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Zhu Y, Zou W, Sun B, Shen K, Xia F, Wang H, Jiang F, Lu Z. Ginsenoside Rg1 Regulates the Activation of Astrocytes Through lncRNA-Malat1/miR-124-3p/Lamc1 Axis Driving PI3K/AKT Signaling Pathway, Promoting the Repair of Spinal Cord Injury. CNS Neurosci Ther 2024; 30:e70103. [PMID: 39491316 PMCID: PMC11532020 DOI: 10.1111/cns.70103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 08/05/2024] [Accepted: 10/17/2024] [Indexed: 11/05/2024] Open
Abstract
AIM To investigate the regulation of ginsenoside Rg1 on the PI3K/AKT pathway through the lncRNA-Malat1/miR-124-3p/ Laminin gamma1 (Lamc1) axis, activating astrocytes (As) to promote the repair of spinal cord injury (SCI). METHODS Bioinformatics analysis was used to predict miRNA targeting Lamc1 and lncRNA targeting miR-124-3p, which were then validated through a dual-luciferase assay. Following transfection, the relationships between Malat1, miR-124-3p, and Lamc1 expression levels were assessed by qRT-PCR and Western blot (WB). Immunofluorescence staining and immunohistochemistry were utilized to measure Lamc1 expression, while changes in cavity area were observed through hematoxylin-eosin (HE) staining. Basso-Beattie-Bresnahan (BBB) scale and footprint analysis were used to evaluate functional recovery. WB was performed to assess the expression of PI3K/AKT pathway-related protein. RESULTS Rg1 was found to upregulate Malat1 expression, which in turn modulated the Malat1/miR-124-3p/Lamc1 axis. Furthermore, Rg1 activated the PI3K/Akt signaling pathway, significantly reducing the SCI cavity area and improving hind limb motor function. However, knockout of Malat1 hindered these effects, and inhibition of miR-124-3p reversed the silencing effects of Malat1. CONCLUSIONS Rg1 can induce Malat1 expression to activate the Lamc1/PI3K/AKT signaling pathway by sponging with miR-124-3p, thereby regulating As activity to repair SCI.
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Affiliation(s)
- Yin Zhu
- Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
- Department of OrthopedicsThe Affiliated Zhangjiagang Hospital of Soochow UniversityZhangjiagangChina
| | - Wenjun Zou
- Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Baihan Sun
- Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
- Department of OrthopedicsXuzhou City Hospital of TCMXuzhouChina
| | - Kelv Shen
- Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Feiyun Xia
- Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Hao Wang
- Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Fengxian Jiang
- Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
| | - Zhengfeng Lu
- Department of OrthopedicsThe Second Affiliated Hospital of Soochow UniversitySuzhouChina
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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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Liu R, Wang W, Li W. Bezafibrate mitigates cardiac injury against coronary microembolization by preventing activation of p38 MAPK/NF-κB signaling. Aging (Albany NY) 2024; 16:12769-12780. [PMID: 39383058 PMCID: PMC11501380 DOI: 10.18632/aging.205707] [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: 10/09/2023] [Accepted: 01/08/2024] [Indexed: 10/11/2024]
Abstract
Coronary microembolization (CME)-induced inflammatory response and cardiomyocyte apoptosis are the main contributors to CME-associated myocardial dysfunction. Bezafibrate, a peroxisome proliferator-activated receptors (PPARs) agonist, has displayed various benefits in different types of diseases. However, it is unknown whether Bezafibrate possesses a protective effect in myocardial dysfunction against CME. In this study, we aimed to investigate the pharmacological function of Bezafibrate in CME-induced insults in myocardial injury and progressive cardiac dysfunction and explore the underlying mechanism. A CME model was established in rats, and cardiac function was detected. The levels of injury biomarkers in serum including CK-MB, AST, and LDH were determined using commercial kits, and pro-inflammatory mediators including TNF-α and IL-6 were detected using ELISA kits. Our results indicate that Bezafibrate improved cardiac function after CME induction. Bezafibrate reduced the release of myocardial injury indicators such as CK-MB, AST, and LDH in CME rats. We also found that Bezafibrate ameliorated oxidative stress by increasing the levels of the antioxidant GPx and the activity of SOD and reducing the levels of TBARS and the activity of NOX. Bezafibrate inhibited the expression of pro-inflammatory cytokines such as TNF-α and IL-6. Importantly, Bezafibrate was found to mitigate CME-induced myocardial apoptosis by increasing the expression of Bcl-2 and reducing the levels of Bax and cleaved caspase-3. Mechanistically, Bezafibrate could prevent the activation of p38 MAPK/NF-κB signaling. These findings suggest that Bezafibrate may be a candidate therapeutic agent for cardioprotection against CME in clinical applications.
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Affiliation(s)
- Ruijie Liu
- Department of Cardiology, Dongguan Songshan Lake Central Hospital, Dongguan 523326, Guangdong Province, China
| | - Wenfang Wang
- Department of Cardiology, The First Affiliated Hospital of Ji’nan University, Guangzhou 510627, Guangdong Province, China
| | - Wenfeng Li
- Department of Cardiology, Chongyi People’s Hospital, Ganzhou 341399, Jiangxi Province, China
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Jiang Z, Lu H, Gao B, Huang J, Ding Y. Transcriptomic Analysis of Cardiac Tissues in a Rodent Model of Coronary Microembolization. J Inflamm Res 2024; 17:6645-6659. [PMID: 39345897 PMCID: PMC11437660 DOI: 10.2147/jir.s469297] [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: 03/17/2024] [Accepted: 09/13/2024] [Indexed: 10/01/2024] Open
Abstract
Purpose Coronary microembolization (CME) can result in cardiac dysfunction, severe arrhythmias, and a reduced coronary flow reserve. Impairment of mitochondrial energy metabolism has been implicated in the progression and pathogenesis of CME; however, its role remains largely undetermined. This study aimed to explore alterations in mitochondria-related genes in CME. Methods A rat model of CME was successfully established by injecting plastic microspheres into the left ventricle. The cardiac tissues of the two groups were sequenced and mitochondrial functions were assessed. Results Using RNA-Seq, together with GO and KEGG enrichment analyses, we identified 3822 differentially expressed genes (DEGs) in CME rats compared to control rats, and 101 DEGs were mitochondria-related genes. Notably, 36 DEGs were up-regulated and 65 DEGs were down-regulated (CME vs control). In particular, the oxidative phosphorylation (OXPHOS) and mitochondrial electron transport were obviously down-regulated in the CME group. Functional analysis revealed that CME mice exhibited marked reductions in ATP and mitochondrial membrane potential (MMP), by contrast, the production of reactive oxygen species (ROS) was much higher in CME mice than in controls. Protein-protein interaction (PPI) and quantitative PCR (qPCR) validation suggested that eight hub genes including Cmpk2, Isg15, Acsl1, Etfb, Ndufa8, Adhfe1, Gabarapl1 and Acot13 were down-regulated in CME, whereas Aldh18a1 and Hspa5 were up-regulated. Conclusion Our findings suggest that dysfunctions in mitochondrial activity and metabolism are important mechanisms for CME, and mitochondria-related DEGs may be potential therapeutic targets for CME.
