariable logistic regression was constructed to explore the associated factors. Results: During 1991-2015, increasing trends were revealed in BP and hypertension prevalence (P < 0.001) in Chinese children and adolescents. For ISH, IDH and SDH, the age-standardized prevalence increased dramatically from 0.9 to 2.2%, from 6.2 to 14.1%, and from 1.4 to 2.9%, respectively (all P < 0.001). Adolescents aged 13-17 years (OR = 1.76, 95% CI: 1.56-1.97, P < 0.001), general obesity (OR = 2.69, 95% CI: 2.10-3.44, P < 0.001) and central obesity (OR = 1.49, 95% CI: 1.21-1.83, P < 0.001) were positively associated with hypertension, whereas the South region (OR = 0.65, 95% CI: 0.58-0.73, P < 0.001) was a negative factor. Furthermore, body mass index (BMI) and general obesity were linked to the presence of ISH, IDH and SDH. Age, waist circumference (WC) and central obesity were additionally associated with ISH, and sex, age, urban/rural setting, North/South region, WC and central obesity were additionally associated with IDH. Conclusion: BP levels and prevalence of hypertension and phenotypes increased dramatically in Chinese children and adolescents from 1991 to 2015. Regional discrepancy, demographic features, BMI, WC and overweight/obesity status were associated factors of hypertension among youths.
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Affiliation(s)
- Xinxin Ye
- School of Public Health, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Qian Yi
- School of Public Health, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Jing Shao
- School of Nursing, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Yan Zhang
- Faculty of Life Science and Medicine, Kings College London, London, United Kingdom
| | - Mingming Zha
- Medical School Southeast University, Nanjing, China
| | - Qingwen Yang
- Medical School Southeast University, Nanjing, China
| | - Wei Xia
- School of Nursing, Sun Yat-Sen University, Guangdong, China
| | - Zhihong Ye
- School of Nursing, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
| | - Peige Song
- School of Public Health, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China.,Women's Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, China
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31
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Zheng S, Huang H, Li Y, Wang Y, Zheng Y, Liang J, Zhang S, Liu M, Fang Z. Yin-xing-tong-mai decoction attenuates atherosclerosis via activating PPARγ-LXRα-ABCA1/ABCG1 pathway. Pharmacol Res 2021; 169:105639. [PMID: 33932607 DOI: 10.1016/j.phrs.2021.105639] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 03/30/2021] [Accepted: 04/20/2021] [Indexed: 12/23/2022]
Abstract
Atherosclerosis is now the major cause of mortality and morbidity worldwide. Formation of macrophage-derived foam cells is a hallmark of atherosclerosis, which is regulated by cholesterol uptake, intracellular metabolism, and efflux. PPARγ-LXRα-ABCA1/ABCG1 pathway plays an important part in regulating cholesterol efflux and this pathway could be a promising target for treating atherosclerosis. However, due to undesirable systemic effects, PPARγ agonist therapy for atherosclerosis remains challenging. Many traditional Chinese medicine has been well accepted and applied in atherosclerosis treatment. Yin-xing-tong-mai decoction (YXTMD) has been applied for treating atherosclerosis for decades. However, the mechanism remains to be explored. Here, we showed that YXTMD effectively attenuated atherosclerosis in ApoE-/- mice. YXTMD increased cholesterol efflux of foam cell by upregulation of ABCA1 and ABCG1 in vivo and in vitro. Through bioinformatic analysis and experimental validation, we found that PPARγ was an important downstream effector of YXTMD in macrophages. Reduction of PPARγ significantly decreased LXRα, ABCA1, and ABCG1 expression in macrophages, with reduced cholesterol efflux. In conclusion, these findings confirmed that YXTMD attenuated atherosclerosis by activating the PPARγ-LXRα- ABCA1/ABCG1 pathway to enhance cholesterol efflux.
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Affiliation(s)
- Shasha Zheng
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hong Huang
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yizhuo Li
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ye Wang
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yawei Zheng
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Junya Liang
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Siqi Zhang
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ming Liu
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
| | - Zhuyuan Fang
- Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
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32
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Chen J, Zhang Y, Wang Y, Jiang P, Zhou G, Li Z, Yang J, Li X. Potential mechanisms of Guizhi decoction against hypertension based on network pharmacology and Dahl salt-sensitive rat model. Chin Med 2021; 16:34. [PMID: 33906674 PMCID: PMC8077739 DOI: 10.1186/s13020-021-00446-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2021] [Accepted: 04/20/2021] [Indexed: 12/11/2022] Open
Abstract
Background Guizhi decoction (GZD), a classical Chinese herbal formula, has been widely used to treat hypertension, but its underlying mechanisms remain elusive. The present study aimed to explore the potential mechanisms and therapeutic effects of GZD on hypertension by integrating network pharmacology and experimental validation. Methods The active ingredients and corresponding targets were collected from the Traditional Chinese Medicine Systems Pharmacology database and Analysis Platform (TCMSP). The targets related to hypertension were identified from the CTD, GeneCards, OMIM and Drugbank databases. Multiple networks were constructed to identify the key compounds, hub targets, and main biological processes and pathways of GZD against hypertension. The Surflex-Dock software was used to validate the binding affinity between key targets and their corresponding active compounds. The Dahl salt-sensitive rat model was used to evaluate the therapeutic effects of GZD against hypertension. Results A total of 112 active ingredients, 222 targets of GZD and 341 hypertension-related targets were obtained. Furthermore, 56 overlapping targets were identified, five of which were determined as the hub targets for experimental verification, including interleukin 6 (IL-6), C–C motif chemokine 2 (CCL2), IL-1β, matrix metalloproteinase 2 (MMP-2), and MMP-9. Pathway enrichment analysis results indicated that 56 overlapping targets were mainly enriched in several inflammation pathways such as the tumor necrosis factor (TNF) signaling pathway, Toll-like receptor (TLR) signaling pathway and nuclear factor kappa-B (NF-κB) signaling pathway. Molecular docking confirmed that most active compounds of GZD could bind tightly to the key targets. Experimental studies revealed that the administration of GZD improved blood pressure, reduced the area of cardiac fibrosis, and inhibited the expression of IL-6, CCL2, IL-1β, MMP-2 and MMP-9 in rats. Conclusion The potential mechanisms and therapeutic effects of GZD on hypertension may be attributed to the regulation of cardiac inflammation and fibrosis. Supplementary Information The online version contains supplementary material available at 10.1186/s13020-021-00446-x.
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Affiliation(s)
- Jiye Chen
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Yongjian Zhang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Yongcheng Wang
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China
| | - Ping Jiang
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Guofeng Zhou
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Zhaoyu Li
- First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Jinlong Yang
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China
| | - Xiao Li
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, China.
