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Jia S, Chen Q, Liu X, Li Y, Wang L, Li X, Hu S. Efficacy of integrated traditional Chinese and western medicine in managing mild-moderate acute pancreatitis: a real-world clinical perspective analysis. Front Med (Lausanne) 2024; 11:1429546. [PMID: 39554504 PMCID: PMC11566454 DOI: 10.3389/fmed.2024.1429546] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 10/02/2024] [Indexed: 11/19/2024] Open
Abstract
Background Given the prevalent utilization of integrated traditional Chinese and western medicine (ITCWM) in the management of acute pancreatitis, the majority of studies have concentrated on severe cases, lacking robust evidence-based medical research. Real-world investigations can provide an objective assessment of the clinical effectiveness of combining traditional Chinese medicine with western medicine. Consequently, relying on real-world research, we intend to evaluate the clinical efficacy and safety of the combined approach in treating mild to moderate acute pancreatitis. Methods A total of 563 AP patients from Henan Provincial Hospital of Traditional Chinese Medicine were collected from January 2019 to October 2023. A propensity score matching (PSM) analysis was conducted to evaluate the clinical efficacy of traditional Chinese medicine (TCM) in treating mild to moderate acute pancreatitis. Patients were divided into a control group (61 cases) and an integrated traditional Chinese and Western medicine (ITCWM) group (120 cases). To further assess the clinical efficacy of TCM enema in the treatment of mild to moderate acute pancreatitis, PSM analysis was conducted across three groups. The patients were categorized into a control group (n = 49), an oral TCM treatment group (OCM group, n = 274), and an oral TCM plus enema treatment group (OCM+E group, n = 131). Logistic regression was used to analyze factors after treatment in each group, and the Kaplan-Meier method compared symptom duration in each group. Results Compared with the control group, the ITCWM group significantly decreased C-reactive protein (CRP, mg/L) (17.8 [1.2-59.5] vs. 8.0 [3.3-33.5], P = 0.022), shortened the duration of abdominal distension, abdominal pain, nausea and bitter taste symptoms (P < 0.05), and shortened the length of hospital stay (median 19.0 and 11.5 days, respectively, P = 0.001); Compared with the other two groups, the neutrophil percentage (NEUT%) was lower (74.1 vs. 61.9 vs. 59.5, P < 0.05) and serum prealbumin (PA, mg/L) was higher (116.0 vs. 184.4 vs. 220.0, P < 0.05), the length of hospitalization (days) was shortened (19.0 vs.12.0 vs.10.0, P < 0.05) in the OCM+E group. Conclusion The combination of traditional Chinese medicine and modern medicine has been shown to effectively decrease inflammatory indicators in patients with mild to moderate acute pancreatitis, leading to a reduction in symptom duration and hospitalization period, as well as promoting disease recovery. Notably, the use of traditional Chinese medicine in conjunction with enema therapy yields more pronounced benefits.
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Affiliation(s)
- Sailei Jia
- Department of Critical Care Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Qian Chen
- Department of Critical Care Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
- Department of Medical School, Huanghe Science and Technology College, Zhengzhou, China
| | - Xitong Liu
- Department of Gastroenterology, Henan Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Yanhong Li
- Department of Medical School, Huanghe Science and Technology College, Zhengzhou, China
| | - Lihui Wang
- Department of Critical Care Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Xian Li
- Department of Gastroenterology, Henan Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
| | - Shixiang Hu
- Department of Critical Care Medicine, Henan Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, China
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Qiu Q, Fu F, Wu Y, Han C, Pu W, Wen L, Xia Q, Du D. Rhei Radix et Rhizoma and its anthraquinone derivatives: Potential candidates for pancreatitis treatment. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 129:155708. [PMID: 38733906 DOI: 10.1016/j.phymed.2024.155708] [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: 03/01/2024] [Revised: 04/22/2024] [Accepted: 05/02/2024] [Indexed: 05/13/2024]
Abstract
BACKGROUND Pancreatitis is a common exocrine inflammatory disease of the pancreas and lacks specific medication currently. Rhei Radix et Rhizoma (RR) and its anthraquinone derivatives (AQs) have been successively reported for their pharmacological effects and molecular mechanisms in experimental and clinical pancreatitis. However, an overview of the anti-pancreatitis potential of RR and its AQs is limited. PURPOSE To summarize and analyze the pharmacological effects of RR and its AQs on pancreatitis and the underlying mechanisms, and discuss their drug-like properties and future perspectives. METHODS The articles related to RR and its AQs were collected from the Chinese National Knowledge Infrastructure, Wanfang data, PubMed, and the Web of Science using relevant keywords from the study's inception until April first, 2024. Studies involving RR or its AQs in cell or animal pancreatitis models as well as structure-activity relationship, pharmacokinetics, toxicology, and clinical trials were included. RESULTS Most experimental studies are based on severe acute pancreatitis rat models and a few on chronic pancreatitis. Several bioactive anthraquinone derivatives of Rhei Radix et Rhizoma (RRAQs) exert local protective effects on the pancreas by maintaining pancreatic acinar cell homeostasis, inhibiting inflammatory signaling, and anti-fibrosis, and they improve systemic organ function by alleviating intestinal and lung injury. Pharmacokinetic and toxicity studies have revealed the low bioavailability and wide distribution of RRAQs, as well as hepatotoxicity and nephrotoxicity. However, there is insufficient research on the clinical application of RRAQs in pancreatitis. Furthermore, we propose effective strategies for subsequent improvement in terms of balancing effectiveness and safety. CONCLUSION RRAQs can be developed as either candidate drugs or novel lead structures for pancreatitis treatment. The comprehensive review of RR and its AQs provides references for optimizing drugs, developing therapies, and conducting future studies on pancreatitis.
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Affiliation(s)
- Qi Qiu
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Fei Fu
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
| | - Yaling Wu
- Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China
| | - Chenxia Han
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Weiling Pu
- Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Li Wen
- State Key Laboratory of Complex, Severe, and Rare Diseases, Center for Biomarker Discovery and Validation, National Infrastructures for Translational Medicine (PUMCH), Institute of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100073, China
| | - Qing Xia
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
| | - Dan Du
- West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, China; Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610213, China.