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Affiliation(s)
- Zhaochang Jiang
- Department of Pathology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Haohao Lu
- Zhejiang Center of Laboratory Animals, Hangzhou Medical College, Hangzhou, Zhejiang, 310063, People's Republic of China
| | - Beibei Gao
- Department of Cardiology, Hangzhou First People's Hospital, Hangzhou, Zhejiang, 310006, People's Republic of China
| | - Jinyu Huang
- Department of Cardiology, Hangzhou First People's Hospital, Hangzhou, Zhejiang, 310006, People's Republic of China
| | - Yu Ding
- Department of Clinical Laboratory, Hangzhou First People's Hospital, Hangzhou, Zhejiang, 310006, People's Republic of China
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Wang Y, Wang T, Ma T, Zhao J, Qi W. Shexiang tongxin dropping pill alleviates myocardial injury induced by coronary microembolization by down-regulating APOC1 to inhibit STAT3 signaling pathway. Aging (Albany NY) 2024; 16:8484-8496. [PMID: 38771126 PMCID: PMC11164485 DOI: 10.18632/aging.205796] [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: 05/31/2023] [Accepted: 03/03/2024] [Indexed: 05/22/2024]
Abstract
AIM This study determines to validate the mechanism of Shexiang Tongxin dropping pill (STDP) in attenuating coronary microembolization (CME) induced myocardial injury. METHODS CME rat models were established and underwent corresponding treating. Gene chip analysis was performed in rat myocardial tissues for GO and KEGG enrichment analysis. The differentially expressed genes were detected by qRT-PCR. H&E staining and ELISA were used for pathological analysis and detection of troponin (cTnI) and Creatine Kinase Isoenzyme (CK-MB). Lipopolysaccharide (LPS) treated primary cardiomyocytes were used to mimic inflammatory in vitro models. Cell viability and apoptosis of cardiomyocytes were determined by MTT and flow cytometry. The expressions of inflammatory cytokines, apoptotic proteins and proteins related to the STAT3 signal pathway were detected by western blot. APOC1 mRNA expression was detected by qRT-PCR. Immunofluorescence (IF) was used for subcellular localization of p-STAT3 and the binding of APOC1 with STAT3 was verified using Co-IP. RESULTS STDP can attenuate myocardial injury in CME rat models, and lead to decreased expression of APOC1 and suppressed STAT3 signal pathway. In vitro models found STDP can suppress the cell viability and cell apoptosis of primary cardiomyocytes, in addition to suppressing the secretions of IL-6, IL-1β and TNF-α, while the protective effect of STDP can be reversed by overexpression of APOC1. Co-IP found that APOC1 can bind STAT3 directly. APOC1 can increase p-STAT3 expression in the nucleus to activate the STAT3 signal pathway. CONCLUSIONS STDP can suppress APOC1 and STAT3 signal pathway to inhibit inflammation and cell apoptosis of cardiomyocytes. APOC1 may be one of the key regulatory factors in CME-induced myocardial injury.
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Affiliation(s)
- Yangui Wang
- Department of General Practice, Shanghai Pudong New Area People’s Hospital, Pudong New Area 201299, Shanghai, P.R. China
| | - Tao Wang
- Department of General Practice, Shanghai Pudong New Area People’s Hospital, Pudong New Area 201299, Shanghai, P.R. China
| | - Tingting Ma
- Department of General Practice, Shanghai Pudong New Area People’s Hospital, Pudong New Area 201299, Shanghai, P.R. China
| | - Jin Zhao
- Department of General Practice, Shanghai Pudong New Area People’s Hospital, Pudong New Area 201299, Shanghai, P.R. China
| | - Weigang Qi
- Department of General Practice, Shanghai Pudong New Area People’s Hospital, Pudong New Area 201299, Shanghai, P.R. China
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Chen S, Liao Z, Zheng T, Zhu Y, Ye L. Protective effect of ligustrazine on oxidative stress and apoptosis following testicular torsion in rats. Sci Rep 2023; 13:20395. [PMID: 37990048 PMCID: PMC10663624 DOI: 10.1038/s41598-023-47210-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 11/10/2023] [Indexed: 11/23/2023] Open
Abstract
Testicular torsion is a common urologic emergency and one of the causes of infertility in males. It has been reported that ligustrazine may decrease oxidative stress and reduce ischemia-reperfusion injury. This study aims to investigate the protective effect of ligustrazine in ischemia-reperfusion injury after testicular torsion-detorsion. First, 40 rats were randomly and equally divided into TMP (Ligustrazine) group, the Testicular torsion (T/D) group, the Sham (Sham operation) group, and Control group. The left testis of rats in the TMP and T/D group was rotated for 2 h. The TMP group was intraperitoneally injected with ligustrazine solution and the T/D and the Sham groups were injected with normal saline. The left testes of four groups were obtained for assay on the 4th day after the operation. Average level of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) were higher in Sham and Control groups than T/D group and TMP group. Conversely, average level of malondialdehyde (MDA) and reactive oxygen species (ROS) was lower in Sham and Control groups than T/D group and TMP group. In contrast with the T/D group, SOD, GPX, and CAT enzymatic activities increased, whereas MDA and ROS content decreased in the TMP group (P < 0.05). Microscopic observation showed that the testicular tissue of the Sham and Control groups were basically normal. The TMP and T/D groups had significant testicular tissue damage, whereas the TMP group had less damage and apoptosis than the T/D group. The apoptotic index of germ cells in the TMP group (13.05 ± 4.41) was lower than the T/D group (30.23 ± 11.31) (P < 0.05) and higher (P < 0.05) than the Sham group (0.56 ± 0.29). So we found that Ligustrazine lowered ischemia-reperfusion injury after testicular torsion-detorsion by decreasing the reactive oxygen species and suppressing apoptosis.
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Affiliation(s)
- Songmao Chen
- Provincial Clinical Medical College of Fujian Medical University, Fuzhou, 350001, Fujian, China
- Department of Urology, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, China
| | - Zhengjian Liao
- Department of Neurosurgery, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, China
| | - Tingting Zheng
- Fujian Medical University, Fuzhou, 350122, Fujian, China
| | - Yuanfan Zhu
- Fujian Medical University, Fuzhou, 350122, Fujian, China
| | - Liefu Ye
- Department of Urology, Fujian Provincial Hospital, Fuzhou, 350001, Fujian, China.
