Synergistic Neuroprotective and Immunomodulatory Effects of Cocoa Seed Husk and Guarana Extract: A Nutraceutical Approach for Parkinson's Disease Management

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder linked to oxidative stress, mitochondrial dysfunction, and neuroinflammation. This study evaluates the neurofunctional and immunomodulatory effects of an aqueous extract combining cocoa seed husk and guarana powder (GuaCa). Eighteen extracts were characterized for flavonoid and polyphenol content, antioxidant activity, and genoprotective potential. The EQF3 extract, rich in catechins, quercetin, and epigallocatechin gallate, was selected for further analysis in three models: Eisenia fetida earthworms, SH-SY5Y neuron cells, and peripheral blood mononuclear cells (PBMCs) from PD patients. Results: The extracts showed antioxidant, genoprotective activity, and flavonoid content. No significant toxicity was observed in E. fetida. In SH-SY5Y cells, GuaCa increased cell viability and brain-derived neurotrophic factor (BDNF) levels and reduced mitochondrial damage by lowering extracellular NDUSF7 (subunit of the NADH dehydrogenase (ubiquinone) complex) levels. In PD-PBMCs cultures, GuaCa reduced pro-inflammatory cytokine IL-6 levels, indicating immunomodulatory effects. Conclusion: GuaCa shows promise as a nutraceutical for managing neuroinflammation and mitochondrial dysfunction in PD. Further clinical studies are needed to confirm its efficacy and potential for neuroprotective dietary strategies.