Efficacy and Mechanisms of Yuye Decoction for Diabetic Nephropathy: A Meta-Analysis and In Silico Study

Yuye decoction (YYD), a traditional Chinese medicinal formula, has the potential to improve renal function and alleviate symptoms in diabetic nephropathy (DN). This study aimed to evaluate the potential clinical effects and explore the pharmacological mechanisms of YYD in DN using meta-analysis and in silico approaches.

We conducted a systematic review of randomized controlled trials (RCTs) on YYD for treating DN, searching databases including China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang Data, VIP, PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar, with a cutoff date of June 2025. Eligible RCTs compared YYD combined with standard Western treatment with Western treatment alone. The primary outcome was renal function improvement, while secondary outcomes included overall clinical efficacy, glycemic control, and adverse events. Network pharmacology and molecular dynamics simulations were conducted to explore potential mechanisms.

Thirteen RCTs involving 961 patients were included. Compared with conventional treatment alone, YYD combination therapy was associated with reductions in serum creatinine (WMD = -11.64, 95% CI [-19.04, -4.24]), blood urea nitrogen (WMD = -0.59, 95% CI [-0.93, -0.25]), and 24-hour urinary protein excretion (MD = -39.59, 95% CI [-62.07, -17.11]). An increased overall clinical efficacy rate was observed as a secondary outcome (RR = 1.43, 95% CI [1.31, 1.56]). Network pharmacology suggested that YYD may modulate inflammation-, metabolism-, and fibrosis-related pathways via targets such as SRC, PIK3R1, and PIK3CA. Molecular dynamics simulations indicated stable binding between Bifendate and SRC kinase.

These findings suggest that YYD may exert renoprotective effects through multi-target and multi-pathway mechanisms, particularly involving inflammatory regulation, metabolic processes, and fibrosis inhibition. However, the included studies showed variability in methodological quality and sample size, which may affect the robustness of the conclusions. Furthermore, the in silico results require experimental validation to confirm their biological relevance.

YYD combined with conventional therapy may improve renal function in patients with DN. Nevertheless, the overall certainty of the evidence remains limited, and further large-scale, high-quality randomized trials and mechanistic studies are warranted.