XQ-1H alleviates cerebral ischemia in mice through inhibition of apoptosis and promotion of neurogenesis in a Wnt/β-catenin signaling dependent way

Publication date: Available online 6 September 2019Source: Life SciencesAuthor(s): Dan Xu, Kai Hou, Fengyang Li, Shijie Chen, Weirong Fang, Yunman LiAbstractAims10-O-(N,N-dimethylaminoethyl)-ginkgolide B methanesulfonate (XQ-1H), a new derivative of ginkgolide B, has drawn great attention for its potent bioactivities against ischemia-induced injury. The purpose of this study was to further investigate the effect of XQ-1H against acute ischemic stroke by inducing middle cerebral artery occlusion/reperfusion (MCAO/R) injuries in mice.Main methodsTreatment of XQ-1H (78 or 39 mg/kg, i.g., bid) 2 h after MCAO improved motor skills and ameliorated the severity of brain infarction and apoptosis seen in the mice by diminishing pathological changes and the activation of a pro-apoptotic protein Cleaved-Caspase-3, which in turn induced anti-apoptotic Bcl-xL. Through introducing Wnt/β-catenin signaling inhibitor XAV-939, XQ-1H was proven to intensively promoted neurogenesis in the peri-infarct cortex, subventricular area (SVZ) and the dentate gyrus (DG) subgranular area (SGZ) in a Wnt signal dependent way by compromising the activation of GSK3β, which in turn upregulated Wnt1, β-catenin, Neuro D1 and Cyclin D1, most possibly through the activation of PI3K/Akt signaling via the upregulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF).Key findingsWe conclude that XQ-1H preserved the motor functions, limited apoptosis, and concomitantly promoted neurogen...
Source: Life Sciences - Category: Biology Source Type: research