Bavachinin Induces Oxidative Damage in HepaRG Cells through p38/JNK MAPK Pathways

Toxins

Xiaobo Sun¹  Xiao Sun¹  Shan Wang²  Yu Tian²  Guibo Sun²  Min Wang³ 

[1] Peking Union Medical College, Beijing 100193, China;;Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences &Harbin University of Commerce, Harbin 150076, China;

关键词: drug-induced liver injury;    Bavachinin;    reactive oxygen species;    p38 MAPK;    JNK MAPK;   

DOI  :  10.3390/toxins10040154

来源: DOAJ

【 摘 要 】

Drug-induced liver injury is one of the main causes of drug non-approval and drug withdrawal by the Food and Drug Administration (FDA). Bavachinin (BVC) is a natural product derived from the fruit of the traditional Chinese herb Fructus Psoraleae (FP). There have been reports of acute liver injury following the administration of FP and its related proprietary medicines. To explore BVC hepatotoxicity and its mechanisms, we used the HepaRG cell line. In our recent research, we showed that BVC induces HepaRG cell death, mainly via BVC-induced oxidative damage. The formation of ROS is closely related to the activation of the stress-activated kinases, JNK and p38, while SP600125 (SP, JNK inhibitor) and SB203580 (SB, p38 inhibitor) pretreatment inhibited the generation of ROS. On the other hand, N-acetylcysteine (NAC) pretreatment prevented the phosphorylation of p38 but not that of JNK. Taken together, these data reveal that BVC induces HepaRG cell death via ROS and the JNK/p38 signaling pathways.

【 授权许可】

Unknown