Nootkatone confers hepatoprotective and anti‐fibrotic actions in a murine model of liver fibrosis by suppressing oxidative stress, inflammation, and apoptosis

In this study, the hepatoprotective and anti‐fibrotic actions of nootkatone (NTK) were investigated using carbon tetrachloride (CCl4)‐induced liver fibrosis in mice. CCl4 administration elevated serum aspartate and alanine transaminases levels, respectively. In addition, CCl4 produced hepatic oxidative and nitrative stress, characterized by diminished hemeoxygenase‐1 expression, antioxidant defenses, and accumulation of 4‐hydroxynonenal and 3‐nitrotyrosine. Furthermore, CCl4 administration evoked profound expression of pro‐inflammatory cytokine expressions such as tumor necrosis factor‐α, monocyte chemoattractant protein‐1, and interleukin‐1β in hepatic tissues, which corroborated with nuclear factor κB activation. Additionally, CCl4‐treated animals exhibited higher apoptosis, characterized by increased caspase 3 activity, DNA fragmentation, and poly (ADP‐ribose) polymerase activation. Moreover, histological and biochemical investigations revealed marked fibrosis in the livers of CCl4‐administered animals. However, NTK treatment mitigated CCl4‐induced phenotypic changes. In conclusion, our findings suggest that NTK exerts hepatoprotective and anti‐fibrotic actions by suppressing oxidative stress, inflammation, and apoptosis.