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Du S, Wang T, Li Z, Li T, Miao Z, Chen Y, Zhu S, Wei W, Deng H. Therapeutic Potential of Qilianxiaopi Formula: Targeting ADAM17-Mediated Chronic Inflammation in Atrophic Gastritis. Pharmaceuticals (Basel) 2025; 18:435. [PMID: 40143211 PMCID: PMC11944831 DOI: 10.3390/ph18030435] [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: 02/13/2025] [Revised: 03/09/2025] [Accepted: 03/14/2025] [Indexed: 03/28/2025] Open
Abstract
Background: Gastric cancer (GC) is a leading cause of mortality worldwide, particularly in China. Chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are recognized as precancerous conditions contributing to GC development. Qilianxiaopi formula (QLXP), a traditional Chinese medicine (TCM), has demonstrated significant therapeutic effects on CAG and IM; however, its underlying mechanisms remain poorly understood. Methods: This study utilized chromatography-mass spectrometry to identify the major compounds in QLXP. Network pharmacology was used to predict the associated targets of these components. Thermal proteome profiling (TPP) pinpointed the potential binding proteins of QLXP, which were validated by bioinformatic analyses. Bio-layer interferometry (BLI) was used to analyze the interactions between QLXP and its key target proteins, thereby determining their binding components. Molecular docking predicted the binding modes between the components and proteins. Results: ADAM17 was identified as a key binding protein for QLXP. Further investigation revealed that QLXP inhibits the enzymatic activity of ADAM17, thereby reducing the secretion of the pro-inflammatory cytokine TNF-α, contributing to the anti-inflammatory properties of QLXP. BLI confirmed direct and reversible binding interactions between QLXP and ADAM17. Narirutin, isolated from the ADAM17 binding fraction, displayed the highest affinity for QLXP. Conclusions: This study highlights ADAM17 as a key molecular target of QLXP and narirutin as its principal binding component. The integrated approach combining chromatography-mass spectrometry, network pharmacology, TPP, BLI, and molecular docking provides a robust framework for elucidating the mechanisms of action of TCM.
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Affiliation(s)
- Sijing Du
- MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; (S.D.)
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
| | - Tianxiang Wang
- MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; (S.D.)
| | - Zhiqiang Li
- MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; (S.D.)
| | - Ting Li
- MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; (S.D.)
| | - Zelong Miao
- MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; (S.D.)
| | - Yuling Chen
- MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; (S.D.)
| | - Songbiao Zhu
- Chinese Institutes for Medical Research (CIMR), Beijing 100069, China
| | - Wei Wei
- Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
| | - Haiteng Deng
- MOE Key Laboratory of Bioinformatics, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China; (S.D.)
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Liu C, Gao P, Liu X, Kuang M, Xu H, Wu Y, Liu W, Wang S. Reunderstanding the classical prescription Banxia Xiexin Decoction: new perspectives from a comprehensive review of clinical research and pharmacological studies. Chin Med 2025; 20:39. [PMID: 40102869 PMCID: PMC11921579 DOI: 10.1186/s13020-025-01087-0] [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: 11/19/2024] [Accepted: 03/05/2025] [Indexed: 03/20/2025] Open
Abstract
Classical prescriptions of Chinese medicine represent the crystallized wisdom of millennia of clinical practice, enduring as cornerstones of therapeutic intervention due to their demonstrated efficacy across generations. Their evolving role in modern healthcare systems reflects shifting disease patterns, scientific advancements, and global health priorities. Banxia Xiexin Decoction (BXD), formulated by Zhang Zhongjing in the Treatise on Febrile and Miscellaneous Diseases (Shanghanlun), is a time-honored classical prescription renowned for its therapeutic versatility in managing gastrointestinal disorders, both in China and internationally. Recent advancements in clinical research and pharmacological studies on BXD underscore the necessity for a comprehensive bibliometric analysis to summarize and elucidate its specific clinical benefits. Through an extensive literature review of publications from the Web of Science, PubMed, Scopus, and the China National Knowledge Infrastructure (CNKI) between 1997 and 2024, 11 major categories of clinical applications for BXD were identified, along with an analysis of the potential pharmacological mechanisms, such as chronic gastritis, functional dyspepsia, and inflammatory bowel disease. We believe this review will provide new insights into the understanding of clinical value of BXD and identify potential future perspectives for its research and development.
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Affiliation(s)
- Chang Liu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
- Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
| | - Pengwei Gao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
| | - Xiaoying Liu
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
| | - Min Kuang
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, China
- Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, China
| | - Haoran Xu
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, China
- Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, China
| | - Yangming Wu
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, China
- Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, China
| | - Wenjun Liu
- State Key Laboratory for the Modernization of Classical and Famous Prescriptions of Chinese Medicine, Nanchang, China.
- Research and Development Department, Jiangzhong Pharmaceutical Co., Ltd., Nanchang, China.
| | - Shengpeng Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
- Macao Centre for Research and Development in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China.
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Wang L, Lian YJ, Dong JS, Liu MK, Liu HL, Cao ZM, Wang QN, Lyu WL, Bai YN. Traditional Chinese medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets. World J Gastroenterol 2025; 31:102053. [DOI: 10.3748/wjg.v31.i9.102053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/06/2024] [Accepted: 01/21/2025] [Indexed: 02/18/2025] Open
Abstract
Chronic atrophic gastritis (CAG) is an important stage of precancerous lesions of gastric cancer. Effective treatment and regulation of CAG are essential to prevent its progression to malignancy. Traditional Chinese medicine (TCM) has shown multi-targeted efficacy in CAG treatment, with advantages in enhancing gastric mucosal barrier defense, improving microcirculation, modulating inflammatory and immune responses, and promoting lesion healing, etc. Clinical studies and meta-analyses indicate that TCM provides significant benefits, with specific Chinese herbal compounds and monomers demonstrating protective effects on the gastric mucosa through mechanisms including anti-inflammation, anti-oxidation, and regulation of cellular proliferation and apoptosis, etc. Finally, it is pointed out that the efficacy of TCM in the treatment of CAG requires standardized research and unified standards, and constantly clarifies and improves the evaluation criteria of each dimension of gastric mucosal barrier function.