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Liu X, Wang Y, Tian Y, Hu J, Liu Z, Ma Y, Xu W, Wang W, Gao J, Wang T. The Water Extract of Rhubarb Prevents Ischemic Stroke by Regulating Gut Bacteria and Metabolic Pathways. Metabolites 2024; 14:216. [PMID: 38668344 PMCID: PMC11052393 DOI: 10.3390/metabo14040216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 04/05/2024] [Accepted: 04/07/2024] [Indexed: 04/28/2024] Open
Abstract
Rhubarb (RR), Chinese name Dahuang, is commonly used in the treatment of ischemic stroke (IS). However, its potential mechanism is not fully elucidated. This study intended to verify the effect of RR on IS and investigate the possible mechanism of RR in preventing IS. IS in male rats was induced by embolic middle cerebral artery occlusion (MCAO) surgery, and drug administration was applied half an hour before surgery. RR dramatically decreased the neurological deficit scores, the cerebral infarct volume, and the cerebral edema rate, and improved the regional cerebral blood flow (rCBF) and histopathological changes in the brain of MCAO rats. The 16S rRNA analysis showed the harmful microbes such as Fournierella and Bilophila were decreased, and the beneficial microbes such as Enterorhabdus, Defluviitaleaceae, Christensenellaceae, and Lachnospira were significantly increased, after RR pretreatment. 1H-nuclear magnetic resonance (1H-NMR) was used to detect serum metabolomics, and RR treatment significantly changed the levels of metabolites such as isoleucine, valine, N6-acetyllysine, methionine, 3-aminoisobutyric acid, N, N-dimethylglycine, propylene glycol, trimethylamine N-oxide, myo-inositol, choline, betaine, lactate, glucose, and lipid, and the enrichment analysis of differential metabolites showed that RR may participate in the regulation of amino acid metabolism and energy metabolism. RR exerts the role of anti-IS via regulating gut bacteria and metabolic pathways.
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Affiliation(s)
- Xiaoyao Liu
- School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; (X.L.); (J.H.)
| | - Yuxi Wang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China; (Y.W.); (Y.M.)
| | - Yuan Tian
- School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China; (Y.T.); (Z.L.); (W.X.)
| | - Jiahui Hu
- School of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China; (X.L.); (J.H.)
| | - Zhen Liu
- School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China; (Y.T.); (Z.L.); (W.X.)
| | - Yuncheng Ma
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China; (Y.W.); (Y.M.)
| | - Wenhui Xu
- School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China; (Y.T.); (Z.L.); (W.X.)
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Weiling Wang
- School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China; (Y.T.); (Z.L.); (W.X.)
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jian Gao
- School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China; (Y.T.); (Z.L.); (W.X.)
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Ting Wang
- School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China; (Y.T.); (Z.L.); (W.X.)
- Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
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Li L, Liu Q, Le C, Zhang H, Liu W, Gu Y, Yang J, Zhang X. Toll-like receptor 2 deficiency alleviates acute pancreatitis by inactivating the NF-κB/NLRP3 pathway. Int Immunopharmacol 2023; 121:110547. [PMID: 37356124 DOI: 10.1016/j.intimp.2023.110547] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Revised: 06/09/2023] [Accepted: 06/18/2023] [Indexed: 06/27/2023]
Abstract
The early aseptic immune response is the key factor leading to the aggravation of acute pancreatitis (AP). Toll-like receptor (TLR) 2 is an important member of the TLR family, but the role of TLR2 in AP remains to be investigated. In the present study, we found that TLR2 expression was significantly increased in AP patients. In a mouse model of cerulein-induced AP, TLR2 deficiency resulted in reduced inflammation, reduced infiltration of pancreatic neutrophils and macrophages, and decreased expression of proinflammatory cytokines such as interleukin (IL)-1β, IL-6, IL-17 and IL-18. In addition, transcriptomic analysis revealed that nod-like receptor family pyrin domain-containing 3 (NLRP3) expression was increased in AP, and there was a significant correlation between NLRP3 and TLR2. This study found that TLR2 deficiency can lead to a decrease in the activation of the NF-κB/NLRP3 signalling pathway, and the NLRP3 inhibitor MCC950 can alleviate AP in mice. Therefore, this study confirmed that TLR2 participates in the development of AP by activating the NF-κB/NLRP3 pathway. This study suggested that TLR2 might be a novel therapeutic target for AP.
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Affiliation(s)
- Lingyun Li
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China; Hangzhou Institute of Digestive Disease, Hangzhou 310006, China
| | - Qiang Liu
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China; Hangzhou Institute of Digestive Disease, Hangzhou 310006, China
| | - Chenyu Le
- The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China
| | - Hongchen Zhang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China
| | - Wenfei Liu
- Chinese PLA 305 Hospital, Beijing 100018, China
| | - Ye Gu
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China
| | - Jianfeng Yang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China; Hangzhou Institute of Digestive Disease, Hangzhou 310006, China
| | - Xiaofeng Zhang
- Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China; The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310006, China; Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310006, China; Hangzhou Institute of Digestive Disease, Hangzhou 310006, China.
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Wang J, Jiang M, Hu Y, Lei Y, Zhu Y, Xiong H, He C. Lactulose regulates gut microbiota dysbiosis and promotes short-chain fatty acids production in acute pancreatitis patients with intestinal dysfunction. Biomed Pharmacother 2023; 163:114769. [PMID: 37116350 DOI: 10.1016/j.biopha.2023.114769] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 04/07/2023] [Accepted: 04/22/2023] [Indexed: 04/30/2023] Open
Abstract
BACKGROUND Intestinal dysfunction is one of the common complications in the early stage of acute pancreatitis (AP), which often associates with bad outcome. Lactulose, as a prebiotic, has been widely used to improve gut health, yet its effect on AP is unclear. METHODS This was a prospective, randomized trial of moderate severe AP patients complicated with intestinal dysfunction. A total of 73 participants were randomly assigned to receive either lactulose or Chinese herb rhubarb for 1 week. The primary efficacy endpoint was the recovery of intestinal function. The serum levels of inflammatory cytokines and gut barrier indexes were examined. The fecal samples from patients before and after treatment were collected. 16 S rRNA gene sequencing analysis was performed to explore the composition of gut microbiota and the amount of short-chain fatty acids (SCFAs) were detected by gas chromatography-mass spectrometry (GC-MS). RESULTS The intestinal dysfunction was prominently improved after 7 days of treatment with either lactulose or rhubarb. The serum levels of cytokines and gut permeability index were decreased after treatment, with stronger down-regulated degree in lactulose group than rhubarb. The potential beneficial genus Bifidobacterium was enriched in lactulose group, while pathogenic bacteria including Escherichia-Shigella and Neisseria were abundant in rhubarb group. Of note, the level of SCFAs was remarkably increased after treatment, with higher amount in lactulose group than rhubarb group. CONCLUSIONS Lactulose could not only restore intestinal function but also regulate gut microbiota and promote the production of SCFAs.
