Effects of Resveratrol on MCP-1/CCL2-Related Readouts in Preclinical Animal Models: A Systematic Review and...

Background: Resveratrol is a plant-derived polyphenol with reported anti-inflammatory activity, and the MCP-1/CCL2 axis is a key mediator of monocyte recruitment and inflammatory tissue remodeling. Although individual preclinical studies have examined resveratrol effects on MCP-1/CCL2-related outcomes, the overall in vivo evidence has not been quantitatively synthesized. This systematic review and meta-analysis evaluated whether resveratrol treatment is associated with reduced MCP-1/CCL2-related inflammatory readouts in animal models. Methods: The protocol was registered in PROSPERO (CRD420261339126), and reporting followed the PRISMA 2020 statement. PubMed was searched from inception to 12 March 2026, with additional reference-list screening. Eligible studies were in vivo animal experiments comparing resveratrol-treated and control groups with extractable quantitative MCP-1/CCL2-related outcomes. Effect sizes were calculated as Hedges' g with 95% confidence intervals and pooled using random-effects models fitted by restricted maximum likelihood. Subgroup, sensitivity, cumulative, influence, funnel-plot, dose meta-regression, and SYRCLE-based risk-of-bias analyses were conducted. Results: Twenty-seven studies contributing 29 analyzable datasets were included. The overall pooled effect was -3.74 (95% confidence interval, -4.50 to -2.98), indicating lower MCP-1/CCL2-related readouts in resveratrol-treated groups than in controls, with substantial heterogeneity (I2 = 78.9%). The negative association was driven mainly by rat and mouse datasets, whereas the piglet estimate was directionally opposite and the rabbit estimate came from a single dataset. Funnel-plot inspection suggested asymmetry, and dose meta-regression did not significantly explain between-study variation (slope = -0.17, p = 0.482). Leave-one-out and cumulative analyses indicated directional stability but did not resolve the underlying heterogeneity. Conclusions: These preclinical data indicate lower MCP-1/CCL2-related readouts after resveratrol treatment, but high heterogeneity, PubMed-only retrieval, and pharmacokinetic limitations limit direct clinical inference.