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Affiliation(s)
- Li Wang
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yan-Jie Lian
- Division of Cardiovascular, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China
| | - Jin-Sheng Dong
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Ming-Kun Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Hong-Liang Liu
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Zheng-Min Cao
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Qing-Nan Wang
- Department of Dermatology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Wen-Liang Lyu
- Department of Infectious Diseases, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Yu-Ning Bai
- Department of Gastroenterology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
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Dai ZQ, Guo ZQ, Zhang T, Chu YF, Yan Y, Gao F, Li SL, Gu YH, Jiao JY, Lin YX, Zhao SW, Xu B, Lei HM. Integrating network pharmacology and transcriptomics to study the potential mechanism of Jingzhi Niuhuang Jiedu tablet in rats with accumulation of heat in the lungs and stomach. JOURNAL OF ETHNOPHARMACOLOGY 2025; 337:118890. [PMID: 39366495 DOI: 10.1016/j.jep.2024.118890] [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: 07/07/2024] [Revised: 09/30/2024] [Accepted: 10/01/2024] [Indexed: 10/06/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Accumulation of heat in the lungs and stomach (AHLS) is an important syndrome within the realm of traditional Chinese medicine (TCM). It is the fundamental reason behind numerous illnesses, including mouth ulcers, dermatological conditions, acne, and pharyngitis. Jingzhi Niuhuang Jiedu tablet (JN) serves as the representative prescription for treatment of AHLS clinically. However, the effective components and mechanism of JN's impact on AHLS remain unexplored. AIM OF THE STUDY The objective of this research was to analyze the effective components of JN and investigate the therapeutic effect and potential mechanism of JN on AHLS. MATERIALS AND METHODS The effective compounds of JN extract were analyzed and identified using UHPLC-Q-Exactive/HRMS. Utilizing network pharmacology to investigate JN's multi-target, multi-pathway process in treating AHLS. Subsequently, anti-inflammatory activities of JN extract were evaluated in the RAW264.7 cells stimulated by lipopolysaccharide (LPS). In addition, a rat AHLS model induced by LPS and dried ginger was established. Pathological changes in rat lung and stomach tissues observed by HE staining and Masson's trichrome staining. Additionally, the expression of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid (BALF) was identified through the ELISA assay. For a deeper understanding of how JN might affect AHLS, transcriptomics was utilized to examine differential genes and their underlying mechanisms. Concurrently, techniques like quantitative polymerase chain reaction (q-PCR), immunofluorescence, and western blotting (WB) were employed to confirm various mRNA and protein expression, including Il17ra, Il17re, IL-17A, IL-1β, IL-6, PPARγ, PGC1-α and UCP1. RESULTS We identified 178 potential effective components in the JN extract. Network pharmacology analysis showed that the 144 components in JN act on 200 key targets for the treatment of AHLS by suppressing inflammation, regulating energy metabolism, and gastric function. In addition, JN suppressed the LPS-stimulated generation of NO, TNF-α, IL-1β, and IL-6 in RAW264.7 cells. And JN treatment effectively alleviated lung and stomach injury and reduced inflammation in rats. Analysis of RNA-seq from lung tissues revealed JN's substantial control over crucial genes in the IL-17 signaling pathway, including Il1b and Il17ra. Likewise, RNA sequencing of stomach tissues revealed that JN markedly decreased crucial genes in the Thermogenesis pathway, including Ppargc1a and Ppara. Additional experimental findings confirmed that treatment with JN significantly reduced the expression levels of mRNA (Il17ra, Il17re, Il1b, Ppargc1a and Ucp1), and the expression levels of protein (IL-17A, IL-1β, IL-6, PPARγ, PGC1-α and UCP1). CONCLUSION This study not only analyzes the effective components of JN but also reveals that JN could effectively ameliorate AHLS by inhibiting IL-17 signaling pathway and Thermogenesis pathway, which provides evidence for subsequent clinical studies and drug development.
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Affiliation(s)
- Zi-Qi Dai
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China
| | - Zhuo-Qian Guo
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China
| | - Tong Zhang
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China
| | - Ya-Fen Chu
- Beijing Tongrentang Science and Technology Development Co. Technology Development Co., Ltd., Beijing, 100079, China
| | - Ying Yan
- Beijing Tongrentang Science and Technology Development Co. Technology Development Co., Ltd., Beijing, 100079, China
| | - Feng Gao
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China
| | - Shan-Lan Li
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China
| | - Yu-Hao Gu
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China
| | - Jing-Yi Jiao
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China
| | - Yi-Xuan Lin
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China
| | - Shu-Wu Zhao
- Beijing Tongrentang Science and Technology Development Co. Technology Development Co., Ltd., Beijing, 100079, China.
| | - Bing Xu
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China.
| | - Hai-Min Lei
- School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 100102, China.
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He C, Zhou J, Zhang W, Zhang T, Pu Y. Study on the bioactive components of Banxia Xiexin Decoction with different decocting methods and its effects on ulcerative colitis rats from the perspective of phase states. JOURNAL OF ETHNOPHARMACOLOGY 2024; 335:118626. [PMID: 39053716 DOI: 10.1016/j.jep.2024.118626] [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: 05/14/2024] [Revised: 07/18/2024] [Accepted: 07/22/2024] [Indexed: 07/27/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Banxia Xiexin Decoction (BXD) is one of the seven classic prescriptions of the special decoction method (SDM) of "removing dregs and decocting again", which has been widely used in inflammatory bowel diseases such as ulcerative colitis (UC). However, the impacts of SDM have not been fully investigated, either on the components or on the biological effects. AIM OF THE STUDY This study aimed to investigate the rational of SDM traditionally recorded about BXD, re-decoction after dreg-removal, by comparing with the contemporary general decoction method (GDM) from the perspective of phase states, in the bioactive components from the perspective of phase states, and their corresponding pharmacodynamic effects on a particular UC rat model. METHODS The BXD decoctions were respectively obtained by SDM and GDM, together with the different samples with different decocting time. The phase state samples (true solution, colloidal phase, and precipitated phase), were also obtained after a series of separation process and characterized. The multi-components in the in-process decoctions, original decoctions and phase state samples were quantitatively determined. HPLC fingerprint spectrum of the samples were also detected and compared with chemometrics analysis. A rat model of ulcerative colitis with cold-heat complex syndrome was established, on which the pharmacodynamic effects of different phases of SDM-made BXD were investigated. RESULTS The results showed that the contents of eight marker components in SDM-made decoction were significantly higher than those in GDM-made decoction. Compared with the precipitated phases and true solutions, the colloidal phase was confirmed to obtain absolutely higher contents of the components (except berberine). The analysis on HPLC fingerprints also revealed that the profiles of colloidal phase showed the majority of the characteristics of original decoctions, when compared with the other phases. The results showed the BXD group, precipitated phase group and colloidal phase group had certain therapeutic effects on the ulcerative colitis rats with cold-heat complex syndrome, among which the original decoction group showed optimal effects, followed by the colloidal phase. CONCLUSION The study has provided the experimental evidence of the bioactive components and pharmacodynamic effects on the rational of SDM, as originally recorded about the classic prescription, which might provide useful idea for the interpretation on medicinal properties of TCM compound prescriptions, and contemporary TCM innovative drug developments.
