Neuroprotective Effects of Carica papaya in Experimental Models of Neurodegeneration: A Comprehensive Review

Carica papaya (C. papaya) has long been used in traditional medicine, and experimental studies have reported neuroprotective effects across several models; however, the available evidence is distributed across different plant parts, preparations, and experimental systems. This review synthesizes existing evidence from in vitro and in vivo studies assessing the neuroprotective, antioxidant, anti-inflammatory, and neuromodulatory effects of C. papaya extracts derived from seeds, leaves, pulp, fruit, and fermented preparations. A comprehensive literature search of PubMed, Scopus, Web of Science, Google Scholar, and ScienceDirect identified relevant studies across multiple experimental models through 22 September 2026. Findings show that in Alzheimer's disease (AD) models, aluminum-induced neurotoxicity, D-galactose-induced brain aging, 6-hydroxydopamine (6-OHDA)-mediated oxidative damage, and chemically induced neurotoxicity (cyclophosphamide, acrylamide, and fluoride), C. papaya preparations were associated with improvements in selected cognitive, behavioral, biochemical, and oxidative-stress-related outcomes across the included experimental models. Toxicity studies generally reported no mortality within the tested dose ranges; however, behavioral, biochemical, and mild histopathological alterations were observed in some studies, particularly at higher doses, indicating that safety may vary according to extract type, dose, and duration of exposure. Overall, the available preclinical evidence suggests that C. papaya preparations may affect multiple pathways relevant to oxidative-stress-associated neurodegeneration. However, further mechanistic studies, bioactive compound isolation, pharmacokinetic assessments, and well-designed clinical trials are essential to support its future therapeutic development.