Meta-analysis of salidroside in diabetic nephropathy animal models shows mixed renal outcomes with high heterogeneity.

BackgroundSalidroside (SAL), a principal bioactive constituent of Rhodiola species, has demonstrated renoprotective potential in diabetic nephropathy (DN). However, the magnitude of SAL’s effects on renal functional outcomes and key mechanistic biomarkers remains unclear.MethodsThis study was conducted in accordance with PRISMA 2020 guidelines. A comprehensive search was performed in PubMed, Embase, Web of Science, the Cochrane Library, and major Chinese databases from inception to 24 November 2025. Preclinical studies evaluating SAL monotherapy in DN animal models were included. Risk of bias was assessed using the SYRCLE tool and summarized in Review Manager (RevMan) 5.4. Meta-analysis was performed using Stata 18.0.ResultsFourteen studies (257 animals) were included. Pooled estimates suggested SAL was associated with improved renal function and lower blood glucose levels, despite substantial heterogeneity. Specifically, SAL-treated groups exhibited lower serum creatinine (Hedges’ g = −3.83, 95% CI -5.34 to −2.31), blood urea nitrogen (Hedges’ g = −2.90, 95% CI -4.50 to −1.30), and kidney index (Hedges’ g = −2.68, 95% CI -4.71 to −0.65) than controls. SAL also enhanced antioxidant capacity and suppressed inflammatory mediators. For TGF-β1, the pooled estimate did not reach statistical significance and showed heterogeneity, while sensitivity analyses suggested the direction of effect may favor SAL.ConclusionSAL provides preliminary preclinical evidence of renoprotection in DN models, potentially by modulating oxidative stress and inflammation. However, interpretation is constrained by high heterogeneity and possible small-study or publication effects. Anti-fibrotic effects, particularly TGF-β1, remain sensitive to methodology, necessitating caution. Rigorous, pre-registered animal trials are required to strengthen the evidence base.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251239960, identifier CRD420251239960.