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Affiliation(s)
- Chao He
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Jingwen Zhou
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Weijia Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
| | - Tong Zhang
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
| | - Yiqiong Pu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
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Jiang Y, Huang Y, Hu Y, Yang Y, You F, Hu Q, Li X, Zhao Z. Banxia Xiexin Decoction delays colitis-to-cancer transition by inhibiting E-cadherin/β-catenin pathway via Fusobacterium nucleatum FadA. JOURNAL OF ETHNOPHARMACOLOGY 2024; 328:117932. [PMID: 38382652 DOI: 10.1016/j.jep.2024.117932] [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: 12/04/2023] [Revised: 02/07/2024] [Accepted: 02/17/2024] [Indexed: 02/23/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Colitis is an important risk factor for the occurrence of colorectal cancer (CRC), and the colonization of Fusobacterium nucleatum (Fn) in the intestines accelerates this transformation process. Banxia Xiexin Decoction (BXD), originating from Shanghanlun, is a classic prescription for treating gastrointestinal diseases. Current researches indicate that BXD can effectively delay the colitis-to-cancer transition, but it is still unclear whether it can inhibit Fn colonization to achieve this delaying effect. AIM OF STUDY This study explored the effect and mechanism of BXD in inhibiting Fn intestinal colonization to delay colitis-to-cancer transition. MATERIALS AND METHODS We constructed a mouse model of colitis-to-cancer transition by regularly gavaging Fn combined with azoxymethane (AOM)/dextran sodium sulfate (DSS), and administered BXD by gavage. We monitored the body weight of mice, measured the length and weight of their colons, and calculated the disease activity index (DAI) score. The growth status of colon tumors was observed by hematoxylin and eosin (H&E) staining, and the changes in gut microbiota in each group of mice were detected by 16S rDNA analysis. Immunohistochemistry was used to detect the expression of E-cadherin and β-catenin in colon tissues, and immunofluorescence was used to observe the infiltration of M2 macrophages in colon tissues. In cell experiments, we established a co-culture model of Fn and colon cancer cells and intervened with BXD-containing serum. Malignant behaviors such as cell proliferation, invasion, and migration were detected, as well as changes in their cell cycle. We examined the protein levels of E-cadherin, β-catenin, Axin2, and Cyclin D1 in each group were detected by Western blot. We used US1 strain (fadA-) as a control and observed the effects of BXD-containing serum on Fn attachment and invasion of colon cancer cells through attachment and invasion experiments. RESULTS BXD can inhibit the colitis-to-cancer transition in mice infected with Fn, reduce crypt structure damage, improve gut microbiota dysbiosis, upregulate E-cadherin and decrease β-catenin expression, and reduce infiltration of M2 macrophages, thus inhibiting the process of colitis-to-cancer transition. Cell experiments revealed that BXD-containing serum can inhibit the proliferation, migration, and invasion of colon cancer cells infected with Fn and regulate their cell cycle. More importantly, we found that BXD-containing serum can inhibit the binding of Fn's FadA adhesin to E-cadherin, reduce Fn's attachment and invasion of colon cancer cells, thereby downregulating the E-cadherin/β-catenin signaling pathway. CONCLUSIONS These findings show that BXD can inhibit Fn colonization by interfering with the binding of FadA to E-cadherin, reducing the activation of the E-cadherin/β-catenin signaling pathway, and ultimately delaying colitis-to-cancer transition.
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Affiliation(s)
- Yifang Jiang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, PR China
| | - Yuqing Huang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, PR China
| | - Yane Hu
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, PR China
| | - Yi Yang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, PR China
| | - Fengming You
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, PR China; Cancer Institute, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan Province, PR China
| | - Qiongying Hu
- Department of Laboratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China, Chengdu, 610072, Sichuan Province, PR China.
| | - Xueke Li
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, PR China.
| | - Ziyi Zhao
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072, Sichuan Province, PR China.
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Li Y, Li L, Wang X, Huang H, Han T. Determining the Mechanism of Banxia Xiexin Decoction for Gastric Cancer Treatment through Network Analysis and Experimental Validation. ACS OMEGA 2024; 9:10119-10131. [PMID: 38463316 PMCID: PMC10918669 DOI: 10.1021/acsomega.3c06330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 01/18/2024] [Accepted: 02/05/2024] [Indexed: 03/12/2024]
Abstract
Gastric cancer (GC) is a widespread malignancy. Banxia Xiexin decoction (BXD) has been used for GC treatment, but the specific mechanisms underlying its therapeutic effects remain controversial. This study used a comprehensive approach to network pharmacology combined with experimental validation to elucidate the mechanism of BXD's anti-GC effects. Initially, we used the UHPLC-LTQ-Orbitrap-MS/MS technology to identify the main chemical constituents of BXD, as well as potential targets associated with these constituents. Then, we employed the Genecard and Online Mendelian Inheritance in Man (OMIM) to determine the targets specifically related to GC. We employed a combination of Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction analysis to predict the crucial targets of BXD and uncover the pathways involved in its therapeutic effects against GC. The results were subsequently verified through cell experiments. The analysis revealed 174 common targets shared by BXD and GC. GO enrichment analysis highlighted biological processes, such as autophagy, protein kinase activity, and apoptosis. Moreover, the enrichment analysis revealed several significant pathways that serve as the primary mechanisms by which BXD exerts its effects. Notably, these pathways include PI3K-Akt, HIF-1, and Pathways in cancer. Subsequent in vitro experiments demonstrated that BXD effectively hindered GC cell proliferation, stimulated autophagy, and facilitated apoptosis by PI3K-Akt-mTOR signaling pathway regulation. These findings reveal the effectiveness of BXD against GC through diverse components, targets, and pathways, indicating that BXD holds potential therapeutic value in GC treatment. This study uncovers the intricate biological mechanisms that underlie BXD's efficacy in treating GC through the integration of network pharmacology analysis and rigorous in vitro experiments.
