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| Main Authors: | , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
Gene
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/39884402/ |
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Table of Contents:
- Chryxanthone A, an extracted substance from endophytic fungal Aspergillus versicolor, produces anti-oxidant neuroprotection possibly via the action on mTOR/CREB axis. Zhang, Xinyu Hong, Yirui Hu, Chenwei Zhai, Yijie Pan, Nanyi Ding, Lijian Han, Wenbo Cui, Wei Aspergillus TOR Serine-Threonine Kinases Mice Oxidative Stress Antioxidants Animals Molecular Docking Simulation Reactive Oxygen Species Cell Line Cyclic AMP Response Element-Binding Protein Signal Transduction Neuroprotective Agents Neurons Hydrogen Peroxide Xanthones Neurons are susceptible to oxidative stress due to the elevated reactive oxygen species (ROS) production and the limited antioxidant defense mechanisms. Therefore, it is possible to treat oxidative stress-related neurological disorders via the inhibition of oxidative stress. Chryxanthone A is an extracted substance derived from the endophytic fungal Aspergillus versicolor, with an atypical dihydropyran ring. However, it is unknown whether and how chryxanthone A could produce anti-oxidant protection. The activity and mechanisms underlying the anti-oxidant protection of chryxanthone A were explored in the study. HT22 neuronal cells were used to evaluate the anti-oxidant protection of chryxanthone A. Comprehensive bioinformatic methods, including RNA-seq analysis, transcription factor prediction, CMap prediction and molecular docking analysis, were utilized to explore the molecular mechanisms how chryxanthone A prevented oxidative stress, which was confirmed by Western blotting analysis. Chryxanthone A concentration-dependently prevented HO-induced cell death and increase in intracellular ROS in HT22 cells. Results from RNA-seq and bioinformatic analysis indicated that chryxanthone A might act on mTOR/CREB axis, possibly via binding to the Val2227 site within ATP binding pocket of mTOR. The action of chryxanthone A on HO-induced alteration of mTOR/CREB axis were further confirmed in HT22 cells. These results suggested that chryxanthone A produced anti-oxidant protection via the action on mTOR/CREB axis, providing a support that chryxanthone A might be developed as a novel drug candidate for the treatment of oxidative stress-related disorders.