Protective effects of resveratrol in animal models of chronic obstructive pulmonary disease: a preclinical systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to quantitatively evaluate the protective effects of resveratrol (RES) in animal models of chronic obstructive pulmonary disease (COPD) and systematically summarize its potential molecular regulatory mechanisms. METHODS: Eight databases were systematically searched for eligible animal studies from inception to February 2026. Methodological quality was assessed using the SYRCLE tool. Meta-analyses were performed using Review Manager 5.4 and Stata 18.0. RESULTS: This meta-analysis included 14 preclinical studies involving a total of 377 experimental animals (experimental group: 239; control group: 138). The results showed that RES significantly alleviated airflow limitation and improved pulmonary function in COPD models (FEV0.3/FVC: SMD = 1.79, 95% CI [0.94, 2.63], P < 0.0001; lung compliance: SMD = 1.63, 95% CI [0.92, 2.33], P < 0.00001). Regarding inflammatory regulation, RES significantly reduced serum levels of pro-inflammatory cytokines, including TNF-α (SMD = -3.18, 95% CI [-4.92, -1.44], P = 0.0003), IL-8 (SMD = -2.79, 95% CI [-4.71, -0.86], P = 0.005), and IL-6 (SMD = -1.28, 95% CI [-2.03, -0.53], P = 0.0008). At the pulmonary level, RES also downregulated both the protein (SMD = -6.57, 95% CI [-9.94, -3.20], P = 0.0001) and mRNA (SMD = -1.48, 95% CI [-2.22, -0.73], P = 0.0001) expression of TNF-α in lung tissue. Furthermore, RES attenuated oxidative stress-related injury in lung tissue, as reflected by decreased malondialdehyde (MDA) levels (SMD = -2.64, 95% CI [-3.93, -1.35], P < 0.0001) and increased superoxide dismutase (SOD) activity (SMD = 3.52, 95% CI [1.22, 5.82], P = 0.003). Substantial heterogeneity was observed in some pooled outcomes, and Egger's test suggested potential publication bias. CONCLUSION: Current preclinical evidence suggests that RES may improve pulmonary function and attenuate inflammatory responses and oxidative stress-related injury in COPD animal models. However, these findings should be considered preliminary, and further well-designed studies are needed to validate the translational relevance of RES in COPD. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261309405, identifier CRD420261309405.