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El-Hilaly J, Amarouch MY, Morel N, Lyoussi B, Quetin-Leclercq J. Ajuga iva water extract antihypertensive effect on stroke-prone spontaneously hypertensive rats, vasorelaxant effects ex vivo and in vitro activity of fractions. JOURNAL OF ETHNOPHARMACOLOGY 2021; 270:113791. [PMID: 33444718 DOI: 10.1016/j.jep.2021.113791] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 12/18/2020] [Accepted: 01/02/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ajuga iva (L.) Schreb. (Labiatae) (AI) is used in folk medicine for a variety of ailments, including diabetes mellitus and hypertension. AIM OF THE STUDY In this work, we aimed to investigate the antihypertensive and vasorelaxant effects of AI aqueous extract in stroke prone spontaneously hypertensive rats (SHR-SP). MATERIAL AND METHODS Male SHR-SP rats were orally force-fed AI aqueous extract (500 mg/kg body weight) daily for one week. Systolic blood pressure and urine output were recorded in vivo by non-invasive methods. AI vasoactive effects on noradrenaline contractile response and acetylcholine-evoked relaxation were assessed ex vivo on aorta rings of treated and untreated SHR-SP rats. AI extract was then subjected to bio-guided fractionation using solvents of increasing polarity. For each fraction, in vitro vasorelaxation assay was performed on noradrenaline-precontracted aorta of Wistar rats, in the absence/presence of N-nitro-L-arginine (L-NNA). HPLC analysis of AI total extract, and the most in vitro active AI residual aqueous extract fraction (A1) was performed using naringin, naringenin, apigenin, apigenin 7-O-glucoside as marker compounds. RESULTS AI aqueous extract (500 mg/kg) significantly (P < 0.05) decreased systolic blood pressure (SBP) in SHR-SP rats, while not affecting the urine output. In ex vivo experiments, the total extract decreased contractile response to noradrenaline of aortic rings isolated from AI-treated SHR-SP rats with or without addition of N-nitro-L-arginine, but endothelium dependent relaxation evoked by acetylcholine in noradrenaline-contracted aortic rings was not affected by the extract treatment. In vitro experiments on AI aqueous extract fractions showed that its polar fraction was the only one affecting in vitro noradrenaline induced contractions, but only in an endothelium dependent manner. This fraction was shown by HPLC-UV to contain flavonoid glycosides among other polar compounds whose activity and mode of action may be modified in vivo by metabolization. CONCLUSION These results support the use of AI as antihypertensive treatment in folk medicine. The systolic blood pressure decrease may be attributed at least in part to vasorelaxant glycosylated/polar phenolic compounds as flavonoids and/or their metabolites.
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Affiliation(s)
- Jaouad El-Hilaly
- Laboratory of Engineering Pedagogy and Sciences Didactics, Department of Life Sciences, Regional Center of Education and Training Careers (CRMEF), Fez, Morocco; R.N.E Laboratory, Multidisciplinary Faculty of Taza, University Sidi Mohamed Ben Abdellah, Fez, Morocco; Louvain Drug Research Institute, Pharmacognosy Research Group, Université catholique de Louvain, UCLouvain, Brussels, Belgium.
| | - Mohamed-Yassine Amarouch
- R.N.E Laboratory, Multidisciplinary Faculty of Taza, University Sidi Mohamed Ben Abdellah, Fez, Morocco.
| | - Nicole Morel
- Laboratoire de Physiologie Cellulaire, CEMO, Université catholique de Louvain, UCLouvain, Brussels, Belgium.
| | - Badiaâ Lyoussi
- Laboratory of Natural Substances, Pharmacology, Environment, Modeling, Health and Quality of Life (SNAMOPEQ), University Sidi Mohamed Ben Abdellah, Fez, Morocco.
| | - Joëlle Quetin-Leclercq
- Louvain Drug Research Institute, Pharmacognosy Research Group, Université catholique de Louvain, UCLouvain, Brussels, Belgium.
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Severe hypertension in China: results from the China PEACE million persons project. J Hypertens 2021; 39:461-470. [PMID: 33038086 PMCID: PMC7928212 DOI: 10.1097/hjh.0000000000002675] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Revised: 09/03/2020] [Accepted: 09/15/2020] [Indexed: 01/13/2023]
Abstract
INTRODUCTION People with severe hypertension have high risk of target organ damage, yet few studies focus specifically on this population. We sought to assess the characteristics, prevalence, awareness, and treatment patterns of severe hypertension among middle-aged adults in China. METHODS We enrolled 2 660 666 participants aged 35-75 years from 31 provinces between 2014 and 2018 in the cross-sectional China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project. Severe hypertension was defined as SBP of at least 160 mmHg or DBP of at least 100 mmHg. Awareness and treatment were defined as self-reported diagnosis of hypertension and current use of antihypertensive medication, respectively. Analyses were completed in 2019. RESULTS Our sample included 2 618 757 adults with a mean age of 55.6 years (SD 9.8), 59.6% of whom were women. A total of 378 457 (14.5%) participants had severe hypertension, of whom 222 533 (58.8%) were untreated. The age--sex-standardized rate of severe hypertension was 11.6% based on the 2010 Chinese Census data. Advanced age, female sex, current drinking, obesity, lower income, diabetes, and prior cardiovascular events were associated with higher risk of severe hypertension (all P < 0.01). Of untreated participants with severe hypertension, only 60 484 (27.1%) were aware of their conditions. Among participants with severe hypertension despite treatment, 84.7% reported taking one class of antihypertensive medication; only 15% reported taking guideline-recommended combination therapy. CONCLUSION Many millions of people in China have severe hypertension and the vast majority are unaware of their condition and undertreated. There are immense opportunities to improve outcomes in this high-risk group.