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Affiliation(s)
- Jinyun Wang
- Department of Gastroenterology, Digestive disease hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Meilan Jiang
- Department of Gastroenterology, Digestive disease hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yang Hu
- Department of Gastroenterology, Digestive disease hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yupeng Lei
- Department of Gastroenterology, Digestive disease hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Digestive disease hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Huifang Xiong
- Department of Gastroenterology, Digestive disease hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
| | - Cong He
- Department of Gastroenterology, Digestive disease hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
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Izadparast F, Riahi-Zajani B, Yarmohammadi F, Hayes AW, Karimi G. Protective effect of berberine against LPS-induced injury in the intestine: a review. Cell Cycle 2022; 21:2365-2378. [PMID: 35852392 PMCID: PMC9645259 DOI: 10.1080/15384101.2022.2100682] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2022] [Revised: 07/03/2022] [Accepted: 07/08/2022] [Indexed: 12/11/2022] Open
Abstract
Sepsis is a systemic inflammatory condition caused by an unbalanced immunological response to infection, which affects numerous organs, including the intestines. Lipopolysaccharide (LPS; also known as endotoxin), a substance found in Gram-negative bacteria, plays a major role in sepsis and is mostly responsible for the disease's morbidity and mortality. Berberine is an isoquinoline alkaloid found in a variety of plant species that has anti-inflammatory properties. For many years, berberine has been used to treat intestinal inflammation and infection. Berberine has been reported to reduce LPS-induced intestinal damage. The potential pathways through which berberine protects against LPS-induced intestinal damage by inhibiting NF-κB, suppressing MAPK, modulating ApoM/S1P pathway, inhibiting COX-2, modulating Wnt/Beta-Catenin signaling pathway, and/or increasing ZIP14 expression are reviewed.Abbreviations: LPS, lipopolysaccharide; TLR, Toll-like receptor; MD-2, myeloid differentiation factor 2; CD14, cluster of differentiation 14; LBP, lipopolysaccharide-binding protein; MYD88, myeloid differentiation primary response 88; NF-κB, nuclear factor kappa light-chain enhancer of activated B cells; MAPK, mitogen-activated protein kinase; IL, interleukin; TNFα, tumor necrosis factor-alpha; Caco-2, cyanocobalamin uptake by human colon adenocarcinoma cell line; MLCK, myosin light-chain kinase; TJ, tight junction; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; IBS, irritable bowel syndrome; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase (JNK; GVB, gut-vascular barrier; ApoM, apolipoprotein M; S1P, sphingosine-1-phosphate; VE-cadherin, vascular endothelial cadherin; AJ, adherens junction; PV1, plasmalemma vesicle-associated protein-1; HDL, high-density lipoprotein; Wnt, wingless-related integration site; Fzd, 7-span transmembrane protein Frizzled; LRP, low-density lipoprotein receptor-related protein; TEER, transendothelial/transepithelial electrical resistance; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; ZIP, Zrt-Irt-like protein; PPAR, peroxisome proliferator-activated receptors; p-PPAR, phosphorylated-peroxisome proliferator-activated receptors; ATF, activating transcription factors; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; SARA, subacute ruminal acidosis; IPEC-J2, porcine intestinal epithelial cells; ALI, acute lung injury; ARDS, acute respiratory distress syndrome.
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Affiliation(s)
- Faezeh Izadparast
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Bamdad Riahi-Zajani
- Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Yarmohammadi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - A. Wallace Hayes
- Center for Environmental Occupational Risk Analysis and Management, College of Public Health, University of South Florida, Tampa, FL, USA
| | - Gholamreza Karimi
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
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Yang Z, Liu Y, Wang L, Lin S, Dai X, Yan H, Ge Z, Ren Q, Wang H, Zhu F, Wang S. Traditional Chinese medicine against COVID-19: Role of the gut microbiota. Biomed Pharmacother 2022; 149:112787. [PMID: 35279010 PMCID: PMC8901378 DOI: 10.1016/j.biopha.2022.112787] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 02/26/2022] [Accepted: 03/02/2022] [Indexed: 01/08/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and it has become a public health concern worldwide. In addition to respiratory symptoms, some COVID‑19 patients also show various gastrointestinal symptoms and even consider gastrointestinal symptoms to be the first manifestation. A large amount of evidence has shown that SARS-CoV-2 infection could disrupt the gut microbiota balance, and disorders of the gut microbiota could aggravate the condition of COVID-19 patients. Therefore, maintaining the gut microbiota balance is expected to become a potential new therapeutic target for treating COVID-19. Traditional Chinese medicine (TCM) has significant effects in all stages of the prevention and treatment of COVID-19. It can adjust the gut microbiota and is an ideal intestinal microecological regulator. This review summarizes the advantages and clinical efficacy of TCM in the treatment of COVID-19 and expounds on the relationship between TCM and the gut microbiota, the relationship between COVID-19 and the gut microbiota, the mechanism of gut microbiota disorders induced by SARS-CoV-2, the relationship between cytokine storms and the gut microbiota, and the role and mechanism of TCM in preventing and treating COVID-19 by regulating the gut microbiota to provide new research ideas for TCM in the prevention and treatment of COVID-19.
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Affiliation(s)
- Zhihua Yang
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Yangxi Liu
- Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Lin Wang
- Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Shanshan Lin
- Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Xiangdong Dai
- State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Haifeng Yan
- The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450000, China
| | - Zhao Ge
- Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Qiuan Ren
- Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Hui Wang
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300381, China
| | - Feng Zhu
- Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
| | - Shuping Wang
- Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin 300162, China.
