Persea americana Seed Extract Mitigates 3-NPA-Induced Neurotoxicity in a Rat Model of Huntington’s Disease via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms

Introduction: The global rise in age-related neurodegenerative disorders, including Alzheimer’s, Huntington’s, and Parkinson’s diseases, represents a major health challenge, as existing therapies are largely symptomatic and fail to prevent progressive neuronal loss. Consequently, increasing attention has focused on natural compounds with neuroprotective and antioxidant properties. This study investigated the neuroprotective potential of Persea americana (avocado) seed extract (ASD) against 3-nitropropionic acid (3-NPA)-induced neurotoxicity, with emphasis on its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

Methods: Methanol-extracted P. americana seed powder was orally administered to thirty-six male Wistar rats (150–200 g), randomly divided into six groups (n = 6): control, 3-NPA only, 3-NPA + 300 mg/kg ASD, 3-NPA + 600 mg/kg ASD, 300 mg/kg ASD only, and 600 mg/kg ASD only. The extract was administered for one week prior to 3-NPA exposure (10 mg/kg, intraperitoneally) and continued for two additional weeks. Behavioural, biochemical, and histopathological evaluations were performed. Oxidative stress indices, antioxidant enzyme activities, and succinate dehydrogenase (SDH) activity were measured, alongside gene expression analyses of Keap1, NF-κB, TNF-α, COX-2, Bad, and Bcl2.

Results: Persea americana seed extract significantly attenuated 3-NPA-induced behavioural deficits and restored SDH and antioxidant enzyme activities. The extract reduced lipid peroxidation and markedly downregulated the expression of NF-κB, TNF-α, COX-2, Bad, and Keap1, while upregulating the anti-apoptotic gene Bcl2. Histopathological examination further demonstrated reduced neuronal degeneration in extract-treated groups.

Conclusion: These findings indicate that Persea americana seed extract confers substantial neuroprotection against 3-NPA-induced neurotoxicity through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. The results suggest that the extract holds promise as a natural therapeutic candidate for oxidative stress-associated neurodegenerative disorders.