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35
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Comparative transcriptomic analysis revealed novel potential therapeutic targets of traditional Chinese medicine (Pinggan-Qianyang decoction) on vascular remodeling in spontaneously hypertensive rats. Chin Med 2021; 16:21. [PMID: 33568194 PMCID: PMC7877093 DOI: 10.1186/s13020-021-00431-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2020] [Accepted: 01/29/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Both experimental and clinical studies have revealed satisfactory effects with the traditional Chinese formula Pinggan Qianyang decoction (PGQYD) for improving vascular remodeling caused by essential hypertension. The present study explored various therapeutic targets of PGQYD using mRNA transcriptomics. METHODS In this study, rats were randomly divided into three groups: Wistar-Kyoto (WKY; normal control), spontaneously hypertensive (SHR), and PGQYD-treated rat groups. After 12 weeks of PGQYD treatment, behavioral tests were employed and the morphology of thoracic aortas were examined with hematoxylin-eosin (HE) and Masson staining and electron microscopy. The mRNA expression profiles were identified with RNA-Seq and quantitative real-time PCR to validate changes in gene expression observed with microarray analysis. The gene ontology and pathway enrichment analyses were carried out to predict gene function and gene co-expressions. Pathway networks were constructed to identify the hub biomarkers, which were further validated by western blotting and immunofluorescence analysis. RESULTS After PGQYD treatment, the behavioral tests and histological and morphological findings of vascular remodeling were obviously meliorated compared with the SHR group. In the rat thoracic aorta tissues, 626 mRNAs with an exact match were identified. A total of 129 of mRNAs (fold change > 1.3 and P-value < 0.05) were significantly changed in the SHR group compared to the WKY group. Among them, 16 mRNAs were markedly regulated by PGQYD treatment and validated with quantitative real-time PCR. Additionally, target prediction and bioinformatics analyses revealed that these mRNAs could play therapeutic roles through biological processes for regulating cell metabolic processes (such as glycation biology), biological adhesions, rhythmic processes, and cell autophagy. The cellular signaling pathways involved in autophagy may be AGE-RAGE/PI3K/Akt/mTOR signaling pathway. CONCLUSION The present study provides novel insights for future investigations to explore the mechanisms by which PGQYD may effectively inhibit vascular remodeling by activating the AGE-RAGE/PI3K/Akt/mTOR signal pathway in cell autophagy biology.
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36
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Alharbi H, Ahmad M, Tian Z, Yu R, Li YL. Therapeutic value of the metabolomic active neurotransmitter isorhynchophylline in the treatment of spontaneously hypertensive rats by regulating neurotransmitters. Transl Neurosci 2021; 12:425-431. [PMID: 34760298 PMCID: PMC8562224 DOI: 10.1515/tnsci-2020-0185] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 11/29/2022] Open
Abstract
Hypertension is one of the most reported cardiovascular and cerebrovascular diseases with significantly high morbidity and mortality rates. This condition threatens the very existence of human beings. Numerous studies conducted earlier revealed the good therapeutic effect of isorhynchophylline on hypertension since the former regulates the metabolic disorders in neurotransmitters. However, the mechanism behind this action is yet to be deciphered. The current study followed the targeted metabolomics method to investigate the changes in the neurotransmitter level in the hippocampus of spontaneously hypertensive rats (SHRs) after the rats were treated with isorhynchophylline. The authors predicted the metabolic pathways involved in extensively modified neurotransmitters. Further, the expressions of metabolism-key enzymes in mRNA and protein levels were also determined. When treated with isorhynchophylline, it induced notably varying metabolomic profiles of the hippocampus in SHRs. Isorhynchophylline perturbed a total of seven extensively modified neurotransmitters as well as the primarily related pathways such as tyrosine and glutamate metabolism. An increase in the key metabolic enzymes such as DDC, MAO, COMT, TH, and DβH was observed in the SHR group, whereas their levels decreased after treatment with isorhynchophylline. The expression of GAD67 established cross-current validity. So, isorhynchophylline has been proved to have potential therapeutic value to treat hypertension via tyrosine and glutamate metabolism in the hippocampus. Further, the current study also opened new ventures to further investigate the working mechanism of isorhynchophylline in hypertension.
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Affiliation(s)
- Homood Alharbi
- Department of Medical Surgical Nursing, College of Nursing, King Saud University, Riyadh, Saudi Arabia
| | - Mohammad Ahmad
- Department of Medical Surgical Nursing, College of Nursing, King Saud University, Riyadh, Saudi Arabia
| | - Zhenhua Tian
- Department of Pharmaceutical Sciences, Traditional Chinese Medicine, Shandong University, Jinan, China
| | - Ruixue Yu
- Department of Pharmaceutical Sciences, Traditional Chinese Medicine, Shandong University, Jinan, China
| | - Yun Lun Li
- Department of Pharmaceutical Sciences, Traditional Chinese Medicine, Shandong University, Jinan, China
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Heese K. Gastrodia elata Blume (Tianma): Hope for Brain Aging and Dementia. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2020; 2020:8870148. [PMID: 33424999 PMCID: PMC7781687 DOI: 10.1155/2020/8870148] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Revised: 10/26/2020] [Accepted: 11/03/2020] [Indexed: 12/12/2022]
Abstract
Since aging-related diseases, including dementia, represent major public health threats to our society, physician-scientists must develop innovative, interdisciplinary strategies to open new avenues for development of alternative therapies. One such novel approach may lie in traditional Chinese medicine (TCM). Gastrodia elata Blume (G. elata, tianma) is a TCM frequently used for treatment of cerebrocardiovascular diseases (CCVDs). Recent studies of G. elata-based treatment modalities, which have investigated its pharmacologically relevant activity, potential efficacy, and safety, have employed G. elata in well-characterized, aging-related disease models, with a focus on models of aging-related dementia, such as Alzheimer's disease (AD). Here, I examine results from previous studies of G. elata, as well as related herbal preparations and pure natural products, as prophylaxis and remedies for aging-related CCVDs and dementia. Concluding, data suggest that tianma treatment may be used as a promising complementary therapy for AD.
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Affiliation(s)
- Klaus Heese
- Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133791, Republic of Korea
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Tan YM, Hu J, Wu Q, Zhang Y, Suo WD, Zhou YT, Guo H, Ni Q. Fufang Xueshuantong for Diabetic Kidney Disease: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2020; 2020:9326948. [PMID: 39295893 PMCID: PMC11410445 DOI: 10.1155/2020/9326948] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2020] [Revised: 08/30/2020] [Accepted: 10/27/2020] [Indexed: 09/21/2024]
Abstract
Objective The objective of this meta-analysis was to systematically assess the efficacy and safety of patented Chinese medicine Fufang Xueshuantong (FFXST) for the treatment of diabetic kidney disease (DKD). Methods Randomized controlled trials (RCTs) of FFXST for DKD treatment were searched until May 31, 2020, in seven electronic databases: PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and Chinese Biomedical Literature. The Cochrane risk test from the Cochrane Handbook was used as a bias tool to assess the methodological quality, and Review Manager (RevMan) 5.3 was used to analyze the results. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria were used to classify the quality of evidence. Results Thirteen RCTs involving 1,186 patients were included. The meta-analysis revealed that the efficacy of FFXST in treatment of DKD was significantly superior to that of the control treatment (P=0.0006). The urinary albumin excretion rate (P < 0.01), urinary albumin creatinine ratio (P < 0.0001), and microalbumin (P < 0.0001) were lower in the treatment groups than in the control group. There was also a decrease in low-density lipoprotein cholesterol (P < 0.0001), serum triglyceride (P=0.001), and C-reactive protein (P < 0.0001) in the treatment groups compared with those in the control group. No significant difference in hemoglobin A1c level (P=0.76) and systolic blood pressure (P=0.34) was noted between the treatment and control groups. Three studies reported adverse events, including dizziness and intolerance. In the other 10 trials, adverse events were not mentioned. Conclusion FFXST appears to be effective in the treatment of DKD. However, the low methodological quality of the RCTs suggests that larger, better-designed RCTs are required to verify the clinical effectiveness and safety of FFXST.
