Neuroprotective Effects of Epicatechin against Oxidative Stress-Induced Cognitive Impairment: A Systematic Review and Meta-Analysis

Abstract

Oxidative stress is crucial in the pathogenesis of cognitive impairment and neurodegenerative diseases. Epicatechin, a natural flavanol abundant in cocoa, is a promising neuroprotective agent because of its antioxidant and anti-inflammatory properties. This meta-analysis aimed to evaluate the efficacy of epicatechin in mitigating oxidative stress-induced cognitive impairment in animal models. A systematic review of in vivo rodent studies was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including studies reporting cognitive- and brain-based biochemical outcomes following epicatechin administration. The results indicated that epicatechin significantly improved the cognitive performance of rodents in the Morris water maze test, including improved spatial learning (reduced escape latency), memory retention (increased time spent in the target quadrant), and memory precision (increased island crossings). At the molecular level, epicatechin treatment increased the expression or activity of superoxide dismutase, catalase, and nuclear factor erythroid 2-related factor 2 and reduced the levels of nitric oxide, malondialdehyde, tumor necrosis factor-alpha, and interleukin-1 beta. These findings support the role of epicatechin in enhancing antioxidant defense and modulating neuroinflammation. Collectively, the results highlight that epicatechin has the therapeutic potential for preventing or mitigating oxidative stress-related cognitive dysfunction.

Keywords: Morris water maze; antioxidant defense system; cognitive impairment; epicatechin; meta-analysis; neuroinflammation; oxidative stress.

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PRISMA flowchart of the study selection process (Created in BioRender. Cho, I. (2025) https://BioRender.com/t7w7k4j).

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Meta-analysis results of Morris water maze test: (A) escape latency, (B) time spent in the target quadrant, (C) island crossings, and (D) swimming speed.

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Meta-analysis results of antioxidant defense system markers: (A) SOD (superoxide dismutase), (B) CAT (catalase), and (C) Nrf2 (nuclear factor erythroid 2-related factor 2).

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Meta-analysis results of oxidative stress markers: (A) NO (nitric oxide) and (B) MDA (malondialdehyde).

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Meta-analysis results of neuroinflammation markers: (A) NF-κB (nuclear factor kappa B), (B) IL-1β (interleukin-1 beta), and (C) TNF-α (tumor necrosis factor-alpha).