目的 基于网络药理学和分子对接技术探讨毛蕊异黄酮治疗代谢相关脂肪性肝病的潜在作用靶点及分子机制。方法 通过TCMIP和SwissTargetPrediction数据库预测毛蕊异黄酮的作用靶点；通过OMIM和GeneCards数据库收集代谢相关脂肪性肝病相关疾病靶点。将药物靶点与疾病靶点取交集后，通过STRING数据库构建蛋白质相互作用（PPI）网络，并筛选核心靶点。利用DAVID数据库进行基因本体（GO）功能注释及京都基因和基因组百科全书（KEGG）通路富集分析；进一步借助Cytoscape软件构建“药物–靶点–通路”调控网络。采用CB-Dock2在线平台对关键活性成分与核心靶点进行分子对接验证。结果 共获得毛蕊异黄酮作用靶点252个，代谢相关脂肪性肝病疾病靶点2 607个，交集靶点89个。共筛选出过氧化物酶体增殖激活受体γ（PPARG）、细胞色素P450 3A4酶（CYP3A4）、过氧化物酶体增殖物激活受体α（PPARA）、丝裂原活化蛋白激酶1（MAPK1）、雄激素受体（AR）、孕激素受体（PGR）等核心靶点。GO富集分析显示，核心靶点主要涉及RNA聚合酶II介导的转录正调控、细胞核、DNA结合转录因子活性等。KEGG通路分析表明，毛蕊异黄酮可能通过调节脂肪细胞因子信号通路、PPAR信号通路、白细胞介素（IL）-17信号通路、脂质与动脉粥样硬化等途径发挥治疗作用。分子对接结果显示，毛蕊异黄酮与PPARG、CYP3A4、PPARA、MAPK1、AR、PGR均能稳定结合。结论 毛蕊异黄酮可能通过多靶点、多通路协同作用治疗代谢相关脂肪性肝病，为其药理机制研究和临床应用提供了科学依据。

Objective To investigate the potential targets and molecular mechanism of calycosin in treating metabolic dysfunction-associated fatty liver disease based on network pharmacology and molecular docking technology. Methods Targets of calycosin were predicted using the TCMIP and SwissTargetPrediction database. Disease targets were collected from OMIM and GeneCards database. The common targets were obtained by intersecting the drug and disease targets. PPI network was constructed using the STRING database, and core targets were screened. GO functional annotation and KEGG pathway enrichment analysis were performed using the DAVID database. “Drug-target-pathway” regulatory network was constructed using Cytoscape software. Molecular docking validation of the key active ingredient with the core targets was performed using the CB-Dock2 online platform. Results A total of 252 targets of calycosin, and 2 607 metabolic dysfunction-associated fatty liver disease -related disease targets were obtained, resulting in 89 common intersection targets. A total of core targets such as PPARG, CYP3A4, PPARA, MAPK1, AR, and PGR were identified. GO enrichment analysis indicated that the core targets were primarily involved in biological processes such as the positive regulation of transcription by RNA polymerase II, cellular components like the nucleus, and molecular functions including DNA-binding transcription factor activity. KEGG pathway analysis suggested that calycosin might exert its therapeutic effects by regulating pathways such as the adipocytokine signaling pathway, PPAR signaling pathway, IL-17 signaling pathway, and lipid and atherosclerosis. Molecular docking results showed that calycosin could bind stably with targets like PPARG, CYP3A4, PPARA, MAPK1, AR, and PGR. Conclusion Calycosin may treat metabolic dysfunction-associated fatty liver disease through multi-target and multi-pathway synergistic effects, providing a scientific basis for further pharmacological research and clinical application.

R965;R975

临沂市重点研发计划项目（2022001）