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

Abstract

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, Holothuria leucospilota, could alleviate Parkinsonism in Caenorhabditis elegans PD models. In this study, we found that the effective neuroprotective activity is attributed to HLEA-P1 compound chemically isolated and identified in H. leucospilota ethyl acetate. We reported here that HLEA-P1 could attenuate DAergic neurodegeneration, improve DAergic-dependent behaviors, reduce oxidative stress in 6-OHDA-induced C. elegans. In addition, HLEA-P1 reduced α-synuclein aggregation, improved behavior deficit and recovered lipid deposition in transgenic C. elegans 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 sod-3) and small heat shock proteins (such as hsp16.1, hsp16.2, and hsp12.6) in 6-OHDA-induced worms. In α-synuclein-overexpressed C. elegans strain, treatment with 5 μg/ml of HLEA-P1 significantly activated mRNA expression of sod-3 and hsp16.2. Chemical analysis demonstrated that HLEA-P1 compound is decanoic acid/capric acid. Taken together, our findings revealed that decanoic acid isolated from H. leucospilota exerts anti-Parkinson effect in C. elegans PD models by partly modulating IIS/DAF-16 pathway.

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

“…From the structural elucidation by using 1 H and 13 C NMR analysis, HLEA-P3 was identified as palmitic acid or hexadecanoic acid [ 18 ]. HLEA-P3 is a white powder.…”

“…The procedures for handling the sea cucumbers were ethically performed under the guidelines of MU-IACUC according to the protocol number MUSC60-049-399. The extraction and isolation of H. leucospilota compounds were performed, as described previously [ 18 ]. Briefly, the black sea cucumber H. leucospilota samples were provided by Coastal Fisheries Research and Development Center, Prachuap Khiri Khan, Thailand.…”

“…Saponin-rich butanol extract of H. leucospilota upregulated stress resistance, decreased aging biomarkers and extended lifespan of C. elegans via DAF-16 signaling [ 16 ]. Ethyl acetate fraction of H. leucospilota (HLEA) and the HLEA-P1 compound or decanoic acids purified from this fraction have been shown to possess neuroprotective effects against DAergic neurodegeneration and α-synuclein toxicity in C. elegans PD models [ 17 , 18 ]. Apart from HLEA-P1/decanoic acid, HLEA-P3 compound has been found in the HLEA fraction.…”

Marine natural products

“…621 With the common occurrence of steroidal glycosides in sea cucumbers, and the knowledge that saponins act as membrane disruptors, the authors noted the ability of the marine organisms to produce larger quantities of lathosterol and related sterols that appear to confer protection from saponin self-poisoning. Further biological evaluation of sea cucumber metabolites has identified the simple fatty acid decanoic acid as being active in a number of Parkinson's disease related models and assays, 622 desulfated echinoside A has much reduced haemolytic activities and can still act to lower lipid levels in vitro and in vivo , 623 and the saponin stichloroside C2 is cytotoxic towards triple-negative breast cancer cells via mechanisms that include inhibition of epithelial–mesenchymal transition and the induction of apoptosis via the MAPK signalling pathway. 624…”

2-Butoxytetrahydrofuran, Isolated from Holothuria scabra, Attenuates Aggregative and Oxidative Properties of α-Synuclein and Alleviates Its Toxicity in a Transgenic Caenorhabditis elegans Model of Parkinson’s Disease

“…The fluorescence intensity of YFP-tagged α-synuclein in the body wall muscle cells was semiquantified using ImageJ software (National Institute of Health, NIH, Bethesda, MD, USA). 69 3.6. Confocal Microscopic Imaging.…”