* 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.
† Medical College of Dalian University, Dalian 251122, Liaoning Province, China.
Am J Chin Med. 2019;47(3):577-594. doi: 10.1142/S0192415X19500307. Epub 2019 Apr 11.
Thymoquinone (TQ) is a main aromatic component of L. seeds or (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 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.
姜酮（TQ）是 L. 种子或（Fisch. & C.A.Mey.）Kuntze 的主要芳香成分。然而，TQ 对醋氨酚（APAP）诱导的急性肝损伤的保护机制尚不清楚。我们旨在研究 TQ 对 APAP 诱导的急性肝损伤发展的肝保护机制。雄性昆明小鼠在单次 APAP 注射前用 TQ 或 N-乙酰半胱氨酸（NAC）预处理。人 Chang 肝细胞在存在 APAP 的情况下用 TQ、SP600125 或 AICAR 孵育 24 小时。TQ 预处理通过抑制 CYP2E1 表达降低血清转氨酶水平，增加肝谷胱甘肽和谷胱甘肽过氧化物酶活性。TQ 抑制 APAP 诱导的 JNK、ERK 和 P38 磷酸化。同时，TQ 抑制 PI3K/mTOR 信号激活并激活 AMPK 磷酸化。此外，TQ 防止了 Bcl-2 和 Bax 调节的 APAP 诱导的肝细胞凋亡。此外，TQ 抑制了 APAP 诱导的急性肝损伤中 STAT3 的磷酸化。此外，TQ 还显著抑制了 P2X7R 蛋白表达和 IL-1 的释放。在 Chang 肝细胞中也观察到 APAP 增强的 JNK 磷酸化和 APAP 抑制的 AMPK 磷酸化，这些变化通过用 TQ、SP600125 和 AICAR 预处理得到恢复。我们的研究结果表明，TQ 可能积极预防 APAP 诱导的急性肝损伤，其作用可能是通过 JNK 和 AMPK 信号通路介导的。
