Inhibitory Effects of β-Chamigrenal, Isolated from the Fruits of Schisandra chinensis, on Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production in RAW 264.7 Macrophages

Much is known about the bioactive properties of lignans from the fruits of Schisandra chinensis. However, very little work has been done to determine the properties of sesquiterpenes in the fruits of S. chinensis. The aim of the present study was to investigate the anti-inflammatory potential of new sesquiterpenes (beta-chamigrenal, beta-chamigrenic acid, alpha-ylangenol, and alpha-ylangenyl acetate) isolated from the fruits of S. chinensis and to explore their effect on macrophages stimulated with lipopolysaccharide. Of these four sesquiterpenes, beta-chamigrenal most significantly suppressed lipopolysaccharide-induced nitric oxide and prostaglandin E-2 production in RAW 264.7 macrophages (47.21 +/- 4.54% and 51.61 +/- 3.95% at 50 mu M, respectively). Molecularly, the inhibitory activity of beta-chamigrenal on nitric oxide production was mediated by suppressing inducible nitric oxide synthase activity but not its expression. In the prostaglandin E-2 synthesis pathway, beta-chamigrenal prevented the upregulation of inducible microsomal prostaglandin E synthase-1 expression after stimulation with lipopolysaccharide. Conversely, beta-chamigrenal had no effect on the expression and enzyme activity of cyclooxygenase-2. In addition, the expression of early growth response factor-1, a key transcription factor of microsomal prostaglandin E synthase-1 expression, was inhibited by beta-chamigrenal. These results may suggest a possible anti-inflammatory activity of beta-chamigrenal which has to be proven in in vivo experiments.