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Affiliation(s)
- Yu-Meng Tan
- Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Jun Hu
- Department of Cardiovascular, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Qian Wu
- Beijing University of Chinese Medicine, Beijing, China
| | - Yi Zhang
- Beijing University of Chinese Medicine, Beijing, China
| | - Wen-Dong Suo
- Beijing University of Chinese Medicine, Beijing, China
| | - Yu-Tong Zhou
- Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - He Guo
- Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Qing Ni
- Department of Endocrinology, Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
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Zhang DY, Cheng YB, Guo QH, Shan XL, Wei FF, Lu F, Sheng CS, Huang QF, Yang CH, Li Y, Wang JG. Treatment of Masked Hypertension with a Chinese Herbal Formula. Circulation 2020; 142:1821-1830. [DOI: 10.1161/circulationaha.120.046685] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background:
Masked hypertension is associated with adverse cardiovascular outcomes. Nonetheless, no randomized controlled trials exist in the treatment of masked hypertension. The aim of this randomized, placebo-controlled trial was to investigate the efficacy and safety of blood pressure (BP)–lowering treatment with a Chinese herbal formula, gastrodia-uncaria granules, in patients with masked hypertension.
Methods:
Patients with an office BP of <140/90 mm Hg and daytime ambulatory BP of 135 to 150 mm Hg systolic or 85 to 95 mm Hg diastolic were randomly assigned 1:1 to the treatment of gastrodia-uncaria granules or placebo 5 to 10 g twice daily for 4 weeks. The primary efficacy variable was the change in daytime ambulatory BP.
Results:
At baseline, office and daytime BP of the 251 participants (mean age, 50.4 years; 53.4% men; mean body mass index 24.5 kg/m
2
; and 2.8%, 1.6%, and 30.7% with cardiovascular disease, diabetes, and smoking, respectively) averaged 129/82 and 135/89 mm Hg, respectively. In the intention-to-treat analysis, daytime systolic/diastolic BP was reduced by 5.44/3.39 and 2.91/1.60 mm Hg in the gastrodia-uncaria granules and placebo groups, respectively. The between-group difference in BP reductions was significant for the daytime (2.52/1.79 mm Hg;
P
≤0.025) and 24-hour BP (2.33/1.49 mm Hg;
P
≤0.012), but not for the clinic and nighttime BPs (
P
≥0.162). The per-protocol analysis in 229 patients produced similar results. Only 1 adverse event (sleepiness during the day) was reported, and no serious adverse event occurred.
Conclusions:
BP-lowering treatment with Chinese traditional medicine gastrodia-uncaria granules is efficacious for patients with masked hypertension.
Registration:
URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02156024.
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Affiliation(s)
- Dong-Yan Zhang
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
| | - Yi-Bang Cheng
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
| | - Qian-Hui Guo
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
| | - Xiao-Li Shan
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
| | - Fang-Fei Wei
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
| | - Feng Lu
- Department of Cardiovascular Diseases, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, China (F.L., C.-H.Y.)
| | - Chang-Sheng Sheng
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
| | - Qi-Fang Huang
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
| | - Chuan-Hua Yang
- Department of Cardiovascular Diseases, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan, China (F.L., C.-H.Y.)
| | - Yan Li
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
| | - Ji-Guang Wang
- Centre for Epidemiological Studies and Clinical Trials and Centre for Vascular Evaluations, Shanghai Key Laboratory of Hypertension, National Key Laboratory of Medical Genomics, The Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China (D.-Y.Z., Y.-B.C., Q.-H.G., X.-L.S., F.-F.W., C.-S.S., Q.-F.H., Y.L., J.-G.W.)
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Tianma Gouteng Decoction Exerts Cardiovascular Protection by Upregulating OPG and TRAIL in Spontaneously Hypertensive Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:3439191. [PMID: 33133215 PMCID: PMC7593748 DOI: 10.1155/2020/3439191] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/03/2020] [Revised: 09/29/2020] [Accepted: 10/10/2020] [Indexed: 11/24/2022]
Abstract
Tianma Gouteng Decoction (TGD) is widely used in traditional Chinese medicine for the treatment of hypertension and its related complications, but its mechanisms remain incompletely defined. We now aim to assess the protective effect of TGD against cardiovascular damage and to investigate its characteristics and underlying mechanisms. Blood pressure was determined in TGD-treated spontaneously hypertensive rats (SHR) by noninvasive measurements. Echocardiography was performed to assess cardiac function and structure and sirius red staining to evaluate cardiac fibrosis, and the degree of vascular remodeling was evaluated. Additionally, vasoconstriction and relaxation factor expression changes were examined by means of ELISA. Protein expression changes were verified by western blot. Compared with untreated SHR, TGD-treated SHR exhibited cardiovascular traits more akin to those of the normotensive Wistar Kyoto (WKY) rats. That is, they had lower diastolic blood pressure, systolic blood pressure and mean BP, and increased expression of vasodilation factor. We also found that TGD reduces ventricular and vascular remodeling and improves cardiac function in SHR. Finally, we tested the antiapoptosis effect TGD exerts in SHR, ostensibly by upregulating the expression of OPG, TRAIL, and death receptor 5 (DR5) and downregulating caspases 8, 7, and 3. TRAIL may also exert antiapoptotic and prosurvival effects by upregulating AKT expression. Therefore, TGD may reverse cardiovascular remodeling in SHR by upregulating the expression of OPG and TRAIL, upregulating AKT, and inhibiting apoptosis, at least in part. For the first time, we have shown that OPG and TRAIL play complimentary cardioprotective roles in SHR.
