Abstract
Background/AimsIschemic stroke is a leading cause of death and disability worldwide. Early intervention of cell death in the penumbra can greatly reduce the infarct volume, thereby, alleviating the ischemic progress. Ferroptosis is a form of regulated cell death that is dependent on iron and reasctive oxygen species and is characterized by lipid peroxidation. Mitochondrial ROS are of importance in ferroptosis. Recent studies showed that it also implicated in the pathological cell death associated with stroke. Here, we studied the effect of 15,16‐Dihydrotanshinone I (DHT), a lipophilic tanshinone extracted from the root of Salvia miltiorrhiza Bunge (Danshen), on ischemic stroke and its underlying mechanism.MethodsPermanent middle cerebral artery occlusion (pMCAO)‐induced focal cerebral ischemia rats and tert‐butyl hydroperoxide (t‐BHP) injured PC12 cells were used to interpret the neuroprotective effect, especially the anti‐ferroptosis effect of DHT in vivo and in vitro.ResultsThe results showed that DHT protected t‐BHP injured PC12 cells and reversed ferroptosis induced by t‐BHP in vitro. It also protected rats subjected to pMCAO from ferroptosis in vivo. Furthermore, DHT ameliorated neurological score, infarct volume, cerebral blood flow, cerebral edema and microstructure of white‐grey matter in pMCAO rat in vivo.ConclusionThe data in this study demonstrated that DHT might have therapeutic potential for ischemic stroke and play its protective role against ferroptosis. This study reported that ferroptosis in the ischemic stroke represents a potential therapeutic target for the first time, and it might provide new insight into the prevention of ischemic stroke.Support or Funding Informationthe Science and Technology Development Fund of Macau Special Administrative Region (FDCT) (No. 078/2016/A2) , the Research Fund of University of Macau (MYRG2016‐00043‐ICMS‐QRCM), the National Natural Science Foundation of China (No. 81274133), the Major Scientific and Technological Special Project for “Significant New Drugs Creation” (No. 2018ZX09201008‐001, 2012ZX09103‐201‐055, ), the Fundamental Research Funds for the Central public welfare research institutes of China (ZZ2014060,ZXKT17040)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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