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Yang L, Jian Y, Zhang ZY, Qi BW, Li YB, Long P, Yang Y, Wang X, Huang S, Huang J, Zhou LF, Ma J, Jiang CQ, Hu YH, Xiao WJ. Network-pharmacology-based research on protective effects and underlying mechanism of Shuxin decoction against myocardial ischemia/reperfusion injury with diabetes. World J Diabetes 2023; 14:1057-1076. [PMID: 37547579 PMCID: PMC10401449 DOI: 10.4239/wjd.v14.i7.1057] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 04/14/2023] [Accepted: 05/05/2023] [Indexed: 07/12/2023] Open
Abstract
BACKGROUND Patients with diabetes mellitus are at higher risk of myocardial ischemia/ reperfusion injury (MI/RI). Shuxin decoction (SXT) is a proven recipe modi-fication from the classic herbal formula "Wu-tou-chi-shi-zhi-wan" according to the traditional Chinese medicine theory. It has been successfully used to alleviate secondary MI/RI in patients with diabetes mellitus in the clinical setting. However, the underlying mechanism is still unclear.
AIM To further determine the mechanism of SXT in attenuating MI/RI associated with diabetes.
METHODS This paper presents an ensemble model combining network pharmacology and biology. The Traditional Chinese Medicine System Pharmacology Database was accessed to select key components and potential targets of the SXT. In parallel, therapeutic targets associated with MI/RI in patients with diabetes were screened from various databases including Gene Expression Omnibus, DisGeNet, Genecards, Drugbank, OMIM, and PharmGKB. The potential targets of SXT and the therapeutic targets related to MI/RI in patients with diabetes were intersected and subjected to bioinformatics analysis using the Database for Annotation, Visualization and Integrated Discovery. The major results of bioinformatics analysis were subsequently validated by animal experiments.
RESULTS According to the hypothesis derived from bioinformatics analysis, SXT could possibly ameliorate lipid metabolism disorders and exert anti-apoptotic effects in MI/RI associated with diabetes by reducing oxidized low density lipoprotein (LDL) and inhibiting the advanced glycation end products (AGE)-receptor for AGE (RAGE) signaling pathway. Subsequent animal experiments confirmed the hypothesis. The treatment with a dose of SXT (2.8 g/kg/d) resulted in a reduction in oxidized LDL, AGEs, and RAGE, and regulated the level of blood lipids. Besides, the expression of apoptosis-related proteins such as Bax and cleaved caspase 3 was down-regulated, whereas Bcl-2 expression was up-regulated. The findings indicated that SXT could inhibit myocardial apoptosis and improve cardiac function in MI/RI in diabetic rats.
CONCLUSION This study indicated the active components and underlying molecular therapeutic mechanisms of SXT in MI/RI with diabetes. Moreover, animal experiments verified that SXT could regulate the level of blood lipids, alleviate cardiomyocyte apoptosis, and improve cardiac function through the AGE-RAGE signaling pathway.
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Affiliation(s)
- Ling Yang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
| | - Yang Jian
- Department of Clinical Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Zai-Yuan Zhang
- College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Bao-Wen Qi
- South China Hospital of Shenzhen University, Shenzhen 518116, Guangdong Province, China
| | - Yu-Bo Li
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
| | - Pan Long
- Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Yao Yang
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Xue Wang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
| | - Shuo Huang
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
| | - Jing Huang
- College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Long-Fu Zhou
- Department of Biomedical Engineering, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Jie Ma
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Chang-Qing Jiang
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
| | - Yong-He Hu
- School of Clinical Medicine, Chengdu University of TCM, Chengdu 610072, Sichuan Province, China
- College of Medicine, Southwest Jiaotong University, Chengdu 610031, Sichuan Province, China
| | - Wen-Jing Xiao
- Department of Pharmacy, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China
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Wang YL, Zhang HX, Chen YQ, Yang LL, Li ZJ, Zhao M, Li WL, Bian YY, Zeng L. Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion. Chin J Integr Med 2023; 29:556-565. [PMID: 37052766 DOI: 10.1007/s11655-023-3735-0] [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] [Accepted: 06/13/2022] [Indexed: 04/14/2023]
Abstract
Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.
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Affiliation(s)
- Ya-Li Wang
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Hui-Xiang Zhang
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yan-Qi Chen
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Li-Li Yang
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- Jingwen Library, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Zheng-Jun Li
- College of Health Economics Management, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Min Zhao
- School of Chinese Medicine, School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Wen-Lin Li
- Jingwen Library, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Yao-Yao Bian
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China
- School of Second Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Li Zeng
- School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
- Jiangsu Provincial Engineering Center of Traditional Chinese Medicine External Medication Researching and Industrializing, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
- Jingwen Library, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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Liu D, Liu Y, Qian X, Yang J, Li C, Zhu L, Zhou J. Pharmacokinetic study on the effect of ligustrazine-tangeretin co-administration on the pharmacokinetics of ligustrazine and its potential mechanism in rats. Pharmacol Res Perspect 2023; 11:e01058. [PMID: 36852752 PMCID: PMC9972364 DOI: 10.1002/prp2.1058] [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: 10/27/2022] [Revised: 12/08/2022] [Accepted: 01/16/2023] [Indexed: 03/01/2023] Open
Abstract
Both ligustrazine and tangeretin are usually prescribed in the treatment of cardiovascular diseases, which makes their co-administration possible. The investigation of the interaction between ligustrazine and tangeretin is necessary for the clinical compatibility of their source herbs. This study aimed to investigate the interaction of ligustrazine and tangeretin during their co-administration. The pharmacokinetics of ligustrazine (15 mg/kg) was investigated in the presence of 50, 100, and 150 mg/kg tangeretin in rats with six of each. A single dose of ligustrazine was set as the control. The effect of tangeretin on the in vitro metabolic stability of ligustrazine was also investigated in rat liver microsomes. Tangeretin significantly reduced the system exposure of ligustrazine under all experimental concentrations. Specifically, tangeretin reduced the AUC (from 48.86 ± 12.57 to 41.02 ± 4.85 (50 mg/kg tangeretin), 31.47 ± 5.26 (100 mg/kg tangeretin), and 27.55 ± 9.60 (150 mg/kg) μg/mL × h), MRT (from 7.05 ± 0.26 to 6.33 ± 0.48, 5.53 ± 0.68, and 5.21 ± 1.31 h), Cmax (from 7.45 ± 0.44 to 6.03 ± 0.44, 5.24 ± 0.47, and 5.02 ± 0.56 μg/mL), and t1/2 (from 5.90 ± 1.27 to 4.84 ± 1.19, 3.48 ± 1.33, 3.09 ± 0.62 h) in rats. In vitro, tangeretin also reduced the metabolic stability of ligustrazine behaved as the decreased half-life and increased intrinsic clearance rate. Co-consumption of ligustrazine with tangeretin induced interactions, which shortens the system exposure of ligustrazine. This study provides theoretical guidance for the clinical prescription of ligustrazine- and tangeretin-containing herbs.