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Affiliation(s)
- Yaxing Li
- Pharmacology
of Traditional Chinese Medical Formulas, College of Traditional Chinese
Medicine, Shandong University of Traditional
Chinese Medicine, Jinan, Shandong 250000, China
| | - Ling Li
- Pharmacology
of Traditional Chinese Medical Formulas, College of Traditional Chinese
Medicine, Shandong University of Traditional
Chinese Medicine, Jinan, Shandong 250000, China
| | - Xue Wang
- Pharmacology
of Traditional Chinese Medical Formulas, College of Traditional Chinese
Medicine, Shandong University of Traditional
Chinese Medicine, Jinan, Shandong 250000, China
| | - Hailiang Huang
- Rehabilitation
Medicine and Physiotherapy, School of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, China
| | - Tao Han
- Pharmacology
of Traditional Chinese Medical Formulas, College of Traditional Chinese
Medicine, Shandong University of Traditional
Chinese Medicine, Jinan, Shandong 250000, China
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Chen L, Wei S, He Y, Wang X, He T, Zhang A, Jing M, Li H, Wang R, Zhao Y. Treatment of Chronic Gastritis with Traditional Chinese Medicine: Pharmacological Activities and Mechanisms. Pharmaceuticals (Basel) 2023; 16:1308. [PMID: 37765116 PMCID: PMC10537303 DOI: 10.3390/ph16091308] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 08/14/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023] Open
Abstract
Chronic gastritis (CG) is a common clinical digestive system disease, which is not easyily cured and is prone to recurrence. Traditional Chinese medicine (TCM) plays a significant role in the treatment of CG and has attracted increasing attention for clinical applications. In recent years, a large number of reports have shown that TCM has good therapeutic effect on CG. The aim of this paper is to investigate the pharmacological activities and mechanism of action of TCM in the treatment of CAG. Therefore, by searching the databases of Pubmed, China National Knowledge Infrastructure, Wanfang, and Baidu academic databases, this paper has summarized the molecular mechanisms of TCM in improving CG. The results show that the improvement of GC by TCM is closely related to a variety of molecular mechanisms, including the inhibition of Helicobacter pylori (Hp) infection, alleviation of oxidative stress, improvement of gastric function, repair of gastric mucosa, inhibition of inflammatory response, and apoptosis. More importantly, IRF8-IFN-γ, IL-4-STAT6, Hedgehog, pERK1/2, MAPK, PI3K-Akt, NF-κB, TNFR-c-Src-ERK1/2-c-Fos, Nrf2/HO-1, and HIF-1α/VEGF signaling pathways are considered as important molecular targets for TCM in the treatment of GC. These important findings will provide a direction and a basis for further exploring the pathogenesis of GC and tapping the potential of TCM in clinical treatment. This review also puts forward a bright prospect for future research of TCM in the treatment of CG.
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Affiliation(s)
- Lisheng Chen
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
- Department of Pharmacy, General Hospital of PLA, Beijing 100039, China
| | - Shizhang Wei
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Yong He
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Xin Wang
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Tingting He
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing 100039, China; (T.H.); (A.Z.); (R.W.)
| | - Aozhe Zhang
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing 100039, China; (T.H.); (A.Z.); (R.W.)
| | - Manyi Jing
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Haotian Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
| | - Ruilin Wang
- Division of Integrative Medicine, The Fifth Medical Center, General Hospital of PLA, Beijing 100039, China; (T.H.); (A.Z.); (R.W.)
| | - Yanling Zhao
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; (L.C.); (Y.H.); (X.W.); (M.J.); (H.L.)
- Department of Pharmacy, General Hospital of PLA, Beijing 100039, China
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9
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Zhou Z, An R, You L, Liang K, Wang X. Banxia Xiexin decoction: A review on phytochemical, pharmacological, clinical and pharmacokinetic investigations. Medicine (Baltimore) 2023; 102:e34891. [PMID: 37657053 PMCID: PMC10476818 DOI: 10.1097/md.0000000000034891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 08/02/2023] [Indexed: 09/03/2023] Open
Abstract
Banxia Xiexin decoction (BXD), a famous traditional Chinese prescription constituted by Pinelliae Rhizoma, Zingiberis Rhizoma, Scutellariae Radix, Coptidis Rhizoma, Ginseng Radix et Rhizoma, Jujubae Fructus and Glycyrrhizae Radix et Rhizoma Praeparata Cum Mell, has notable characteristics of acrid-opening, bitter down-bearing and sweet-tonification, interfering with tumors, gastrointestinal diseases, central nervous system diseases and much more. Based on the wide clinical applications, current investigations of BXD focused on several aspects: chemical analysis to explore the underlying substrates responsible for the therapeutic effects; basic studies on pharmacological actions of the whole prescription or of those representative ingredients to demonstrate the intriguing molecular targets for specific pathological processes; pharmacokinetic feature studies of single or all components of BXD to reveal the chemical basis and synergistic actions contributing to the pharmacological and clinically therapeutic effects. In this review, we summarized the main achievements of phytochemical, pharmacological, clinical and pharmacokinetic profiles of BXD and its herbal or pharmacologically active chemicals, as well as discussions of our understanding which further reveals the significance of BXD clinically.
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Affiliation(s)
- Zehua Zhou
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Rui An
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Lisha You
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Kun Liang
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xinhong Wang
- Shanghai University of Traditional Chinese Medicine, Shanghai, China
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10
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Ji W, Liu W, Huo Y, Hu C, Zhang Y. Banxia Xiexin decoction ameliorates dextran sulfate sodium (DSS)-induced ulcerative colitis via inhibiting serine-threonine protein kinase (Akt)/mitogen-activated protein kinase (MAPK) signaling pathway. Biotechnol Appl Biochem 2023; 70:1530-1542. [PMID: 36806191 DOI: 10.1002/bab.2451] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 02/02/2023] [Accepted: 02/11/2023] [Indexed: 02/19/2023]
Abstract
Banxia Xiexin decoction (BXD), a traditional Chinese medicine, was widely used in treating ulcerative colitis (UC). However, the active components of BXD and its mechanism in UC remain elusive. Therefore, we used network pharmacology in vivo experiments, molecular docking, and surface plasmon resonance strategy (SPR) to uncover BXD's potential mechanism. A UC rat model was established by orally administering 7% dextran sulfate sodium (DSS) in drinking water, BXD and palmatine were orally administered for 7 days. Network pharmacology was used to investigate the main bioactive components and crucial targets of BXD in treating UC. Molecular docking was used to investigate interactions between components and crucial targets, verifying the results by SPR. By network pharmacology predicting, 20 active components and 44 candidate anti-UC targets of BXD were identified, and the crucial proteins were screeded from PPI network, including extracellular regulated protein kinases (ERK), AKT1, and tumor necrosis factor-α (TNF). In addition, some key active components (palmatine, sexangularetin, and skullcapflavone II) were screened out from the active components-targets network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and in vivo experiments showed that protein-serine-threonine kinase (Akt)/MAPK pathway was involved in BXD treatment for UC; BXD and palmatine significantly ameliorated the severity of DSS-induced UC in rats. Our study might assist in further investigation of the active components in Chinese medicine.
