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Open AccessArticle

Neuroprotective Effect of CR-777, a Glutathione Derivative of Withaferin A, Obtained through the Bioconversion of Withania somnifera (L.) Dunal Extract by the Fungus Beauveria bassiana

1
Laboratoire Ethnodyne, 151 Boulevard Haussmann, 75008 Paris, France
2
Institut de Chimie des Substances Naturelles ICSN, Centre National de la Recherche Scientifique, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France
*
Author to whom correspondence should be addressed.
Academic Editors: Salvatore Genovese and Serena Fiorito
Molecules 2019, 24(24), 4599; https://doi.org/10.3390/molecules24244599
Received: 30 November 2019 / Revised: 11 December 2019 / Accepted: 13 December 2019 / Published: 16 December 2019
(This article belongs to the Special Issue Current Trends in the Analysis of Medicinal Plants)
The bioconversion of Withania somnifera extract by the fungus Beauveria bassiana leads to cysteine and glutathione derivatives of withaferin A at the C-6 position. The compounds were purified and fully characterized by 1D-NMR, 2D-NMR, and HRMS analysis. The glutathione derivative CR-777 was evaluated as a neuroprotective agent from damage caused by different neurotoxins mimicking molecular symptoms in Parkinson´s disease (PD), including 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA), and α-synuclein (α-Syn). CR-777, at nanomolar concentrations, protected dopaminergic and cortical neurons. In 6-OHDA-treated neurons, CR-777 increased cell survival and neurite network and decreased the expression of α-Syn. Using specific inhibitors of cell toxicity signaling pathways and specific staining experiments, the observed role of CR-777 seemed to involve the PI3K/mTOR pathway. CR-777 could be considered as a protective agent against a large panel of neuronal stressors and was engaged in further therapeutic development steps. View Full-Text
Keywords: Withania somnifera; bioconversion; withaferin A; glutathione conjugate; Alzheimer’s disease; Parkinson’s disease; neuroprotection Withania somnifera; bioconversion; withaferin A; glutathione conjugate; Alzheimer’s disease; Parkinson’s disease; neuroprotection
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MDPI and ACS Style

Rabhi, C.; Arcile, G.; Le Goff, G.; Da Costa Noble, C.; Ouazzani, J. Neuroprotective Effect of CR-777, a Glutathione Derivative of Withaferin A, Obtained through the Bioconversion of Withania somnifera (L.) Dunal Extract by the Fungus Beauveria bassiana. Molecules 2019, 24, 4599.

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