Genistein in the Treatment of Alzheimer’s Disease: A Systematic Review and Meta-Analysis of Preclinical Studies

Genistein is a phytoestrogen distributed in fruits, seeds, and vegetables that holds great promise against a variety of Aβ-induced damage. However, the exact molecular mechanisms underlying the neuroprotective effects of genistein on Alzheimer's disease (AD) remain unknown. Here, we assessed the potential mechanisms and effectiveness of genistein for AD treatment using a systematic review and meta-analysis of preclinical trials. Preclinical studies published prior to September 21, 2022 were retrieved from Web of Science, PubMed, CNKI, and CBM. The CAMARADES list was used to evaluate the quality of included studies. Meta-analyses of AD pathology and animal model studies evaluating parameters and other indicators were performed. Overall, 14 articles involving more than 800 animals were included. We analyzed in vivo and in vitro studies about genistein's effects, including antiamyloidogenesis, antioxidation, antiapoptosis, inhibition of inflammation, and improvement of the lipid composition of neurons. In behavioral assessment, genistein significantly improved the time in the platform quadrant (I2 = 76%, p < 0.00001) in the Morris water maze test, spontaneous alternation behavior (I2 = 94%, p < 0.00001) in Y-maze tests, and the time entering the dark compartment (I2 = 81%, p = 0.02) in a single-trial passive avoidance test. Genistein therapy in rodent models of AD indicates it reduces Aβ deposition and improves memory in preclinical trials.