Resveratrol delays the progression of diabetic nephropathy through multiple pathways: A dose-response meta-analysis based on animal models

Abstract

Objective: Accumulating experimental evidence has shown that resveratrol supplementation is effective for treating diabetic nephropathy (DN) in animal models. In this systematic review and meta-analysis, we assessed the effects and multiple mechanisms of resveratrol in animal models of DN.

Methods: Before September 2023, preclinical literature was systematically searched and screened across PubMed, Web of Science, EMBASE, and the Cochrane Library. Forty-two studies were included, and the risk of bias tool from SYRCLE was used to assess the methodological quality. Pooled overall effect sizes of the results were generated by STATA 16.0.

Results: The overall results provide preliminary evidence that the consumption of resveratrol can significantly reduce the mesangial index, glomerular basement membrane thickness, glomerular hypertrophy, serum creatinine, blood urea nitrogen, 24-h urinary protein, blood glucose, kidney index, total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. In contrast, the levels of albumin and high-density lipoprotein cholesterol are significantly increased. However, resveratrol did not significantly reduce creatinine clearance or glycated hemoglobin levels. Dose-response analysis revealed that resveratrol was most effective at improving kidney function and reducing DN when administered at lower doses of ≤15 mg/kg/day or higher doses of 100-200 mg/kg/day, with significant improvements in biochemical kidney injury markers and a better effect on dysglycemia.

Conclusions: The benefits of resveratrol in DN are likely due to its anti-inflammatory, antioxidant, metabolic regulatory, and autophagy-promoting effects. To confirm these findings for clinical use, further large-scale, long-term, high-quality preclinical trials are warranted to accurately assess the anti-DN effects and safety of resveratrol.

Keywords: animal model; diabetic nephropathy; meta‐analysis; renal pathology; resveratrol; systematic review.

FIGURE 1

The chemical structure of resveratrol.

FIGURE 2

Chart of selection process following selection criteria.

FIGURE 3

Study characteristics of eligible studies. Distribution of (A) model species and strains, (B) sex/gender, (C) methods of model establishment, and (D) duration of intervention.

FIGURE 4

GRADE evidence summary table.

FIGURE 5

Forest plot: Effect of resveratrol on pathological indicators.

FIGURE 6

Forest plot: Effect of resveratrol on kidney functional parameters. (A) Overall effect of resveratrol on Scr. (B) Overall effect of resveratrol on BUN. (C) Overall effect of resveratrol on CCr.

FIGURE 7

Forest plot: Effect of resveratrol on 24hUTP.

FIGURE 8

Forest plot: Effect of resveratrol on blood sugar indicators. (A) The overall effect of resveratrol on BG. (B) The overall effect of resveratrol on HbA1c.

FIGURE 9

Forest plot: Effect of resveratrol on KI.

FIGURE 10

Dose–response radar maps of (A) resveratrol therapy and BG, (B) resveratrol therapy and Scr, (C) resveratrol therapy and BUN, and (D) resveratrol therapy and 24hUTP.