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

Abstract

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 Cucumaria frondosa and ginsenoside Rg3 (Rg3) from Panax notoginseng in C. elegans 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 C. elegans. 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, egl-1 and ced-3, and upregulation of sod-3 and cat-2. Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including ubh-4, hsf-1, hsp-16.1 and hsp-16.2. This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced C. elegans 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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“…In addition, since muscle cells are larger than neurons, visualization of protein aggregation is also straightforward. Indeed, these strains expressing the pathological protein in muscles have been widely used to evaluate the anti-proteotoxic potential of different compounds (McColl et al, 2012;Sanchis et al, 2019;Chalorak et al, 2021). As expected, in both strains we observed an age-dependent locomotion impairment probably due to progressive muscular damage induced by protein aggregation (Supplementary Figure S4).…”

1-Mesityl-3-(3-Sulfonatopropyl) Imidazolium Protects Against Oxidative Stress and Delays Proteotoxicity in C. elegans

“…In addition, since muscle cells are larger than neurons, visualization of protein aggregation is also straightforward. Indeed, these strains expressing the pathological protein in muscles have been widely used to evaluate the anti-proteotoxic potential of different compounds ( McColl et al, 2012 ; Sanchis et al, 2019 ; Chalorak et al, 2021 ).…”

Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegans

“…Dopaminergic neuron degeneration was induced by 50 mM 6-OHDA in C. elegans as described previously ( Tucci et al, 2011 ). Briefly, the synchronized nematodes were immersed in M9 buffer containing MT or 6a for 48 h at 20°C, and then L1 worms were transferred to OP50/NGM plates at 20°C for 65 h (L3 stage), after which they were exposed to 50 mM 6-OHDA for 1 h. After exposure, the worms were washed with M9 buffer and transferred to OP50/NGM plates containing 0.04 mg/ml FUDR for 3 days at 20 °C for various assays ( Chalorak et al, 2021 ; Ma et al, 2021 ).…”