LAUSR

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.