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J Ethnopharmacol
2021 Oct 28;279:114347. doi: 10.1016/j.jep.2021.114347.
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Diterpene glycosides from Holothuria scabra exert the α-synuclein degradation and neuroprotection against α-synuclein-Mediated neurodegeneration in C. elegans model.
Chalorak P
,
Sornkaew N
,
Manohong P
,
Niamnont N
,
Malaiwong N
,
Limboonreung T
,
Sobhon P
,
Aschner M
,
Meemon K
.
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ETHNOPHARMACOLOGICAL RELEVANCE: Holothuria (Metriatyla) scabra Jaeger (H. scabra), sea cucumber, is the marine organism that has been used as traditional food and medicine to gain the health benefits since ancient time. Although our recent studies have shown that crude extracts from H. scabra exhibited neuroprotective effects against Parkinson's disease (PD), the underlying mechanisms and bioactive compounds are still unknown.
AIM OF THE STUDY: In the present study, we examined the efficacy of purified compounds from H. scabra and their underlying mechanism on α-synuclein degradation and neuroprotection against α-synuclein-mediated neurodegeneration in a transgenic Caenorhabditis elegans PD model.
MATERIAL AND METHODS: The H. scabra compounds (HSEA-P1 and P2) were purified and examined for their toxicity and optimal dose-range by food-clearance and lifespan assays. The α-synuclein degradation and neuroprotection against α-synuclein-mediated neurodegeneration were determined using transgenic C. elegans model, Punc-54::α-syn and Pdat-1:: α-syn; Pdat-1::GFP, respectively, and then further investigated by determining the behavioral assays including locomotion rate, basal slowing rate, ethanol avoidance, and area-restricted searching. The underlying mechanisms related to autophagy were clarified by quantitative PCR and RNAi experiments.
RESULTS: Our results showed that HSEA-P1 and HSEA-P2 significantly diminished α-synuclein accumulation, improved motility deficits, and recovered the shortened lifespan. Moreover, HSEA-P1 and HSEA-P2 significantly protected dopaminergic neurons from α-synuclein toxicity and alleviated dopamine-associated behavioral deficits, i.e., basal slowing, ethanol avoidance, and area-restricted searching. HSEA-P1 and HSEA-P2 also up-regulated autophagy-related genes, including beclin-1/bec-1, lc-3/lgg-1, and atg-7/atg-7. RNA interference (RNAi) of these genes in transgenic α-synuclein worms confirmed that lc-3/lgg-1 and atg-7/atg-7 were required for α-synuclein degradation and DAergic neuroprotection activities of HSEA-P1 and HSEA-P2. NMR and mass spectrometry analysis revealed that the HSEA-P1 and HSEA-P2 contained diterpene glycosides.
CONCLUSION: These findings indicate that diterpene glycosides extracted from H. scabra decreases α-synuclein accumulation and protects α-synuclein-mediated DAergic neuronal loss and its toxicities via lgg-1 and atg-7.
Ardah,
Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.
2015, Pubmed
Ardah,
Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils.
2015,
Pubmed
Bengoa-Vergniory,
Alpha-synuclein oligomers: a new hope.
2017,
Pubmed
Bodhicharla,
Effects of α-synuclein overexpression in transgenic Caenorhabditis elegans strains.
2012,
Pubmed
Bordbar,
High-value components and bioactives from sea cucumbers for functional foods--a review.
2011,
Pubmed
,
Echinobase
Brenner,
The genetics of Caenorhabditis elegans.
1974,
Pubmed
Chaiyamoon,
Distribution and dynamic expression of serotonin and dopamine in the nervous system and ovary of Holothuria scabra during ovarian maturation.
2018,
Pubmed
,
Echinobase
Chalorak,
Holothuria scabra extracts exhibit anti-Parkinson potential in C. elegans: A model for anti-Parkinson testing.
2018,
Pubmed
,
Echinobase
Chalorak,
Downregulation of eEF1A/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in C. elegans Model.
2020,
Pubmed
Chen,
Traditional Chinese Medicine symptom pattern analysis for Parkinson's disease.
2017,
Pubmed
Chen,
Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease.
2005,
Pubmed
Corona,
Natural Compounds for the Management of Parkinson's Disease and Attention-Deficit/Hyperactivity Disorder.
2018,
Pubmed
Cuervo,
Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy.
2004,
Pubmed
Dauer,
Parkinson's disease: mechanisms and models.
2003,
Pubmed
Eslamboli,
Long-term consequences of human alpha-synuclein overexpression in the primate ventral midbrain.
2007,
Pubmed
Gao,
Autophagy activation promotes clearance of α-synuclein inclusions in fibril-seeded human neural cells.
2019,
Pubmed
Giménez-Xavier,
LC3-I conversion to LC3-II does not necessarily result in complete autophagy.
2008,
Pubmed
Grishchuk,
Beclin 1-independent autophagy contributes to apoptosis in cortical neurons.
2011,
Pubmed
Guo,
Systems pharmacology-based drug discovery for marine resources: an example using sea cucumber (Holothurians).
2015,
Pubmed
,
Echinobase
Harrington,
Functional analysis of VPS41-mediated neuroprotection in Caenorhabditis elegans and mammalian models of Parkinson's disease.
2012,
Pubmed
Heng,
Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model by targeting α-synuclein abnormalities in the substantia nigra.
2016,
Pubmed
Hills,
Dopamine and glutamate control area-restricted search behavior in Caenorhabditis elegans.