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Affiliation(s)
- Wanli Ji
- School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Wangzhenzu Liu
- School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Huo
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Cheng Hu
- Science and Technology Experiment Center, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yifan Zhang
- School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China
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11
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Yang L, Liu X, Zhu J, Zhang X, Li Y, Chen J, Liu H. Progress in traditional Chinese medicine against chronic gastritis: From chronic non-atrophic gastritis to gastric precancerous lesions. Heliyon 2023; 9:e16764. [PMID: 37313135 PMCID: PMC10258419 DOI: 10.1016/j.heliyon.2023.e16764] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 05/13/2023] [Accepted: 05/26/2023] [Indexed: 06/15/2023] Open
Abstract
Chronic gastritis (CG) is a persistent inflammation of the gastric mucosa that can cause uncomfortable symptoms in patients. Traditional Chinese medicine (TCM) has been widely used to treat CG due to its precise efficacy, minimal side effects, and holistic approach. Clinical studies have confirmed the effectiveness of TCM in treating CG, although the mechanisms underlying this treatment have not yet been fully elucidated. In this review, we summarized the clinical research and mechanisms of TCM used to treat CG. Studies have shown that TCM mechanisms for CG treatment include H. pylori eradication, anti-inflammatory effects, immune modulation, regulation of gastric mucosal cell proliferation, apoptosis, and autophagy levels.
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Affiliation(s)
- Liangjun Yang
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Xinying Liu
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Jiajie Zhu
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Xi Zhang
- Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Ya Li
- Lin ‘an Hospital of Traditional Chinese Medicine, Hangzhou 311300, China
| | - Jiabing Chen
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
| | - Haiyan Liu
- Tongde Hospital of Zhejiang Province, Hangzhou 310012, China
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12
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Zhang D, Lu R, Wang M, Ji J, Zhang S, Wang S, Zhang D, Chen M. Effects of Banxia Xiexin Decoction on apoptosis of interstitial cells of cajal by regulation of MiR-451-5p: An in vivo and in vitro study. JOURNAL OF ETHNOPHARMACOLOGY 2023; 314:116606. [PMID: 37192721 DOI: 10.1016/j.jep.2023.116606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 04/19/2023] [Accepted: 05/04/2023] [Indexed: 05/18/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Banxia Xiexin Decoction (BXD) is a traditional Chinese medical formula applied to gastrointestinal (GI) motility disorders. Previous studies showed that miR-451-5p was down-regulated in rats with GI motility disorders induced by gastric electrical dysrhythmia. Interstitial cells of cajal (ICCs) are pacemakers for GI motility, while loss of ICCs is responsible for GI motility disturbance. Thus, the underlying interaction mechanisms for BXD regulating ICCs apoptosis via miR-451-5p remain to be explored. AIM OF THE STUDY In this work, the main objectives were to examine the efficacy of BXD on ICCs via miR-451-5p both in GI motility disorders rats model and in vitro, as well as the potential contributions of SCF/c-kit signaling. MATERIALS AND METHODS Rats with gastric electrical dysrhythmia were established in male SD rats by using a single-day diet and a double fasting method (drinking diluted hydrochloric acid water during the period) for 4 weeks. The gastric slow wave (GSW) recording, RT-qPCR, and western blot were performed to examine the effects of BXD on ICCs apoptosis in rats with GED and miR-451-5p expression. In vitro assays included CCK-8, flow cytometry analysis, RT-qPCR, and western blot were applied to investigate the potential molecular mechanism of BXD on ICCs apoptosis via miR-451-5p. RESULTS BXD promoted gastric motility, reduced ICCs apoptosis, and elevated miR-451-5p in GED rats. In addition, miR-451-5p was significantly up-regulated in ICCs after BXD treatment compared with that in ICCs with miR-451-5p inhibitor transfection. Meanwhile, high miR-451-5p expression with either BXD treatment or miRNA mimics enhanced ICCs proliferation and inhibit apoptosis. Moreover, overexpression of miR-451-5p can reverse G0/G1 arrest in ICCs by BXD treatment. Further, SCF and c-kit protein levels were detected to demonstrate that modulation of miR-451-5p by BXD treatment was involved in this signaling. CONCLUSIONS Through this study, we demonstrated that BXD could promote ICCs proliferation and inhibit apoptosis via miR-451-5p and may involve the modulations of SCF/c-kit signaling, thus suggesting a new therapy basis for GI motility dysfunction from the perspective of modulation of ICCs apoptosis by targeting miR-451-5p.
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Affiliation(s)
- Di Zhang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, NO.11 North Third Ring Road East, Chaoyang District, Beijing, 100029, PR China.
| | - Ruimin Lu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, NO.11 North Third Ring Road East, Chaoyang District, Beijing, 100029, PR China.
| | - Mengwei Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, NO.11 North Third Ring Road East, Chaoyang District, Beijing, 100029, PR China.
| | - Jing Ji
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, NO.11 North Third Ring Road East, Chaoyang District, Beijing, 100029, PR China.
| | - Shujing Zhang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, NO.11 North Third Ring Road East, Chaoyang District, Beijing, 100029, PR China.
| | - Shuyan Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, NO.11 North Third Ring Road East, Chaoyang District, Beijing, 100029, PR China.
| | - Dongmei Zhang
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, No.5 Haiyuncang Road, Dongcheng District, Beijing, 101121, PR China.
| | - Meng Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, NO.11 North Third Ring Road East, Chaoyang District, Beijing, 100029, PR China.
