ABSTRACT
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 ß 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.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Acetaminophen/administration & dosage , Acetaminophen/adverse effects , Benzoquinones/pharmacology , Benzoquinones/therapeutic use , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/prevention & control , Drug Overdose/complications , MAP Kinase Signaling System/drug effects , Phytotherapy , Signal Transduction/drug effects , Animals , Apoptosis/drug effects , Cells, Cultured , Chemical and Drug Induced Liver Injury/metabolism , Disease Models, Animal , Hepatocytes/drug effects , Humans , Inflammation , Male , MiceABSTRACT
Rhodiola rosea is a perennial plant which grows in the alpine regions of Europe and Asia. Although the protective effects of R. rosea extract from fatigue due to exercise stress have been reported, studies on fermented R. rosea extract remain insufficient to date. Therefore, this study was conducted to examine the protective effects of fermented R. rosea extract against fatigue and exercise stress. As a result, fermented R. rosea extract was found to significantly increase swimming time, hepatic superoxide dismutase content, and serum lactate dehydrogenase in mice, while decreasing serum blood urea nitrogen content compared to R. rosea extract. Given the above results, it is considered that fermented R. rosea extract effectively protects against fatigue caused by strenuous exercise.
