Antioxidant and pro-angiogenic effects of corilagin in rat cerebral ischemia via Nrf2 activation

Abstract

// Yi Ding 1, * , Danjun Ren 1, 2, * , Hang Xu 1, * , Wenxing Liu 1, * , Tianlong Liu 1, * , Liang Li 1 , Jianguang Li 2 , Yuwen Li 1 and AiDong Wen 1 1 Department of Pharmacy, Xijing Hospital, The Fourth Military Medical University, Xi’an 710032, China 2 XinJiang Medical University, Wulumuqi 830001, China * These authors have contributed equally to this work Correspondence to: Jianguang Li, email: L77117@163.com Yuwen Li, email: liyuwenzs@gmail.com AiDong Wen, email: adwen-2004@hotmail.com Keywords: corilagin; Nrf2; oxidative stress; angiogenesis; ischemic stroke Received: August 06, 2017     Accepted: September 23, 2017     Published: October 24, 2017 ABSTRACT The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway has been considered as a potential target for neuroprotection in stroke. The aim of present study was to determine whether corilagin, a novel Nrf2 activator, can protect against ischemia-reperfusion injury and explore the underlying mechanism involved. In vivo , rats exposed to middle cerebral artery occlusion were applied to establish an ischemic stroke model. Posttreatment of corilagin significantly reduced infarct volumes and apoptotic cells as well as improved neurologic score after reperfusion, together with increased vascular density in the ischemic penumbra. Meanwhile, posttreatment with corilagin in MCAO rats significantly decreased malondialdehyde levels, restored the superoxide dismutase and glutathione activity, elevating the Nrf2, heme oxygenase-1, the vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) expression. However, consecutive intrathecal injection of short interference RNAs targeting Nrf2 at 24-h intervals 72 h before ischemia reduced the beneficial effects of corilagin. In primary cultured neurons, corilagin dose-dependently protected against oxygen and glucose deprivation-induced insult, but the protective effect of corilagin was attenuated by knockdown of Nrf2. In conclusion, these findings indicate that corilagin exerts protective effects against cerebral ischemic injury by attenuating oxidative stress and enhancing angiogenesis via activation of Nrf2 signaling pathway.