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Tang T, Wang F, Liu J, Ye W, Zhao T, Li Z. Rhubarb Alleviates Acute Lung Injury by Modulating Gut Microbiota Dysbiosis in Mice. Curr Microbiol 2022; 79:116. [PMID: 35218438 DOI: 10.1007/s00284-022-02811-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 02/14/2022] [Indexed: 12/13/2022]
Abstract
Intestinal microbiota disorders can aggravate pulmonary inflammation during acute lung injury (ALI). As a traditional Chinese herb, Rhubarb can regulated the gut microbiota. Therefore, this study was conducted to test the hypothesis that rhubarb alleviates gut microbiota dysbiosis and inflammation. Feces were collected from patients with ALI to detect the gut microbiota using 16S rDNA sequencing. Subsequently, a mouse model of ALI was established using lipopolysaccharide to investigate changes in the gut microbiota, the peripheral blood was attained for detecting the Th17/Treg cell ratio and the serum level of HDAC6 and HDAC9, and the effect of rhubarb treatment on the gut microbiota and Th17/Treg ratio were also evaluated. The results indicated that both the Firmicutes phylum decreased and the Bacteroidetes phylum increased were identified in patients with ALI, which induced the alternation of histone metabolites. The mice models also showed a similar imbalance in the Firmicutes/Bacteroidetes ratio at phylum of level. Rhubarb treatment alleviated the damaged lung tissue, accelerated Alistipes, Clostridium, and Lactobacillus proliferation at the level of genus, increased the level of HDAC6 in both the mice lung tissue and serum, and markedly reduced the Treg cells and increased the Th17 cells in the spleen tissue. The study suggested that both patients and mouse models with ALI presented gut microbiota dysbiosis, and lead to a Th17/Treg cell imbalance in ALI mouse. Rhubarb promoted Alistipes, Clostridium, and Lactobacillus proliferation, increased the HDAC6 concentration, restored the Th17/Treg cell balance, and protected against ALI.
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Affiliation(s)
- Tingyu Tang
- Department of Respiratory Medicine in Zhejiang Hospital Affiliated To Medical School of Zhejiang University, 1229 Gudun Road, Xihu District, Hangzhou, 310012, Zhejiang, China
| | - Fei Wang
- Department of Respiratory Medicine in Zhejiang Hospital Affiliated To Medical School of Zhejiang University, 1229 Gudun Road, Xihu District, Hangzhou, 310012, Zhejiang, China
| | - Juan Liu
- Department of Respiratory Medicine in Zhejiang Hospital Affiliated To Medical School of Zhejiang University, 1229 Gudun Road, Xihu District, Hangzhou, 310012, Zhejiang, China
| | - Wu Ye
- Department of Respiratory Medicine in Zhejiang Hospital Affiliated To Medical School of Zhejiang University, 1229 Gudun Road, Xihu District, Hangzhou, 310012, Zhejiang, China
| | - Tian Zhao
- Department of Respiratory Medicine in Zhejiang Hospital Affiliated To Medical School of Zhejiang University, 1229 Gudun Road, Xihu District, Hangzhou, 310012, Zhejiang, China
| | - Zhijun Li
- Department of Respiratory Medicine in Zhejiang Hospital Affiliated To Medical School of Zhejiang University, 1229 Gudun Road, Xihu District, Hangzhou, 310012, Zhejiang, China.
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Luo Y, Li Z, Ge P, Guo H, Li L, Zhang G, Xu C, Chen H. Comprehensive Mechanism, Novel Markers and Multidisciplinary Treatment of Severe Acute Pancreatitis-Associated Cardiac Injury - A Narrative Review. J Inflamm Res 2021; 14:3145-3169. [PMID: 34285540 PMCID: PMC8286248 DOI: 10.2147/jir.s310990] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 06/15/2021] [Indexed: 12/12/2022] Open
Abstract
Acute pancreatitis (AP) is one of the common acute abdominal inflammatory diseases in clinic with acute onset and rapid progress. About 20% of the patients will eventually develop into severe acute pancreatitis (SAP) characterized by a large number of inflammatory cells infiltration, gland flocculus flaky necrosis and hemorrhage, finally inducing systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Pancreatic enzyme activation, intestinal endotoxemia (IETM), cytokine activation, microcirculation disturbance, autonomic nerve dysfunction and autophagy dysregulation all play an essential role in the occurrence and progression of SAP. Organ dysfunction is the main cause of early death in SAP. Acute kidney injury (AKI) and acute lung injury (ALI) are common, while cardiac injury (CI) is not, but the case fatality risk is high. Many basic studies have observed obvious ultrastructure change of heart in SAP, including myocardial edema, cardiac hypertrophy, myocardial interstitial collagen deposition. Moreover, in clinical practice, patients with SAP often presented various abnormal electrocardiogram (ECG) and cardiac function. Cases complicated with acute myocardial infarction and pericardial tamponade have also been reported and even result in stress cardiomyopathy. Due to the molecular mechanisms underlying SAP-associated cardiac injury (SACI) remain poorly understood, and there is no complete, unified treatment and sovereign remedy at present, this article reviews reports referring to the pathogenesis, potential markers and treatment methods of SACI in recent years, in order to improve the understanding of cardiac injury in severe pancreatitis.
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Affiliation(s)
- YaLan Luo
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - ZhaoXia Li
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Peng Ge
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - HaoYa Guo
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China.,Laboratory of Integrative Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - Lei Li
- Department of Vascular Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - GuiXin Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - CaiMing Xu
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
| | - HaiLong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People's Republic of China
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10
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Huang SQ, Wen Y, Sun HY, Deng J, Zhang YL, Huang QL, Wang B, Luo ZL, Tang LJ. Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway. World J Gastroenterol 2021; 27:815-834. [PMID: 33727772 PMCID: PMC7941863 DOI: 10.3748/wjg.v27.i9.815] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2020] [Revised: 12/14/2020] [Accepted: 02/01/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood.
AIM To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms.
METHODS SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed.
RESULTS APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury.
CONCLUSION APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.
