Hepato-protective effect of thymoquinone against acetaminophen-induced liver injury is linked with regulation of JNK and AMPK signaling pathway

[Speaker] Ben-Wen Cui:1
[Co-author] Yu Zhang:1, Xia Li:1, Xin Han:1, Yan-Ling Wu:1, Ji-Xing Nan:1, Li-Hua Lian:1
1:Yanbian Univerisity, China

Thymoquinone (TQ), the main aromatic component of Nigella sativa L. seeds or Agastache rugose. We aimed to investigated the hepato-protective mechanism of TQ on the development of acetaminophen (APAP)-induced liver injury. Male kunming mice were pretreated with TQ or N-acetylcysteine before a single APAP injection. And human Chang liver cells were incubated with TQ, SP600125 or AICAR in the presence of APAP for 24 h. TQ pretreatment reduced the levels of serum aminotransferases and increased hepatic glutathione and glutathione peroxidase activities via inhibiting CYP2E1 expression. TQ inhibited JNK, ERK and P38 phosphorylation induced by APAP. Meanwhile, TQ inhibited PI3K/mTOR signaling activation and activated AMPK phosphorylation. Moreover, TQ prevented APAP-induced hepatocytes apoptosis regulated by Bcl-2 and Bax. Furthermore, TQ inhibited STAT3 phosphorylation on APAP-induced liver injury. In addition, TQ significantly inhibited P2X7R protein expression and IL-1alpha release. APAP-Enhanced JNK phosphorylation and -suppressed AMPK phosphorylation was also observed in Chang liver cells, and these changes were recovered by pretreatment with TQ, SP600125 and AICAR. Our findings suggest that TQ may actively prevent APAP-induced liver injury, and this effect may be mediated by JNK and AMPK signaling pathways.
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