scholarly journals 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 ◽  
Vol 24 (24) ◽  
pp. 4599 ◽  
Author(s):  
Chérif Rabhi ◽  
Guillaume Arcile ◽  
Géraldine Le Goff ◽  
Christian Da Costa Noble ◽  
Jamal Ouazzani

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.

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 375
Author(s):  
Jin Young Hong ◽  
Hyunseong Kim ◽  
Junseon Lee ◽  
Wan-Jin Jeon ◽  
Seung Ho Baek ◽  
...  

Inula britannica var. chinensis (IBC) has been used as a traditional medicinal herb to treat inflammatory diseases. Although its anti-inflammatory and anti-oxidative effects have been reported, whether IBC exerts neuroprotective effects and the related mechanisms in cortical neurons remain unknown. In this study, we investigated the effects of different concentrations of IBC extract (5, 10, and 20 µg/mL) on cortical neurons using a hydrogen peroxide (H2O2)-induced injury model. Our results demonstrate that IBC can effectively enhance neuronal viability under in vitro-modeled reaction oxygen species (ROS)-generating conditions by inhibiting mitochondrial ROS production and increasing adenosine triphosphate level in H2O2-treated neurons. Additionally, we confirmed that neuronal death was attenuated by improving the mitochondrial membrane potential status and regulating the expression of cytochrome c, a protein related to cell death. Furthermore, IBC increased the expression of brain-derived neurotrophic factor and nerve growth factor. Furthermore, IBC inhibited the loss and induced the production of synaptophysin, a major synaptic vesicle protein. This study is the first to demonstrate that IBC exerts its neuroprotective effect by reducing mitochondria-associated oxidative stress and improving mitochondrial dysfunction.


2019 ◽  
Vol 29 (1) ◽  
Author(s):  
Monir M. M. El Husseini

AbstractLarval and adult populations of the Egyptian alfalfa weevil (EAW) Hypera brunneipennis (Boheman) (Coleoptera: Curculionidae) was monitored after application of the entomopathogenic fungus Beauveria bassiana in the alfalfa field (Medicago sativa L.) in two successive seasons 2014/2015 and 2015/2016. The second and last generation of the weevil on April 10, 2016, was controlled by only one application with the conidiospores of the entomopathogenic fungus B. bassiana (3 × 108 spores/ml). Accordingly, the larval population decreased from 16.07 ± 1.09 in season 2015/2016 to 7.37 ± 0.05 individuals/50 sweep net double strokes in season 2016/2017. Also, the adult weevil’s population decreased from 5.66 ± 0.8 to 2.55 ± 0.6 individuals/50 sweep net double strokes in the two seasons, respectively. 39.66% mortality rate was recorded in the Hypera brunneipennis adults aestivated under loose bark of the surrounding eucalyptus trees, which received the application of B. bassiana in the field. Another application with the fungus, targeting the second generation of the pest adults in alfalfa each season, will undoubtedly lead to a further decrease in the pest population.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laila Gasmi ◽  
Sehyeon Baek ◽  
Jong Cheol Kim ◽  
Sihyeon Kim ◽  
Mi Rong Lee ◽  
...  

AbstractBeauveria bassiana is a species complex whose isolates show considerable natural genetic variability. However, little is known about how this genetic diversity affects the fungus performance. Herein, we characterized the diversity of genes involved in various mechanisms of the infective cycle of 42 isolates that have different growth rates, thermotolerance and virulence. The analysed genes showed general genetic diversity measured as non-synonymous changes (NSC) and copy number variation (CNV), with most of them being subjected to positive episodic diversifying selection. Correlation analyses between NSC or CNV and the isolate virulence, thermotolerance and growth rate revealed that various genes shaped the biological features of the fungus. Lectin-like, mucin signalling, Biotrophy associated and chitinase genes NSCs correlated with the three biological features of B. bassiana. In addition, other genes (i.e. DNA photolyase and cyclophilin B) that had relatively conserved sequences, had variable CNs across the isolates which were correlated with the variability of either virulence or thermotolerance of B. bassiana isolates. The data obtained is important for a better understanding of population structure, ecological and potential impact when isolates are used as mycoinsecticides and can justify industrialization of new isolates.


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