AUTHOR=Sanguanphun Tanatcha , Sornkaew Nilubon , Malaiwong Nawaphat , Chalorak Pawanrat , Jattujan Prapaporn , Niamnont Nakorn , Sobhon Prasert , Meemon Krai 

TITLE=Neuroprotective effects of a medium chain fatty acid, decanoic acid, isolated from H. leucospilota against Parkinsonism in C. elegans PD model

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1004568

DOI=10.3389/fphar.2022.1004568

ISSN=1663-9812

ABSTRACT=<p>Sea cucumbers are marine organism that have long been used for food and traditional medicine in Asian countries. Recently, we have shown that ethyl acetate fraction (HLEA) of the crude extract of the black sea cucumber, <italic>Holothuria leucospilota,</italic> could alleviate Parkinsonism in <italic>Caenorhabditis elegans</italic> PD models. In this study, we found that the effective neuroprotective activity is attributed to HLEA-P1 compound chemically isolated and identified in <italic>H. leucospilota</italic> ethyl acetate. We reported here that HLEA-P1 could attenuate DAergic neurodegeneration, improve DAergic-dependent behaviors, reduce oxidative stress in 6-OHDA-induced <italic>C. elegans</italic>. In addition, HLEA-P1 reduced α-synuclein aggregation, improved behavior deficit and recovered lipid deposition in transgenic <italic>C. elegans</italic> overexpressing α-synuclein. We also found that HLEA-P1 activates nuclear localization of DAF-16 transcription factor of insulin/IGF-1 signaling (IIS) pathway. Treatment with 25 μg/ml of HLEA-P1 upregulated transcriptional activity of DAF-16 target genes including anti-oxidant genes (such as <italic>sod-3</italic>) and small heat shock proteins (such as <italic>hsp16.1</italic>, <italic>hsp16.2</italic>, and <italic>hsp12.6</italic>) in 6-OHDA-induced worms. In α-synuclein-overexpressed <italic>C. elegans</italic> strain, treatment with 5 μg/ml of HLEA-P1 significantly activated mRNA expression of <italic>sod-3</italic> and <italic>hsp16.2.</italic> Chemical analysis demonstrated that HLEA-P1 compound is decanoic acid/capric acid. Taken together, our findings revealed that decanoic acid isolated from <italic>H. leucospilota</italic> exerts anti-Parkinson effect in <italic>C. elegans</italic> PD models by partly modulating IIS/DAF-16 pathway.</p>