Antioxidant Status of Natural Products in Neurodegenerative Disorders: A Comprehensive Review

Neurodegenerative Disorders (NDDs), including Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Amyotrophic Lateral Sclerosis (ALS), Huntington’s Disease (HD), and Multiple Sclerosis (MS) represent a growing global health burden, affecting hundreds of millions of individuals worldwide. A central mechanistic driver of neurodegeneration is oxidative stress, defined as an imbalance between Reactive Oxygen Species (ROS) generation and endogenous antioxidant defense systems. Natural products derived from plants, fungi, and marine organisms harbor a rich array of antioxidant phytochemicals-including polyphenols, flavonoids, alkaloids, terpenoids, and Vitamins-whose neuroprotective properties are the subject of intense scientific investigation. This review aimed to comprehensively evaluate the antioxidant status and neuroprotective mechanisms of natural products specifically relevant to neurodegenerative disorders, synthesizing evidence from in vitro, in vivo, and clinical research. A systematic literature search was conducted across PubMed, Consensus, and supplemental databases using relevant MeSH terms and keywords, including “natural antioxidants,” “neurodegenerative disorders,” “oxidative stress,” “Nrf2 pathway,” and specific compound names. Priority was given to studies published between 2020 and 2026, with up to five seminal older works included were essential. Evidence indicates that natural antioxidants, such as curcumin, resveratrol, quercetin, Epigallocatechin-3-Gallate (EGCG), baicalein, withanolides, bacosides, and ginsenosides exert neuroprotection through multiple mechanisms: direct ROS scavenging, activation of the Nrf2-Keap1-Antioxidant Response Element (ARE) antioxidant pathway, mitochondrial protection, modulation of neuroinflammatory cascades, and inhibition of pathological protein aggregation (amyloid-β and α-synuclein). Despite robust preclinical data, clinical translation remains challenged by poor bioavailability, rapid metabolism, and limited long-term human trial data. Natural product-derived antioxidants represent a scientifically promising, multi-targeted strategy for the prevention and adjunctive treatment of neurodegenerative disorders. Advances in nanotechnology-based delivery systems and standardized formulations are expected to bridge the gap between preclinical success and clinical efficacy. Rigorous clinical trials with standardized dosing are urgently needed.