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Affiliation(s)
- Dandan Liu
- Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China
| | - Yunjiao Liu
- Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China
| | - Xian Qian
- Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China
| | - Junwei Yang
- Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China
| | - Chengjian Li
- Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China
| | | | - Jin Zhou
- Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China
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Wang M, Zhang L, Huang X, Sun Q. Ligustrazine promotes hypoxia/reoxygenation-treated trophoblast cell proliferation and migration by regulating the microRNA-27a-3p/ATF3 axis. Arch Biochem Biophys 2023; 737:109522. [PMID: 36657605 DOI: 10.1016/j.abb.2023.109522] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 01/06/2023] [Accepted: 01/15/2023] [Indexed: 01/17/2023]
Abstract
OBJECTIVE Preeclampsia (PE) is a pregnancy-specific syndrome. Ligustrazine (LSZ) is involved in hypoxia/reoxygenation (H/R)-treated trophoblast cell regulation, but its mechanism remains elusive. This study explored the mechanism of LSZ in H/R-treated trophoblast cells to provide a theoretical basis for the new treatment method development for PE. METHODS H/R HTR8/SVneo cell model was established for PE simulation to some extent. Trophoblast cell proliferation, apoptosis rate, migration, and invasion were detected by MTT assay, flow cytometry, scratch test, and Transwell assay. miR-27a-3p expression in trophoblast cells was detected by RT-qPCR. Binding sites between miR-27a-3p and ATF3 were predicted using Starbase and verified by dual-luciferase reporter assay. Activating transcription factor 3 (ATF3), β-catenin, Cyclin D1, and c-Myc protein levels were examined using Western blot. After LSZ treatment, H/R-induced HTR8/SVneo cells were delivered with miR-27a-3p mimic or ATF3 siRNA to verify their roles in HTR8/SVneo cells. RESULTS LSZ facilitated the proliferation, migration, and invasion of trophoblast cells and inhibited apoptosis. miR-27a-3p was elevated in H/R-induced HTR8/SVneo cells and miR-27a-3p overexpression annulled the effect of LSZ on trophoblast cells. miR-27a-3p targeted ATF3. ATF3 silencing averted the property of LSZ on trophoblast cells. Wnt/β-catenin pathway-related proteins were repressed in H/R-induced HTR8/SVneo cells, and LSZ activated the Wnt/β-catenin pathway by promoting ATF3 expression. CONCLUSION LSZ mediated the Wnt pathway by regulating the miR-27a-3p/ATF3 axis, thus promoting the proliferation and migration of trophoblast cells. The protective mechanism of LSZ showed the potential application value in the treatment of PE.
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Affiliation(s)
- Min Wang
- Department of Gynaecology and Obstetrics, Jinan Maternity and Child Care Hospital, Jinan, 250001, Shandong Province, China
| | - Li Zhang
- Department of Gynaecology and Obstetrics, Jinan Maternity and Child Care Hospital, Jinan, 250001, Shandong Province, China
| | - Xiuyan Huang
- Department of Gynaecology and Obstetrics, Jinan Maternity and Child Care Hospital, Jinan, 250001, Shandong Province, China
| | - Qian Sun
- Department of Gynaecology and Obstetrics, Jinan Maternity and Child Care Hospital, Jinan, 250001, Shandong Province, China.
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Zhu H, Wang H, Zhu X, Chen Q, Fang X, Xu X, Ping Y, Gao B, Tong G, Ding Y, Chen T, Huang J. The Importance of Integrated Regulation Mechanism of Coronary Microvascular Function for Maintaining the Stability of Coronary Microcirculation: An Easily Overlooked Perspective. Adv Ther 2023; 40:76-101. [PMID: 36279093 DOI: 10.1007/s12325-022-02343-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Accepted: 09/28/2022] [Indexed: 01/25/2023]
Abstract
Coronary microvascular dysfunction (CMD) refers to a group of disorders affecting the structure and function of coronary microcirculation and is associated with an increased risk of major adverse cardiovascular events. At present, great progress has been made in the diagnosis of CMD, but there is no specific treatment for it because of the complexity of CMD pathogenesis. Vascular dysfunction is one of the important causes of CMD, but previous reviews mostly considered microvascular dysfunction as a whole abnormality so the obtained conclusions are skewed. The coronary microvascular function is co-regulated by multiple mechanisms, and the mechanisms by which microvessels of different luminal diameters are regulated vary. The main purpose of this review is to revisit the mechanisms by which coronary microvessels at different diameters regulate coronary microcirculation through integrated sequential activation and briefly discuss the pathogenesis, diagnosis, and treatment progress of CMD from this perspective.
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Affiliation(s)
- Houyong Zhu
- Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, Zhejiang, China.
| | - Hanxin Wang
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Xinyu Zhu
- Department of Cardiology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310006, Zhejiang, China
| | - Qilan Chen
- Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, Zhejiang, China
| | - Xiaojiang Fang
- Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, Zhejiang, China
| | - Xiaoqun Xu
- Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Zhejiang, China
| | - Yan Ping
- Department of Cardiology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310006, Zhejiang, China
| | - Beibei Gao
- Department of Cardiology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310006, Zhejiang, China
| | - Guoxin Tong
- Department of Cardiology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310006, Zhejiang, China
| | - Yu Ding
- Department of Cardiology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310006, Zhejiang, China
| | - Tielong Chen
- Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, 310007, Zhejiang, China.
| | - Jinyu Huang
- Department of Cardiology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310006, Zhejiang, China.
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Liu Y, Yang G, Cui W, Zhang Y, Liang X. Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: A review. Front Pharmacol 2022; 13:948600. [PMID: 36133805 PMCID: PMC9483103 DOI: 10.3389/fphar.2022.948600] [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: 05/20/2022] [Accepted: 08/05/2022] [Indexed: 11/13/2022] Open
Abstract
Central nervous system (CNS) diseases can lead to motor, sensory, speech, cognitive dysfunction, and sometimes even death. These diseases are recognized to cause a substantial socio-economic impact on a global scale. Tetramethylpyrazine (TMP) is one of the main active ingredients extracted from the Chinese herbal medicine Ligusticum striatum DC. (Chuan Xiong). Many in vivo and in vitro studies have demonstrated that TMP has a certain role in the treatment of CNS diseases through inhibiting calcium ion overload and glutamate excitotoxicity, anti-oxidative/nitrification stress, mitigating inflammatory response, anti-apoptosis, protecting the integrity of the blood-brain barrier (BBB) and facilitating synaptic plasticity. In this review, we summarize the roles and mechanisms of action of TMP on ischemic cerebrovascular disease, spinal cord injury, Parkinson’s disease, Alzheimer’s disease, cognitive impairments, migraine, and depression. Our review will provide new insights into the clinical applications of TMP and the development of novel therapeutics.
