Cyclohexylethanoid derivative and rearranged abietane diterpenoids with anti-inflammatory activities from Clerodendrum bungei and C. inerme

One new dimeric cyclohexylethanoid derivative (1) and one new rearranged abietane diterpenoid (2) were isolated from Clerodendrum bungei and C. inerme, respectively, together with 11 known compounds. The struc-tures of the isolated compounds were elucidated by detailed spectroscopic and ECD analyses. The absolute configuration of 2 was unequivocally determined using single-crystal X-ray diffraction analysis. Compound 1 showed the greatest inhibitory effect on NO production in RAW 264.7 murine macrophages induced by lipo-polysaccharide (LPS) with the IC50 value of 6.328 mu M. Compound 1 also suppressed the proinflammatory cy-tokines IFN-gamma, TNF-alpha, IL-1 beta, iNOS and IL-6 mRNA expression, while increased the mRNA expression of the anti-inflammatory cytokines IL-4, IL-10 and Arg-1 through NF-kappa B signaling pathway. The further experiments confirmed that compound 1 demonstrated the strong in vivo anti-inflammatory effect by reducing mortality, the serum TNF-alpha, IL-6 and IFN-gamma levels, and tissue toxicity in CLP-induced septic mice. Collectively, these findings suggested that compound 1 might serve as a potential anti-inflammatory agent candidate for the sepsis treatment.