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…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in computer models (in silico), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health. Reported size: 1,443 participants or records.
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