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Affiliation(s)
- Yue Liu
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Guang Yang
- Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wenqiang Cui
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Yunling Zhang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Yunling Zhang, ; Xiao Liang,
| | - Xiao Liang
- Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- *Correspondence: Yunling Zhang, ; Xiao Liang,
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Xuan L, Fu D, Zhen D, Bai D, Yu L, Gong G. Long non-coding RNA Sox2OT promotes coronary microembolization-induced myocardial injury by mediating pyroptosis. ESC Heart Fail 2022; 9:1689-1702. [PMID: 35304834 PMCID: PMC9065873 DOI: 10.1002/ehf2.13814] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 12/06/2021] [Accepted: 01/12/2022] [Indexed: 12/31/2022] Open
Abstract
OBJECTIVE As a common complication of coronary microembolization (CME), myocardial injury (MI) implies high mortality. Long non-coding RNAs (lncRNAs) are rarely studied in CME-induced MI. Herein, this study intended to evaluate the role of lncRNA Sox2 overlapping transcript (Sox2OT) in CME-induced MI. METHODS The CME rat models were successfully established by injection of microemboli. Rat cardiac functions and MI were observed by ultrasonic electrocardiogram, HE staining, and HBFP staining. Functional assays were utilized to test the inflammatory responses, oxidative stress, and pyroptosis using reverse transcription quantitative polymerase chain reaction, Western blotting, immunohistochemistry, immunofluorescence, and ELISA. Dual-luciferase reporter gene assay and RNA immunoprecipitation were conducted to clarify the targeting relations between Sox2OT and microRNA (miRNA)-23b and between miR-23b and toll-like receptor 4 (TLR4). RESULTS Rat CME disrupted the cardiac functions and induced inflammatory responses and oxidative stress, and activated the nuclear factor-kappa B (NF-κB) pathway and pyroptosis (all P < 0.05). An NF-κB inhibitor downregulated the NF-κB pathway, reduced pyroptosis, and relieved cardiomyocyte injury and pyroptosis. Compared with the sham group (1.05 ± 0.32), lncRNA Sox2OT level (4.41 ± 0.67) in the CME group was elevated (P < 0.05). Sox2OT acted as a competitive endogenous RNA (ceRNA) of miR-23b to regulate TLR4. Silencing of Sox2OT favoured miR-23b binding to 3'UTR of TLR4 mRNA leading to suppressed TLR4-mediated NFKB signalling and pyroptosis in myocardial tissues harvested from CME rat models. In addition, miR-23b overexpression could supplement the cytosolic miR-23b reserves to target TLR-4 and partially reverse Sox2OT-mediated pyroptosis in LPS-treated H9C2 cells. CONCLUSIONS This study supported that silencing Sox2OT inhibited CME-induced MI by eliminating Sox2OT/miR-23b binding and down-regulating the TLR4/NF-κB pathway. This investigation may provide novel insights for the treatment of CME-induced MI.
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Affiliation(s)
- Liying Xuan
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, No. 1742 Holin River Street, Tongliao, Inner Mongolia, 028002, China
- Inner Mongolia Key Laboratory, Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, China
| | - Danni Fu
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, No. 1742 Holin River Street, Tongliao, Inner Mongolia, 028002, China
- Inner Mongolia Key Laboratory, Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, China
| | - Dong Zhen
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, No. 1742 Holin River Street, Tongliao, Inner Mongolia, 028002, China
- Inner Mongolia Key Laboratory, Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, China
| | - Dongsong Bai
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, No. 1742 Holin River Street, Tongliao, Inner Mongolia, 028002, China
- Inner Mongolia Key Laboratory, Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, China
| | - Lijun Yu
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, No. 1742 Holin River Street, Tongliao, Inner Mongolia, 028002, China
- Inner Mongolia Key Laboratory, Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, China
| | - Guohua Gong
- Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for Nationalities, No. 1742 Holin River Street, Tongliao, Inner Mongolia, 028002, China
- Inner Mongolia Key Laboratory, Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, China
- First Medical Clinic, Inner Mongolia University for Nationalities, Tongliao, China
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Possible implication of miR-142-3p in coronary microembolization induced myocardial injury via ATXN1L/HDAC3/NOL3 axis. J Mol Med (Berl) 2022; 100:763-780. [PMID: 35414011 DOI: 10.1007/s00109-022-02198-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 03/30/2022] [Accepted: 04/04/2022] [Indexed: 10/18/2022]
Abstract
This study aims to explore the mechanism underlying miR-142-3p regulating myocardial injury induced by coronary microembolization (CME) through ATXN1L. miR-142-3p overexpression or ATXN1L knockout adenovirus vectors were injected into rats before CME treatment. Cardiac functions were examined by echocardiography, and pathologies of myocardial tissues were assessed. Then, serum cTnI and IL-1β contents and concentrations of IL-1β and IL-18 in cell supernatant were measured. Immunofluorescence determined the localization of histone deacetylase 3 (HDAC3). The interaction between miR-142-3p and ATXN1L as well as the binding between HDAC3 and histone 3 (H3) was identified. The binding of ATXN1L and HDAC3 to NOL3 promoter was verified using ChIP. The levels of ATXN1L, NOL3, and miR-142-3p as well as apoptosis- and pyroptosis-related proteins and acetyl-histone 3 (ac-H3) were evaluated. CME treatment impaired the cardiac functions in rats and increased cTnI content. CME rats showed microinfarction foci in myocardial tissues. After CME treatment, miR-142-3p and NOL3 were modestly expressed while ATXN1L content was elevated, in addition to increases in apoptosis and pyroptosis. miR-142-3p overexpression or ATXN1L knockout alleviated CME-induced myocardial injury, cardiomyocyte apoptosis, and pyroptosis in myocardial tissues. miR-142-3p regulated ATXN1L expression in a targeted manner. In the cellular context, miR-142-3p overexpression attenuated apoptosis and pyroptosis in cardiomyocytes, which was partly counteracted by ATXN1L overexpression. ATXN1L functioned on cardiomyocytes by promoting deacetylation of H3 through HDAC3 and thus inhibited NOL3 expression. Inhibition of HDAC3 or overexpression of NOL3 ameliorated the promotive effects of ATXN1L on cardiomyocyte apoptosis and pyroptosis. In vivo and in vitro evidence in this study supported that miR-142-3p could attenuate CME-induced myocardial injury via ATXN1L/HDAC3/NOL3. HIGHLIGHTS: CME model witnessed aberrant expression of miR-142-3p, ATXN1L, and NOL3; miR-142-3p negatively regulated ATXN1L; miR-142-3p mediated CME-induced myocardial injury through ATXN1L; ATXN1L promoted deacetylation of H3 through HDAC3 and thus inhibited NOL3 expression; ATXN1L acted on cardiomyocyte apoptosis and pyroptosis through HDAC3/NOL3 axis.