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Affiliation(s)
- Shang-Qing Huang
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Yi Wen
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Hong-Yu Sun
- Basic Medical Laboratory, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Jie Deng
- Department of Clinical Pharmacy, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Yao-Lei Zhang
- Basic Medical Laboratory, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Qi-Lin Huang
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Bing Wang
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Zhu-Lin Luo
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
| | - Li-Jun Tang
- Department of General Surgery & Pancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater Command (Chengdu Military General Hospital), Chengdu 610083, Sichuan Province, China
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11
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Wei L, Luo Y, Zhang X, Liu Y, Gasser M, Tang F, Ouyang WW, Wei H, Lu S, Yang Z, Waaga-Gasser AM, Deng C, Lin M. Topical therapy with rhubarb navel plasters in patients with chronic constipation: Results from a prospective randomized multicenter study. JOURNAL OF ETHNOPHARMACOLOGY 2021; 264:113096. [PMID: 32693116 DOI: 10.1016/j.jep.2020.113096] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 05/19/2020] [Accepted: 06/06/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Constipation is a functional gastrointestinal disorder and one of the most prevalent conditions encountered in primary care settings. Rhubarb navel dressings have been used for more than 2,000 years in Chinese medicine to treat constipation. However, the effect of topical rhubarb administration has still not been well recognized and this strategy is not yet established as an evidence-based approach. AIM OF THE STUDY In this study, we performed a prospective multicentric randomized controlled trial to evaluate the efficacy and safety of rhubarb navel plasters for patients with chronic constipation. MATERIALS AND METHODS A total of 374 patients from six teaching hospitals were prospectively included between 09/2016 and 10/2017 in the study based on Rome III criteria. All participants were randomly assigned (1:1) into verum/placebo group and given either Rheum officinale rhubarb powder or a placebo flour stick on the navel for 6 h/day/8 days. Primary outcome measures were the Cleveland Constipation Score (CCS) for the feces condition and Bristol Stool Scale (BSS) for stool consistency and 24 h defecation frequency. RESULTS The groups demonstrated no statistical differences in demographic data, clinical diagnoses and concomitant medication at baseline. In patients treated with the verum CCS was 5.61 (day 8, 95% CI 5.15-6.07) compared to 8.62 (95% CI 8.07-9.18) in placebo-treated controls (P < 0.001). The mean change of CCS at the end of treatment (day 8 versus [vs] day 0) was 6.04 in verum-treated vs 2.73 in placebo-treated controls (P < 0.001). Also 24 h defecation frequency (BSS) showed superior results (day 5: 0.84 vs 0.62, 95% CI 0.67-0.80, P < 0.001; day 6: 0.82 vs 0.60, 95% CI 0.64-0.78, P < 0.01 and day 8: 0.82 vs 0.60, 95% CI 0.64-0.78, P < 0.01) and better BSS type classification during treatment than controls (P < 0.05). No significant differences in adverse events between both groups became obvious. CONCLUSION Rhubarb navel plaster administration over an 8-day-treatment period resulted in significantly improved bowel function as demonstrated by the CCS, 24 h defecating frequency and BSS. Our results suggest that rhubarb navel plasters represent a feasible, safe and efficient application route for the treatment of patients suffering from chronic constipation.
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Affiliation(s)
- Lin Wei
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China..
| | - Yueming Luo
- The fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, China.
| | - Xiaopei Zhang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China..
| | - Yangchen Liu
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China..
| | | | - Fang Tang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China..
| | - Wen-Wei Ouyang
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China..
| | - Hengqiu Wei
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
| | - Shengzhen Lu
- Jiangxi Integrated Traditional Chinese and Western Medicine Hospital, Nanchang, China.
| | - Zhen Yang
- The First Affiliated Hospital of Nanchang University, Nanchang, China.
| | | | - Chong Deng
- Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
| | - Meizhen Lin
- The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China..
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12
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Xiang H, Zuo J, Guo F, Dong D. What we already know about rhubarb: a comprehensive review. Chin Med 2020; 15:88. [PMID: 32863857 PMCID: PMC7448319 DOI: 10.1186/s13020-020-00370-6] [Citation(s) in RCA: 71] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 08/19/2020] [Indexed: 02/06/2023] Open
Abstract
Rhubarb (also named Rhei or Dahuang), one of the most ancient and important herbs in traditional Chinese medicine (TCM), belongs to the Rheum L. genus from the Polygonaceae family, and its application can be traced back to 270 BC in "Shen Nong Ben Cao Jing". Rhubarb has long been used as an antibacterial, anti-inflammatory, anti-fibrotic and anticancer medicine in China. However, for a variety of reasons, such as origin, variety and processing methods, there are differences in the effective components of rhubarb, which eventually lead to decreased quality and poor efficacy. Additionally, although some papers have reviewed the relationship between the active ingredients of rhubarb and pharmacologic actions, most studies have concentrated on one or several aspects, although there has been great progress in rhubarb research in recent years. Therefore, this review aims to summarize recent studies on the geographic distribution, taxonomic identification, pharmacology, clinical applications and safety issues related to rhubarb and provide insights into the further development and application of rhubarb in the future.
