山西大学学报（自然科学版）2026，Vol.49Issue(3)：400-415,16.DOI:10.13451/j.sxu.ns.2025134
整合机器学习与分子对接解析附子治疗心力衰竭的分子网络
Integrating Machine Learning and Molecular Docking to Decipher the Molecular Network of Fuzi in Treating Heart Failure
摘要
Abstract
Fuzi is known as the first key medicine to restore depleted Yang and rescue the patient from danger in Traditional Chinese Medicine(TCM)theory and its clinical efficacy in treating heart failure has been definitely demonstrated.However,its molecular regulatory network and specific mechanisms have not yet been systematically and thoroughly elucidated.This study integrated the Gene Expression Omnibus(GEO)database to screen differentially expressed genes related to heart failure and combined public data-bases to identify active components of Fuzi and their target genes.Furthermore,machine learning algorithms and molecular docking technology were applied to select core genes and trace their downstream signaling proteins,systematically analyzing the binding characteristics between active components of Fuzi and target proteins.The results revealed 23 potential targets involved in the anti-heart failure effects of Fuzi.Six key feature genes—C-C Motif Chemokine Receptor 1(CCR1),Epoxide Hydrolase 2(EPHX2),Membrane Metalloendopeptidase(MME),'5'-Nucleotidase Ecto(NT5E),Phosphodiesterase 5A(PDE5A),and Phospholipase A2 Group IIA(PLA2G2A)—were screened using machine learning algorithms.Molecular docking confirmed strong binding specificity between four active components of Fuzi—delphinidin 3,5-diglucoside,bebzoylaconine,ignavine,and evobioside—with three core proteins:EPHX2,MME,and PDE5A.Furthermore,in a doxorubicin(DOX)-induced heart failure model,we discovered that Fuzi rescued DOX-induced myocardial atrophy and reversed cardiac injury by suppressing the expression of EPHX2,MME,and PDE5A.Protein-protein interaction database prediction indicated a direct interaction between PDE5A and RHOBTB1 Rho related BTB do-main containing 1(RHOBTB1)with a binding energy of-66.1 kJ/mol,,suggesting RHOBTB1 as a downstream binding protein of PDE5A.In summary,Fuzi may exert its anti-heart failure effects by regulating the PDE5A/RHOBTB1 signaling axis,providing new insights and a theoretical basis for further elucidating its molecular mechanisms.关键词
附子/心力衰竭/磷酸二酯酶5AKey words
Fuzi/heart failure/Phosphodiesterase 5A分类
医药卫生引用本文复制引用
陈贻丹,姚静静,李震宇,秦雪梅..整合机器学习与分子对接解析附子治疗心力衰竭的分子网络[J].山西大学学报（自然科学版）,2026,49(3):400-415,16.基金项目
国家自然科学基金(82505236) （82505236）
山西省基础研究计划青年项目(202403021212245) （202403021212245）
山西省中医药管理局科研课题(2024ZYY2B059) （2024ZYY2B059）
山西省高等学校科技创新项目(2024L266) （2024L266）
中药生命组学与创新药物研发研究室(zyyyjs2024019) （zyyyjs2024019）
山西中医药大学博士科研启动基金(2024BK01) （2024BK01）
山西中医药大学优秀博士毕业生来晋工作奖励经费科研启动基金(2024BKS04) （2024BKS04）
山西中医药大学科技创新能力培育计划基础与临床合作研究专项(2024PY-JL-20-02) （2024PY-JL-20-02）
山西中医药大学科技创新能力培育计划国家自然科学基金培育专项(2024PY-NS-025) （2024PY-NS-025）
山西中医药大学研究生科研实践创新项目(X2025KY020) （X2025KY020）
