| Summary: | Acute liver injury is a type of liver diseases, and it has raised concerns worldwide due to the lack of effective therapies. The aim of this study is to investigate the protective effects of nootkatone (NOOT) on carbon tetrachloride (CCl<sub>4</sub>)-caused acute liver injury in mice. Mice were randomly divided into control, CCl<sub>4</sub> model, NOOT, and NOOT (5, 10, and 20 mg/kg/day) plus CCl<sub>4</sub> groups, respectively. Mice in the CCl<sub>4</sub> plus NOOT groups were orally administrated with NOOT at 5, 10, and 20 mg/kg/days for seven days prior to 0.3% CCl<sub>4</sub> injection at 10 mL/kg body weight, respectively. Our results showed that NOOT supplementation significantly ameliorated CCl<sub>4</sub>-induced increases of serum AST and ALT levels, hepatocyte necrosis, inflammatory response, oxidative stress, and caspases-9 and -3 activities in the livers of mice. Moreover, NOOT supplementation significantly upregulated the expression of Nrf2 and HO-1 mRNAs but downregulated the expression of NF-κB mRNAs and the levels of IL-1β, IL-6, and TNF-α proteins in the liver tissues, compared to those in the CCl<sub>4</sub> model group. In conclusion, for the first time, our results reveal that NOOT could offer protective effects against CCl<sub>4</sub>-caused oxidative stress and inflammatory response via the opposite regulation of Nrf2/HO-1 pathway and NF-κB pathway.
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