Thymoquinone Exerts Hepatoprotective and Immune Modulatory Effects Mediated by Downregulation of NF‐κB Pathway in Concanavalin A Induced Immune Mediated Liver Damage

Background Immune hepatitis is an inflammatory disorder has been increasing in incidence. Concanavalin A (Con A)‐induced hepatitis is a widely used model, which represents the acute immune‐mediated liver damage model in mice. Many research efforts recently oriented to explore the potential therapeutic activity of the natural products to develop a more eective therapeutic strategies in hepatitis. Here, we investigate the immunomodulatory and liver protective effects of thymoquinone (TQ), the principal active constituent of Nigella sativa oil, using Con A‐induced immune mediated liver damage in mice. Methods : Twenty‐four mice were allocated into 4 groups each with 6: non treated negative control group, Con A treated as a model control group (20mg/Kg I.V.), two treatment groups received TQ 15mg/Kg/day and 30mg/Kg/day orally starting 4 days before Con A. Animals euthanized 8hrs after Con A injection. Results we showed that improved liver damage markers ALT and AST in a dose dependent pattern. For ALT, serum levels significantly reduced in mice treated with TQ 15mg/kg (37.09±10.74 IU/L) and 30mg/kg (31.12±3.82 IU/L) compared to model control group level (122.14±3.33 IU/L). Similar results obtained with AST, were serum levels attenuated in both treatment doses of TQ 15mg/kg (113.84±13.86 IU/L) and 30mg/kg (80.1±11.27 IU/L) compared to model control group (183.65±5.11 IU/L). Inflammatory marker TNFα were also evaluated. We reported that hepatic TNFα levels significantly and dose‐dependently attenuated in mice treated with TQ 15mg/kg (24.27±2.1pg/mg) and 30mg/kg (17.67±1.58 pg/mg) compared to model control group (44.59±2.05 pg/mg). In the same context, INFγ also significantly and dose‐dependently reduced by the administration of TQ 15mg/kg and 30mg/kg compared to model control group. Hepatic INFγ reported were (1.39±0.02pg/mg) and (0.81±0.018 pg/mg) vs. (2.23±0.052 pg/mg), respectively. We also evaluated gene expression of NF‐κB as the upstream inducer of the inflammatory events. Here we showed that hepatic NF‐κB gene expression significantly and dose dependently attenuated in mice treated with TQ 15mg/kg (2.03±0.29) and 30mg/kg (1.6±0.16) compared to model control group (3.56±0.55). In summary, TQ exerted hepatoprotective, anti‐inflammatory effects and immune modulatory effects mediated through downregulation of NF‐κB in Con A induced immune mediated liver damage.