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

被引：13

作者：

Rabhi, Cherif ^{[1
]}

Arcile, Guillaume ^{[2
]}

Le Goff, Geraldine ^{[2
]}

Noble, Christian Da Costa ^{[1
]}

Ouazzani, Jamal ^{[2
]}

机构：

[1] Lab Ethnodyne, 151 Blvd Haussmann, F-75008 Paris, France

[2] CNRS, ICSN, Ave Terrasse, F-91198 Gif Sur Yvette, France

来源：

MOLECULES | 2019年 / 24卷 / 24期

关键词：

Withania somnifera; bioconversion; withaferin A; glutathione conjugate; Alzheimer's disease; Parkinson's disease; neuroprotection; NATURAL-PRODUCTS; MEDICINAL HERBS; BIOCATALYSIS; CULTURES; MODEL;

D O I：

10.3390/molecules24244599

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 alpha-synuclein (alpha-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 alpha-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.

引用

页数：19