天然产物研究与开发 ›› 2022, Vol. 34 ›› Issue (增刊1): 130-141.doi: 10.16333/j.1001-6880.2022.S.019

• 数据研究 • 上一篇    下一篇

基于网络药理学和分子对接研究益气滋阴活血方治疗2型糖尿病的潜在靶标和分子作用机制

李力源1,郭   萧1,王晓莹1,李艺坤1,张   越1,2,杨高山1,2,宋秋航1,2*,李爱英2,3*   

  1. 1河北中医学院基础医学院;2河北省心脑血管病中医药防治重点实验室;3河北中医学院护理学院,石家庄 050200
  • 出版日期:2022-06-01 发布日期:2022-05-19
  • 基金资助:
    河北中医学院博士科研基金(BSZ2020011);河北省重点研发计划项目-生物医药专项(20372501D);国家级大学生创新创业训练计划(202014432017)

Potential targets and molecular mechanisms of Yiqi Ziyin Huoxue Prescription in the treatment of type 2 diabetes mellitus based on network pharmacology and molecular docking

LI Li-yuan1,GUO Xiao1,WANG Xiao-ying1,LI Yi-kun1,ZHANG yue1,2,YANG Gao-shan1,2,SONG Qiu-hang1,2*,LI Ai-ying2,3*   

  1. 1College of Basic Medical Sciences,Hebei University of Chinese Medicine;2Hebei Key Laboratory of Chinese Medicine Research on Cardiocerebrovascular Disease;3College of Nursing,Hebei University of Chinese Medicine,Shijiazhuang 050200,China
  • Online:2022-06-01 Published:2022-05-19

摘要: 基于数据库筛选、核心网络分析、通路富集分析、分子对接技术和GEO转录组学数据分析,探索黄芪、山药、丹参和生地黄组成的益气滋阴活血方医治2型糖尿病(T2DM)的有效化合物及作用机制,得出益气滋阴活血方中丹酚酸J、丹酚酸D、豆甾醇、槲皮素、木犀草素、山奈酚和β-谷甾醇等化合物,可能通过靶向PI3K-Akt信号通路、MAPK信号通路、AGE-RAGE信号通路和IL-17信号通路中的AKT1、MAPK1、IL6和STAT3等核心蛋白发挥治疗T2DM的作用。并发现多个丹酚酸类化合物是靶向AKT1和MAPK1的潜在抑制剂,特别是丹酚酸A、C和H与AKT1和MAPK1结合能力较强,今后可对丹酚酸类化合物的结构进行修饰和改造,使其达到成药标准,成为治疗T2DM的AKT1和MAPK1的靶向抑制剂。本研究为益气滋阴活血方临床治疗T2DM提供思路和参考依据,为筛选、开发天然产物来源的AKT1和MAPK1的靶向抑制剂提供骨架化合物,为进一步阐明益气滋阴活血方用于T2DM的特色防治提供理论基础,也为益气滋阴活血方的现代化应用和天然产物的开发提供新方向。

关键词: 益气滋阴活血方, 2型糖尿病, 网络药理学, 分子对接, GEO

Abstract:

Based on database screening,core network analysis,pathway enrichment analysis,molecular docking and GEO data analysis,to predict and screen the effective compounds and mechanisms of Yiqi Ziyin Huoxue Prescription(YZHP) composed of four herbs (Astragali Radix,Dioscoreae Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma and Rehmanniae Radix) in treating type 2 diabetes mellitus (T2DM).The results showed that the contents of salvianolic acid J,salvianolic acid D,stigmasterol,quercetin, luteolin,kaempferol, β-sitosterol and other compounds can target AKT1,MAPK1,IL6 and STAT3 in PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway and IL-17 signaling pathway to treat T2DM.And found that several salvianolic acids were potential inhibitors of AKT1 and MAPK1,especially salvianolic acids A,C and H have strong binding ability with AKT1 and MAPK1.In the future,the structure of salvianolic acids A,C and H can be modified to make them reach the standard of patent medicine,and become the targeted inhibitors of AKT1 and MAPK1 for the treatment of T2DM.In this paper,providing ideas and reference basis for clinical treatment of T2DM with YZHP,providing leading compounds for screening and developing targeted inhibitors of AKT1 and MAPK1 from natural products,providing theoretical basis for further elucidating the prevention and treatment of T2DM with YZHP,providing theoretical basis for further elucidating the prevention and treatment of T2DM with YZHP.

Key words: Yiqi Ziyin Huoxue Prescription, T2DM, network pharmacology, molecular docking, GEO

中图分类号:  R285