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Affiliation(s)
- Hong Xiang
- Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jiaxin Zuo
- Laboratory of Integrative Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, China
- College of Pharmacy, Dalian Medical University, Dalian, China
| | - Fangyue Guo
- Institute (College) of Integrative Medicine, Dalian Medical University, Dalian, China
| | - Deshi Dong
- Department of Clinical Pharmacy, First Affiliated Hospital of Dalian Medical University, Dalian, China
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13
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Chen X, Yang K, Jing G, Yang J, Li K. Meta‐Analysis of Efficacy of Rhubarb Combined With Early Enteral Nutrition for the Treatment of Severe Acute Pancreatitis. JPEN J Parenter Enteral Nutr 2020; 44:1066-1078. [PMID: 32187391 DOI: 10.1002/jpen.1789] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 10/24/2019] [Accepted: 01/06/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Xinrong Chen
- West China Hospital/West China School of NursingSichuan University Chengdu Sichuan Province China
| | - Kun Yang
- Department of Gastrointestinal SurgeryWest China HospitalSichuan University Chengdu Sichuan Province China
| | - Guanda Jing
- West China Hospital/West China School of NursingSichuan University Chengdu Sichuan Province China
| | - Jie Yang
- Department of Gastrointestinal SurgeryWest China HospitalSichuan University Chengdu Sichuan Province China
| | - Ka Li
- West China Hospital/West China School of NursingSichuan University Chengdu Sichuan Province China
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Schink A, Neumann J, Leifke AL, Ziegler K, Fröhlich-Nowoisky J, Cremer C, Thines E, Weber B, Pöschl U, Schuppan D, Lucas K. Screening of herbal extracts for TLR2- and TLR4-dependent anti-inflammatory effects. PLoS One 2018; 13:e0203907. [PMID: 30307962 PMCID: PMC6181297 DOI: 10.1371/journal.pone.0203907] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2018] [Accepted: 08/29/2018] [Indexed: 12/18/2022] Open
Abstract
Herbal extracts represent an ample source of natural compounds, with potential to be used in improving human health. There is a growing interest in using natural extracts as possible new treatment strategies for inflammatory diseases. We therefore aimed at identifying herbal extracts that affect inflammatory signaling pathways through toll-like receptors (TLRs), TLR2 and TLR4. Ninety-nine ethanolic extracts were screened in THP-1 monocytes and HeLa-TLR4 transfected reporter cells for their effects on stimulated TLR2 and TLR4 signaling pathways. The 28 identified anti-inflammatory extracts were tested in comparative assays of stimulated HEK-TLR2 and HEK-TLR4 transfected reporter cells to differentiate between direct TLR4 antagonistic effects and interference with downstream signaling cascades. Furthermore, the ten most effective anti-inflammatory extracts were tested on their ability to inhibit nuclear factor-κB (NF-κB) translocation in HeLa-TLR4 transfected reporter cell lines and for their ability to repolarize M1-type macrophages. Ethanolic extracts which showed the highest anti-inflammatory potential, up to a complete inhibition of pro-inflammatory cytokine production were Castanea sativa leaves, Cinchona pubescens bark, Cinnamomum verum bark, Salix alba bark, Rheum palmatum root, Alchemilla vulgaris plant, Humulus lupulus cones, Vaccinium myrtillus berries, Curcuma longa root and Arctostaphylos uva-ursi leaves. Moreover, all tested extracts mitigated not only TLR4, but also TLR2 signaling pathways. Seven of them additionally inhibited translocation of NF-κB into the nucleus. Two of the extracts showed impact on repolarization of pro-inflammatory M1-type to anti-inflammatory M2-type macrophages. Several promising anti-inflammatory herbal extracts were identified in this study, including extracts with previously unknown influence on key TLR signaling pathways and macrophage repolarization, serving as a basis for novel lead compound identification.
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Affiliation(s)
- Anne Schink
- Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany
| | - Jan Neumann
- Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany
- Institute of Molecular Biology, Mainz, Germany
| | - Anna Lena Leifke
- Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany
| | - Kira Ziegler
- Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany
| | | | - Christoph Cremer
- Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany
- Institute of Molecular Biology, Mainz, Germany
| | - Eckhard Thines
- Institut für Biotechnologie und Wirkstoff-Forschung gGmbH, Kaiserslautern, Germany
- Institute of Molecular Physiology, Johannes Gutenberg University Mainz, Mainz, Germany
| | - Bettina Weber
- Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany
| | - Ulrich Pöschl
- Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany
| | - Detlef Schuppan
- Institute of Translational Immunology, University of Mainz Medical Center, Mainz, Germany
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States of America
| | - Kurt Lucas
- Multiphase Chemistry Department, Max Planck Institute for Chemistry, Mainz, Germany
- * E-mail:
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15
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Junyuan Z, Hui X, Chunlan H, Junjie F, Qixiang M, Yingying L, Lihong L, Xingpeng W, Yue Z. Quercetin protects against intestinal barrier disruption and inflammation in acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition. Pancreatology 2018; 18:742-752. [PMID: 30115563 DOI: 10.1016/j.pan.2018.08.001] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 07/20/2018] [Accepted: 08/05/2018] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To investigate the effects of quercetin on intestinal barrier disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and its possible mechanism. METHODS ANP was established by retrograde injection of 3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg × 3) was administered by intraperitoneal injection prior to and after ANP induction. Pancreatitis was assessed by pancreatic histopathology, plasma amylase, pancreatic myeloperoxidase (MPO) activity, IL-1β, TNFα and IL-6 levels. Injury of the distal ileum was assessed by histological evaluation. The ultrastructural changes of ileal epithelial cells were examined by transmission electron microscope (TEM). Intestinal barrier function was estimated by plasma diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial translocation. Intestinal inflammation was determined by IL-1β, TNFα and IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress (ERS)-related molecules (Bip, p-IRE1α, sXBP1, p-eIF2α, ATF6) were measured by immunohistochemistry and WB. RESULTS Quercetin intervention attenuated pancreatic and ileal pathological damages in ANP (P < 0.05), ameliorated intestinal barrier disruption and inflammation (P < 0.05). Meantime, QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS activation. CONCLUSIONS Quercetin plays a protective role against intestinal barrier disruption and inflammation in ANP, probably partly by inhibiting TLR4/MyD88/p38 MAPK and ERS activation.