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Huang X, Chen Z, Li M, Zhang Y, Xu S, Huang H, Wu X, Zheng X. Herbal pair Huangqin-Baishao: mechanisms underlying inflammatory bowel disease by combined system pharmacology and cell experiment approach. BMC Complement Med Ther 2020; 20:292. [PMID: 32988394 PMCID: PMC7523401 DOI: 10.1186/s12906-020-03068-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Accepted: 09/01/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a severe digestive system condition, characterized by chronic and relapsing inflammation of the gastrointestinal tract. Scutellaria baicalensis Georgi (Huangqin, HQ) and Paeonia lactiflora Pall (Baishao, BS) from a typical herbal synergic pair in traditional Chinese medicine (TCM) for IBD treatments. However, the mechanisms of action for the synergy are still unclear. Therefore, this paper aimed to predict the anti-IBD targets and the main active ingredients of the HQ-BS herbal pair. METHODS A systems pharmacology approach was used to identify the bioactive compounds and to delineate the molecular targets and potential pathways of HQ-BS herbal pair. Then, the characteristics of the candidates were analyzed according to their oral bioavailability and drug-likeness indices. Finally, gene enrichment analysis with DAVID Bioinformatics Resources was performed to identify the potential pathways associated with the candidate targets. RESULTS The results showed that, a total of 38 active compounds were obtained from HQ-BS herbal pair, and 54 targets associated with IBD were identified. Gene Ontology and pathway enrichment analysis yielded the top 20 significant results with 54 targets. Furthermore, the integrated IBD pathway revealed that the HQ-BS herbal pair probably acted in patients with IBD through multiple mechanisms of regulation of the nitric oxide biosynthetic process and anti-inflammatory effects. In addition, cell experiments were carried out to verify that the HQ-BS herbal pair and their Q-markers could attenuate the levels of nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated THP-1-derived macrophage inflammation. In particular, the crude materials exerted a much better anti-inflammatory effect than their Q-markers, which might be due to their synergistic effect. CONCLUSION This study provides novel insight into the molecular pathways involved in the mechanisms of the HQ-BS herbal pair acting on IBD.
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Affiliation(s)
- Xiaoqi Huang
- Mathematical Engineering Academy of Chinese Medicine, Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou University of Chinese Medicine, 232# Wai Huan East Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China
- Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, 523808, China
| | - Zhiwei Chen
- Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, 523808, China
| | - Minyao Li
- Mathematical Engineering Academy of Chinese Medicine, Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou University of Chinese Medicine, 232# Wai Huan East Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China
| | - Yaomin Zhang
- Mathematical Engineering Academy of Chinese Medicine, Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou University of Chinese Medicine, 232# Wai Huan East Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China
- Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, 523808, China
| | - Shijie Xu
- Mathematical Engineering Academy of Chinese Medicine, Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou University of Chinese Medicine, 232# Wai Huan East Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China
| | - Haiyang Huang
- Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Dongguan, 523808, China
| | - Xiaoli Wu
- School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, 100# Wai Huan West Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China.
| | - Xuebao Zheng
- Mathematical Engineering Academy of Chinese Medicine, Guangdong Provincial Key Laboratory of New Chinese Medicinal Development and Research, Guangzhou University of Chinese Medicine, 232# Wai Huan East Road, Guangzhou Higher Education Mega Center, Guangzhou, 510006, China.
- Dongguan Songshan Lake Yi Dao TCM Clinic, Dongguan, 523808, China.
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Zhang X, Tan R, Lam WC, Yao L, Wang X, Cheng CW, Liu F, Chan JC, Aixinjueluo Q, Lau CT, Chen Y, Yang K, Wu T, Lyu A, Bian Z. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Extension for Chinese Herbal Medicines 2020 (PRISMA-CHM 2020). THE AMERICAN JOURNAL OF CHINESE MEDICINE 2020; 48:1279-1313. [PMID: 32907365 DOI: 10.1142/s0192415x20500639] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Chinese Herbal Medicines (CHM) are the most common interventions of traditional Chinese medicine (TCM), typically administered as either single herbs or formulas. Systematic reviews (SRs) are essential references for evaluating the efficacy and safety of CHM treatments accurately and reliably. Unfortunately, the reporting quality of SRs with CHM is not optimal, especially the reporting of CHM interventions and the rationale of why these interventions were selected. To address this problem, a group of TCM clinical experts, methodologists, epidemiologists, and editors has developed a PRISMA extension for CHM interventions (PRISMA-CHM) through a comprehensive process, including registration, literature review, consensus meeting, three-round Delphi survey, and finalization. The PRISMA checklist was extended by introducing the concept of TCM Pattern and the characteristics of CHM interventions. A total of twenty-four items (including sub-items) are included in the checklist, relating to title (1), structured summary (2), rationale (3), objectives (4), eligibility criteria (6), data items (11), synthesis of results (14, 21), additional analyses (16, 23), study characteristics (18), summary of evidence (24), and conclusions (26). Illustrative examples and explanations are also provided. The group hopes that PRISMA-CHM 2020 will improve the reporting quality of SRs of CHM.
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Affiliation(s)
- Xuan Zhang
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Ran Tan
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Wai Ching Lam
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Liang Yao
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Xiaoqin Wang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Chung Wah Cheng
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Fan Liu
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.,Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Jacky Cp Chan
- Department of Computer Science, HKBU Faculty of Science, Hong Kong Baptist University, Hong Kong
| | - Qiying Aixinjueluo
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Chung Tai Lau
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Yaolong Chen
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China
| | - Taixiang Wu
- Chinese Cochrane Centre, West China Hospital, Sichuan University, China Trial Registration Center, Chengdu, Sichuan 610041, China
| | - Aiping Lyu
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
| | - Zhaoxiang Bian
- Chinese Clinical Trial Registry (Hong Kong), Hong Kong Chinese Medicine Clinical Study Centre, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong
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43
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Tong Y, Liu W, Xu L, Ou Y, Li K, Yang T, Zhao T, Guan R, Fan Y. Nonsurgical treatment of chronic subdural hematoma with Chinese herbal medicine: A STROBE-compliant retrospective study. Medicine (Baltimore) 2020; 99:e21674. [PMID: 32872034 PMCID: PMC7437851 DOI: 10.1097/md.0000000000021674] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
The aim of the study was to observe the efficacy of nonsurgical treatment with Chinese herbal medicine (CHM) for chronic subdural hematoma (CSDH). This study includes clinical results of a STROBE-compliant retrospective study.Forty patients diagnosed with CSDH were recruited from outpatient. Different CHM prescriptions were dispensed for each patient based on syndrome differentiation until the patient had a stable neurologic condition for 2 weeks and/or CSDH completely resolved according to the computed tomography scan. Markwalder grading scale for neurologic symptoms and head computed tomography scan for hematoma volumes were performed before and after CHM treatment to evaluate efficacy.Patients received uninterrupted CHM treatment for 2.81 ± 1.45 months (0.75-6 months). The hematoma volume significantly reduced from 73.49 ± 35.43 mL to 14.72 ± 15.94 mL (P < .001). The Markwalder grading scale scores of patients at the end of CHM treatment decreased significantly, from 1.3 ± 0.69 to 0.15 ± 0.36 (P < .001). Ninety percent of the patients showed >50% decrease in the hematoma volume and complete improvement in neurologic symptoms. The linear regression analysis suggested that change in hematoma was significantly related to the duration of CHM treatment (R = 0.334; P < .001; Ŷ = 25.03 + 11.91X). Leonurus heterophyllus Sweet (Yi-Mu-Cao, 90.5%), Semen persicae (Tao-Ren, 88.8%), and Acorus tatarinowii Schott (Shi-Chang-Pu, 86.2%) were the top 3 single Chinese herbs prescribed in CHM treatment.The CHM treatment for CSDH based on syndrome differentiation with appropriate duration relieved neurologic symptoms quickly and promoted hematoma absorption effectively. It could be an effective nonsurgical therapy for CSDH.