2004,
Pubmed
Jattujan,
Holothuria scabra extracts possess anti-oxidant activity and promote stress resistance and lifespan extension in Caenorhabditis elegans.
2018,
Pubmed
,
Echinobase
Javed,
Plant Extracts and Phytochemicals Targeting α-Synuclein Aggregation in Parkinson's Disease Models.
2018,
Pubmed
Kerr,
In vivo and in vitro biosynthesis of saponins in sea cucumbers.
1995,
Pubmed
,
Echinobase
Kiew,
Jewel of the seabed: sea cucumbers as nutritional and drug candidates.
2012,
Pubmed
,
Echinobase
Kim,
Neuroprotective effects of the new diterpene, CBNU06 against beta-amyloid-induced toxicity through the inhibition of NF-kappaB signaling pathway in PC12 cells.
2009,
Pubmed
Kim,
Therapeutic Potential of Volatile Terpenes and Terpenoids from Forests for Inflammatory Diseases.
2020,
Pubmed
King,
Autophagy across the eukaryotes: is S. cerevisiae the odd one out?
2012,
Pubmed
Komatsu,
Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice.
2005,
Pubmed
Krum,
Haloperidol Interactions with the dop-3 Receptor in Caenorhabditis elegans.
2021,
Pubmed
Lakso,
Dopaminergic neuronal loss and motor deficits in Caenorhabditis elegans overexpressing human alpha-synuclein.
2003,
Pubmed
Lee,
Ethanol preference in C. elegans.
2009,
Pubmed
Li,
Structural Elucidation and Biological Activity of a Highly Regular Fucosylated Glycosaminoglycan from the Edible Sea Cucumber Stichopus herrmanni.
2017,
Pubmed
,
Echinobase
Limanaqi,
Phytochemicals Bridging Autophagy Induction and Alpha-Synuclein Degradation in Parkinsonism.
2019,
Pubmed
López,
Stevia rebaudiana ethanolic extract exerts better antioxidant properties and antiproliferative effects in tumour cells than its diterpene glycoside stevioside.
2016,
Pubmed
Malaiwong,
Anti-Parkinson activity of bioactive substances extracted from Holothuria leucospilota.
2019,
Pubmed
,
Echinobase
Martin,
Mitochondrial permeability transition pore regulates Parkinson's disease development in mutant α-synuclein transgenic mice.
2014,
Pubmed
Mei,
Cryptotanshinione inhibits β-amyloid aggregation and protects damage from β-amyloid in SH-SY5Y cells.
2012,
Pubmed
Metcalf,
Autophagy and misfolded proteins in neurodegeneration.
2012,
Pubmed
Mizuno,
α-Synuclein Transgenic Drosophila As a Model of Parkinson's Disease and Related Synucleinopathies.
2010,
Pubmed
Moors,
Therapeutic potential of autophagy-enhancing agents in Parkinson's disease.
2017,
Pubmed
Noonong,
Neuroprotective and Neurorestorative Effects of Holothuria scabra Extract in the MPTP/MPP+-Induced Mouse and Cellular Models of Parkinson's Disease.
2020,
Pubmed
,
Echinobase
Poewe,
Parkinson disease.
2017,
Pubmed
Reeve,
Ageing and Parkinson's disease: why is advancing age the biggest risk factor?
2014,
Pubmed
Ruggieri,
Drugs from the sea.
1976,
Pubmed
Sampaio-Marques,
α-Synuclein toxicity in yeast and human cells is caused by cell cycle re-entry and autophagy degradation of ribonucleotide reductase 1.
2019,
Pubmed
Sawin,
C. elegans locomotory rate is modulated by the environment through a dopaminergic pathway and by experience through a serotonergic pathway.
2000,
Pubmed
Sharma,
A new clerodane furano diterpene glycoside from Tinospora cordifolia triggers autophagy and apoptosis in HCT-116 colon cancer cells.
2018,
Pubmed
Shi,
Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against beta-amyloid peptide-induced toxicity in SH-SY5Y cells.
2009,
Pubmed
Shinde,
Marine natural products as source of new drugs: a patent review (2015-2018).
2019,
Pubmed
Suwansa-Ard,
Transcriptomic discovery and comparative analysis of neuropeptide precursors in sea cucumbers (Holothuroidea).
2018,
Pubmed
,
Echinobase
Ustyuzhanina,
Structure and Anti-Inflammatory Activity of a New Unusual Fucosylated Chondroitin Sulfate from Cucumaria djakonovi.
2018,
Pubmed
,
Echinobase
Voisine,
Identification of potential therapeutic drugs for huntington's disease using Caenorhabditis elegans.
2007,
Pubmed
Voon,
Impulse control disorders and levodopa-induced dyskinesias in Parkinson's disease: an update.
2017,
Pubmed
Wakamatsu,
Selective loss of nigral dopamine neurons induced by overexpression of truncated human alpha-synuclein in mice.
2008,
Pubmed
Waxman,
Molecular mechanisms of alpha-synuclein neurodegeneration.
2009,
Pubmed
Wilhelm,
Autophagy during ageing - from Dr Jekyll to Mr Hyde.
2018,
Pubmed
Wu,
Amyloid-beta-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans.
2006,
Pubmed
Xilouri,
Autophagy and Alpha-Synuclein: Relevance to Parkinson's Disease and Related Synucleopathies.
2016,
Pubmed