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15
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Li D, Long Y, Yu S, Shi A, Wan J, Wen J, Li X, Liu S, Zhang Y, Li N, Zheng C, Yang M, Shen L. Research Advances in Cardio-Cerebrovascular Diseases of Ligusticum chuanxiong Hort. Front Pharmacol 2022; 12:832673. [PMID: 35173614 PMCID: PMC8841966 DOI: 10.3389/fphar.2021.832673] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 12/28/2021] [Indexed: 12/22/2022] Open
Abstract
Cardio-cerebrovascular diseases (CVDs) are a serious threat to human health and account for 31% of global mortality. Ligusticum chuanxiong Hort. (CX) is derived from umbellifer plants. Its rhizome, leaves, and fibrous roots are similar in composition but have different contents. It has been used in Japanese, Korean, and other traditional medicine for over 2000 years. Currently, it is mostly cultivated and has high safety and low side effects. Due to the lack of a systematic summary of the efficacy of CX in the treatment of CVDs, this article describes the material basis, molecular mechanism, and clinical efficacy of CX, as well as its combined application in the treatment of CVDs, and has been summarized from the perspective of safety. In particular, the pharmacological effect of CX in the treatment of CVDs is highlighted from the point of view of its mechanism, and the complex mechanism network has been determined to improve the understanding of CX's multi-link and multi-target therapeutic effects, including anti-inflammatory, antioxidant, and endothelial cells. This article offers a new and modern perspective on the impact of CX on CVDs.
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Affiliation(s)
- Dan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu Long
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Shuang Yu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ai Shi
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinyan Wan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jing Wen
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiaoqiu Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Songyu Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yulu Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Nan Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Chuan Zheng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ming Yang
- Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Lin Shen
- Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
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YQHX Alleviates H/R-Induced Cardiomyocyte Apoptosis by Downregulating miR-1. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2021; 2021:4852406. [PMID: 34765002 PMCID: PMC8577916 DOI: 10.1155/2021/4852406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 09/24/2021] [Accepted: 10/08/2021] [Indexed: 11/17/2022]
Abstract
Yiqi Huoxue granule (YQHX) inhibits cardiomyocyte apoptosis in myocardial ischemia-reperfusion injury (MIRI); however, the underlying mechanism is unknown. In this study, hypoxia-reoxygenation (H/R) models were established using rat myocardial primary cells and H9c2 cells, lactate dehydrogenase (LDH), and creatine kinase (CK) levels and cardiomyocyte apoptosis were determined. LDH release, CK activity, caspase-3 activation, mRNA and protein ratio of Bax/Bcl-2, and miR-1 expression were significantly higher (p < 0.01) in the H/R model of rat myocardial primary cells and H9c2 cells compared with the control group and was inhibited by YQHX treatment (p < 0.01 or p < 0.05). We also found that miR-1 overexpression could enhance apoptosis in cardiomyocytes, whereas apoptosis could be reduced by YQHX treatment (p < 0.01). In conclusion, YQHX alleviates H/R-induced cardiomyocyte apoptosis by inhibiting miR-1 expression, suggesting the potential of YQHX in preventing MIRI.
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Ligustrazine Attenuates Gastric Inflammation and Apoptosis in Helicobacter pylori-induced Gastric Epithelial Cells. Jundishapur J Microbiol 2021. [DOI: 10.5812/jjm.116612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Stomach disorders, including gastric cancer and gastritis, are associated with the pathogenic bacterium Helicobacter pylori. Enhanced inflammation is the characteristic of H. pylori-induced gastritis. Ligustrazine exerts anti-inflammatory properties in mouse asthma models and acute kidney injury. Objectives: To determine the role of ligustrazine in H. pylori-induced gastritis. Methods: Normal gastric epithelial cell line (GES-1) was cultured with H. pylori at a multiplicity of infection (MOI) of 100: 1 for 24 hours. GES-1 cell line under H. pylori condition was incubated with 100 or 200 μM ligustrazine for 24 hours. Cell viability and apoptosis were investigated by MTT and flow cytometry assays, respectively. Inflammation was assessed by determining the levels and mRNA expression of interleukins (IL)-6/8, tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein 1 (MCP-1) using ELISA and qRT-PCR analysis, respectively. Results: Helicobacter pylori infection reduced the viability and promoted the apoptosis of GES-1 cell line, accompanied by the enhanced activities of caspases 3 and 9. However, ligustrazine reversed the H. pylori-induced infection decreased viability, while increased apoptosis and caspases 3/9 activities in GES-1 cell line. Moreover, ligustrazine attenuated H. pylori-induced secretions of pro-inflammatory factors, IL-6/8, TNF-α, and MCP-1, in GES-1 cell line. The protein expression of inhibitor of NF-κB (IκBα) was downregulated in GES-1 cell line after H. pylori infection, while the protein expression levels of p65 and phosphorylation of IκBα were upregulated by H. pylori infection. On the contrary, ligustrazine decreased H. pylori-induced protein expression of IκBα, whereas increased protein expression of p65 and phosphorylation of IκBα. Conclusions: Ligustrazine exerted protective effects on H. pylori-induced gastric epithelial cells through inhibition of gastric inflammation and apoptosis and inactivation of NF-κB pathway.
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Mu D, Feng J, Sun F. CHANGES OF SERUM CARDIAC TROPONIN I IN EXERCISE STRESS TEST AND AFTER EXERCISE. REV BRAS MED ESPORTE 2021. [DOI: 10.1590/1517-8692202127072021_0343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
ABSTRACT Introduction: Cardiac Troponin (CTN) has a strong organ specificity, which indicates that myocardial injury is present. However, it is worth noting that the increase does not suggest that the myocardium necessarily presents ischemic necrosis. Objective: To observe the changes in serum kerocalin I (CTNI) content after exercise, explore the effects of exercise training on hematocytes and that cause damage to myocardial cell stimulation. Methods: 18 rats were divided into three groups in this study, and three exercises were conducted separately. Results: After 6 weeks of exercise training, the number of red blood cells increased and the content of troponin I (CTNI) in the serum also significantly increased. The serum CTNI of the disposable large strength group was significantly higher than that of the quiet group (P <0.001). The serum CTNI in the 6-week exercise group was significantly higher than that of the quiet group (P <0.001), but the serum CTNI level between the two sports groups was not different. Conclusions: The motion training model used in this study can improve the number of red blood cells in the blood, improve synchronous blood capacity, and help the body's aerobic capacity increase. Level of evidence II; Therapeutic studies - investigation of treatment results.
