Anti-Obesity Effect of α-Cubebenol Isolated from Schisandra chinensis in 3T3-L1 Adipocytes

The efficacy of alpha-cubebenol isolated from Schisandra chinensis has been studied in several diseases, including cecal ligation, puncture challenge-induced sepsis, and degranulation of neutrophils. To identify the novel functions of alpha-cubebenol on lipid metabolism, alterations on the regulation of lipogenesis, lipolysis, and inflammatory response were observed in 3T3-L1 adipocytes treated with alpha-cubebenol. Most lipogenic targets, including lipid accumulation, level of lipogenic transcription factors, and expression of lipogenic regulators, were suppressed in MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-stimulated 3T3-L1 adipocytes treated with alpha-cubebenol without significant cytotoxicity. In addition, similar inhibition effects were observed in the iNOS-induced COX-2 mediated pathway and NLRP3 inflammasome pathway of MDI-stimulated 3T3-L1 cells treated with alpha-cubebenol. Lipolytic targets, such as cAMP concentration, expression of adenylyl cyclase and PDE4, and their downstream signaling pathway, in MDI-stimulated 3T3-L1 cells were stimulated by the alpha-cubebenol treatment. The levels of transcription factors and related proteins for beta-oxidation were significantly higher in the MDI + alpha-cubebenol treated group than in the MDI + Vehicle treated group. These results show that alpha-cubebenol has a novel role as a lipogenesis inhibitor, lipolysis and beta-oxidation stimulator, and inflammasome suppressor in MDI-stimulated 3T3-L1 adipocytes.