Department of Pharmacology, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P.R. China.
Food Funct. 2020 Feb 26;11(2):1754-1763. doi: 10.1039/c9fo02037c.
Carvacryl acetate (CA) is a semisynthetic monoterpenic ester obtained from essential oils, and it exerts an antioxidation effect. The purpose of our study was to investigate whether CA could provide neuroprotection against oxidative stress caused by cerebral ischemia-reperfusion injury (CIRI) and elucidate the underlying mechanism. Middle cerebral artery occlusion (MCAO)-induced damage was established in Sprague Dawley (SD) rats and PC12 cells were exposed to hydrogen peroxide (H2O2) to imitate oxidative stress damage. TTC, HE and Nissl staining were used to observe the pathological morphology of lesions. The contents of ROS and MDA, and the activity of SOD were measured to reflect the level of oxidative stress. In addition, the TUNEL method was used to assess injuries in vitro, and the expression of Nrf2 was determined by immunohistochemical staining and western blot analysis. Importantly, we constructed and validated Nrf2 knockdown PC12 cells to confirm the key role of Nrf2 in the neuroprotective effect of CA against oxidative stress injuries. CA alleviated CIRI in rats with MCAO, as shown by brain tissue pathophysiology. The contents of ROS and MDA were reduced, and the SOD activity was augmented by the simultaneous promotion of Nrf2 expression. In addition, the H2O2-induced injury in Nrf2-knockdown PC12 cells was more serious than it was in control cells, and CA-mediated neuroprotection was exclusively inhibited by the knock down of Nrf2 in PC12 cells. In conclusion, it is shown here that CA has the effect of relieving cerebral ischemia reperfusion-induced oxidative stress injury via the Nrf2 signalling pathway.
醋酸香芹酯（CA）是一种从精油中提取的半合成单萜酯，具有抗氧化作用。本研究旨在探讨 CA 是否能对脑缺血再灌注损伤（CIRI）引起的氧化应激提供神经保护作用，并阐明其潜在机制。采用大脑中动脉闭塞（MCAO）诱导损伤建立 Sprague Dawley（SD）大鼠模型，并用过氧化氢（H2O2）处理 PC12 细胞模拟氧化应激损伤。TTC、HE 和尼氏染色用于观察病变的病理形态。测量 ROS 和 MDA 含量以及 SOD 活性以反映氧化应激水平。此外，采用 TUNEL 法评估体外损伤，并用免疫组化染色和 Western blot 分析测定 Nrf2 的表达。重要的是，我们构建并验证了 Nrf2 敲低 PC12 细胞，以确认 Nrf2 在 CA 对氧化应激损伤的神经保护作用中的关键作用。CA 减轻了 MCAO 大鼠的 CIRI，这表现在脑组织的病理生理学上。ROS 和 MDA 的含量减少，SOD 活性增加，同时促进了 Nrf2 的表达。此外，Nrf2 敲低的 PC12 细胞中 H2O2 诱导的损伤比对照细胞更严重，而 CA 介导的神经保护作用仅被 PC12 细胞中 Nrf2 的敲低所抑制。总之，本研究表明 CA 通过 Nrf2 信号通路缓解脑缺血再灌注引起的氧化应激损伤。