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吴 胜, 张 露, 樊 红, 黄 艳, 宗 巧, 高 琴, 李 正. [PI3K/Akt signaling pathway mediates the protective effect of endomorphin-1 postconditioning against myocardial ischemia-reperfusion injury in rats]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2021; 41:870-875. [PMID: 34238739 PMCID: PMC8267992 DOI: 10.12122/j.issn.1673-4254.2021.06.09] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the role of PI3K/Akt signaling pathway in mediating the protective effect of endomorphin-1 against myocardial ischemia-reperfusion (IR) injury. OBJECTIVE Fifty SD male rats were randomly divided into sham operation group, myocardial IR group, endomorphin-1 post-treatment group (EM50 group), endomorphin-1+wortmannin (a PI3K/Akt signaling pathway inhibitor) treatment group (EM50+Wort group), and wortmannin treatment group (Wort group). Rat models of myocardial IR injury were established by ligation of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. The heart rate and mean arterial pressure were monitored during the experiment. Plasma levels of LDH, CK-MB, cTnI, IL-6, TNF-α, SOD and MDA were measured after reperfusion. The mRNA expression of Bax and Bcl-2 was detected using RT-PCR, and the expression of apoptosis-related protein cleaved caspase-3, phosphorylated Akt protein and total Akt protein in myocardial tissue was detected using Western blotting. OBJECTIVE Myocardial IR injury significantly decreased heart rate and blood pressure of the rats in comparison with the sham operation (P < 0.05). Compared with those in the IR group, the rats in EM50 group showed significantly increased heart rate and blood pressure (P < 0.05) with decreased plasma LDH, CK-MB, cTnI, IL-6, TNF-α and MDA levels (P < 0.05), increased SOD activity (P < 0.05), increased expression of p-Akt protein and Bcl-2 mRNA (P < 0.05), and decreased expression of Bax mRNA and cleaved caspase-3 protein (P < 0.05). In EM50+Wort group, the heart rate and blood pressure were significantly lowered (P < 0.05), plasma LDH, CK-MB, cTnI, IL-6, TNF-α and MDA levels increased (P < 0.05), SOD activity decreased (P < 0.05), the expression of p-Akt protein and Bcl-2 mRNA was reduced (P < 0.05), and the expression of Bax mRNA and cleaved caspase-3 protein increased (P < 0.05) as compared with those in EM50 group. OBJECTIVE EM-1 postconditioning can regulate cardiac myocyte apoptosis and reduce myocardial IR injury in rats. The PI3K/Akt signaling pathway may play a role in mediating the myocardial protective effects of EM-1 postconditioning.
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Affiliation(s)
- 胜男 吴
- 蚌埠医学院生理教研室，安徽 蚌埠 233030Department of Physiology, Bengbu Medical College, Bengbu 233030, China
| | - 露 张
- 蚌埠医学院生理教研室，安徽 蚌埠 233030Department of Physiology, Bengbu Medical College, Bengbu 233030, China
| | - 红莲 樊
- 蚌埠医学院药学院，安徽 蚌埠 233030School of Pharmacy, Bengbu Medical College, Bengbu 233030, China
| | - 艳平 黄
- 蚌埠医学院药学院，安徽 蚌埠 233030School of Pharmacy, Bengbu Medical College, Bengbu 233030, China
| | - 巧凤 宗
- 蚌埠医学院生理教研室，安徽 蚌埠 233030Department of Physiology, Bengbu Medical College, Bengbu 233030, China
| | - 琴 高
- 蚌埠医学院科研中心，安徽 蚌埠 233030Research Center, Bengbu Medical College, Bengbu 233030, China
| | - 正红 李
- 蚌埠医学院生理教研室，安徽 蚌埠 233030Department of Physiology, Bengbu Medical College, Bengbu 233030, China
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Chen ZQ, Zhou Y, Huang JW, Chen F, Zheng J, Li HL, Li T, Li L. Puerarin pretreatment attenuates cardiomyocyte apoptosis induced by coronary microembolization in rats by activating the PI3K/Akt/GSK-3β signaling pathway. THE KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY : OFFICIAL JOURNAL OF THE KOREAN PHYSIOLOGICAL SOCIETY AND THE KOREAN SOCIETY OF PHARMACOLOGY 2021; 25:147-157. [PMID: 33602885 PMCID: PMC7893491 DOI: 10.4196/kjpp.2021.25.2.147] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 10/15/2020] [Accepted: 10/26/2020] [Indexed: 01/13/2023]
Abstract
Coronary microembolization (CME) is associated with cardiomyocyte apoptosis and cardiac dysfunction. Puerarin confers protection against multiple cardiovascular diseases, but its effects and specific mechanisms on CME are not fully known. Hence, our study investigated whether puerarin pretreatment could alleviate cardiomyocyte apoptosis and improve cardiac function following CME. The molecular mechanism associated was also explored. A total of 48 Sprague-Dawley rats were randomly divided into CME, CME + Puerarin (CME + Pue), sham, and sham + Puerarin (sham + Pue) groups (with 12 rats per group). A CME model was established in CME and CME + Pue groups by injecting 42 μm microspheres into the left ventricle of rats. Rats in the CME + Pue and sham + Pue groups were intraperitoneally injected with puerarin at 120 mg/kg daily for 7 days before operation. Cardiac function, myocardial histopathology, and cardiomyocyte apoptosis index were determined via cardiac ultrasound, hematoxylin-eosin (H&E) and hematoxylin-basic fuchsin-picric acid (HBFP) stainings, and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. Western blotting was used to measure protein expression related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. We found that, puerarin significantly ameliorated cardiac dysfunction after CME, attenuated myocardial infarct size, and reduced myocardial apoptotic index. Besides, puerarin inhibited cardiomyocyte apoptosis, as revealed by decreased Bax and cleaved caspase-3, and up-regulated Bcl-2 and PI3K/Akt/GSK-3β pathway related proteins. Collectively, puerarin can inhibit cardiomyocyte apoptosis and thus attenuate myocardial injury caused by CME. Mechanistically, these effects may be achieved through activation of the PI3K/Akt/GSK-3β pathway.
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Affiliation(s)
- Zhi-Qing Chen
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrov
| | - You Zhou
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrov
| | - Jun-Wen Huang
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrov
| | - Feng Chen
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China
| | - Jing Zheng
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrov
| | - Hao-Liang Li
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrov
| | - Tao Li
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrov
| | - Lang Li
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-cerebrov
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Chen ZQ, Zhou Y, Chen F, Huang JW, Zheng J, Li HL, Li T, Li L. Breviscapine Pretreatment Inhibits Myocardial Inflammation and Apoptosis in Rats After Coronary Microembolization by Activating the PI3K/Akt/GSK-3β Signaling Pathway. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:843-855. [PMID: 33658766 PMCID: PMC7920514 DOI: 10.2147/dddt.s293382] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 02/05/2021] [Indexed: 01/28/2023]
Abstract
Purpose Coronary microembolization (CME) can cause myocardial inflammation, apoptosis and progressive cardiac dysfunction. On the other hand, breviscapine exerts a significant cardioprotective effect in many cardiac diseases although its role and the potential mechanisms in CME remain unclear. Therefore, the present study aimed to ascertain whether pretreatment with breviscapine could improve CME-induced myocardial injury by alleviating myocardial inflammation and apoptosis. The possible underlying mechanisms were also explored. Methods In this study, 48 Sprague-Dawley (SD) rats were randomly assigned to the CME, CME + breviscapine (CME + BE), CME + breviscapine + LY294002 (CME + BE + LY) and sham groups (12 rats per group). In addition, the CME model was successfully established by injecting 42 μm inert plastic microspheres into the left ventricle of rats. Rats in the CME + BE and CME + BE + LY groups received 40 mg/kg/d of breviscapine for 7 days before inducing CME. Moreover, rats in the CME + BE + LY group were intraperitoneally injected with the phosphoinositide 3-kinase (PI3K) specific inhibitor, LY294002 (10 mg/kg) 30 minutes before CME modeling. 12 h after surgery, the study measured cardiac function, the serum levels of markers of myocardial injury, myocardial inflammation-associated mRNAs and proteins, myocardial apoptosis-associated mRNAs and proteins and conducted myocardial histopathology. Results The findings demonstrated that pretreatment with breviscapine alleviated myocardial injury following CME by improving cardiac dysfunction, decreasing the serum levels of markers of myocardial injury, reducing the size of myocardial microinfarct and lowering the cardiomyocyte apoptotic index. More importantly, pretreatment with breviscapine resulted to a decrease in the levels of inflammatory and pro-apoptotic mRNAs and proteins in myocardial tissues and there was an increase in the levels of anti-apoptotic mRNAs and proteins. However, these protective effects were eliminated when breviscapine was combined with LY294002. Conclusion The findings from this study indicated that breviscapine may inhibit myocardial inflammation and apoptosis by regulating the PI3K/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway, thereby ameliorating CME-induced cardiac dysfunction and reducing myocardial injury.
