The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China.
Sci Rep. 2024 Oct 29;14(1):25983. doi: 10.1038/s41598-024-77897-3.
We used network pharmacology, molecular docking, and in vitro experiments to explore the mechanisms of Astragali Radix in the treatment of lupus nephritis. We screened compounds and targets of Astragali Radix, as well as related genes of lupus nephritis from databases. We identified 211 common genes and 44 compounds between the herb and the disease, and constructed global, narrowed, hierarchical Compound-Target Interaction networks to illustrate the possible mechanism. We found that the PI3K/AKT/mTOR pathway is a core target gene set identified through enrichment analysis, PPI analysis and MCODE analysis. In vitro experiments showed that freeze-dried Astragali powder inhibits activation of PI3K, AKT1 and mTOR in TGF-β1 stimulated HK-2 cells. Molecular docking demonstrated that (R)-isomucronulatol, 3,9,10-trimethoxypterocarpan and astrapterocarpan exhibited promising binding affinity to PI3K, AKT, and mTOR proteins.
我们运用网络药理学、分子对接和体外实验的方法来探讨黄芪治疗狼疮性肾炎的作用机制。我们从数据库中筛选出黄芪的化合物和靶点，以及狼疮性肾炎的相关基因。我们发现该草药与疾病之间有 211 个共有基因和 44 个化合物，并构建了全局、细化和分层的化合物-靶点相互作用网络，以阐明可能的作用机制。我们发现，PI3K/AKT/mTOR 通路是通过富集分析、PPI 分析和 MCODE 分析鉴定的核心靶基因集。体外实验表明，冻干黄芪粉可抑制 TGF-β1 刺激的 HK-2 细胞中 PI3K、AKT1 和 mTOR 的激活。分子对接表明，（R）-异槲皮苷、3,9,10-三甲氧基紫檀烷和黄芪紫檀烷对 PI3K、AKT 和 mTOR 蛋白具有较好的结合亲和力。
