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

  • Baskar Selvaraj (Natural Product Research Center, Institute of Natural Product, Korea Institute of Science and Technology) ;
  • Dae Won Kim (Department of Biochemistry and Molecular Biology, Research Institute of Oral Science, College of Dentistry, Gangneung Wonju National University) ;
  • Ki-Yeon Yoo (Department of Anatomy, College of Dentistry, Gangneung Wonju National University) ;
  • Keunwan Park (Natural Product Informatics Research Center, Institute of Natural Product, Korea Institute of Science and Technology) ;
  • Thi Thu Thuy Tran (Institute of Natural Product Chemistry, Vietnam Academy of Science and Technology) ;
  • Jae Wook Lee (Natural Product Research Center, Institute of Natural Product, Korea Institute of Science and Technology) ;
  • Heesu Lee (Department of Anatomy, College of Dentistry, Gangneung Wonju National University)
  • Received : 2024.02.13
  • Accepted : 2024.03.08
  • Published : 2024.03.31

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.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea and KIST internal grants (grant number NRF-2019K1A3A1A82113697, 2Z06821, and 2Z06983).

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