基于多靶点虚拟筛选、网络药理学分析和体外实验，探讨强肝胶囊(QGC)治疗非酒精性脂肪性肝病(NAFLD)的潜在作用机制。利用基于PPARα/γ、FXR及sEH的多靶点虚拟筛选选出QGC中具有治疗NAFLD的活性成分，运用网络药理学预测活性成分靶点、疾病相关靶点，筛选调控疾病的关键靶点，通过Discovery Studio 2020软件和Gromacs软件对关键活性成分和关键靶点进行分子对接和分子动力学模拟分析。最后，通过实验验证QGC中的关键活性成分对肝细胞脂肪变性的改善作用。多靶点虚拟筛选得到235个QGC活性成分，网络药理学分析得到320个成分-疾病共同靶点。分子对接结果表明，芹菜素、异鼠李素、迷迭香酸、大黄素甲醚、木犀草素与关键靶点PTPN1、PPARα、PPARγ、AR具有良好的结合能力。分子动力学模拟进一步验证了迷迭香酸、大黄素甲醚等化合物与关键靶点具有良好的结合稳定性。体外实验结果显示，5个关键活性成分均能改善HepG2细胞的脂肪变性，其中异鼠李素、迷迭香酸、大黄素甲醚改善细胞脂肪变性模型的效果最佳。本研究通过多层面探讨，为QGC在NAFLD治疗中的开发和应用提供理论依据。
Analysis of Network Pharmacology of Qianggan Capsulein in Treating Nonalcoholic Fatty Liver Disease
This study preliminarily investigated the potential mechanisms of the Qianggan capsule(QGC)in treating nonalcoholic fatty liver disease(NAFLD)through a combination of multi-target virtual screening,network pharmacology,and in vitro experiment verification.A multi-target virtual screening based on PPARα/γ,FXR and sEH was utilized to select the active ingredients in QGC with therapeutic properties for NAFLD.The systematic pharmacological approach has been used to predict active ingredient targets and disease-relevant targets,and ultimately to screen key targets for disease modulation.Molecular docking and molecular dynamics simulation analysis of key active ingredients and key targets were performed through Discovery Studio 2020 software and Gromacs software.Finally,an experimental verification of the efficacy of the key compounds in the mitigation of hepatocyte steatosis was carried out.The results indicated that 235 active ingredients of QGC and 320 ingredients-disease common targets were identified by multiple-target virtual screening and network pharmacology analysis,respectively.Molecular docking revealed that apigenin,isorhamnetin,rosmarinic acid,physcion,and luteolin showed strong binding capacity to PTPN1,PPARα,PPARγ,and AR,respectively.Molecular dynamics simulations further verified that compounds such as rosmarinic acid and physcion had good binding stability with key targets.In vitro testing showed that the five key active ingredients could improve the steatosis of HepG2 cells.Notably,rosmarinic acid,physcion,and isorhamnetin exhibited the highest potency among them.This study provides a theoretical basis for the development and application of QGC in the treatment of NAFLD through multi-level discussions.
万方数据
维普
