Wang Xiaokun, Li Ming, Cao Yuze, Wang Jianjian, Zhang Huixue, Zhou Xueling, Li Qian, Wang Lihua
Department of neurology, The Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China.
Intensive care unit, The Second Affiliated Hospital, Harbin Medical University, Harbin 150081, China.
Eur J Pharmacol. 2017 Aug 15;809:196-202. doi: 10.1016/j.ejphar.2017.05.004. Epub 2017 May 3.
Tenuigenin (TGN), a major active component of polygala tenuifolia root, has been reported to have anti-inflammatory effect. In this study, we investigated the anti-neuroinflammatory effects of TGN on LPS-induced inflammation both in vitro and in vivo. The levels of tumor necrosis factor -α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), and prostaglandin E2 (PGE) were measured by ELISA. The expression of Nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected by western blot analysis. The results showed that TGN strongly inhibited LPS-induced TNF-α, IL-1β, IL-6, and PGE production. The expression of Nrf2 and HO-1 were up-regulated by TGN in a dose-dependent manner. Furthermore, the anti-inflammatory effects of TGN were significantly inhibited by transfection with Nrf2 siRNA or protoporphyrin (SnPP), an HO-1 activity inhibitor. In vivo, TGN attenuated LPS-induced memory deficit in the Morris water maze and passive avoidance tasks. Also, TGN inhibited LPS-induced TNF-α and IL-1β expression in brain tissues. In conclusion, the results of this study indicated that TGN inhibited LPS-induced inflammatory responses in microglia via activating the Nrf2-mediated HO-1 signaling pathway.
远志皂苷元（TGN）是远志根的主要活性成分，据报道具有抗炎作用。在本研究中，我们研究了TGN在体外和体内对脂多糖（LPS）诱导的炎症的抗神经炎症作用。通过酶联免疫吸附测定（ELISA）测量肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和前列腺素E2（PGE）的水平。通过蛋白质印迹分析检测核因子E2相关因子2（Nrf2）和血红素加氧酶1（HO-1）的表达。结果表明，TGN强烈抑制LPS诱导的TNF-α、IL-1β、IL-6和PGE的产生。TGN以剂量依赖性方式上调Nrf2和HO-1的表达。此外，用Nrf2小干扰RNA（siRNA）或HO-1活性抑制剂原卟啉（SnPP）转染可显著抑制TGN的抗炎作用。在体内，TGN减轻了LPS诱导的Morris水迷宫和被动回避任务中的记忆缺陷。此外，TGN抑制LPS诱导的脑组织中TNF-α和IL-1β的表达。总之，本研究结果表明，TGN通过激活Nrf2介导的HO-1信号通路抑制LPS诱导的小胶质细胞炎症反应。
