Int J Oral Biol.  2024 Mar;49(1):10-17. 10.11620/IJOB.2024.49.1.10.

Neuroprotective mechanism of corydaline in glutamate-induced neurotoxicity in HT22 cells

Affiliations
  • 1Natural Product Research Center, Institute of Natural Product, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea
  • 2Convergence Research Center of Dementia, Brain Science Institute, Korea Institute of Science and Technology, Seoul 02792, Republic of Korea
  • 3Division of Bio-Medical Science and Technology, University of Science and Technology, Daejun 34113, Republic of Korea
  • 4Department of Biochemistry and Molecular Biology, Research Institute of Oral Science, College of Dentistry, Gangneung Wonju National University, Gangneung 25457, Republic of Korea
  • 5Department of Anatomy, College of Dentistry, Gangneung Wonju National University, Gangneung 25457, Republic of Korea
  • 6Natural Product Informatics Research Center, Institute of Natural Product, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea
  • 7Institute of Natural Product Chemistry, Vietnam Academy of Science and Technology, Hanoi, Vietnam

Abstract

Glutamate-mediated oxidative stress causes neuronal cell death by increasing intracellular Ca2+ uptake, reactive oxidative species (ROS) generation, mitogen-activated protein kinase (MAPK) activation, and translocation of apoptosis-inducing factor (AIF) to the nucleus. In the current study, we demonstrated that corydaline exerts potent neuroprotective effects against glutamate-induced neurotoxicity. Treatment with 5 mmol/L glutamate increased cellular Ca2+ influx, ROS generation, MAPK activation, and AIF translocation. In contrast, corydaline treatment decreased cellular Ca2+ influx and ROS generation. Western blot analysis revealed that glutamate-mediated MAPK activation was attenuated by corydaline treatment. We further demonstrated that corydaline treatment inhibited the glutamate-mediated translocation of AIF to the nucleus. We propose that corydaline is a promising lead structure for the development of safe and effective neuroprotectants.

Keyword

Glutamate-induced neurotoxicity; HT22 mouse hippocampal neuronal cells; Corydaline
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