Neuroprotective activity of mung bean (Vigna radiata) coat extract via AMPK-dependent autophagy in Alzheimer’s and Parkinson’s models

Abstract

Objective Alzheimer’s disease (AD) and Parkinson’s disease (PD) are major age-related neurodegenerative disorders that currently lack effective disease-modifying therapies. This study investigated the neuroprotective potential and underlying mechanisms of natural products derived from medicine-food homology (MFH) plants, with a focus on autophagy modulation in AD and PD models. Methods Twenty MFH plant extracts were screened using the Caenorhabditis elegans amyloid-β peptide (Aβ) proteotoxicity model CL4176. Mung bean coat extract (MBCE) was identified as a promising candidate and subsequently evaluated in transgenic C. elegans models of AD and PD to assess its effects on pathological protein aggregation, oxidative stress, and behavioral impairments. Autophagy activation was assessed using fluorescence microscopy and lysosomal activity assays. MBCE’s effects on protein aggregation and apoptosis were further validated in rat pheochromocytoma (PC-12) cells. Mechanistic insights were obtained through pharmacological inhibition of autophagy and AMP-activated protein kinase (AMPK) signaling, as well as AMPK knockdown. A bioactivity-guided analysis was performed to identify the major active constituents of MBCE. Results MBCE significantly alleviated Aβ- and microtubule-associated protein tau (Tau)-induced neurotoxicity in C. elegans by reducing protein aggregation, oxidative stress, and locomotor deficits. It also suppressed α-synuclein accumulation and preserved dopaminergic neuron integrity in PD models. MBCE enhanced stress resistance and activated autophagy, as evidenced by increased autophagosome formation, decreased sequestosome-1 (p62/SQSTM1) levels, and elevated lysosomal activity. RNA interference knockdown assays confirmed that MBCE’s neuroprotective effects were dependent on autophagy activation. In PC-12 cells, MBCE similarly induced AMPK-mediated autophagy, reduced the accumulation of disease-related proteins, and mitigated cytotoxicity. Notably, genetic knockdown or pharmacological inhibition of AMPK or autophagy abolished these effects. Vitexin and isovitexin, the main constituents of MBCE, were identified as key contributors to its autophagy-inducing and neuroprotective activities. Conclusion MBCE mitigates neurodegenerative pathology in AD and PD models by promoting AMPK-dependent autophagy and reducing toxic protein aggregation. These findings support the potential of MBCE as a functional food-based therapeutic strategy for neurodegenerative diseases. Please cite this article as: Chen ZX, Wang FP, Li YP, Wu MT, Chen MY, Huang FH, Wen YP, Wang XH, Yu L, Wu JM, Wu AG, Zhou XG. Neuroprotective activity of mung bean ( Vigna radiata ) coat extract via AMPK-dependent autophagy in Alzheimer’s and Parkinson’s models. J Integr Med . 2025; Epub ahead of print.