BPB Reports

Paper Details

BPB Reports
Vol. 4 No. 5 p.155-161 2021
Huperzia serrata and the Constitute of Huperzine A Attenuate MK-801-Induced Cognitive Dysfunction in Mice via PKC-Erk Pathway
  • Hideaki Hara (Gifu Pharmaceutical University / hidehara@gifu-pu.ac.jp)
Takuya Ohba 1) , Honoka Fujimori 1) , Shinsuke Nakamura 1) , Yoshihiro Hayashi 2) , Hiroyuki Kono 2) , Masamitsu Shimazawa 1) , Hideaki Hara 1)
1) Gifu Pharmaceutical University , 2) Api Co. Ltd.
Received: December 11, 2020;   Accepted: July 28, 2021;   Released: September 30, 2021
Keywords: huperzia serrata, huperzine A, MK-801, NMDA receptor, cognitive dysfunction

N-methyl-D-aspartate (NMDA) receptor has important role in synapse function and neurotransmission by the high permeability of Ca2+. In Alzheimer's disease (AD), NMDA mediated neurotransmission is impaired by decreasing NMDA receptor subunits and increasing glutamate, which is an NMDA receptor ligand. Therefore, the NMDA antagonist (memantine) is used as a therapeutic drug of AD. Huperzia serrata is a traditional Chinese herbal medicine, and the constitute huperzine A has been reported to inhibit NMDA receptor. In this study, we clarified the effect of Huperzia serrata and the constitute huperzine A on MK-801-induced cognitive dysfunction. Memantine, Huperzia serrata and huperzine A were administered orally once a day and Y-maze test was performed at day 7 to investigate cognitive function. After Y-maze test, mice brains were collected and evaluated the expression levels of glutamate receptors and Ca2+ signalling associated protein. Memantine (5 mg/kg, p.o.), Huperzia serrata (1000 mg/kg, p.o.) and huperzine A (0.7 mg/kg, p.o.) were improved collect alternation behaviour in Y-maze test. Treatment of memantine, Huperzia serrata and huperzine A also improved the total arm entries increased by MK-801. The expression level of NMDA receptor subunit NR2A was increased by Huperzia serrata and huperzine A treatment. In addition, the decreased expression level of PKCĪ± and phosphorylation of Erk1/2 by MK-801 were improved. These results suggest that Huperzia serrata and the constitute huperzine A improve cognitive dysfunction through NMDA receptor function and glutaminergic signaling pathway.