Preclinical Evidence and Potential Mechanisms of Ellagic Acid in Animal Models of Parkinson’s Disease: A Systematic Review and Meta-Analysis

Ellagic acid (EA), a natural polyphenol, has demonstrated potential in preclinical Parkinson’s disease (PD) research; however, a systematic synthesis of the evidence has been lacking. As the first preclinical meta-analysis evaluating EA in PD animal models, this study aimed to synthesize existing evidence and explore potential mechanisms. We systematically searched six databases until February 2025, ultimately including 13 controlled trials. Meta-analysis results demonstrated that compared to PD controls, EA significantly improved motor function, protected dopaminergic neurons in the substantia nigra, and reduced oxidative stress (e.g., MDA) and neuroinflammation (e.g., IL-1β, TNF-α). Subgroup analyses suggested that intragastric delivery and interventions longer than one week yielded stronger effects. Based on interspecies scaling, a human-equivalent starting dose of 252 mg/day was derived for Phase I clinical trials. These findings support EA as a neuroprotective natural compound, warranting further validation in future studies.