Network pharmacology to unveil the mechanism of Astragali Radix in the treatment of lupus nephritis via PI3K/AKT/mTOR pathway

Abstract

Abstract 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.