Thymoquinone reduces mortality and suppresses early acute inflammatory markers of sepsis in a mouse model

Background: Sepsis is a severe systemic condition caused by an excessive inflammatory response to microbial infections, which often results in high mortality. Aims: In the present study, the therapeutic effects of thymoquinone were investigated for Gram-negative bacteria-induced sepsis in mice. Methods: Thymoquinone was administered as 1 or 2 mg/kg intraperitoneally 2 h after Escherichia coli (E. coli) challenge. Animal morality was assessed up to 96 h post infection and inflammatory proteins levels were measured 6 h after thymoquinone treatment in various groups using enzyme-linked immunosorbent assay (ELISA) techniques. Key findings: The E. coli inoculation markedly increased the level of plasma cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-2, IL-6 and IL-10. In addition, the levels of selected early sepsis biomarkers such as CRP, VEGF and ESM-1 were amplified in the septic group. Treatment with thymoquinone significantly downregulated the circulating concentrations of the inflammatory proteins (p < 0.05). In addition, similar to 75% of mice in the thymoquinone (1 mg/kg) group survived at 96h of observation compared with similar to 8% of the untreated group (p = 0.0016). Significance: The present results indicate that thymoquinone suppresses acute inflammatory responses induced by sepsis including early stage biomarkers and reduces sepsis-related mortality. These findings suggest that thymoquinone could be of a potential therapeutic value in the management of sepsis.