基于网络药理学的“柴胡-黄芩”药对治疗糖尿病的“理法-方药-成分-靶标-活性”关联研究

Exploration of “principle-recipe-composition-target-activity” association of Bupleuri Radix and Scutellariae Radix drug pair for diabetes treatment based on network pharmacology

本文以"柴胡-黄芩"药对为研究对象,借助中药整合药理学平台,结合中医药大数据,按照"理法-方药-成分-靶标-通路-活性"关联性研究,预测其治疗糖尿病的药效物质基础及作用机制。本研究预测得到活性成分共计59个,分别作用于22个直接靶标和26条主要通路,其药效物质基础主要为皂苷、黄酮、挥发油和脂肪酸等成分。其治疗糖尿病作用涉及的22个直接靶标主要有:精氨酸加压素受体基因、视网膜母细胞瘤1、受体活性修饰蛋白、血小板生长因子受体、胰岛素受体和α-葡萄糖苷酶等;其治疗糖尿病作用涉及内分泌系统、循环系统、消化系统、甲状腺信号通路、Erb B信号通路和PI3K-Akt信号通路等。采用分子对接技术进行的虚拟筛选,结果表明,"柴胡-黄芩"药对中的黄酮类化合物易与过氧化物酶体增殖物激活受体γ及糖原合成酶激酶-3β形成较好的对接模式与较高亲和力,具有治疗糖尿病的活性。本研究为进一步研究该药对治疗糖尿病作用机制提供科学依据,为药对及中药复方的研究探索新的思路。

By using the integrated pharmacology platform and the big data of traditional Chinese medicine combined with the pharmacology thinking of ＂principle-recipe-composition-target-pathway-activity＂ in this study, we predicted the material basis and mechanisms of Bupleuri Radix and Scutellariae Radix drug pair for the treatment of diabetes. Fifty-nine active components were predicted, which included saponins, flavones, essential oil, fatty acids and so on. They acted on twenty-two direct targets and twenty-six main pathways respectively. The known disease targets of diabetes include arginine vasopressin receptor gene（AVP）, retinoblastoma（RB1）, receptor active modified protein（RAMP）, platelet growth factor receptor（PDGFR）, insulin receptor（INSR）, α-glucosidase（GAA）, etc. The pathways with diabetes effect involves endocrine system, circulatory system, digestive system, thyroid hormone signaling pathway, Erb B signaling pathway, PI3K-Akt signaling pathway, lipid metabolism and other related biological processes and metabolic pathways. The results of virtual screening in molecular docking technology indicate that flavonoids from Bupleuri Radix and Scutellariae Radix drug pair can easily form good docking mode and high affinity with peroxisome proliferators activated receptor γ（PPAR-γ） and glycogen synthase kinase-3β（GSK-3β）, showing antidiabetic activity. The study provides information for the treatment of diabetes by Bupleuri Radix and Scutellariae Radix drug pair, and a new thought for the study of drug pair and complex prescription.