Ganoderic acid A alleviates hypoxia-induced apoptosis, autophagy, and inflammation in rat neural stem cells through the PI3K/AKT/mTOR pathways.

Abstract

Effects of ganoderic acid A (GAA), a lanostane triterpene, on hypoxia-ischemia encephalopathy (HIE) remain unclear. We aimed to figure out the specific role of GAA in hypoxia-treated neural stem cells (NSCs) as well as the regulatory mechanisms. Primary rat NSCs were incubated under hypoxia to simulate HIE. Viability and apoptosis of hypoxia-injured NSCs were measured by cell counting kit-8 and flow cytometry assays, respectively. Proteins related to apoptosis, autophagy, and the PI3K/AKT/mTOR pathways were evaluated by Western blot analysis. LY294002 and rapamycin were added to inhibit the PI3K/AKT pathway and mTOR pathway, respectively. Enzyme-linked immunosorbent assay was carried out to test the release of proinflammatory cytokines. We found that hypoxia-induced decrease of cell viability, increases of apoptotic cells and autophagy, and the release of IL-6, IL-1β, and TNF-α were all attenuated by GAA stimulation. Activation of caspases induced by hypoxia was alleviated by GAA. Furthermore, we found that inhibition of the PI3K/AKT pathway eliminated the effects of GAA on apoptosis and proinflammatory cytokines release in hypoxia-injured NSCs. Meanwhile, inhibition of the mTOR pathway abrogated the effects of GAA on cell autophagy in hypoxia-injured NSCs. In conclusion, GAA alleviated hypoxia-induced injury in NSCs might be through activating the PI3K/AKT and mTOR pathways.

• Authors: Yanhua Chang, Ruifang Kong
• Journal: Phytotherapy research : PTR (Phytother Res) Vol. 33 Issue 5 Pg. 1448-1456 (May 2019) ISSN: 1099-1573 [Electronic] England
• PMID: 30838711 (Publication Type: Journal Article, Retracted Publication)
• Copyright: © 2019 John Wiley & Sons, Ltd.

Chemical References

• Heptanoic Acids
• Lanosterol
• ganoderic acid A
• mTOR protein, rat
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Cell Hypoxia (physiology)
• Cell Survival (drug effects)
• Heptanoic Acids (pharmacology)
• Inflammation (metabolism)
• Lanosterol (analogs & derivatives, pharmacology)
• Neural Stem Cells (drug effects)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Rats
• Rats, Sprague-Dawley
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (metabolism)