Anti-Parkinson activity of bioactive substances extracted from Holothuria leucospilota

Nawaphat Malaiwong; Pawanrat Chalorak; Prapaporn Jattujan; Preeyanuch Manohong; Nakorn Niamnont; Worawit Suphamungmee; Prasert Sobhon; Krai Meemon

doi:10.1016/j.biopha.2018.11.063

Anti-Parkinson activity of bioactive substances extracted from Holothuria leucospilota

Biomed Pharmacother. 2019 Jan:109:1967-1977. doi: 10.1016/j.biopha.2018.11.063. Epub 2018 Nov 26.

Authors

Nawaphat Malaiwong¹, Pawanrat Chalorak¹, Prapaporn Jattujan², Preeyanuch Manohong³, Nakorn Niamnont³, Worawit Suphamungmee¹, Prasert Sobhon⁴, Krai Meemon⁵

Affiliations

¹ Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand.
² Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand; Chulabhorn International College of Medicine, Thammasat University, Pathumthani, 12121, Thailand.
³ Department of Chemistry, Faculty of Science, King Mongkut's University of Technology Thonburi, Bang Mod, Bangkok, 10140, Thailand.
⁴ Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand; Faculty of Allied Health Sciences, Burapha University, Chonburi 20131, Thailand.
⁵ Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand. Electronic address: krai.mee@mahidol.ac.th.

PMID: 30551452
DOI: 10.1016/j.biopha.2018.11.063

Abstract

Parkinson's disease (PD) is a well-known neurodegenerative disorder characterized by dopaminergic (DA) neuron loss and α-synuclein aggregation. Recent study revealed that the extracts from sea cucumber, Holothuroidea spp., exhibited neuroprotective and lifespan extension effects in Caenorhabditis elegans model. Interestingly, the black sea cucumber, Holothuria leucospilota, possesses body wall and a specialized organ called cuvierian tubules containing high amount of bioactive compounds. In this study, the neuroprotective effects of the body wall (BW) and cuvierian tubules (CT) from this sea cucumber against PD were evaluated using C. elegans as a model. H. leucospilota were extracted using ethanol (ET), ethyl acetate (EA), butanol (BU) and aqueous (AQ) fractions. Extracts from these fractions were used to treat the 6-OHDA-induced BZ555 and α-synuclein expressing NL5901 strains of C. elegans. Treatment with ET, EA, BU and AQ fractions of H. leucospilota extracts could significantly prevent degeneration of DA neurons in 6-OHDA-induced worms, improve food-sensing behavior mediated by DA neurons, and up-regulate cat-2 and sod-3 gene expressions. These results indicate the neuroprotective activity of the extracts which may be attributed to the anti-oxidant activity of the bioactive compounds. Moreover, α-synuclein aggregation was significantly reduced together with the recovery of lipid deposition upon the treatment with H. leucospilota extracts. In addition, treatment with H. leucospilota extracts was able to increase the lifespan of 6-OHDA-induced N2. NMR analysis revealed the major chemical components in the effective EA fractions were terpenoids, steroids, saponins, and glycosides. In summary, H. leucospilota extracts exhibited anti-Parkinson effect in both toxin-induced and transgenic C. elegans models of PD. Further study will be performed to elucidate the most effective anti-PD molecules which will lead to the development of anti-PD drug.

Keywords: Caenorhabditis elegans; Dopaminergic neuron; Holothuria leucospilota; Neurodegeneration; Neuroprotective; Parkinson’s disease; α-synuclein.

MeSH terms

Animals
Animals, Genetically Modified
Antiparkinson Agents / pharmacology*
Disease Models, Animal
Dopamine / metabolism
Dopaminergic Neurons / drug effects
Dopaminergic Neurons / metabolism
Holothuria / chemistry*
Nerve Degeneration / drug therapy
Neuroprotective Agents / pharmacology
Parkinson Disease / drug therapy*
Parkinson Disease / metabolism
alpha-Synuclein / metabolism

Substances

Antiparkinson Agents
Neuroprotective Agents
alpha-Synuclein
Dopamine