Protective properties of Huperzine A through activation Nrf2/ARE-mediated transcriptional response in X-rays radiation-induced NIH3T3 cells

J Cell Biochem. 2018 Nov;119(10):8359-8367. doi: 10.1002/jcb.26919. Epub 2018 Jun 22.

Abstract

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.

Keywords: Huperzine A; NIH3T3 cells; Nrf2; X-rays radiation; protective effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Antioxidant Response Elements*
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Apoptosis / radiation effects
  • Catalase / genetics
  • Catalase / metabolism
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Cycle / radiation effects
  • Chromones / pharmacology
  • Flavonoids / pharmacology
  • Gene Expression Regulation
  • Glutathione Peroxidase / genetics
  • Glutathione Peroxidase / metabolism
  • Imidazoles / pharmacology
  • Kelch-Like ECH-Associated Protein 1 / antagonists & inhibitors
  • Kelch-Like ECH-Associated Protein 1 / genetics*
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Lipid Peroxides / antagonists & inhibitors
  • Lipid Peroxides / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Morpholines / pharmacology
  • NF-E2-Related Factor 2 / agonists
  • NF-E2-Related Factor 2 / genetics*
  • NF-E2-Related Factor 2 / metabolism
  • NIH 3T3 Cells
  • Oxidative Stress
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pyridines / pharmacology
  • Radiation-Protective Agents / pharmacology*
  • Reactive Oxygen Species / antagonists & inhibitors*
  • Reactive Oxygen Species / metabolism
  • Sesquiterpenes / pharmacology*
  • Signal Transduction
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • X-Rays
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Alkaloids
  • Chromones
  • Flavonoids
  • Imidazoles
  • Keap1 protein, mouse
  • Kelch-Like ECH-Associated Protein 1
  • Lipid Peroxides
  • Morpholines
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Pyridines
  • Radiation-Protective Agents
  • Reactive Oxygen Species
  • Sesquiterpenes
  • huperzine A
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Proto-Oncogene Proteins c-akt
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one