Department of Radiotherapy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, P.R. China.
J Cell Biochem. 2018 Nov;119(10):8359-8367. doi: 10.1002/jcb.26919. Epub 2018 Jun 22.
Huperzine A (HupA), derived from Huperzia Serrata, has exhibited a variety of biological actions, in particular neuroprotective effect. However, the protective activities of HupA on murine embryonic fibroblast NIH3T3 cells after X-rays radiation have not been fully elucidated. Herein, HupA treatment dramatically promoted cell viability, abated a G0/G1 peak accumulation, and ameliorated increase of cell apoptosis in NIH3T3 cells after X-rays radiation. Simultaneously, HupA notably enhanced activities of anti-oxidant enzymes, inhibited activity of lipid peroxide, and efficiently eliminated production of reactive oxygen species in NIH3T3 cells after X-rays radiation. Dose-dependent increase of antioxidant genes by HupA were associated with up-regulated Nrf2 and down-regulated Keap-1 expression, which was confirmed by increasing nuclear accumulation, and inhibiting of degradation of Nrf2. Notably, augmented luciferase activity of ARE may explained Nrf2/ARE-mediated signaling pathways behind HupA protective properties. Moreover, expression of Nrf2 HupA-mediated was significant attenuated by AKT inhibitor (LY294002), p38 MAPK inhibitor (SB202190) and ERK inhibitor (PD98059). Besides, HupA-mediated cell viability, and ROS production were dramatically bated by LY294002, SB202190, and PD98059. Taken together, HupA effectively ameliorated X-rays radiation-induced damage Nrf2-ARE-mediated transcriptional response via activation AKT, p38, and ERK signaling in NIH3T3 cells.
石杉碱甲（HupA）来源于石杉属植物，具有多种生物学作用，特别是神经保护作用。然而，HupA 对 X 射线照射后鼠胚胎成纤维细胞 NIH3T3 细胞的保护作用尚未完全阐明。本文研究表明，HupA 处理可显著促进细胞活力，减轻 G0/G1 峰积聚，并改善 NIH3T3 细胞在 X 射线照射后的细胞凋亡增加。同时，HupA 明显增强了抗氧化酶的活性，抑制了脂质过氧化物的活性，并有效地消除了 NIH3T3 细胞在 X 射线照射后的活性氧的产生。HupA 依赖性增加抗氧化基因与上调 Nrf2 和下调 Keap-1 表达有关，这通过增加核积累和抑制 Nrf2 的降解来证实。值得注意的是，ARE 的增强的荧光素酶活性可以解释 HupA 保护特性背后的 Nrf2/ARE 介导的信号通路。此外，Nrf2 的表达被 AKT 抑制剂（LY294002）、p38 MAPK 抑制剂（SB202190）和 ERK 抑制剂（PD98059）显著减弱。此外，HupA 介导的细胞活力和 ROS 产生也被 LY294002、SB202190 和 PD98059 显著抑制。综上所述，HupA 通过激活 AKT、p38 和 ERK 信号通路，有效改善了 Nrf2-ARE 介导的转录反应，减轻了 X 射线照射诱导的损伤。
