Thymoquinone Attenuates Acetaminophen Overdose-Induced Acute Liver Injury and Inflammation Via Regulation of JNK and AMPK Signaling Pathway.

Autor:	Cui BW; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Bai T; † Medical College of Dalian University, Dalian 251122, Liaoning Province, China., Yang Y; † Medical College of Dalian University, Dalian 251122, Liaoning Province, China., Zhang Y; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Jiang M; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Yang HX; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Wu M; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Liu J; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Qiao CY; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Zhan ZY; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Wu YL; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Kang DZ; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Lian LH; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China., Nan JX; Key Laboratory for Natural Resource of Changbai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Clinical Research Center, Yanbian University Hospital, Yanji 133002, Jilin Province, China.
Jazyk:	angličtina
Zdroj:	The American journal of Chinese medicine [Am J Chin Med] 2019; Vol. 47 (3), pp. 577-594. Date of Electronic Publication: 2019 Apr 11.
DOI:	10.1142/S0192415X19500307
Abstrakt:	Thymoquinone (TQ) is a main aromatic component of Nigella sativa L. seeds or Agastache rugosa (Fisch. & C.A.Mey.) Kuntze. The protective mechanism of TQ against acute liver injury induced by acetaminophen (APAP), however, remains unclear. We aimed to investigated the hepato-protective mechanism of TQ on the development of APAP-induced acute liver injury. Male kunming mice were pretreated with TQ or N-acetylcysteine (NAC) before a single APAP injection. Human Chang liver cells were incubated with TQ, SP600125 or AICAR in presence of APAP for 24 h. TQ pretreatment reduced 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 acute liver injury. In addition, TQ significantly inhibited P2X7R protein expression and IL-1 β release. APAP-enhanced JNK phosphorylation and APAP-suppressed AMPK phosphorylation were 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 acute liver injury, and the effect may be mediated by JNK and AMPK signaling pathways.
Databáze:	MEDLINE
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