基于网络药理学方法探究蚕沙“异病同治”作用机制

Exploration of the mechanism of homotherapy for heteropathy of Faeces Bombycis based on network pharmacology

目的探究蚕沙防治类风湿关节炎合并糖尿病的药效物质基础及其作用靶点,揭示其多成分、多靶点、多途径的作用特点。方法结合文献检索和数据库挖掘对蚕沙中的主要化学成分进行整理,通过Parm Mapper反向分子对接方法预测蚕沙主要活性成分的作用靶点,利用UniProt数据库校正蛋白名称,疾病靶点数据库(TTD)校正靶点相关疾病信息,筛选出与类风湿关节炎、糖尿病相关的作用靶点;利用Cytoscape软件构建蚕沙"成分-靶点-疾病"网络,及其蛋白相互作用(PPI)网络,并对蚕沙治疗类风湿关节炎和糖尿病的相关作用靶点进行基因本体论(GO)功能注释及京都基因与基因组百科全书(KEGG)信号通路富集分析。结果经筛选和分析,获得蚕沙主要活性成分为β-胡萝卜素(beta-Carotene)、β-谷甾醇(beta-Sitosterol)、胆甾醇(Cholesterol)和山豆根黄烷酮A7(Euchrenone A7);与类风湿关节炎和糖尿病相关的作用靶点共计37个,其中与2种疾病均相关的作用靶点共计6个,包括SEC14样蛋白2(S14L2)、二肽基肽酶-4(DPP4)、皮质类固醇11-β-脱氢酶同工酶1(DHI1)、半胱天冬酶1(CASP1)、过氧化物酶体增殖物激活受体γ(PPARG)、α-生育酚转移蛋白(TTPA)。经GO功能注释分析得到GO条目7个(P<0.05),其中涉及生物过程条目3个,分子功能条目4个。KEGG信号通路筛选出催乳素(prolactin)、破骨细胞分化(Osteoclast differentiation)、Th17细胞分化(Th17 cell differentiation)、过氧化物酶体增殖物激活受体(PPAR)等4条信号通路。结论蚕沙在防治类风湿关节炎合并糖尿病方面体现了中药多成分、多靶点、多途径的作用特点,为深入阐释蚕沙防治疾病的作用机制提供参考,为蚕沙"异病同治"研究提供科学依据,但其关键靶点和调控机制仍需进一步的实验验证。

Objective To explore the main active compositions and their targets of Cansha(Faeces Bombycis)in the prevention and treatment of rheumatoid arthritis combined with diabetes,and to reveal its characteristics of multi-composition,multi-target and multi-channel.Methods The main ingredients of Cansha were sorted out combining literature search and database mining,and the targets of main active compositions were predicted by using Parm Mapper reverse molecular docking method.The names of predicted protein were revised by using UniProt database and the information of related-diseases were revised by using Therapeutic target database(TTD).The targets,related to rheumatoid arthritis and diabetes,were screened out.The composition-target-disease networks of Cansha and protein-protein interaction(PPI)networks were constructed by using Cytoscape software.Functional annotation analysis of Gene Ontology(GO)and signaling pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed on the related targets of Cansha in treatment for rheumatoid arthritis and diabetes.Results After screening and analysis,the main active compositions of Cansha included beta-Carotene,beta-Sitosterol,cholesterol and euchrenone A7.Network pharmacology analysis showed that 37 targets related to rheumatoid arthritis and/or diabetes,among which 6 targets related to both rheumatoid arthritis and diabetes,such as SEC14-like protein 2(S14 L2),dipeptidyl peptidase 4(DPP4),corticosteroid 11-beta-dehydrogenase isozyme(DHI1),caspase-1(CASP1),peroxisome proliferator-activated receptor gamma(PPARG)and alpha-tocopherol transfer protein(TTPA).Through GO functional annotation analysis 7 GO items were obtained(P<0.05),of which three involved biological processes items and four molecular function items.And there were 4 signaling pathways(P<0.05)in the KEGG signaling pathway analysis,involving prolactin signaling pathway,Osteoclast differentiation signaling pathway,Th17 cell differentiation signaling pathway and PPAR signaling pathway.Conclusion Cansha is characterized by multi-composition,multi-target and multi-channel in the clinical prevention and treatment of rheumatoid arthritis combined with diabetes.This study provided a reference for further expounding on the mechanism of clinical prevention and treatment of diseases of Cansha,and the scientific basis for the study of homotherapy for heteropathy of Cansha.However,further experiments are warranted to verify key targets and regulatory mechanisms.