中药系统药理学分析平台——TCMSP(Traditional Chinese Medicines Systems Pharmacology Platform)作为一个全新的以系统药理学为基础的中药研究平台及数据库,主要使用了系统药理学技术,给出了《中国药典》收录的所有中草药的组分和分...中药系统药理学分析平台——TCMSP(Traditional Chinese Medicines Systems Pharmacology Platform)作为一个全新的以系统药理学为基础的中药研究平台及数据库,主要使用了系统药理学技术,给出了《中国药典》收录的所有中草药的组分和分子结构、关键ADME参数、成分作用靶点以及相关疾病等关键信息。从介绍TCMSP数据库和该数据库的应用领域及应用情况入手,简要的分析和论述了近年来TCMSP数据库的应用和影响。该数据库被广泛的应用在确定中药成分及ADME性质、作用靶点及相关疾病信息、作用机制研究、新药开发和复方改良及中医经典理论研究等方面,其优势在于提供了ADME参数OB,Caco-2,Half-life,BBB等参数,并且具有独特的筛选功能。展开更多
BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese me...BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier func展开更多
目的:探讨四君子汤治疗慢性萎缩性胃炎的有效活性成分及作用机制。方法:本研究通过TCMSP数据库选取四君子汤中党参、茯苓、白术、甘草含有的491个化合物,筛选其活性成分及潜在靶点;同时,通过GeneCards数据库挖掘慢性萎缩性胃炎疾病靶点...目的:探讨四君子汤治疗慢性萎缩性胃炎的有效活性成分及作用机制。方法:本研究通过TCMSP数据库选取四君子汤中党参、茯苓、白术、甘草含有的491个化合物,筛选其活性成分及潜在靶点;同时,通过GeneCards数据库挖掘慢性萎缩性胃炎疾病靶点;结合化合物及疾病靶点,构建化合物-靶点网络、进行GO富集分析及KEGG通路富集分析。结果:四君子汤中含有123个活性成分,对应慢性萎缩性胃炎78个靶点;GO生物过程相关条目36个;KEGG通路14条,涉及肿瘤信号通路(pathways in cancer)、TNF信号通路、P53信号通路等。结论:四君子汤主要通过调控细胞炎症、增殖、凋亡、代谢来治疗漫性萎缩性胃炎,这为阐明四君子汤治疗慢性萎缩性胃炎的作用机制、开展实验验证提供依据。展开更多
AIM To investigate the protective effects of Ampelopsis grossedentata(AMP) on dextran sulfate sodium(DSS)-induced colitis in mice based on systems pharmacology approach.METHODS Systems pharmacology approach was used t...AIM To investigate the protective effects of Ampelopsis grossedentata(AMP) on dextran sulfate sodium(DSS)-induced colitis in mice based on systems pharmacology approach.METHODS Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis(UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSSinduced colitis model in C57 BL/6 mice(n = 10/group) was constructed and treated with 5-aminosalicylic acid(100 mg/kg/d) and AMP(400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and immunohistochemistry.RESULTS The therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-α and RANKL/RANK, a receptor activator of NF-κB signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and IL-8.CONCLUSION AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways.展开更多
Objective:To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction(二仙汤,EXD)as a treatment for premature ovarian failure(POF)using a syste...Objective:To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction(二仙汤,EXD)as a treatment for premature ovarian failure(POF)using a systems pharmacology approach.Methods:The compounds present in EXD were obtained from three databases.The active ingredient was identified by analyzing the values of oral bioavailability(OB),drug-like ness(DL),and Lipin ski's rule(LR).The active in gredients were further searched in research articles,drug targets in the DrugBank database,and the C-T and T-P networks,as well as by pathway analysis using the Cytoscape platform.Results:A total of 728 compounds were identified in EXD.Of these,59 were identified as active compounds that conformed to the criteria with OB>30%and DL>0.18.By further searches in the literature,126 related targets were ide ntified that could in teract with the active compounds.Additi on ally,it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immline system,modulation of estrogen levels,and anti-oxidative activities,and that it may act in a synergistic or cooperative manner with other therapeutic agents.Conclusions:The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF.The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.展开更多
文摘中药系统药理学分析平台——TCMSP(Traditional Chinese Medicines Systems Pharmacology Platform)作为一个全新的以系统药理学为基础的中药研究平台及数据库,主要使用了系统药理学技术,给出了《中国药典》收录的所有中草药的组分和分子结构、关键ADME参数、成分作用靶点以及相关疾病等关键信息。从介绍TCMSP数据库和该数据库的应用领域及应用情况入手,简要的分析和论述了近年来TCMSP数据库的应用和影响。该数据库被广泛的应用在确定中药成分及ADME性质、作用靶点及相关疾病信息、作用机制研究、新药开发和复方改良及中医经典理论研究等方面,其优势在于提供了ADME参数OB,Caco-2,Half-life,BBB等参数,并且具有独特的筛选功能。
基金Supported by the National Natural Science Funds of China,No.81573892,No.81873253,and No.81704009