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13
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Liao XX, Hu K, Xie XH, Wen YL, Wang R, Hu ZW, Zhou YL, Li JJ, Wu MK, Yu JX, Chen JW, Ren P, Wu XY, Zhou JJ. Banxia Xiexin decoction alleviates AS co-depression disease by regulating the gut microbiome-lipid metabolic axis. JOURNAL OF ETHNOPHARMACOLOGY 2023; 313:116468. [PMID: 37044233 DOI: 10.1016/j.jep.2023.116468] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 04/02/2023] [Accepted: 04/04/2023] [Indexed: 05/08/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Banxia Xiexin decoction (BXD) is a classic Chinese herbal formulation consisting of 7 herbs including Pinelliae Rhizoma, Scutellariae Radix, Zingiberis Rhizoma, Ginseng Radix, Glycyrrhizae Radix, Coptidis Rhizoma, and Jujubae Fructus, which can exert effects on lowering lipids and alleviating depressive mood disorders via affecting gastrointestinal tract. AIM OF THE STUDY The pathogenesis of atherosclerosis (AS) co-depression disease has not been well studied, and the current clinical treatment strategies are not satisfactory. As a result, it is critical to find novel methods of treatment. Based on the hypothesis that the gut microbiome may promote the development of AS co-depression disease by regulating host lipid metabolism, this study sought to evaluate the effectiveness and action mechanism of BXD in regulation of the gut microbiome via an intervention in AS co-depression mice. MATERIALS AND METHODS To determine the primary constituents of BXD, UPLC-Q/TOF-MS analysis was carried out. Sixteen C56BL/6 mice were fed normal chow as a control group; 64 ApoE-/- mice were randomized into four groups (model group and three treatment groups) and fed high-fat chow combined with daily bind stimulation for sixteen weeks to develop the AS co-depression mouse model and were administered saline or low, medium or high concentrations of BXD during the experimental modeling period. The antidepressant efficacy of BXD was examined by weighing, a sucrose preference test, an open field test, and a tail suspension experiment. The effectiveness of BXD as an anti-AS treatment was evaluated by means of biochemical indices, the HE staining method, and the Oil red O staining method. The impacts of BXD on the gut microbiome structure and brain (hippocampus and prefrontal cortex tissue) lipids in mice with the AS co-depression model were examined by 16S rDNA sequencing combined with lipidomics analysis. RESULTS The main components of BXD include baicalin, berberine, ginsenoside Rb1, and 18 other substances. BXD could improve depression-like behavioral characteristics and AS-related indices in AS co-depression mice; BXD could regulate the abundance of some flora (phylum level: reduced abundance of Proteobacteria and Deferribacteres; genus level: reduced abundance of Clostridium_IV, Helicobacter, and Pseudoflavonifractor, Acetatifactor, Oscillibacter, which were significantly different). The lipidomics analysis showed that the differential lipids between the model and gavaged high-dose BXD (BXH) groups were enriched in glycerophospholipid metabolism, and lysophosphatidylcholine (LPC(20:3)(rep)(rep)) in the hippocampus and LPC(20:4)(rep) in the prefrontal cortex both showed downregulation in BXH. The correlation analysis illustrated that the screened differential lipids were mainly linked to Deferribacteres and Actinobacteria. CONCLUSION BXD may exert an anti-AS co-depression therapeutic effect by modulating the abundance of some flora and thus intervening in peripheral lipid and brain lipid metabolism (via downregulation of LPC levels).
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Affiliation(s)
- Xing-Xing Liao
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Ke Hu
- Department of Rehabilitation Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Xin-Hua Xie
- Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, 341000, China
| | - You-Liang Wen
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Rui Wang
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Zi-Wei Hu
- Department of Rehabilitation, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China
| | - Yu-Long Zhou
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Jia-Jun Li
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Ming-Kun Wu
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Jing-Xuan Yu
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Jia-Wei Chen
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Peng Ren
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China
| | - Xiao-Yun Wu
- School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China.
| | - Jun-Jie Zhou
- School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, Jiangxi, 341000, China; Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, 341000, China.
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14
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Bao Z, Wu G, Du J, Ye Y, Zheng Y, Wang Y, Ji R. The comparative efficacy and safety of 9 traditional Chinese medicines combined with standard quadruple therapy for Helicobacter pylori-associated gastritis: a systematic review and network meta-analysis. ANNALS OF TRANSLATIONAL MEDICINE 2022; 10:1349. [PMID: 36660649 PMCID: PMC9843361 DOI: 10.21037/atm-22-5421] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 12/08/2022] [Indexed: 01/01/2023]
Abstract
Background There are 9 traditional Chinese medicines (TCMs) combined with standard quadruple (SQ) available for the treatment of Helicobacter pylori (Hp)-associated gastritis, but their relative efficacy and best options in clinical decision making are unknown due to a lack of high-quality head-to-head randomized controlled trials (RCTs). This study aimed to explore which formulas are the most effective and/or safest for Hp-associated gastritis. Methods We performed a search of electronic databases including PubMed, Web of Science, Cochrane Library, Embase, Chinese databases and South Korean database from inception to March 2022 to identify all relevant RCTs on the comparison between TCM combined with SQ and SQ for Hp-associated gastritis. Efficacy outcomes were the eradication rate of Hp and therapeutic response rate, and safety outcome was incidence of adverse reactions. Publication bias was assessed quantitatively using Egger's regression analysis and qualitatively using trim-and-fill method. Quality assessment was performed using Cochrane Risk of Bias, version 2 (ROB 2) tool. The Bayesian methods were applied to compare each treatment. Results A total of 55 trials with 6,187 patients were involved. The experimental group included 9 TCMs combined with SQ. The control group was SQ. The pair-wise meta-analysis demonstrated that compared with control group, 8 TCMs combined with SQ could statistically improve the eradication rate of Hp in patients with gastritis, 9 TCMs combined with SQ could significantly improve the therapeutic response rate. Additionally, Banxia Xiexin decoction combined with SQ (BXS) could statistically decrease the incidence of adverse reactions. The network meta-analysis results showed that BXS, Xiangsha Liujunzi combined with SQ (XSS), and Huangqi Jianzhong decoction combined with SQ (HQS) was the best measures to effectively eradicate Hp, enhance therapeutic effect, and decrease adverse reactions, respectively. The results of trim-and-fill method indicated that the results were stable and less affected by publication bias. Conclusions Compared with SQ, TCM combined with SQ generally has a better clinical effect and higher safety in patients with Hp-associated gastritis. BXS, XSS, and HQS are recommended based on the patient's condition and needs in clinical practice. Further high-quality double-blinded RCTs are warranted to validate the conclusions.
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Affiliation(s)
- Zhixian Bao
- The First Clinical Medical College, Lanzhou University, Lanzhou, China;,Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China;,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Guobing Wu
- The First Clinical Medical College, Lanzhou University, Lanzhou, China;,Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China;,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Jie Du
- School of Public Health, Lanzhou University, Lanzhou, China
| | - Yuwei Ye
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China;,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Ya Zheng
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China;,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Yuping Wang
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China;,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
| | - Rui Ji
- Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China;,Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, China
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15
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Jin W, Zhong J, Song Y, Li MF, Song SY, Li CR, Hou WW, Li QJ. Chinese herbal formula shen-ling-bai-zhu-san to treat chronic gastritis: Clinical evidence and potential mechanisms. World J Gastroenterol 2022; 28:4890-4908. [PMID: 36156925 PMCID: PMC9476852 DOI: 10.3748/wjg.v28.i33.4890] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 03/16/2022] [Accepted: 08/06/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Chronic gastritis (CG) is an inflammatory disease of the gastric mucosa. Shen-ling-bai-zhu san (SLBZS), a traditional Chinese medicine formula, is widely used for treating CG. Nevertheless, its effects are currently unclear.
AIM To determine the clinical evidence and potential mechanisms of SLBZS for the treatment of CG.
METHODS We systematically searched 3 English (PubMed, Embase, Medline) and 4 Chinese databases (Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure database, Wanfang Data Knowledge Service Platform, and the VIP information resource integration service platform) without language or publication bias restriction. Qualified studies were selected according to pre-set inclusion and exclusion criteria. RevMan 5.3 software was used for meta-analysis and literature quality assessment, Stata 14.0 software was used for sensitivity analysis, GRADE profiler 3.6 was used to evaluate the quality of evidence. And then, network pharmacology analysis was applied to primary research the mechanisms of action of SLBZS on CG.
