Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in <i>C. elegans</i> Model of Parkinson’s Disease

Parkinson’s disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective...

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Main Authors: Pawanrat Chalorak, Tanatcha Sanguanphun, Tanapol Limboonreung, Krai Meemon
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/26/16/4843
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author Pawanrat Chalorak
Tanatcha Sanguanphun
Tanapol Limboonreung
Krai Meemon
author_facet Pawanrat Chalorak
Tanatcha Sanguanphun
Tanapol Limboonreung
Krai Meemon
author_sort Pawanrat Chalorak
collection DOAJ
description Parkinson’s disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective effects against neurodegenerative disorders. Interestingly, saponin can also be found in marine organisms such as the sea cucumber, but little is known about its effect in neurodegenerative disease, including PD. In this study, we investigated the anti-Parkinson effects of frondoside A (FA) from <i>Cucumaria frondosa</i> and ginsenoside Rg3 (Rg3) from <i>Panax notoginseng</i> in <i>C. elegans</i> PD model. Both saponins were tested for toxicity and optimal concentration by food clearance assay and used to treat 6-OHDA-induced BZ555 and transgenic α-synuclein NL5901 strains in <i>C. elegans</i>. Treatment with FA and Rg3 significantly attenuated DAergic neurodegeneration induced by 6-OHDA in BZ555 strain, improved basal slowing rate, and prolonged lifespan in the 6-OHDA-induced wild-type strain with downregulation of the apoptosis mediators, <i>egl-1</i> and <i>ced-3</i>, and upregulation of <i>sod-3</i> and <i>cat-2</i>. Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including <i>ubh-4</i>, <i>hsf-1</i>, <i>hsp-16.1</i> and <i>hsp-16.2</i>. This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced <i>C. elegans</i> model through suppressing apoptosis mediators and stimulating antioxidant enzymes. In addition, FA could attenuate α-synuclein aggregation through the protein degradation process.
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spelling doaj.art-7407f7abb5da4fd989fb4160453442d52023-11-22T08:52:46ZengMDPI AGMolecules1420-30492021-08-012616484310.3390/molecules26164843Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in <i>C. elegans</i> Model of Parkinson’s DiseasePawanrat Chalorak0Tanatcha Sanguanphun1Tanapol Limboonreung2Krai Meemon3Department of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, ThailandDepartment of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, ThailandFaculty of Dentistry, King Mongkut’s Institute of Technology Ladkrabang, Ladkrabang, Bangkok 10520, ThailandDepartment of Anatomy, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, ThailandParkinson’s disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective effects against neurodegenerative disorders. Interestingly, saponin can also be found in marine organisms such as the sea cucumber, but little is known about its effect in neurodegenerative disease, including PD. In this study, we investigated the anti-Parkinson effects of frondoside A (FA) from <i>Cucumaria frondosa</i> and ginsenoside Rg3 (Rg3) from <i>Panax notoginseng</i> in <i>C. elegans</i> PD model. Both saponins were tested for toxicity and optimal concentration by food clearance assay and used to treat 6-OHDA-induced BZ555 and transgenic α-synuclein NL5901 strains in <i>C. elegans</i>. Treatment with FA and Rg3 significantly attenuated DAergic neurodegeneration induced by 6-OHDA in BZ555 strain, improved basal slowing rate, and prolonged lifespan in the 6-OHDA-induced wild-type strain with downregulation of the apoptosis mediators, <i>egl-1</i> and <i>ced-3</i>, and upregulation of <i>sod-3</i> and <i>cat-2</i>. Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including <i>ubh-4</i>, <i>hsf-1</i>, <i>hsp-16.1</i> and <i>hsp-16.2</i>. This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced <i>C. elegans</i> model through suppressing apoptosis mediators and stimulating antioxidant enzymes. In addition, FA could attenuate α-synuclein aggregation through the protein degradation process.https://www.mdpi.com/1420-3049/26/16/4843Parkinson’s diseasedopaminergic neuronsneurodegenerationα-Synucleinfrondoside Aginsenoside Rg3
spellingShingle Pawanrat Chalorak
Tanatcha Sanguanphun
Tanapol Limboonreung
Krai Meemon
Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in <i>C. elegans</i> Model of Parkinson’s Disease
Molecules
Parkinson’s disease
dopaminergic neurons
neurodegeneration
α-Synuclein
frondoside A
ginsenoside Rg3
title Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in <i>C. elegans</i> Model of Parkinson’s Disease
title_full Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in <i>C. elegans</i> Model of Parkinson’s Disease
title_fullStr Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in <i>C. elegans</i> Model of Parkinson’s Disease
title_full_unstemmed Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in <i>C. elegans</i> Model of Parkinson’s Disease
title_short Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in <i>C. elegans</i> Model of Parkinson’s Disease
title_sort neurorescue effects of frondoside a and ginsenoside rg3 in i c elegans i model of parkinson s disease
topic Parkinson’s disease
dopaminergic neurons
neurodegeneration
α-Synuclein
frondoside A
ginsenoside Rg3
url https://www.mdpi.com/1420-3049/26/16/4843
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