文摘BACKGROUND Given the complex pathogenesis of ulcerative colitis (UC), the conventional therapeutic methods are not fully curative. As a sort of systematic complementary and alternative medicine, traditional Chinese medicine (TCM) provides new options for the standard therapy. Nevertheless, there are still numerous problems with the promotion of TCM attributed to its complexity, and consequently, new research approaches are urgently needed. Thus, we explored the protective effects of Jian-Pi Qing-Chang (JPQC) decoction on UC based on systems pharmacology approach, which might fill the current innovation gap in drug discovery and clinical practice pertaining to TCM. AIM To investigate the protective mechanisms of JPQC decoction on UC based on systems pharmacology approach. METHODS We performed systems pharmacology to predict the active ingredients, the matched targets, and the potential pharmacological mechanism of JPQC on UC. In vivo, we explored the effects of JPQC in a colitis model induced by dextran sulfate sodium. In vitro, we adopted the bone marrow-derived macrophages (BMDMs) as well as BMDMs co-cultured with Caco2 cells to verify the underlying mechanisms and effects of JPQC on UC under TNF-α stimulation. RESULTS Systems pharmacology revealed 170 targets for the 107 active ingredients of JPQC and 112 candidate targets of UC. Protein-protein interaction networks were established to identify the underlying therapeutic targets of JPQC on UC. Based on enrichment analyses, we proposed our hypothesis that JPQC might have a protective effect on UC via the NF-κB/HIF-1α signalling pathway. Subsequent experimental validation revealed that treatment with TNFα activated the NF-κB/HIF-1α signalling pathway in BMDMs, thereby damaging the epithelial barrier permeability in co-cultured Caco2 cells, while JPQC rescued this situation. The findings were also confirmed in a dextran sulfate sodium-induced colitis model. CONCLUSION JPQC could improve the mucosal inflammatory response and intestinal epithelial barrier func
文摘目的:探讨四君子汤治疗慢性萎缩性胃炎的有效活性成分及作用机制。方法:本研究通过TCMSP数据库选取四君子汤中党参、茯苓、白术、甘草含有的491个化合物,筛选其活性成分及潜在靶点;同时,通过GeneCards数据库挖掘慢性萎缩性胃炎疾病靶点;结合化合物及疾病靶点,构建化合物-靶点网络、进行GO富集分析及KEGG通路富集分析。结果:四君子汤中含有123个活性成分,对应慢性萎缩性胃炎78个靶点;GO生物过程相关条目36个;KEGG通路14条,涉及肿瘤信号通路(pathways in cancer)、TNF信号通路、P53信号通路等。结论:四君子汤主要通过调控细胞炎症、增殖、凋亡、代谢来治疗漫性萎缩性胃炎,这为阐明四君子汤治疗慢性萎缩性胃炎的作用机制、开展实验验证提供依据。
文摘AIM To investigate the protective effects of Ampelopsis grossedentata(AMP) on dextran sulfate sodium(DSS)-induced colitis in mice based on systems pharmacology approach.METHODS Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis(UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSSinduced colitis model in C57 BL/6 mice(n = 10/group) was constructed and treated with 5-aminosalicylic acid(100 mg/kg/d) and AMP(400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and immunohistochemistry.RESULTS The therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-α and RANKL/RANK, a receptor activator of NF-κB signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and IL-8.CONCLUSION AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways.
基金Supported by Liaoning Natural Science Foundation of China(No.2017011854-301)Jinzhou Science and Technology Project,China(No.16B1G35)
文摘Objective:To predict the chemical compositions and drug targets and to systematically dissect the pharmacological mechanism of Erxian Decoction(二仙汤,EXD)as a treatment for premature ovarian failure(POF)using a systems pharmacology approach.Methods:The compounds present in EXD were obtained from three databases.The active ingredient was identified by analyzing the values of oral bioavailability(OB),drug-like ness(DL),and Lipin ski's rule(LR).The active in gredients were further searched in research articles,drug targets in the DrugBank database,and the C-T and T-P networks,as well as by pathway analysis using the Cytoscape platform.Results:A total of 728 compounds were identified in EXD.Of these,59 were identified as active compounds that conformed to the criteria with OB>30%and DL>0.18.By further searches in the literature,126 related targets were ide ntified that could in teract with the active compounds.Additi on ally,it was found that the beneficial effects of EXD in POF are probably exerted via regulation of the immline system,modulation of estrogen levels,and anti-oxidative activities,and that it may act in a synergistic or cooperative manner with other therapeutic agents.Conclusions:The systems pharmacology approach is a comprehensive system that was used to elucidate the pharmacological mechanism of EXD as a treatment for POF.The results of this study will also facilitate the application of traditional medicine in modern treatment strategies.