RESULTS Fourteen studies were finally included, covering 1335 participants. Meta-analysis indicated that: (1) SLBZS was superior to conventional therapies [risk ratio (RR): 1.29, 95% confidence interval (CI): 1.21 to 1.37, P < 0.00001]; (2) SLBZS was better than conventional therapies [RR: 0.24, 95% confidence interval (95%CI): 0.11 to 0.55, P = 0.0007] in terms of recurrence rate and reversal of Helicobacter pylori positivity (RR: 1.20, 95%CI: 1.11 to 1.30, P < 0.00001); and (3) The safety of SLBZS for CG remains unclear. According to the GRADE method, the quality of evidence was not high. Besides, SNZJS might treat CG by acting on related targets and pathways such as EGFR tyrosine kinase inhibitor resistance, the PI3K-Akt signaling pathway, and others.
CONCLUSION SLBZS might be useful in treating CG, but long-term effects and specific clinical mechanisms of it maintain unclear. More samples and high-quality clinical experiments should be assessed and verified in the next step.
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Affiliation(s)
- Wei Jin
- Department of Emergency, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Juan Zhong
- Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Yang Song
- Department of Emergency, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Ming-Fei Li
- Department of Emergency, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Shi-Yi Song
- Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Chun-Run Li
- Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Wei-Wei Hou
- Department of Emergency, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
| | - Qing-Jie Li
- Interventional Operation Room, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
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16
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Xie L, Luo M, Li J, Huang W, Tian G, Chen X, Ai Y, Zhang Y, He H. Gastroprotective mechanism of modified lvdou gancao decoction on ethanol-induced gastric lesions in mice: Involvement of Nrf-2/HO-1/NF-κB signaling pathway. Front Pharmacol 2022; 13:953885. [PMID: 36120337 PMCID: PMC9475313 DOI: 10.3389/fphar.2022.953885] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 08/09/2022] [Indexed: 11/13/2022] Open
Abstract
Modified Lvdou Gancao decoction (MLG), a traditional Chinese medicine formula, has been put into clinical use to treat the diseases of the digestive system for a long run, showing great faculty in gastric protection and anti-inflammatory, whereas its protective mechanisms have not been determined. The current study puts the focus on the protective effect and its possible mechanisms of MLG on ethanol-induced gastric lesions in mice. In addition to various gastric lesion parameters and histopathology analysis, the activities of a list of relevant indicators in gastric mucosa were explored including ALDH, ADH, MDA, T-SOD, GSH-Px, and MPO, and the mechanisms were clarified using RT-qPCR, ELISA Western Blot and immunofluorescence staining. The results showed that MLG treatment induced significant increment of ADH, ALDH, T-SOD, GSH-Px, NO, PGE2 and SS activities in gastric tissues, while MPO, MDA, TNF-α and IL-1β levels were on the decline, both in a dose-dependent manner. In contrast to the model group, the mRNA expression of Nrf-2 and HO-1 in the MLG treated groups showed an upward trend while the NF-κB, TNFα, IL-1β and COX2 in the MLG treated groups had a downward trend simultaneously. Furthermore, the protein levels of p65, p-p65, IκBα, p-IκBα, iNOS, COX2 and p38 were inhibited, while Nrf2, HO-1, SOD1, SOD2 and eNOS were ramped up in MLG treatment groups. Immunofluorescence intensities of Nrf2 and HO-1 in the MLG treated groups were considerably enhanced, with p65 and IκBα diminished simultaneously, exhibiting similar trends to that of qPCR and western blot. To sum up, MLG could significantly ameliorate ethanol-induced gastric mucosal lesions in mice, which might be put down to the activation of alcohol metabolizing enzymes, attenuation of the oxidative damage and inflammatory response to maintain the gastric mucosa. The gastroprotective effect of MLG might be achieved through the diminution of damage factors and the enhancement of defensive factors involving NF-κB/Nrf2/HO-1 signaling pathway. We further confirmed that MLG has strong potential in preventing and treating ethanol-induced gastric lesions.
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Affiliation(s)
- Lei Xie
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Minyi Luo
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Junlin Li
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Wenguan Huang
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Guangjun Tian
- Liver Diseases Center, Guangdong Provincial Hospital of Chinese Medicine, Zhuhai, Guangdong, China
| | - Xiuyun Chen
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Ying Ai
- Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Yan Zhang
- First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China
| | - Haolan He
- Guangzhou Eighth People's Hospital, Guangzhou, Guangdong, China
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17
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Efficacy of Shugan Hewei Therapy for Chronic Atrophic Gastritis: A Systematic Review and Meta-Analysis. CHINESE MEDICINE AND CULTURE 2022. [DOI: 10.1097/mc9.0000000000000015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
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18
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Yang H, Zhou X, Hu B. The 'reversibility' of chronic atrophic gastritis after the eradication of Helicobacter pylori. Postgrad Med 2022; 134:474-479. [PMID: 35382697 DOI: 10.1080/00325481.2022.2063604] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gram-negative bacterium Helicobacter pylori (H. pylori) infection is lifelong and usually acquired in childhood, which is etiologically linked to gastric cancer (GC). H. pylori gastritis is defined as an infectious disease with varying severity in virtually all infected subjects. Chronic atrophic gastritis (CAG) is the precancerous condition with the decrease or the loss of gastric glands, which can further be replaced by metaplasia or fibrosis. Patients with advanced stages of CAG are at higher risk of GC and should be followed up with a high-quality endoscopy every 3 years. H. pylori infection is the most common cause and its eradication is recommended, which may contribute to the regression of CAG. However, it is controversial whether CAG is reversible after eradication therapy. In the review, we discuss recent studies which provide important insights into whether CAG is 'reversibility' and when it may progress into GC after eradicating H. pylori.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xinyue Zhou
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Xu W, Li B, Xu M, Yang T, Hao X. Traditional Chinese medicine for precancerous lesions of gastric cancer: A review. Biomed Pharmacother 2021; 146:112542. [PMID: 34929576 DOI: 10.1016/j.biopha.2021.112542] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 12/12/2021] [Accepted: 12/13/2021] [Indexed: 01/30/2023] Open
Abstract
Gastric cancer (GC) is the fifth most common type of cancer and the third leading cause of death due to cancer worldwide. The gastric mucosa often undergoes many years of precancerous lesions of gastric cancer (PLGC) stages before progressing to gastric malignancy. Unfortunately, there are no effective Western drugs for patients with PLGC. In recent years, traditional Chinese medicine (TCM) has been proven effective in treating PLGC. Classical TCM formulas and chemical components isolated from some Chinese herbal medicines have been administered to treat PLGC, and the main advantage is their comprehensive intervention with multiple approaches and multiple targets. In this review, we focus on recent studies using TCM treatment for PLGC, including clinical observations and experimental research, with a focus on targets and mechanisms of drugs. This review provides some ideas and a theoretical basis for applying TCM to treat PLGC and prevent GC.
