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.
Department of Neurosurgery, Affiliated Longhua People's Hospital, Southern Medical University, Guangzhou, China.
Psychopharmacology (Berl). 2020 Nov;237(11):3283-3293. doi: 10.1007/s00213-020-05610-z. Epub 2020 Jul 29.
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.
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.
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.
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.
缺血性脑卒中是一种严重的心血管疾病，具有高发病率和死亡率，影响着全球数百万人。目前，唯一被证明对急性缺血性脑卒中有效的治疗方法是阿替普酶，但它仍然存在许多缺点和局限性。因此，我们从中药中筛选新的化合物，以探索其对缺血再灌注损伤的疗效。原花青素是一种从葡萄籽中提取的天然产物，已被证明可以改善脑缺血损伤。然而，其潜在机制尚不清楚。本研究旨在探讨原花青素对大脑中动脉闭塞/再灌注（MCAO/R）介导的脑缺血损伤的影响及其潜在的可能机制。
采用 SD 大鼠评估原花青素对体内 MCAO/R 诱导的脑缺血损伤的影响。采用组织学分析评估神经元凋亡情况。采用 Western blot 检测细胞信号。
在这项研究中，我们发现原花青素可以显著改善大脑中动脉闭塞/再灌注（MCAO/R）介导的神经功能缺损，并减轻脑水肿、脑梗死体积、组织病理学损伤和大鼠细胞凋亡。此外，原花青素还可以显著抑制 TLR4-p38-NF-κB-NLRP3 信号通路在体外和体内的MCAO/R 和氧葡萄糖剥夺/再氧合（OGD/R）介导的激活。此外，原花青素可以抑制 MCAO/R 和 OGD/R 诱导的炎症细胞因子如白细胞介素-1β（IL-1β）在体外和体内的产生。此外，BV2 细胞中 TLR4 抑制剂（Cli-095）的治疗也表现出相同的效果。
综上所述，这些数据表明，原花青素通过抑制 TLR4-p38-NF-κB-NLRP3 信号通路在 MCAO/R 大鼠的脑内发挥潜在的神经保护作用。
