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

Abstract

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.

Application of 3Rs in Caenorhabditis elegans Research for the Identification of Health-Promoting Natural Products

“…The mutant C. elegans strain NL5901 expresses the human α -synuclein gene in its body wall cells, which is, among others, associated with Parkinsonʼs disease 38 , as overexpressed α -synuclein leads to the formation of Lewy bodies and dopaminergic neurodegeneration 39 . In NL5901, the human α -synuclein is fused to yellow fluorescent protein (YFP), enabling the visualization of α -synuclein aggregation under a fluorescence microscope 38 .…”

“…This results in a rapid and reproducible paralysis [36], which lacks the formation of Aβ deposits [37] but allows for the assignment of effects to Aβ toxicity while excluding life span effects, which is hardly possible using CL2006 [36]. The mutant C. elegans strain NL5901 expresses the human α-synuclein gene in its body wall cells, which is, among others, associated with Parkinsonʼs disease [38], as overexpressed α-synuclein leads to the formation of Lewy bodies and dopaminergic neurodegeneration [39]. In NL5901, the human α-synuclein is fused to yellow fluorescent protein (YFP), enabling the visualization of α-synuclein aggregation under a fluorescence microscope [38].…”

Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds

“…It was discovered through transcriptomic research that palmitic acid affected many signaling pathways, including lipid metabolism in neurons. On the other hand, excessive ingestion of palmitic acid has been linked to neurodegenerative conditions, such as Parkinson's disease [ 150 , 151 ]. To prevent harmful effects such as oxidative stress, PLA has a critical role in low levels of stress, which can activate the stress response pathway.…”

Anti-Obesity Effects of Marine Macroalgae Extract Caulerpa lentillifera in a Caenorhabditis elegans Model

“…There was a study reporting that PA inhibits the key molecules of the PI3K/AKT pathway to suppress the proliferation and metastasis of prostate cancer cells [51]. Recently, we found that Holothuria leucospilota-derived palmitic acid obtained from an ethyl acetate fraction was able to restore the viability of dopaminergic neurons and decrease α-synuclein aggregation, oxidative stress, and lipid accumulation, as well as extending the lifespan of a C. elegans model of Parkinson's disease [52]. Moreover, the PA obtained from the methanolic extract of Syzygium litoralle (Myrtaceae) showed antioxidant activity, with an IC50 value of 44.85 µg/mL [53].…”