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Affiliation(s)
- Weichao Xu
- Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine Gastroenterology, Shijiazhuang 050011, China
| | - Bolin Li
- Hebei Hospital of Traditional Chinese Medicine, Shijiazhuang 050011, China; Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine Gastroenterology, Shijiazhuang 050011, China
| | - Miaochan Xu
- Hebei University of Chinese Medicine, Shijiazhuang 050200, China
| | - Tianxiao Yang
- Hebei University of Chinese Medicine, Shijiazhuang 050200, China
| | - Xinyu Hao
- Peking University Third Hospital, Beijing 100191, China.
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Kim YH, Kim JY, Kwon OJ, Jung SY, Joung JY, Yang CS, Lee JH, Cho JH, Son CG. Efficacy of a Traditional Herbal Formula, Banha-Sasim-Tang in Functional Dyspepsia Classified as Excess Pattern. Front Pharmacol 2021; 12:698887. [PMID: 34512334 PMCID: PMC8429799 DOI: 10.3389/fphar.2021.698887] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Accepted: 08/16/2021] [Indexed: 12/12/2022] Open
Abstract
This study evaluated the efficacy and safety of Banha-sasim-tang (BST) in patients with functional dyspepsia (FD). BST (Banxia-xiexin-tang in traditional Chinese medicine and Hange-shashin-to in Kampo medicine) is traditionally prescribed for the treatment of dyspepsia with epigastric stiffness and gastric fullness in China, Japan, and Korea. Patients with FD were randomly administered an oral dose (10 g) of BST syrup or placebo, twice a day for 4 weeks. The primary outcome was the symptom checklist part of the Nepean dyspepsia index (NDI). The secondary outcomes were the quality of life (QoL) part of the NDI, functional dyspepsia-related QoL (FD-QoL), and visual analog scale (VAS). A total of 60 patients with FD were screened, and 50 were randomized into BST group (n = 25) and placebo group (n = 25). Two patients in the placebo group withdrew before the start of the treatment. Administration of BST syrup resulted in improvement in the symptom-related NDI score in the BST group compared with that in the control group; however, the difference was not significant. BST syrup significantly improved "fullness after eating" index of NDI at follow-up time point (2.88 ± 2.65 vs 4.78 ± 2.69, p = 0.0081). In the total score of the QoL section of the NDI and FD-QoL scales, there was no significant improvement in the BST group compared to that in the placebo group. With regard to improvement in overall FD symptoms, the VAS scale showed improvement in both groups, but the difference was not significant. Interestingly, follow-up investigation showed a significantly beneficial effect of BST on FD symptoms, when compared to placebo. Significant improvement observed in VAS score (39.60 ± 22.29 vs 52.17 ± 20.55, p = 0.048). This indicated that the effect of BST lasted even after the completion of the medication regimen. Overall, our data suggest that while BST showed no significant improvement in the symptom-related NDI score and the QoL related scores in NDI and FD-QoL after 4 weeks of treatment, it effectively improved the VAS score and fullness after eating-related symptoms in the follow-up visit. Clinical Trial Registration:https://cris.nih.go.kr; Identifier KCT 0002013.
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Affiliation(s)
- Yun Hee Kim
- Korean Medicine Convergence Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - Jun Young Kim
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
| | - O-Jin Kwon
- Korean Medicine Clinical Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - So Young Jung
- Korean Medicine Clinical Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - Jin-Yong Joung
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
| | - Chang Sop Yang
- Korean Medicine Clinical Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - Jun-Hwan Lee
- Korean Medicine Clinical Research Division, Korea Institute of Oriental Medicine (KIOM), Daejeon, Korea
| | - Jung-Hyo Cho
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
| | - Chang-Gue Son
- Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, Daejeon, Korea
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Sun X, Xue D, Zhang K, Jiang F, Li D. Acrid-release and bitter-downbearing therapy and banxia xiexin decoction regulate Wnt/β-catenin pathway, inhibit proliferation and invasion, and induce apoptosis in gastric cancer cells. Am J Transl Res 2021; 13:6211-6220. [PMID: 34306360 PMCID: PMC8290735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 03/07/2021] [Indexed: 06/13/2023]
Abstract
OBJECTIVE To explore the efficacy of the acrid-release and bitter-downbearing therapy and Banxia Xiexin Decoction (BXD) in treating gastric cancer (GC). METHODS BXD was decocted, and serum containing medicine was prepared from rats. The SNU-16 cells were cultured with different concentrations of BXD serum (25, 50, 100 μL/mL). Then, those were treated with BXD and Wnt/β-catenin pathway activator (LiCl) and divided into three groups: Control group, BXD group and BXD+LiCl group. Activation of the Wnt/β-catenin pathway was detected by immunofluorescence staining, qRT-PCR, and western blot. Cell activity, clone formation, invasion, metastasis and apoptosis in each group were examined by MTT, clone formation test, Transwell and flow cytometry. The oxidative stress measures in cells of each group were tested by an oxidative stress kit. RESULTS With increasing BXD concentration, the clonogenic ability of cells was inhibited. BXD can inhibit cell activity, clone formation, invasion and metastasis, promote oxidative stress, and induce apoptosis. It can also inhibit the activation of Wnt/β-catenin signaling pathway. A Wnt/β-catenin signaling pathway activator could partially inhibit the action of BXD. CONCLUSION BXD participates in GC treatment by inhibiting Wnt/β-catenin signaling pathway, thus inhibiting GC cell activity and clone formation, promoting oxidative stress, and inducing apoptosis.
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Affiliation(s)
- Xiaofen Sun
- Department of Gastroenterology, The 943 Hospital of The Joint Logistics Support Unit of The Chinese People’s Liberation ArmyWuwei, Gansu Province, China
| | - Dewen Xue
- Department of Nephrology, The 943 Hospital of The Joint Logistics Support Unit of The Chinese People’s Liberation ArmyWuwei, Gansu Province, China
| | - Kanru Zhang
- Department of Gastroenterology, The 943 Hospital of The Joint Logistics Support Unit of The Chinese People’s Liberation ArmyWuwei, Gansu Province, China
| | - Fang Jiang
- Department of Outpatient, The 943 Hospital of The Joint Logistics Support Unit of The Chinese People’s Liberation ArmyWuwei, Gansu Province, China
| | - Duoqiao Li
- Department of Gastroenterology, The 943 Hospital of The Joint Logistics Support Unit of The Chinese People’s Liberation ArmyWuwei, Gansu Province, China
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