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Affiliation(s)
- Zheng Junyuan
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Xu Hui
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Huang Chunlan
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Fan Junjie
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Mei Qixiang
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Lu Yingying
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
| | - Lou Lihong
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
| | - Wang Xingpeng
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
| | - Zeng Yue
- Shanghai Key Laboratory of Pancreatic Disease & Department of Gastroenterology, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
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16
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Zhang X, Wang L, Chen DC. Effect of Rhubarb on Gastrointestinal Dysfunction in Critically Ill Patients: A Retrospective Study Based on Propensity Score Matching. Chin Med J (Engl) 2018; 131:1142-1150. [PMID: 29722333 PMCID: PMC5956764 DOI: 10.4103/0366-6999.231523] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Background: Gastrointestinal dysfunction plays a critical role in the prognosis of critically ill patients. Previous studies showed rhubarb, a traditional Chinese herb, can protect the intestinal barrier function, prevent intestinal bacterial translocation, and promote gastrointestinal peristalsis, but the clinical studies are less. The aim of this study was to evaluate the effects of rhubarb on gastrointestinal dysfunction in critically ill patients. Methods: From June 2015 to May 2017, a total of 368 critically ill patients with Grade I–III acute gastrointestinal injury (AGI) were enrolled in this study. Patients were divided into two groups according to the exposure factors (whether the patients received rhubarb treatment): the rhubarb group and the usual treatment group. Clinical data were collected within the first 24 h of the Intensive Care Unit (ICU) admission and 7 days after treatment. Survival data on day 28 after ICU admission and the durations of ICU and total hospitalization were also collected. Propensity score matching (PSM) was conducted to reduce confounding bias between the groups. The logistic regression was conducted to screen the influence factors. Results: The eligible patients were divided into rhubarb group (n = 219, 59.5%) and usual treatment group (n = 149, 40.5%). Before PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group were 59.8% and 39.6%, respectively. After PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group was 77.9% and 30.9%, respectively. The remission rates of feeding intolerance in rhubarb group were significantly higher than those in the usual treatment group (all P < 0.05). Compared with the usual treatment group, the rhubarb group had a higher rate of AGI improvement, lower level of C-reactive protein, shorter stay in ICU before and after PSM (P < 0.05). There was no significant difference in 28-day mortality between rhubarb and usual treatment groups before and after PSM (48 vs. 33, P = 0.959; and 16 vs. 21, P = 0.335). The logistic regression analysis showed that the single factor, whether receiving rhubarb therapy, affected the proportion of patients whose enteral nutrition needs ≥83.7 kJ·kg−1·d−1 after 7 days of treatment (odds ratio: 7.908, 95% confidence interval: 3.661–17.083, P < 0.001). No serious adverse effects were found in two groups. Conclusions: The rhubarb might significantly improve feeding tolerance and relieve gastrointestinal dysfunction in critically ill patients, without serious adverse reactions. It provided proof for the treatment of gastrointestinal dysfunction with rhubarb during clinical practice.
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Affiliation(s)
- Xian Zhang
- Department of Emergency Medicine, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China
| | - Lyu Wang
- Department of Emergency Medicine, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China
| | - De-Chang Chen
- Department of Emergency Medicine, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China
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17
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Liu J, An N, Ma C, Li X, Zhang J, Zhu W, Zhang Y, Li J. Correlation analysis of intestinal flora with hypertension. Exp Ther Med 2018; 16:2325-2330. [PMID: 30210587 PMCID: PMC6122545 DOI: 10.3892/etm.2018.6500] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 06/26/2018] [Indexed: 12/23/2022] Open
Abstract
Relationship between intestinal flora content and hypertension was investigated. Ninety-four patients with hypertension who were admitted and treated in No. 215 Hospital of Shaanxi Nuclear Industry from May 2016 to April 2017 were selected as the observation group; and 94 healthy people from the physical examination center of No. 215 Hospital of Shaanxi Nuclear Industry in the same time period were selected as the control group. The systolic (SBP) and diastolic blood pressure (DBP) of all the participants were measured. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the quantities of Eubacterium rectale, Bacteroides thetaiotaomicron and Bifidobacterium in the intestines, and correlation analyses were performed. The SBP, DBP and content of Eubacterium rectale in the observation group were significantly higher than those in the control group, while the contents of Bacteroides thetaiotaomicron and Bifidobacterium were obviously lower than those in the control group (P<0.05). Pearson's correlation analysis showed that Eubacterium rectale was positively correlated with SBP and DBP, while Bacteroides thetaiotaomicron and Bifidobacterium had a negative correlation with SBP and DBP (P<0.05). The results showed that the quantities of Bifidobacterium and Bacteroides thetaiotaomicron are decreased while the number of Eubacterium rectale is increased in the intestines of patients with hypertension. Moreover, the content of intestinal flora has a significant correlation with hypertension.
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Affiliation(s)
- Jilun Liu
- Department of Cardiology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, Shaanxi 712000, P.R. China
| | - Ning An
- Department of Cardiology, Xingyuan Hospital of Yulin City, Yulin, Shaanxi 719000, P.R. China
| | - Cong Ma
- Department of Clinical Medicine, Medical College of Nanchang University, Nanchang, Jiangxi 330031, P.R. China
| | - Xiaofeng Li
- Department of Clinical Laboratory, Central Hospital of Xi'an City, Xi'an, Shaanxi 710003, P.R. China
| | - Jie Zhang
- Department of Internal Medicine, No. 5 Hospital of Xi'an City, Xi'an, Shaanxi 710082, P.R. China
| | - Wei Zhu
- Department of Clinical Laboratory, Central Hospital of Baoji City, Baoji, Shaanxi 721008, P.R. China
| | - Yihe Zhang
- Department of Cardiovascular Medical Center, Dongguan Cardiovascular and Cerebrovascular Disease Hospital, The Affiliated Hospital of Yan'an University, Yan'an, Shaanxi 716000, P.R. China
| | - Junpeng Li
- Department of Cardiology, No. 215 Hospital of Shaanxi Nuclear Industry, Xianyang, Shaanxi 712000, P.R. China
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Ning Z, Shuangnan Z, Xiaohe X, Zhen W, Yunfeng B, Tingting H, Chao Z, Yao W, Zhou K, Zhongxia W, Bing L, Prokop LJ, Hernandez MC, Jun L, Man G. Rhubarb-based Chinese herbal formulae for hepatic encephalopathy: a systematic review and Meta-analysis. J TRADIT CHIN MED 2017. [DOI: 10.1016/s0254-6272(18)30035-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Cui H, Li S, Xu C, Zhang J, Sun Z, Chen H. Emodin alleviates severe acute pancreatitis-associated acute lung injury by decreasing pre-B-cell colony-enhancing factor expression and promoting polymorphonuclear neutrophil apoptosis. Mol Med Rep 2017; 16:5121-5128. [PMID: 28849044 PMCID: PMC5647045 DOI: 10.3892/mmr.2017.7259] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2016] [Accepted: 04/20/2017] [Indexed: 12/16/2022] Open
Abstract
The present study aimed to evaluate the protective effects of emodin on severe acute pancreatitis (SAP)‑associated acute lung injury (ALI), and investigated the possible mechanism involved. SAP was induced in Sprague‑Dawley rats by retrograde infusion of 5% sodium taurocholate (1 ml/kg), after which, rats were divided into various groups and were administered emodin, FK866 [a competitive inhibitor of pre‑B‑cell colony‑enhancing factor (PBEF)] or dexamethasone (DEX). DEX was used as a positive control. Subsequently, PBEF expression was detected in polymorphonuclear neutrophils (PMNs) isolated from rat peripheral blood by reverse transcription‑quantitative polymerase chain reaction and western blotting. In addition, histological alterations, apoptosis in lung/pancreatic tissues, apoptosis of peripheral blood PMNs and alterations in the expression of apoptosis‑associated proteins were examined by hematoxylin and eosin staining, terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling assay, Annexin V/propidium iodide (PI) assay and western blotting, respectively. Serum amylase activity and wet/dry (W/D) weight ratios were also measured. An in vitro study was also conducted, in which PMNs were obtained from normal Sprague‑Dawley rats and were incubated with emodin, FK866 or DEX in the presence of lipopolysaccharide (LPS). Apoptosis of PMNs and the expression levels of apoptosis‑associated proteins were examined in cultured PMNs in vitro by Annexin V/PI assay and western blotting, respectively. The results demonstrated that emodin, FK866 and DEX significantly downregulated PBEF expression in peripheral blood PMNs. In addition, emodin, FK866 and DEX reduced serum amylase activity, decreased lung and pancreas W/D weight ratios, alleviated lung and pancreatic injuries, and promoted PMN apoptosis by regulating the expression of apoptosis‑associated proteins: Fas, Fas ligand, B‑cell lymphoma (Bcl)‑2‑associated X protein, cleaved caspase‑3 and Bcl‑extra‑large. In addition, the in vitro study demonstrated that emodin, FK866 and DEX significantly reversed the LPS‑induced decrease of apoptosis in PMNs by regulating the expression of apoptosis‑associated proteins. In conclusion, the present study demonstrated that emodin may protect against SAP‑associated ALI by decreasing PBEF expression, and promoting PMN apoptosis via the mitochondrial and death receptor apoptotic pathways.
