Chebulinic acid attenuates glutamate-induced HT22 cell death by inhibiting oxidative stress, calcium influx and MAPKs phosphorylation

• Published in: Bioorganic & medicinal chemistry letters Vol. 28; no. 3; pp. 249 - 253
• Main Authors: Song, Ji Hoon, Shin, Myoung-Sook, Hwang, Gwi Seo, Oh, Seong Taek, Hwang, Jung Jin, Kang, Ki Sung
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2018
• Subjects: Calcium; Chebulinic acid; Glutamate; HT22 cells; Mitogen-activated protein kinase; Reactive oxygen species; Mitogen-activated protein kinase; HT22 cells; Chebulinic acid; Reactive oxygen species; Calcium; Glutamate
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.12.062

[Display omitted] Glutamate-induced excitotoxicity and oxidative stress is a major causative factor in neuronal cell death in acute brain injuries and chronic neurodegenerative diseases. The prevention of oxidative stress is a potential therapeutic strategy. Therefore, in the present study, we aimed to examine a potential therapeutic agent and its protective mechanism against glutamate-mediated cell death. We first found that chebulinic acid isolated from extracts of the fruit of Terminalia chebula prevented glutamate-induced HT22 cell death. Chebulinic acid significantly reduced intracellular reactive oxygen species (ROS) production and Ca2+ influx induced by glutamate. We further demonstrated that chebulinic acid significantly decreased the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, and p38, as well as inhibiting pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 protein expression. Moreover, we demonstrated that chebulinic acid significantly reduced the apoptosis induced by glutamate in HT22 cells. In conclusion, our results in this study suggest that chebulinic acid is a potent protectant against glutamate-induced neuronal cell death via inhibiting ROS production, Ca2+ influx, and phosphorylation of MAPKs, as well as reducing the ratio of Bax to Bcl-2, which contribute to oxidative stress-mediated neuronal cell death.