A natural diarylheptanoid protects cortical neurons against oxygen–glucose deprivation‐induced autophagy and apoptosis. (25th April 2019)

• Record Type: Journal Article
• Authors: Shi, Qiaoyun; Zhang, Qinghua; Peng, Yinghui; Zhang, Xiaoqi; Wang, Ying; Shi, Lei
• Is Part Of: Journal of pharmacy and pharmacology. Volume 71:Number 7(2019)
• Page Start: 1110
• Page End: 1118
• Publication Date: 2019-04-25
• Subjects: apoptosis -- autophagy -- ischaemic -- neuroprotection -- oxygen–glucose deprivation/reperfusion; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.13096
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: Objectives: This study aims to investigate the neuroprotective effects of curcumin analogues, 7‐(4‐Hydroxy‐3‐methoxyphenyl)‐1‐phenyl‐4 E ‐hepten‐3‐one (AO‐2) on oxygen–glucose deprivation and re‐oxygenation (OGD/R) induced injury in cortical neurons, which is a widely accepted in‐vitro model for ischaemic reperfusion. Methods: In this study, AO‐2 was added to cortical neurons for 2 h as pretreatment, and then cortical neurons were subjected to OGD/R in the presence of AO‐2 for 4 h. Cell viability was tested by 2′, 3‐(4, 5‐dimethylthiazol‐2‐yl)‐2, 5‐diphenyl tetrazolium bromide assay and apoptosis by flow cytometry and Live & Dead cell assay. Western blot analysis detected the change in AKT/mTOR (mammalian target of rapamycin) signalling pathway. Key findings: Treatment of AO‐2 increased cell survival of OGD/R‐treated cortical neurons. Transient AKT/mTOR inhibition, induction of the autophagy marker LC3‐II (microtubule‐associated protein 1A/1B‐light chain 3 phosphatidylethanolamine conjugate), and cleavage of the apoptosis marker Caspase‐3 were observed at different stages of OGD/R, and AO‐2 reversed all three events. Importantly, treatment of the mTOR inhibitor rapamycin blocked the neuroprotective effects of AO‐2 on reducing LC3‐II and cleaved Caspase‐3 expression and cancelled AO‐2‐mediated neuronal survival. Conclusions: These results demonstrate that AO‐2 increases resistance of cortical neurons to OGD/R by decreasing autophagy and cell apoptosis, which involves an mTOR‐dependent mechanism.