Anti-Parkinson Effects of Holothuria leucospilota-Derived Palmitic Acid in Caenorhabditis elegans Model of Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative disease which is still incurable. Sea cucumber-derived compounds have been reported to be promising candidate drugs for treating age-related neurological disorders. The present study evaluated the beneficial effects of the Holothuria leucospilota (H. leucospilota)-derived compound 3 isolated from ethyl acetate fraction (HLEA-P3) using Caenorhabditis elegans PD models. HLEA-P3 (1 to 50 µg/mL) restored the viability of dopaminergic neurons. Surprisingly, 5 and 25 µg/mL HLEA-P3 improved dopamine-dependent behaviors, reduced oxidative stress and prolonged lifespan of PD worms induced by neurotoxin 6-hydroxydopamine (6-OHDA). Additionally, HLEA-P3 (5 to 50 µg/mL) decreased α-synuclein aggregation. Particularly, 5 and 25 µg/mL HLEA-P3 improved locomotion, reduced lipid accumulation and extended lifespan of transgenic C. elegans strain NL5901. Gene expression analysis revealed that treatment with 5 and 25 µg/mL HLEA-P3 could upregulate the genes encoding antioxidant enzymes (gst-4, gst-10 and gcs-1) and autophagic mediators (bec-1 and atg-7) and downregulate the fatty acid desaturase gene (fat-5). These findings explained the molecular mechanism of HLEA-P3-mediated protection against PD-like pathologies. The chemical characterization elucidated that HLEA-P3 is palmitic acid. Taken together, these findings revealed the anti-Parkinson effects of H. leucospilota-derived palmitic acid in 6-OHDA induced- and α-synuclein-based models of PD which might be useful in nutritional therapy for treating PD.

 

Comments：

The present study investigated the potential benefits of a compound called HLEA-P3, which is derived from the Holothuria leucospilota sea cucumber, in treating Parkinson's disease using Caenorhabditis elegans PD models. The study found that HLEA-P3 restored the viability of dopaminergic neurons, improved dopamine-dependent behaviors, reduced oxidative stress, and prolonged lifespan of PD worms induced by neurotoxin 6-hydroxydopamine (6-OHDA). Additionally, HLEA-P3 decreased α-synuclein aggregation, improved locomotion, reduced lipid accumulation, and extended lifespan of transgenic C. elegans strain NL5901. Gene expression analysis revealed that treatment with HLEA-P3 upregulated genes encoding antioxidant enzymes and autophagic mediators and downregulated the fatty acid desaturase gene.

The study also identified that HLEA-P3 is composed of palmitic acid, a type of fatty acid commonly found in animal and vegetable fats. The results suggest that HLEA-P3-derived palmitic acid may be a useful nutritional therapy for treating Parkinson's disease. However, further studies are needed to confirm the efficacy and safety of HLEA-P3 in humans.

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