Biological evaluation for anti-inflammatory effect of africane-type sesquiterpenoids

Africane-type sesquiterpenoids are a unique tricyclic carbon architecture sesquiterpenoid isolated as natural products. Δ⁹⁽¹⁵⁾ -africanene has been reported to exhibit anti-inflammatory activity for carrageenan-induced rat foot edema. In this study, we reported structure–activity relationship study of africane-type sesquiterpenoids and found that some africane-type sesquiterpenoid analogs and their synthetic intermediate showed potent anti-inflammatory activity. To identify the mode of action of africane-type sesquiterpenoids and their synthetic intermediate, we evaluated the anti-inflammatory activity using lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. Treatment with the africane-type compounds and their synthetic intermediate suppressed LPS-induced expressions of Cox-2 protein and mRNAs of the inflammatory cytokines IL-1β and IL-6 at the concentrations that did not affect cell viability. Interestingly, although these africane-type compounds and their synthetic intermediate suppressed the pro-inflammatory cytokines’ expressions, the compounds did not modulate NF-κB activation. These results suggest that the africane-type compounds and their synthetic intermediate are anti-inflammatory compounds that suppress the expression of LPS-induced inflammatory mediators independently of NF-κB activation.