# Effects of rutin on renal function, oxidative stress and fibrosis in animal models of diabetic nephropathy: a systematic review and meta-analysis

**Authors:** Zongtao Li, Yashi Wang, Die Fang, Yiman Wang, Hongzhe Han, Xueqin Zhang, Zhiqiang Chen

PMC · DOI: 10.3389/fphar.2026.1771010 · Frontiers in Pharmacology · 2026-02-23

## TL;DR

This study shows that rutin, a natural flavonoid, improves kidney function and reduces damage in diabetic nephropathy animal models by targeting multiple pathways.

## Contribution

The first systematic review and meta-analysis quantifying rutin's renoprotective effects in preclinical diabetic nephropathy models.

## Key findings

- Rutin significantly reduced serum creatinine, blood urea nitrogen, and urinary protein, indicating improved kidney function.
- Rutin lowered oxidative stress markers and profibrotic indicators like transforming growth factor-β.
- Rutin also reduced blood glucose and lipid levels in diabetic nephropathy models.

## Abstract

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.

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-h 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.

Thirteen studies involving 318 animals met the inclusion criteria. Meta-analysis showed that rutin significantly reduced serum creatinine, blood urea nitrogen, and 24-h 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.

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.

https://inplasy.com/inplasy-2025-11-0085, identifier INPLASY2025110085.

## Linked entities

- **Chemicals:** rutin (PubChem CID 5280805)
- **Diseases:** diabetic nephropathy (MONDO:0005016)

## Full-text entities

- **Genes:** Nfe2l2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 83619], Traf6 (TNF receptor associated factor 6) [NCBI Gene 311245], Hdac1 (histone deacetylase 1) [NCBI Gene 297893], Mok (MOK protein kinase) [NCBI Gene 362787] {aka Rage}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Timp1 (TIMP metallopeptidase inhibitor 1) [NCBI Gene 116510] {aka TIMP-1, Timp}, Myd88 (MYD88, innate immune signal transduction adaptor) [NCBI Gene 301059], Nox4 (NADPH oxidase 4) [NCBI Gene 85431], Fn1 (fibronectin 1) [NCBI Gene 25661] {aka FIBNEC, fn-1}, Irak4 (interleukin-1 receptor-associated kinase 4) [NCBI Gene 300177], Aqp3 (aquaporin 3 (Gill blood group)) [NCBI Gene 65133], Avpr2 (arginine vasopressin receptor 2) [NCBI Gene 25108], Vegfa (vascular endothelial growth factor A) [NCBI Gene 83785] {aka VEGF-A, VEGF111, VEGF164, VPF, Vegf}, Agt (angiotensinogen) [NCBI Gene 24179] {aka ANRT, Ang, AngII, PAT}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, Tlr4 (toll-like receptor 4) [NCBI Gene 29260], Il18 (interleukin 18) [NCBI Gene 29197] {aka IL-1 gamma, IL-18}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Smad3 (SMAD family member 3) [NCBI Gene 25631] {aka Madh3, Smad 3, mad3}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, Nqo1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 24314] {aka Dia4}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Aqp2 (aquaporin 2) [NCBI Gene 25386] {aka AQP-2, aquaporin-2}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56718] {aka Frap1, RAFT1}, Egfr (epidermal growth factor receptor) [NCBI Gene 24329] {aka ERBB1, ErbB-1, Errp}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Renbp (renin binding protein) [NCBI Gene 81759], Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 287362] {aka Cias1}, Src (SRC proto-oncogene, non-receptor tyrosine kinase) [NCBI Gene 83805], Hmox1 (heme oxygenase 1) [NCBI Gene 24451] {aka HEOXG, Heox, Hmox, Ho-1, Ho1, hsp32}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Ephb1 (Eph receptor B1) [NCBI Gene 24338] {aka Ephb2, Erk, elk}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 116554] {aka JNK}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Pik3cb (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta) [NCBI Gene 85243], Smad2 (SMAD family member 2) [NCBI Gene 29357] {aka Madh2}
- **Diseases:** lipid abnormalities (MESH:D011017), hyperplasia (MESH:D006965), Diabetic Kidney Disease (MESH:D003928), Scr (MESH:D012713), Kidney Disease (MESH:D007674), ESRD (MESH:D007676), acidosis (MESH:D000138), Glomerulosclerosis (MESH:D005921), hypertension (MESH:D006973), proteinuria (MESH:D011507), renal decline (MESH:D006030), metabolic abnormalities (MESH:D008659), renal structural destruction (MESH:D020914), tubular (MESH:D000230), Diabetes (MESH:D003920), metabolic disturbances (MESH:D024821), Hyperglycemia (MESH:D006943), -fibrosis (MESH:D005355), inflammation (MESH:D007249), Syndrome (MESH:D013577), mitochondrial dysfunction (MESH:D028361)
- **Chemicals:** UTP (MESH:D014544), ROS (MESH:D017382), flavonoid (MESH:D005419), Creatinine (MESH:D003404), Glu (MESH:D005947), GSH (MESH:D005978), rutinose (MESH:C539209), urea nitrogen (MESH:C530477), lipid (MESH:D008055), MDA (MESH:D008315), alloxan (MESH:D000496), -Rhamnosyl-Glucosyl (-), blood glucose (MESH:D001786), cholesterol (MESH:D002784), STZ (MESH:D013311), Quercetin (MESH:D011794), uric acid (MESH:D014527), 3-Rhamnosyl-Glucosyl Quercetin (MESH:D012431), aldosterone (MESH:D000450), TG (MESH:D014280), ammonia (MESH:D000641)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU)

## Full text

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## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12968236/full.md

## References

54 references — full list in the complete paper: https://tomesphere.com/paper/PMC12968236/full.md

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Source: https://tomesphere.com/paper/PMC12968236