SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Renal Pharmacology
Effects of rutin on renal function, oxidative stress and fibrosis in animal models of diabetic nephropathy: a systematic review and meta-analysis
Provisionally accepted
- Hebei University of Chinese Medicine, Shijiazhuang, China
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Background: Diabetic nephropathy is a major microvascular complication of diabetes and a leading cause of end-stage renal disease, while effective disease-modifying therapies remain limited. Rutin, a naturally occurring flavonoid with antioxidant and anti-inflammatory properties, has shown renoprotective effects in experimental diabetic nephropathy; however, its overall efficacy has not been quantitatively synthesized. This study aimed to systematically evaluate the preclinical effects of rutin in animal models of diabetic nephropathy. Methods: A systematic review and meta-analysis of preclinical animal studies was conducted following PRISMA guidelines and prospectively registered in INPLASY (INPLASY2025110085). Six English and Chinese databases, including PubMed and Web of Science, were searched from inception to November 2025. Studies assessing rutin monotherapy in diabetic nephropathy models were included. Primary outcomes were serum creatinine, blood urea nitrogen, and 24-hour urinary protein. Secondary outcomes included blood glucose, lipid parameters, oxidative stress markers, and fibrosis-related indicators. Risk of bias was assessed using SYRCLE's tool, and pooled effect sizes were calculated using standardized mean differences with Stata 17.0. Results: Thirteen studies involving 318 animals met the inclusion criteria. Meta-analysis showed that rutin significantly reduced serum creatinine, blood urea nitrogen, and 24-hour urinary protein levels, indicating improved renal function. Rutin also lowered blood glucose and lipid levels. In addition, rutin attenuated oxidative stress by reducing reactive oxygen species and malondialdehyde while enhancing endogenous antioxidant defenses. Profibrotic markers, including transforming growth factor-β, were also significantly decreased. Sensitivity analyses demonstrated that the pooled estimates were not driven by any single study, while subgroup analyses suggested that differences in study characteristics may partially contribute to heterogeneity without altering the overall direction of effects. Conclusion: This meta-analysis provides quantitative preclinical evidence that rutin exerts broad renoprotective effects in experimental diabetic nephropathy through coordinated regulation of metabolic disturbance, oxidative stress, and fibrosis. These findings support rutin as a potential multi-target candidate for further mechanistic investigation and translational research. Systematic Review Registration: This study was prospectively registered in INPLASY (registration number: INPLASY2025110085).
Keywords: animal model, diabetic nephropathy, Meta-analysis, Oxidative Stress, Preclinical study, renal fibrosis, Rutin
Received: 18 Dec 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Li, Wang, Fang, Wang, Han, Zhang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xueqin Zhang
Zhiqiang Chen
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