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Affiliation(s)
- Zhi-Qing Chen
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China
| | - You Zhou
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China
| | - Feng Chen
- Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Jun-Wen Huang
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China
| | - Jing Zheng
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China
| | - Hao-Liang Li
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China
| | - Tao Li
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China
| | - Lang Li
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China
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Qin Z, Kong B, Zheng J, Wang X, Li L. Alprostadil Injection Attenuates Coronary Microembolization-Induced Myocardial Injury Through GSK-3β/Nrf2/HO-1 Signaling-Mediated Apoptosis Inhibition. Drug Des Devel Ther 2020; 14:4407-4422. [PMID: 33122886 PMCID: PMC7588838 DOI: 10.2147/dddt.s272877] [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: 07/20/2020] [Accepted: 09/19/2020] [Indexed: 11/24/2022] Open
Abstract
Objective Coronary microembolization (CME) results in progressive contractile dysfunction associated with cardiomyocyte apoptosis. Alprostadil injection improves microcirculation, which is effective in treating various cardiovascular disorders. However, the therapeutic effects of alprostadil in CME-induced myocardia injury remain unknown. Therefore, we evaluated the effects of alprostadil injection on cardiac protection in a rat model of CME and explored the underlying mechanisms. Methods A rat model of CME was established by injecting polyethylene microspheres into the left ventricle. After injection of microspheres, rats in the alprostadil group received alprostadil via tail vein within 2 minutes. Cardiac function, histological alterations in myocardium, serum c-troponin I (cTnI) levels, myocardium adenosine triphosphate (ATP) concentrations, the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) content in myocardium, and myocardial apoptosis-related proteins were detected 12 hours after CME modeling. Results Compared with the Sham group, ATP concentrations, SOD activity in the myocardium, and cardiac function were significantly decreased in a rat model of CME. In addition, serum cTnI levels, MDA content, expression levels of pro-apoptotic proteins, and the number of TUNEL-positive nuclei were remarkably higher in CME group than those in the Sham group. However, alprostadil treatment notably reduced serum cTnI levels and expression levels of pro-apoptotic proteins, while noticeably improved cardiac function, and accelerated SOD activity in the myocardium following CME. Additionally, it was unveiled that the protective effects of alprostadil injection inhibit CME-induced myocardial apoptosis in the myocardium potentially through regulation of the GSK-3β/Nrf2/HO-1 signaling pathway. Conclusion Alprostadil injection seems to significantly suppress oxidative stress, alleviate myocardial apoptosis in the myocardium, and improve cardiac systolic and diastolic functions following CME by regulating the GSK-3β/Nrf2/HO-1 signaling pathway.
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Affiliation(s)
- Zhenbai Qin
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Binghui Kong
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jing Zheng
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xiantao Wang
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Lang Li
- Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
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Application of Traditional Chinese Medicines in Postoperative Abdominal Adhesion. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2020; 2020:8073467. [PMID: 32419827 PMCID: PMC7199640 DOI: 10.1155/2020/8073467] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/18/2020] [Revised: 03/05/2020] [Accepted: 03/17/2020] [Indexed: 12/16/2022]
Abstract
Adhesion is a frequent complication after abdominal surgery. Although various methods have been applied to prevent and treat postoperative abdominal adhesion (PAA), few modern drugs designed for clinical applications have reached the expected preventive or therapeutic effect so far. There is an imperative to develop some new strategies for the treatment of PAA. Traditional Chinese medicine (TCM) has been widely practiced for thousands of years and played an indispensable role in the prevention and treatment of diseases. Modern medicine researchers have accepted the therapeutic effects of many active components derived from Chinese medicinal herbs. The review stresses the most commonly used TCM treatment, including Chinese medicinal herbals and monomers, TCM formulas, and acupuncture treatment.
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Ding Y, Zhu HY, Zhang LZ, Gao BB, Zhou L, Huang JY. Shexiang Tongxin Dropping Pill () Reduces Coronary Microembolization in Rats via Regulation of Mitochondrial Permeability Transition Pore Opening and AKT-GSK3β Phosphorylation. Chin J Integr Med 2020; 27:527-533. [PMID: 31903531 DOI: 10.1007/s11655-019-3176-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2019] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To investigate the protective effects of Shexiang Tongxin Dropping Pill (, STDP) following sodium laurate-induced coronary microembolization (CME) in rats. METHODS Forty rats were divided into 4 groups: the control (sham) group, CME group, low-dose STDP pretreatment group (20 mg·kg-1·d-1), and high-dose STDP pretreatment group (40 mg·kg-1·d-1). The rats were intragastric administrated with STDP 2 weeks before operation. Moreover, the histopathological alterations were observed using optical microscopy and transmission electron microscopy. Antioxidant biomarkers were analyzed by enzyme-linked immunosorbent assay. Mitochondrial functions including the mitochondrial permeability transition pore (mPTP) mtDNA copy number were determined and proteins of AKT/GSK3β were analyzed by Western blot. RESULTS The rats in the CME group showed a significant increase in the fibrinogen-like protein 2 expression level and mitochondrial dysfunction and a decrease in the expression level of antioxidant biomarkers (superoxide dismutase and catalase, P<0.01 for all). In contrast, the rats in the low- and high-dose STDP pretreatment groups showed a significant decrease in coronary microthrombi (P<0.05); moreover, STDP restored the antioxidant-related protein activities and mitochondrial function, inhibited mPTP opening, decreased AKT-Ser473 phosphorylation, and increased GSK3β-Ser9 phosphorylation (P<0.05 or P<0.01). CONCLUSION STDP may be useful for treatment of CME, possibly via regulation of mPTP opening and AKT/GSK3β phosphorylation.
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Affiliation(s)
- Yu Ding
- Central Laboratory, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Hou-Yong Zhu
- Department of Cardiology, Hangzhou Chinese Medical Hospital, Hangzhou, 310007, China
| | - Li-Zong Zhang
- Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, 310053, China
| | - Bei-Bei Gao
- Department of Cardiology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Liang Zhou
- Department of Cardiology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Jin-Yu Huang
- Department of Cardiology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
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