Renal protective effects and mechanisms of tripterygium glycosides in animal models of diabetic nephropathy: a preclinical systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus (DM), clinically characterized by progressive loss of renal function and/or persistent albuminuria. Tripterygium glycosides (TGs) have been used in the clinical treatment of DN. There are many animal experiments on TGs intervention in DN, but the evidence from these studies remains unclear. OBJECTIVE: This study aims to summarize the renal protective effects and mechanisms of TGs in DN animal models. METHODS: A comprehensive search of animal studies from the inception of 8 databases to May 2026 was conducted. The bias risk of the included studies was evaluated using SYRCLE's risk of bias tool. The evidence certainty of the outcomes was assessed using the GRADE method. The meta-analysis was conducted using RevMan 5.4 and Stata 17.0 software. RESULTS: A total of 55 studies involving 1,481 animals were included. Analysis showed that TGs significantly reduced Scr, BUN, 24h UP, 24h UA, 24h UMA, KW, KI, BG, TC, TG, MGA, and MGV levels while increasing ALB levels, but did not significantly affect ALT, AST, WBC, RBC, or PLT levels. Additionally, TGs modulated the expression of most markers related to oxidative stress, inflammation, renal fibrosis, podocyte injury, and autophagy. Subgroup analysis by intervention time suggested that longer intervention time (>8 weeks) increased ALT levels. Dose-effect-toxicity analysis indicated that medium doses (6-9 mg/kg/day) balanced efficacy and safety, while high doses (>9 mg/kg/day) elevated AST levels and reduced WBC levels. The methodological quality was moderate to low, and the evidence quality was moderate to very low. CONCLUSION: TGs have a favorable renal protective effect on DN animals, which can improve renal function, basic indicators, glucose and lipid metabolism, and renal tissue pathological changes. For safety reasons, the intervention time (≤8 weeks) and dose (6-9 mg/kg/day) should be strictly restricted to prevent potential hepatotoxicity and hematological toxicity. Its protective mechanisms mainly include anti-oxidative stress, relieving inflammation, inhibiting renal fibrosis, alleviating podocyte injury, and regulating autophagy. Given the limited methodological and evidential quality of existing studies, more high-quality studies are needed to validate this conclusion. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/, Identifier CRD420251251933.