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Affiliation(s)
- Yanping Tong
- Department of Traditional Chinese Medicine Beijing Tiantan Hospital, Capital Medical University
- Beijing Integrative Medicine on Encephalopathy Research Institution, Beijing Tiantan Hospital Capital Medical University
| | - Weiming Liu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Long Xu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yunwei Ou
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Kangning Li
- Department of Traditional Chinese Medicine Beijing Tiantan Hospital, Capital Medical University
- Beijing Integrative Medicine on Encephalopathy Research Institution, Beijing Tiantan Hospital Capital Medical University
| | - Tao Yang
- Department of Traditional Chinese Medicine Beijing Tiantan Hospital, Capital Medical University
- Beijing Integrative Medicine on Encephalopathy Research Institution, Beijing Tiantan Hospital Capital Medical University
| | - Tianyou Zhao
- Department of Traditional Chinese Medicine Beijing Tiantan Hospital, Capital Medical University
- Beijing Integrative Medicine on Encephalopathy Research Institution, Beijing Tiantan Hospital Capital Medical University
| | - Ruixi Guan
- Department of Traditional Chinese Medicine Beijing Tiantan Hospital, Capital Medical University
- Beijing Integrative Medicine on Encephalopathy Research Institution, Beijing Tiantan Hospital Capital Medical University
| | - Yongping Fan
- Department of Traditional Chinese Medicine Beijing Tiantan Hospital, Capital Medical University
- Beijing Integrative Medicine on Encephalopathy Research Institution, Beijing Tiantan Hospital Capital Medical University
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Yu X, Jiao Q, Jiang Y, Guo S, Zhang W, Liu B. Study on the Plasma Protein Binding Rate and Compatibility Regularity of the Constituents Migrating to Blood of Simiao Yong'an Decoction. Curr Drug Metab 2020; 21:979-993. [PMID: 32735517 DOI: 10.2174/1567201817666200731170731] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 06/09/2020] [Accepted: 06/20/2020] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To study the compatibility regularity of Simiao Yong'an decoction by determining the plasma protein binding rate with the constituents in Simiao Yong'an decoction and to preliminarily clarify the effects of the compatibility on the plasma protein binding rate of different components. METHODS Based on the equilibrium dialysis method, high-performance liquid chromatography was used to determine the contents of six constituents, which were divided into a single group and combination groups, in Simiao Yong'an decoction in the internal and external dialysis solutions. The obtained plasma protein binding rate through calculations was an index to evaluate the binding of the above components to plasma protein in different conditions. RESULTS Harpagide, harpagoside, sweroside and loganin showed low plasma protein binding rates, ferulic acid exhibited a moderate plasma protein binding rate, and glycyrrhizic acid showed a high plasma protein binding rate. The compatibility study showed that glycyrrhizic acid promoted the binding of ferulic acid to plasma protein. Glycyrrhizic acid and ferulic acid were the key compounds to promote the binding of harpagide to plasma protein. Glycyrrhizic acid, harpagide, harpagoside and loganin had a significant inhibitory effects on the binding of sweroside to plasma protein. The plasma protein binding capacities of harpagoside and loganin were reduced by the other five constituents. Glycyrrhizic acid had the strongest plasma protein binding effect, and the binding effect was not affected by other components. CONCLUSION This study explores the effects of compound compatibility on effective components from the perspective of plasma protein binding by high-performance liquid chromatography combined with the equilibrium dialysis method, and lays a foundation for clarifying the compatibility rule of Simiao Yong'an decoction and also provides a new idea for the study of the compatibility of traditional Chinese medicine formulas.
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Affiliation(s)
- Xiao Yu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Qishu Jiao
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Yanyan Jiang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Shuzhen Guo
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Wei Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Bin Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
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45
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Singh A, Banerjee P, Anas M, Singh N, Qamar I. Traditional Nutritional and Health Practices Targeting Lifestyle Behavioral Changes in Humans. J Lifestyle Med 2020; 10:67-73. [PMID: 32995333 PMCID: PMC7502895 DOI: 10.15280/jlm.2020.10.2.67] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 07/07/2020] [Indexed: 12/12/2022] Open
Abstract
In this 21st century who isn't enticed by the glamorous and appealing life in the fast lane? We are surrounded by wonders, something we could never have imagined erstwhile. We have everything just a click or a call away. This alluring lifestyle comes with its own perils, the biggest one being concerned with health which is often compromised with check ins and home delivered food but the problem doesn't just lie with the outside food but also with all those chemical enriched engineered expensive food items. The industry often tempers with our food to make it "More Attractive" to the consumer. However, in modern era, availability of drugs and fancy powders has led to imbalance of health and nutrition, contrary to the previous era when home gardening was very common and people preferred fresh-foods which didn't contain added chemicals. They even used to treat some of the health problems with the natural ways that we nowadays refer to DIYs (Do-it-yourselves). Since Ayurveda used natural herbs and plant extracts for treatment, the earth was fresher and less-polluted which led to greater life expectancy. The modern era also has its own benefits like excellences in allopathy medicine has brought a cure to many untreatable diseases of the ancient times, and have even eradicated certain diseases like smallpox and polio. To summarize, both the time had their own pros and cons, so it would be better if we take both of their advantages into consideration and work ahead to live a healthy life.
