Piperine is the key bioactive factor in black pepper, and has been reported to alleviate cerebral ischemic injury. However, the mechanisms underlying its neuroprotective effects following cerebral ischemia remain unclear. In this study, rats were administered vehicle (dimethyl sulfoxide) or piperine, 20 mg/kg, daily for 14 days before focal cerebral artery occlusion. After occlusion for 2 h followed by reperfusion for 24 h. Histological examinations were used to assess whether piperine has a neuroprotective effect in the rat model of cerebral ischemia/reperfusion injury. The levels of proteins in the ischemic penumbra were evaluated by isobaric tags for relative and absolute quantitation-based proteomics. A total of 3687 proteins were identified, including 23 proteins that were highly significantly differentially expressed between the control and piperine groups. The proteomic findings were verified by immunofluorescence and western blot analysis. Interestingly, piperine administration downregulated a number of critical factors in the complement and coagulation cascades, including complement component 3, fibrinogen gamma chain, alpha-2-macroglobulin, and serpin family A member 1. Collectively, our findings suggest that the neuroprotective effects of piperine following cerebral ischemia/reperfusion injury are related to the regulation of the complement and coagulation cascades.

中文翻译：

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基于定量iTRAQ的蛋白质组学分析对胡椒碱保护的大鼠脑缺血/再灌注损伤。

胡椒碱是黑胡椒中的关键生物活性因子，据报道可减轻脑缺血性损伤。然而，尚不清楚其在脑缺血后其神经保护作用的潜在机制。在这项研究中，在局灶性脑动脉闭塞之前，每天给大鼠施用媒介物（二甲亚砜）或胡椒碱20 mg / kg，持续14天。闭塞2小时后，再灌注24小时。使用组织学检查来评估胡椒碱在脑缺血/再灌注损伤的大鼠模型中是否具有神经保护作用。通过等压标记评估基于相对定量和绝对定量的蛋白质组学方法，评估缺血半影中蛋白质的水平。总共鉴定出3687种蛋白质，包括在对照组和胡椒碱组之间高度显着差异表达的23种蛋白质。蛋白质组学发现通过免疫荧光和蛋白质印迹分析得到了证实。有趣的是，胡椒碱管理下调了补体和凝血级联反应中的许多关键因素，包括补体成分3，纤维蛋白原γ链，α-2-巨球蛋白和丝氨酸蛋白酶抑制剂家族A成员1。总的来说，我们的发现表明胡椒碱的神经保护作用脑缺血/再灌注损伤后的发生与补体和凝血级联的调节有关。