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Affiliation(s)
- Hongzhang Cui
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Shu Li
- Department of Chinese Medicine, Dalian Municipal Central Hospital, Dalian, Liaoning 116033, P.R. China
| | - Caiming Xu
- Department of Chinese Medicine, Dalian Obstetrics and Gynecology Hospital, Dalian, Liaoning 116083, P.R. China
| | - Jingwen Zhang
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Zhongwei Sun
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
| | - Hailong Chen
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
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Li J, Zhang S, Zhou R, Zhang J, Li ZF. Perspectives of traditional Chinese medicine in pancreas protection for acute pancreatitis. World J Gastroenterol 2017; 23:3615-3623. [PMID: 28611514 PMCID: PMC5449418 DOI: 10.3748/wjg.v23.i20.3615] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 03/13/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023] Open
Abstract
Acute pancreatitis (AP) is one of the most common diseases. AP is associated with significant morbidity and mortality, but it lacks specific and effective therapies. Traditional Chinese medicine (TCM) is one of the most popular complementary and alternative medicine modalities worldwide for the treatment of AP. The current evidence from basic research and clinical studies has shown that TCM has good therapeutic effects on AP. This review summarizes the widely used formulas, single herbs and monomers that are used to treat AP and the potential underlying mechanisms of TCM. Because of the abundance, low cost, and safety of TCM as well as its ability to target various aspects of the pathogenesis, TCM provides potential clinical benefits and a new avenue with tremendous potential for the future treatment of AP.
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Anchi P, Khurana A, Bale S, Godugu C. The Role of Plant-derived Products in Pancreatitis: Experimental and Clinical Evidence. Phytother Res 2017; 31:591-623. [DOI: 10.1002/ptr.5792] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Revised: 02/03/2017] [Accepted: 02/06/2017] [Indexed: 12/13/2022]
Affiliation(s)
- Pratibha Anchi
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Amit Khurana
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Swarna Bale
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
| | - Chandraiah Godugu
- Department of Regulatory Toxicology; National Institute of Pharmaceutical Education and Research (NIPER), Balanagar; Hyderabad Telangana India
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Zhou Y, Wang L, Huang X, Li H, Xiong Y. Add-on effect of crude rhubarb to somatostatin for acute pancreatitis: A meta-analysis of randomized controlled trials. JOURNAL OF ETHNOPHARMACOLOGY 2016; 194:495-505. [PMID: 27693773 DOI: 10.1016/j.jep.2016.09.053] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2016] [Revised: 09/16/2016] [Accepted: 09/28/2016] [Indexed: 06/06/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhubarb is one of the common herbs used in traditional Chinese complex prescriptions for the treatment of various inflammatory diseases. We sought to determine the add-on effect of crude rhubarb to somatostatin in patients with acute pancreatitis by conducting a meta-analysis. MATERIALS AND METHODS We searched the Pubmed, EMBASE, Cochrane Library, CNKI, Wanfang, VIP databases up to November 2015. Randomized controlled trials (RCTs) comparing crude rhubarb plus somatostatin to somatostatin alone for acute pancreatitis were included. Risk ratio (RR) or weighted mean difference (WMD) with their 95% confidence interval (CI) was calculated between with and without crude rhubarb therapy. RESULTS A total of 19 RCTs involving 1161 patients were identified. Compared with somatostatin alone, crude rhubarb plus somatostatin significantly reduced the total complications (RR 0.55; 95% CI 0.41-0.73) and APACHE Ⅱ scores (WMD -1.16; 95% CI -1.91 to -0.41) as well as shortened the duration of elevated serum amylase (WMD -2.01 days; 95% CI -2.57 to -1.44), duration of abdominal pain (WMD -1.33 days; 95% CI -1.61 to -1.05), the first defecation time (WMD -2.27 days; 95% CI -3.06 to -1.47), and duration of hospital stay (WMD -6.70 days; 95% CI -8.81 to -4.60). However, there were no significant differences in total mortality rates (RR 0.61; 95% CI 0.34 to 1.12) between two groups. CONCLUSIONS Crude rhubarb as adjuvant therapy to somatostatin appears to have additional benefits in patients with acute pancreatitis. However, interpretation of these results should be cautioned due to the methodological flaws.
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Affiliation(s)
- Yejiang Zhou
- Department of Gastrointestinal Surgery, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Lulu Wang
- Department of Pharmacology, School of Medicine, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Xinwu Huang
- Department of Pharmacology, School of Medicine, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Hua Li
- Department of Pharmacology, School of Medicine, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Yuxia Xiong
- Department of Pharmacology, School of Medicine, Southwest Medical University, Luzhou 646000, Sichuan, China.
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