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Affiliation(s)
- Aditi Singh
- School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India
| | - Pallabi Banerjee
- School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India
| | - Mohammad Anas
- School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India
| | - Nagendra Singh
- School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India
| | - Imteyaz Qamar
- School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India
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46
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Li Y, Yan S, Qian L, Wu L, Zheng Y, Fang Z. Danhong Injection for the Treatment of Hypertensive Nephropathy: A Systematic Review and Meta-Analysis. Front Pharmacol 2020; 11:909. [PMID: 32636745 PMCID: PMC7316888 DOI: 10.3389/fphar.2020.00909] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Accepted: 06/03/2020] [Indexed: 12/11/2022] Open
Abstract
Objective Danhong Injection (DHI) has been widely used to treat various diseases in China for many years. The objective of this systematic review was to evaluate the efficacy of DHI combined with antihypertensive drugs for treatment of hypertensive nephropathy. Methods Seven databases were searched from inception to September 21st, 2019. Randomized controlled trials comparing DHI combined with antihypertensive drugs versus antihypertensive drugs alone were extracted. The primary outcome was microalbuminuria (mALB). Secondary outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), and serum creatinine (SCr). Results Fifteen studies were included in the meta-analysis, which indicated that DHI combined with antihypertensive drugs has advantages compared with antihypertensive drugs alone for reducing mALB [weighted mean difference (WMD) = −12.86, 95% confidence interval (CI) (−14.72, −11.0), P < 0.01], lowering SBP [WMD = −2.84, 95% CI (−4.56, −1.12), P = 0.001] and DBP [WMD = −2.38, 95% CI (−4.34, −0.43), P = 0.017], and decreasing SCr [WMD = −40.45, 95% CI (−55.69, −25.21), P < 0.01]. Conclusion The combination of DHI with antihypertensive drugs appears to be more effective than antihypertensive drugs alone for treatment of hypertensive nephropathy. A moderate duration (≤4 weeks) of DHI administration is reasonable, and longer treatment with DHI should be avoided, according to the results of subgroup analysis.
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Affiliation(s)
- YiZhuo Li
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Shihai Yan
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lichao Qian
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lihua Wu
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yawei Zheng
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhuyuan Fang
- Institute of Hypertension, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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47
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Ren W, Wang M, Liao J, Li L, Yang D, Yao R, Huang L. The Effect of Chinese Herbal Medicine Combined With Western Medicine on Vascular Endothelial Function in Patients With Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Pharmacol 2020; 11:823. [PMID: 32612527 PMCID: PMC7308496 DOI: 10.3389/fphar.2020.00823] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 05/19/2020] [Indexed: 11/19/2022] Open
Abstract
Objective Vascular endothelium plays a fundamental role in regulating endothelial dysfunction, resulting in structural changes that may lead to adverse outcomes of hypertension. The aim of this study was to systematically evaluate the effect of a combination of Chinese herbal medicine (CHM) and Western medicine on vascular endothelial function in patients with hypertension. Methods We systematically searched the literature for studies published in Chinese and English in PubMed, Embase, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, China Knowledge Resource Integrated Database, Wanfang Data, and China Science and Technology Journal Database. Databases were searched using terms concerning or describing CHM, hypertension, vascular endothelium, and randomized controlled trials. RevMan 5.3.0 was used for data analysis. If the included studies were sufficiently homogeneous, quantitative synthesis was performed; if studies with different sample sizes and blind methods were used, subgroup analyses were performed. GRADEpro was selected to grade the current evidence to reduce bias in our findings. Results In this review, 30 studies with 3,235 patients were enrolled. A relatively high selection and a performance bias were noted by risk of bias assessments. Meta-analysis showed that the combination of CHM and conventional Western medicine was more efficient than conventional Western medicine alone in lowering blood pressure (risk ratio, 1.21; 95% CI, 1.16 to 1.26) and increasing nitric oxide (95% CI, 1.24 to 2.08; P < 0.00001), endothelin-1 (95% CI, −1.71 to −1.14; P < 0.00001), and flow-mediated dilation (95% CI, 0.98 to 1.31; P <0.00001). No significant difference was observed between the combination of CHM and conventional Western medicine and conventional Western medicine alone for major cardiovascular and cerebrovascular events. CHM qualified for the treatment of hypertension. The GRADEpro presented with low quality of evidence for the available data. Conclusion CHM combined with conventional Western medicine may be effective in lowering blood pressure and improving vascular endothelial function in patients with hypertension. To further confirm this, more well-designed studies with large sample sizes, strict randomization, and clear descriptions about detection and reporting processes are warranted.
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Affiliation(s)
- Weiquan Ren
- Beijing University of Chinese Medicine, Beijing, China.,China-Japan Friendship Hospital, Beijing, China
| | - Miyuan Wang
- Beijing University of Chinese Medicine, Beijing, China
| | | | - Lingling Li
- Beijing University of Chinese Medicine, Beijing, China
| | - Deshuang Yang
- Beijing University of Chinese Medicine, Beijing, China
| | - Ruiqi Yao
- Beijing University of Chinese Medicine, Beijing, China
| | - Li Huang
- China-Japan Friendship Hospital, Beijing, China
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48
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Wu QJ, Lv WL, Li JM, Zhang TT, Zhou WH, Zhang Q, Wang JC, Wang QN, Zhang RX, Zhao X, Chen ST, Liu S, Li GH, Cao ZM, Xu L, Chen J. Efficacy and safety of YinQiSanHuang-antiviral decoction in chronic hepatitis B: study protocol for a randomized, placebo-controlled, double-blinded trial. Trials 2020; 21:482. [PMID: 32503608 PMCID: PMC7275558 DOI: 10.1186/s13063-020-04395-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Accepted: 05/08/2020] [Indexed: 02/07/2023] Open
Abstract
Introduction Chronic hepatitis B (CHB) is a global public health problem. Antiviral therapy is the primary treatment. Studies have shown that a combined therapy of traditional Chinese medicine (TCM) and conventional antiviral drugs has better efficacy than conventional antiviral for treatment of CHB. YinQiSanHuang-antiviral decoction (YQSH) is a TCM compound preparation that has shown an effect on anti-hepatitis B virus and on slowing progression of hepatitis B-related liver diseases. To evaluate the efficacy and safety of YQSH combined with entecavir and its preventive effect on hepatitis B cirrhosis, we designed this randomized, double-blind and placebo-controlled trial. The objective is that the combination of YinQiSanHuang-antiviral decoction with entecavir will reduce the annual incidence of liver fibrosis/cirrhosis to 1%. Methods This is a multicenter, randomized, placebo-controlled, double-blinded trial involving five hospitals. A total of 802 patients are randomly allocated to two groups: the YQSH group (n = 401) or the placebo group (n = 401). The YQSH group receives YQSH with entecavir; the placebo group receives granules of placebo with entecavir. Patients receive treatment for 52 weeks and then are followed up for 52 ± 2 weeks. The primary outcome measure is the annual incidence of cirrhosis. The secondary outcome measures are hepatitis B virus DNA negative rate, hepatitis B surface antigen negative rate, hepatitis B e antigen seroconversion rate, liver function (alanine aminotransferase, aspartate aminotransferase , gamma-glutamyl transferase , alkaline phosphatase , serum albumin, and total bilirubin), spleen thickness, evaluation scores of patients’ clinical symptoms, and safety assessment. Outcomes will be assessed at baseline and after treatment. Discussion Combination therapy could become a trend for treatment of CHB, and this trial expects to provide credible clinical evidence for the future combination of TCM and conventional antiviral drugs for the treatment of CHB. Trial registration Chinese Clinical Trial Registry: ChiCTR1900021521. Registered on 25 February 2019.
