title: Anti-inflammatory activity of diterpenes from Croton stellatopilosus on LPS-induced RAW264.7 cells.
abstract: An acyclic diterpene (plaunotol; 1) and two furanoditerpenes (plaunolide, 2 and plaunol E, 3), were isolated from Croton stellatopilosus leaves, and assessed for their inhibitory activity on nitric oxide (NO) production by lipopolysaccharide (LPS)-induced RAW264.7 cells. Plaunotol, plaunolide and plaunol E exhibited inhibitory activity with IC(50) values of 3.41, 17.09 and 2.79 μM, respectively. Cytotoxic effects were observed at concentrations of ≥100 μM for plaunotol and ≥10 μM for plaunol E. In order to understand the mechanism of this anti-inflammatory activity, transcription profiles of the COX-1, COX-2 and iNOS genes were measured using a quantitative RT-PCR technique. The level of gene expression was expressed as a relative quantitation according to the comparative C (T) method. The results indicated that plaunotol stimulated the COX-1 and COX-2 genes, and suppressed expression of the iNOS gene. Treatment of cells with plaunolide caused a downregulation of the expressions of the COX-1, COX-2 and iNOS genes. In contrast, plaunol E inhibited the expression of the COX-2, stimulated COX-1 and iNOS expressions. In summary, the present study shows that different diterpenes from C. stellatopilosus leaves exhibit anti-inflammatory activity towards LPS-activated RAW264.7 cells by different mechanisms. Our results provide data to support further investigations into the possibility that these diterpenes could be alternatives to act as anti-inflammatory agents.
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Botany, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
authors.forename: Charoenwong
authors.initials: C
authors.lastname: Premprasert
authors.forename: Supinya
authors.initials: S
authors.lastname: Tewtrakul
authors.forename: Anuchit
authors.initials: A
authors.lastname: Plubrukarn
authors.forename: Juraithip
authors.initials: J
authors.lastname: Wungsintaweekul
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D002460:Cell Line; D029802:Croton / Q000737:chemistry*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D005233:Fatty Alcohols; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D005233:Fatty Alcohols; D008070:Lipopolysaccharides; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C047686:plaunotol