Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disor...Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.展开更多
[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analys...[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)获取木防己汤的主要有效成分及治疗靶点,同时使用人类基因数据库(Human Gene Database,GeneCards)数据库、药物靶标数据库(Therapeutic Target Database,TTD)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)数据库、药品数据与药物靶点(DrugBank)、遗传药理学与药物基因组学数据库(Pharmacogenetics and Pharmacogenomics Knowledge Base,PharmGkb)等数据库获取CHF的相关基因,并通过Cytoscape 3.9软件构建木防己汤-靶点-CHF网络;对获取的治疗靶点分别进行蛋白互作(protein-protein interaction,PPI)分析、基因本体(gene ontology,GO)富集分析及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,最后使用AutoDockVina、PyMol软件对木防己汤治疗CHF主要成分及核心靶点进行分子对接验证。[结果]共获取木防己汤主要有效成分32个,治疗靶点326个,CHF相关基因10693个,木防己汤治疗CHF靶点104个。KEGG分析显示脂质与动脉粥样硬化、肿瘤受体激活、神经活性配体与受体相互作用、阿尔茨海默病、钙信号通路排名靠前。拓扑分析结果显示木防己汤治疗CHF核心靶点为热休克蛋白90α家族A类成员1(heat shock protein 90ɑfamily class A member 1,HSP90AA1)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)。分子对接结果显示木防己汤治疗CHF关键靶点与主要活性成分对接良好。[结论]木防己汤治疗CHF具有多靶点、多通路的特点,其治疗机制涉及HSP90AA1、PTGS2等蛋白,本研究为CHF相关生物实验研究及新药开发提供了临床支持及理论参考。展开更多
基金supported by the Qingdao Medical Research Guidance Plan(2020-WJZD049).
文摘Background:Mufangji tang(MFJT)is composed of Ramulus Cinnamomi,Radix Ginseng,Cocculus orbiculatus(Linn.)DC.,and Gypsum.In clinical settings,MFJT has been effectively employed in addressing a range of respiratory disorders,notably including pulmonary arterial hypertension(PAH).However,the mechanism of action of MFJT on PAH remains unknown.Methods:In this study,a monocrotaline-induced PAH rat model was established and treated with MFJT.The therapeutic effects of MFJT on PAH rat model were evaluated.Network pharmacology was conducted to screen the possible targets for MFJT on PAH,and the molecular docking between the main active components and the core targets was carried out.The key targets identified from network pharmacology were tested.Results:Results showed significant therapeutic effects of MFJT on PAH rat model.Analysis of network pharmacology revealed several potential targets related to apoptosis,inflammation,oxidative stress,and vascular remodeling.Molecular docking showed that the key components were well docked with the core targets.Further experimental validation results that MFJT treatment induced apoptosis(downregulated Bcl-2 levels and upregulated Bax levels in lung tissue),inhibited inflammatory response and oxdative stress(decreased the levels of IL-1β,TNF-α,inducible NOS,and malondialdehyde,and increased the levels of endothelial nitric oxide synthase,nitric oxide,glutathione and superoxide dismutase),reduced the proliferation of pulmonary arterial smooth muscle cells(downregulated ET-1 andβ-catenin levels and ERK1/2 phosphorylation,increased GSK3βlevels).Conclusion:Our study revealed MFJT treatment could alleviate PAH in rats via induction of apoptosis,inhibition of inflammation and oxidative stress,and the prevention of vascular remodeling.
文摘[目的]通过网络药理学及分子对接分析木防己汤治疗慢性心力衰竭(chronic heart failure,CHF)的具体机制并进行验证。[方法]使用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)获取木防己汤的主要有效成分及治疗靶点,同时使用人类基因数据库(Human Gene Database,GeneCards)数据库、药物靶标数据库(Therapeutic Target Database,TTD)、人类孟德尔遗传在线(Online Mendelian Inheritance in Man,OMIM)数据库、药品数据与药物靶点(DrugBank)、遗传药理学与药物基因组学数据库(Pharmacogenetics and Pharmacogenomics Knowledge Base,PharmGkb)等数据库获取CHF的相关基因,并通过Cytoscape 3.9软件构建木防己汤-靶点-CHF网络;对获取的治疗靶点分别进行蛋白互作(protein-protein interaction,PPI)分析、基因本体(gene ontology,GO)富集分析及京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,最后使用AutoDockVina、PyMol软件对木防己汤治疗CHF主要成分及核心靶点进行分子对接验证。[结果]共获取木防己汤主要有效成分32个,治疗靶点326个,CHF相关基因10693个,木防己汤治疗CHF靶点104个。KEGG分析显示脂质与动脉粥样硬化、肿瘤受体激活、神经活性配体与受体相互作用、阿尔茨海默病、钙信号通路排名靠前。拓扑分析结果显示木防己汤治疗CHF核心靶点为热休克蛋白90α家族A类成员1(heat shock protein 90ɑfamily class A member 1,HSP90AA1)、前列腺素内过氧化物合酶2(prostaglandin-endoperoxide synthase 2,PTGS2)。分子对接结果显示木防己汤治疗CHF关键靶点与主要活性成分对接良好。[结论]木防己汤治疗CHF具有多靶点、多通路的特点,其治疗机制涉及HSP90AA1、PTGS2等蛋白,本研究为CHF相关生物实验研究及新药开发提供了临床支持及理论参考。