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Affiliation(s)
- Qing-Juan Wu
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Wen-Liang Lv
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China.
| | - Juan-Mei Li
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Ting-Ting Zhang
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Wen-Hui Zhou
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Qiang Zhang
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Jiu-Chong Wang
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Qing-Nan Wang
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Ruo-Xuan Zhang
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China.,Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Xin Zhao
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China.,Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Si-Tong Chen
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China.,Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Shuang Liu
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Gao-Hui Li
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
| | - Zheng-Min Cao
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China.,Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Lei Xu
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China.,Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Jing Chen
- Guang'anmen Hospital of China Academy of Chinese Medical Sciences, Beijing, China
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49
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Qian X, Chen Z, Chen SS, Liu LM, Zhang AQ. Integrated Analyses Identify Immune-Related Signature Associated with Qingyihuaji Formula for Treatment of Pancreatic Ductal Adenocarcinoma Using Network Pharmacology and Weighted Gene Co-Expression Network. J Immunol Res 2020; 2020:7503605. [PMID: 32537471 PMCID: PMC7256764 DOI: 10.1155/2020/7503605] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 04/15/2020] [Indexed: 02/06/2023] Open
Abstract
The study aimed to clarify the potential immune-related targets and mechanisms of Qingyihuaji Formula (QYHJ) against pancreatic cancer (PC) through network pharmacology and weighted gene co-expression network analysis (WGCNA). Active ingredients of herbs in QYHJ were identified by the TCMSP database. Then, the putative targets of active ingredients were predicted with SwissTargetPrediction and the STITCH databases. The expression profiles of GSE32676 were downloaded from the GEO database. WGCNA was used to identify the co-expression modules. Besides, the putative targets, immune-related targets, and the critical module genes were mapped with the specific disease to select the overlapped genes (OGEs). Functional enrichment analysis of putative targets and OGEs was conducted. The overall survival (OS) analysis of OGEs was investigated using the Kaplan-Meier plotter. The relative expression and methylation levels of OGEs were detected in UALCAN, human protein atlas (HPA), Oncomine, DiseaseMeth version 2.0 and, MEXPRESS database, respectively. Gene set enrichment analysis (GSEA) was conducted to elucidate the key pathways of highly-expressed OGEs further. OS analyses found that 12 up-regulated OGEs, including CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 that could be utilized as potential diagnostic indicators for PC. Further, methylation analyses suggested that the abnormal up-regulation of these OGEs probably resulted from hypomethylation, and GSEA revealed the genes markedly related to cell cycle and proliferation of PC. This study identified CDK1, PLD1, MET, F2RL1, XDH, NEK2, TOP2A, NQO1, CCND1, PTK6, CTSE, and ERBB2 might be used as reliable immune-related biomarkers for prognosis of PC, which may be essential immunotherapies targets of QYHJ.
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Affiliation(s)
- Xiang Qian
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, China
- Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Cancer Hospital, Hangzhou, China
| | - Zhuo Chen
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, China
- Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Cancer Hospital, Hangzhou, China
| | - Sha Sha Chen
- Department of Traditional Chinese Medicine, Taizhou Cancer Hospital, Zhejiang, China
| | - Lu Ming Liu
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, China
| | - Ai Qin Zhang
- Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, China
- Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, China
- Zhejiang Cancer Hospital, Hangzhou, China
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50
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Traditional Chinese Patent Medicine for Primary Hypertension: A Bayesian Network Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:6701272. [PMID: 32382302 PMCID: PMC7196995 DOI: 10.1155/2020/6701272] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 03/16/2020] [Indexed: 12/25/2022]
Abstract
Background Traditional Chinese Patent Medicine (TCPM) is now being used more and more extensively for primary hypertension in China. However, the comparative efficacy and safety of it need more clarified evidence. Thus, we conducted a Bayesian network meta-analysis to compare TCPMs with other interventions. Methods We searched China National Knowledge Infrastructure (CNKI), WanFang Data, PubMed, Embase, and Cochrane Library from inception to April 2019 for randomized controlled trials (RCTs) with diagnosis of primary hypertension that compared the efficacy of TCPMs with antihypertension drugs (ADs). Two researchers screened literature, extracted data, and evaluated risk of bias independently. The primary outcomes were systolic blood pressure (SBP) and diastolic blood pressure (DBP). The secondary outcomes were adverse effects (AEs), total cholesterol (TC), and triglyceride (TG). We used the Bayesian network meta-analysis to compare interventions and described the categorical variable and the continuous variable as odds ratio (OR) and mean difference (MD), respectively. Besides, we ranked all interventions via the Surface Under the Cumulative Ranking (SUCRA) values and conducted metaregression with nine covariates as additional analysis. Results We included 192 studies with 23366 patients diagnosed as primary hypertension in total. For SBP reduction, eighteen interventions were significantly better than AD. Among them, Yinxingye (YXY) + AD (MD = −12, 95% CrI [−16, −8.5]) was superior to others in the rank plot with SUCRA 0.91. For DBP reduction, sixteen interventions were significantly better than AD. Among them, Qinggan Jiangya (QGJY) + AD (MD = −8.7, 95% CrI [−12, −5.5]) and Qiju Dihuang (QJDH) + AD (MD = −8.8, 95% CrI [−12, −5.2]) were superior to others in the rank plot with SUCRA 0.89. To summarize the SUCRA values, we found that QGJY + AD and YXY + AD had the most significant reductions for both SBP and DBP. YXY + AD was the best one for both TC (MD = −1.3, 95% CrI [−1.9, −0.64]) and TG (MD = −0.52, 95% CrI [−0.92, −0.11]) reductions. Considering adverse effects, we found two interventions had significant differences comparing with AD. Among them, YXY + AD was the best one with SUCRA of 0.01. Conclusion In all TCPMs, QGJY + AD and YXY + AD may be the best options for hypertension. Meanwhile, YXY + AD can improve blood lipids in patients with hypertension. However, due to the vague reports of adverse effects and other limitations, more evidence, especially that provided by high-quality studies, is needed to prove the advantages of TCMPs.
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