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Investigating Neuroprotective Effects of Berberine on Mitochondrial Dysfunction and Autophagy Impairment in Parkinson’s Disease

Hae-Rim Cha,Jin-Seok Kim,Jin-Hyeob Ryu,Hyun-Jeong Cho

Published 2025 in International Journal of Molecular Sciences

ABSTRACT

Parkinson’s disease (PD) is a common neurodegenerative disorder with substantial global impact. Although current therapies can provide symptomatic relief, they are often associated with high costs and adverse effects. Natural compounds with a history of traditional medicinal use have emerged as promising alternatives. In this study, we investigated the therapeutic potential and underlying mechanisms of berberine in both cellular and animal models of PD. In vitro, SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA) exhibited decreased viability and increased oxidative stress, both of which were significantly alleviated by berberine treatment based on cell viability assays and DCFH-DA staining. Western blot analysis revealed that berberine modulated the AMPK–PGC-1α–SIRT1 signaling pathway and restored the expression of autophagy-related proteins LC3B and P62, suggesting that berberine could improve mitochondrial function and autophagy balance. In vivo studies using a 6-OHDA-induced PD mouse model further confirmed these effects, showing that berberine could improve motor function and lead to molecular changes consistent with in vitro studies. Additionally, safety evaluations indicated no significant hepatotoxicity based on AST and ALT levels. Body weight also remained stable throughout treatment. Collectively, our findings suggest that berberine can not only alleviate PD-related symptoms but also target key pathological mechanisms, supporting its potential as a therapeutic candidate for PD and other neurodegenerative diseases.

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