基于网络药理学探讨薏苡附子败酱散治疗肝细胞癌的作用机制

Mechanism of Yiyi Fuzi Baijiang powder in treatment of hepatocellular carcinoma on network pharmacology

目的通过网络药理学方法探讨薏苡附子败酱散治疗肝细胞癌的作用机制。方法运用中药系统药理学数据库和分析平台(TCMSP)获取薏苡仁、附子、败酱草的活性成分和作用靶点,从GeneCards数据库中获取肝细胞癌候选靶点,并筛选出中药与疾病的交集靶点;采用STRING数据库构建蛋白-蛋白相互作用(PPI)网络,g:Profiler数据分析平台进行GO富集和KEGG通路富集分析。通过Cytoscape 3.7.2软件构建疾病-活性成分-关键靶点-通路网络并进行拓扑结构分析。结果最终筛选获得薏苡附子败酱散活性成分43个,205个潜在靶点,肝细胞癌候选靶点6330个,两者交集关键靶点172个。通过评估口服药物生物利用度和类药性的大小筛选核心活性成分有豆甾醇、谷甾醇等,通过PPI网络分析筛选出TP53、热休克蛋白90α家族A级成员1(HSP90AA1)等主要作用靶点,GO富集分析条目1515条,涉及酶结合、蛋白质二聚活性等生物过程;KEGG富集分析119条,主要调控糖基化终产物及其受体(AGE-RAGE)信号通路、白细胞介素(IL)-17通路、乙型肝炎病毒(HBV)通路等。结论薏苡附子败酱散通过谷甾醇、豆甾醇等活性成分作用于TP53、HSP90AA1等靶点治疗肝细胞癌,其机制可能与调控AGE-RAGE、IL-17、HBV等信号通路有关。

AIM To explore the mechanism of Yiyi Fuzi Baijiang powder in the treatment of hepatocellular carcinoma by network pharmacology.METHODS The active components and targets of coix seed,prepared commonot and dahurian patrinia herb were obtained from the Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),the candidate targets of hepatocellular carcinoma were obtained from GeneCards database,and the intersection targets of traditional Chinese medicine and disease were screened.The protein-protein interaction(PPI)network was constructed by STRING database,and the g:Profiler data analysis platform was used for GO enrichment and KEGG pathway enrichment analysis.The disease active component key target pathway network was constructed by Cytoscape 3.7.2 software and the topological structure was analyzed.RESULTS Through screening,43 active components,205 potential targets,6330 candidate targets of hepatocellular carcinoma and 172 intersection key targets were obtained.By evaluating the oral bioavailability and druglike properties,the main active components were screened out,mainly including sitosterol,stigmasterol,etc.Through PPI network analysis,the main targets of TP53,heat shock protein 90αfamily A member 1(HSP90 AA1)and other major targets were screened out.GO enrichment analysis showed 1515 items,involved in enzyme binding,protein dimerization and other biological processes.KEGG enrichment analysis showed 119 items mainly regulated advanced glycation end products and its recepter(AGE-RAGE)signaling pathway,interleukin(IL)-17 pathway,hepatitis B virus(HBV)pathway,etc.CONCLUSION Yiyi Fuzi Baijiang powder act on TP53,HSP90AA1 and other targets through active components such as sitosterol and stigmasterol in the treatment of hepatocellular carcinoma,and its mechanism related to regulating AGE-RAGE,IL-17,HBV and other signaling pathways.