Medicine-food homology bioactives in Parkinson's disease: multi-target oxidative-stress modulation and translation to dietary supplements.

Abstract

No proven disease-modifying therapy exists for Parkinson's disease (PD), and prior single-target antioxidants have shown limited, unsustained benefits, highlighting the need for safe multi-target strategies. To synthesize how medicine-food homology (MFH) compounds from Traditional Chinese Medicine (TCM)-polysaccharides, saponins/triterpenoids, polyphenols, carotenoids, and aromatic phenylpropanoids-modulate oxidative stress and PD-related neurodegeneration, and to outline formulation routes toward dietary-supplement development. We searched PubMed, Web of Science Core Collection, Embase (Ovid), and the Cochrane Library from inception through August 1, 2025 with prespecified concept blocks ("Parkinson's disease," "oxidative stress," Nrf2/ARE, NF-κB, PI3K/Akt, autophagy, and MFH terms). English-language in-vitro, invertebrate, and PD-specific rodent studies, selected epidemiology, and formulation/dose/regulatory reports were narratively appraised; no meta-analysis or tool-based risk-of-bias scoring was performed. MFH compounds converge on Nrf2/ARE activation, NF-κB suppression, autophagy promotion, and mitochondrial stabilization; nano-/micro-delivery may improve bioavailability and brain exposure in preclinical models. Evidence is predominantly preclinical, with heterogeneous methods and sparse PD-specific randomized trials; epidemiologic signals are suggestive but non-causal. PD-specific oxidative stress arises from dopamine auto-oxidation, neuromelanin-iron catalysis, and complex-I hypofunction; Latest studies further bind these to ferroptosis-linked lipid peroxidation. Clinical evidence remains sparse and PK-limited for MFH actives (e.g., curcumin, EGCG); dose-response, safety monitoring (including liver signals for catechins), and regulatory constraints frame translation. MFH compounds are promising, hypothesis-generating candidates for adjunctive nutrition in PD, pending clinical dose-response and long-term safety validation. No clinical efficacy has been established.