Bo Yang1,2, Yanxia Sun3, Chunchao Lv2, Wei Zhang4, Yizhao Chen5,6. 1. Department of Neurosurgery, Zhujiang Hospital, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Engineering Technology Research Center of Education Ministry of China, Southern Medical University, Guangzhou, 510282, China. 2. Department of Neurosurgery, Affiliated Longhua People's Hospital, Southern Medical University, Guangzhou, China. 3. Department of Cardiology, Affiliated Longhua People's Hospital, Southern Medical University, Guangzhou, China. 4. Department of Neurosurgery, Ji Mine Hospital, Ji Xi, Heilongjiang Province, China. 5. Department of Neurosurgery, Zhujiang Hospital, The National Key Clinical Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Engineering Technology Research Center of Education Ministry of China, Southern Medical University, Guangzhou, 510282, China. cyz2020_sci@163.com. 6. Department of Neurosurgery, Zhujiang Hospital, No. 253, middle Industrial Avenue, Guangzhou, 510280, Guangdong Province, China. cyz2020_sci@163.com.
Abstract
BACKGROUND: Ischemic stroke is a serious cardiovascular disease with high morbidity and mortality rates that affects millions of people worldwide.Currently, the only therapy with proven efficacy for acute ischemic stroke is alteplase, however, it still has many shortcomings and limitations. Therefore,we screen new compounds from traditional Chinese medicine to explore their efficacy against ischemic reperfusion injury. Procyanidins, a natural productextracted from grapes seed, which have been shown can ameliorate cerebral ischemic injury. However, the underlying mechanism is still not very clear. Theaim of this study was to investigate the effect of procyanidins on middle cerebral artery occlusion/reperfusion (MCAO/R)-mediated cerebral ischemic injuryand its underlying possible mechanisms. METHODS: SD rats were used to evaluate the effect of procyanidins on MCAO/R induced cerebral ischemic injury in vivo. Histological analysis was used toassess neuronal apoptosis. Cell signaling was assayed by Western blot. RESULTS: In this study, we found that procyanidins can significantly ameliorate the middle cerebral artery occlusion/reperfusion (MCAO/R)-mediatedneurological deficits, and relieved brain edema, cerebral infarction volume, histopathological damage and apoptosis in rats. In addition, procyanidins canalso markedly inhibit MCAO/R and oxygen-glucose deprivation/reoxygenation (OGD/R)-mediated activation of TLR4-p38-NF-κB-NLRP3 signalingpathway in vitro and in vivo. Moreover, procyanidins can inhibit MCAO/R and OGD/R-induced the production of inflammatory cytokines such asinterleukin-1β (IL-1β) in vitro and in vivo. Besides, treatment with TLR4 inhibitor (Cli-095) in BV2 cell also shows the same effect. CONCLUSION: Altogether, these data suggested that procyanidins exerted a potential neuroprotective effect may by inhibit the TLR4-p38-NF-κB-NLRP3signaling pathway in the brain in MCAO/R rats.
BACKGROUND:Ischemic stroke is a serious cardiovascular disease with high morbidity and mortality rates that affects millions of people worldwide.Currently, the only therapy with proven efficacy for acute ischemic stroke is alteplase, however, it still has many shortcomings and limitations. Therefore,we screen new compounds from traditional Chinese medicine to explore their efficacy against ischemic reperfusion injury. Procyanidins, a natural productextracted from grapes seed, which have been shown can ameliorate cerebral ischemic injury. However, the underlying mechanism is still not very clear. Theaim of this study was to investigate the effect of procyanidins on middle cerebral artery occlusion/reperfusion (MCAO/R)-mediated cerebral ischemic injuryand its underlying possible mechanisms. METHODS: SD rats were used to evaluate the effect of procyanidins on MCAO/R induced cerebral ischemic injury in vivo. Histological analysis was used toassess neuronal apoptosis. Cell signaling was assayed by Western blot. RESULTS: In this study, we found that procyanidins can significantly ameliorate the middle cerebral artery occlusion/reperfusion (MCAO/R)-mediatedneurological deficits, and relieved brain edema, cerebral infarction volume, histopathological damage and apoptosis in rats. In addition, procyanidins canalso markedly inhibit MCAO/R and oxygen-glucose deprivation/reoxygenation (OGD/R)-mediated activation of TLR4-p38-NF-κB-NLRP3 signalingpathway in vitro and in vivo. Moreover, procyanidins can inhibit MCAO/R and OGD/R-induced the production of inflammatory cytokines such asinterleukin-1β (IL-1β) in vitro and in vivo. Besides, treatment with TLR4 inhibitor (Cli-095) in BV2 cell also shows the same effect. CONCLUSION: Altogether, these data suggested that procyanidins exerted a potential neuroprotective effect may by inhibit the TLR4-p38-NF-κB-NLRP3signaling pathway in the brain in MCAO/R rats.