NEUROPROTECTIVE SECONDARY METABOLITES: MECHANISMS AND THERAPEUTIC POTENTIAL IN NEURODEGENERATIVE DISEASES

Abstract

Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and cerebral ischemia, represent an escalating global health crisis with limited effective therapies. The multifactorial pathogenesis of these disorders, encompassing protein aggregation, oxidative stress, neuroinflammation, and mitochondrial dysfunction, necessitates therapeutic approaches that target multiple pathways. Plant secondary metabolites have emerged as promising neuroprotective agents, offering multi-targeted mechanisms and favorable safety profiles. This review comprehensively examines the neuropharmacology of key secondary metabolites, including huperzine A, curcumin, resveratrol, epigallocatechin gallate (EGCG), and ginsenosides, focusing on their mechanisms against neurodegeneration. We critically evaluate evidence for neuroprotection through acetylcholinesterase inhibition, antioxidant and anti-inflammatory effects, mitochondrial protection, and modulation of protein aggregation pathways. Furthermore, we assess the therapeutic potential of these compounds in Alzheimer's disease, Parkinson's disease, and cerebral ischemia, evaluating preclinical and clinical evidence. Polyphenols, including curcumin and resveratrol, exert significant inhibitory effects on the NF-κB pathway, making them promising candidates for treating neurological disorders. Despite promising findings, challenges including bioavailability, blood-brain barrier penetration, and clinical translation persist. This review identifies research gaps and discusses emerging strategies for optimizing neuroprotective natural products for clinical application.