Efficacy and potential pharmacological mechanism of Astragalus-Salvia miltiorrhiza combination in diabetic nephropathy: integrating meta-analysis, network pharmacology, molecular docking, and experimental validation.

Abstract

Background: Diabetic nephropathy (DN) is a diabetes mellitus (DM)-induced complication that poses high morbidity and mortality risks. The Astragalus and Salvia miltiorrhiza couplet medicines (AS) are commonly employed in DN clinical treatment in China, but their clinical efficacy and potential pharmacological mechanisms are yet to be evaluated.

Material and methods: A meta-analysis of 15 studies involving 1,443 patients was conducted. Furthermore, network pharmacology predicted components and targets, which were verified by molecular docking and in vivo validation.

Results: In our meta-analysis, AS notably elevated clinical outcomes and renal function among patients with DN. Meanwhile, when the treatment duration exceeds 12 weeks, AS demonstrated a significant reduction in fasting blood glucose levels, indicating a time-dependent effect. Moreover, based on network pharmacology results, AS likely enhanced clinical outcomes by interacting with vital signaling pathways, including PI3K/Akt, MAPK, and NF-kappa B. Molecular docking studies have confirmed that PTGS2, the key therapeutic target of AS, can be closely combined with bioactive components GLY, quercetin, apigenin, and daidzein. Additionally, in vivo experiments have corroborated that AS can ameliorate renal function, UACR, and biomarkers associated with iron metabolism, such as GPX4, PTGS2, FTH1, and FTL1.

Conclusion: Through rigorous experimental validation, our study demonstrates AS's significant clinical efficacy in managing DN. Specifically, AS has been shown to enhance renal function, ameliorate renal fibrosis, and positively influence iron metabolism. Despite these promising outcomes, future research with a larger sample size must be conducted to further substantiate these findings.