六味地黄汤中药成分-靶标-疾病网络分析及效应机制预测

Chinese Herbal Medicine Compound-Target-Disease Network Analysis and Effective Mechanisms Prediction of Liuwei Dihuangtang

目的:运用网络药理学技术预测六味地黄汤的化学成分、药物靶标以及可能治疗的疾病,探讨其配伍及对多种疾病"异病同治"的分子机制。方法:采用TCMSP数据库的口服生物利用度(OB)和类药性指数(DL),筛选六味地黄汤的活性成分和相关疾病,从Drugbank数据库获得药物靶标,用Cytoscape软件构建中药成分-靶标-疾病网络,并进行网络拓扑分析及靶标功能和信号通路分析。结果:在六味地黄汤507种化合物中符合OB≥30%,DL≥0.18有42种,其相关靶标有221个,并富集出九大类56种疾病,以肿瘤、心血管系统疾病以及呼吸系统疾病的网络相关度最大。六味地黄汤、三补和三泻的配伍都能调节细胞凋亡、代谢、增殖、以及血管平滑肌收缩;六味地黄汤还有调控蛋白的合成修饰和分泌作用;三补能够调控离子跨膜转运、血压以及前列腺素、视黄酸的代谢等;三泻则侧重于对细胞的信号传导以及细胞的生物合成作用的影响。结论:本研究筛选出六味地黄汤活性成分42种,预测靶标221个及疾病56个,其三补三泻的配伍使药物作用产生了1+1>2的效应机制。六味地黄汤对多种疾病"异病同治"具有多靶标、多功能以及多通路的调节机制。

Objective： To predict the active compounds, therapy targets of Liuwei Dihuangtang （LWDHT） as well as possible diseases, and explore the molecular mechanism of its compatibility and its efficacy on diseases under the guidance of ＇treating different diseases with the same method＇. Method： Oral bioavailability （OB） and drug-likeness （DL） based on TCMSP database were used to screen the active compounds of LWDHT and its related diseases. Therapy targets were obtained from the Drugbank database, and then the Chinese herbal medicine （CHM） compound-targets-disease network was constructed by using cytoscape software. The network topology analysis, target function and signaling pathway analysis were also performed. Result： The 42 of 507 compounds in LWDHT were screened out （OB ≥ 30% , drug-likeness index ≥ 0. 18）. The 221 related targets were found and 9 categories of diseases involving 56 diseases were enriched, among which tumor, cardiovascular and respiratory diseases were most closely correlated with the formula. The compatibility of LWDHT, ＇ Sanbu＇ with reinforcing effect and ＇ Sanxie＇ with reducing effect can regulate cellular apoptosis, metabolism, proliferation, and vascular smooth muscle contraction. Besides, LWDHT also can regulate protein synthesis modification and secretion. The ＇Sanbu＇ with reinforcing effect can regulate transmembrane transport activity of ion, blood pressure, the metabolic process of prostaglandin and retinoic acid. The ＇Sanxie＇ with reducing effect can regulate cell signaling and biosynthetic process. Conclusion： In this study, 42 compounds were screened out as the potential effective compounds of LWDHT, and 221 targets and 56 diseases were predicted to be associated with the formula. The compatibility of ＇ Sanbu＇ and ＇ Sanxie＇ made 1 ＋ 1 〉 2 synergistic effect mechanism. LWDHT owned multiple targets and multiple pathways to treat various diseases under the guidance of ＇treating different diseases with the same method＇.