Artesunate promotes the proliferation of neural stem/progenitor cells and alleviates Ischemia-reperfusion Injury through PI3K/Akt/FOXO-3a/p27kip1 signaling pathway.

In this study, our results showed that following the treatment with artesunate (ART, 150 mg/kg), the functional recovery was significantly improved, the infarct volume was notably reduced, and the expression of Nestin, a proliferation marker of NSPCs in the infarcted cortex, was also increased. Additionally, the proliferative activity of NSPCs with or without oxygen-glucose deprivation/reperfusion was significantly promoted by ART treatment, and the therapeutic concentration was 0.8 μmol/L (without OGD/R) or 0.4 μmol/L (with OGD/R) in the in vitro model. Furthermore, the effects of ART can be abolished by the treatment of PI3K inhibitor wortmannin. The expression levels of related molecules in PI3K/Akt/FOXO-3a/p27kip1 signaling pathway (p-AKT, p-FOXO-3a, p27kip1) were examined using western blotting. The results suggested ART could inhibit the transcriptional function of FOXO-3a by inducing its phosphorylation, subsequently downregulating p27kip1 and enhancing neural stem cell proliferation in the infarcted cortex via PI3K/AKT signaling, further alleviating ischemia-reperfusion injury after ischemic stroke.
PMID: 32379706 [PubMed - as supplied by publisher]

Source: Aging - May 6, 2020 Category: Biomedical Science Authors: Zhang K, Yang Y, Ge H, Wang J, Chen X, Lei X, Zhong J, Zhang C, Xian J, Lu Y, Tan L, Feng H Tags: Aging (Albany NY) Source Type: research