Anti-resorptive saurolactam exhibits in vitro anti-inflammatory activity via ERK-NF-kappaB signaling pathway.
Natural products and their derivatives have historically been an invaluable a source of therapeutic agents. In this report, we demonstrated the anti-inflammatory activity of saurolactam, a compound isolated from the aerial portions of the Chinese lizard, Saururus chinensis. In RAW264.7 macrophage cells, saurolactam significantly inhibited the lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 and, consequently, inhibited the release of NO and prostaglandin E2. Moreover, real-time PCR and multiplex cytokine assays showed that saurolactam (10 microM) significantly inhibited the LPS-induced mRNA and protein expression levels of pro-inflammatory genes, including interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha. Finally, western blot analysis showed that saurolactam dose-dependently inhibited LPS-induced extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase activation and nuclear factor (NF)-kappaB translocation into the nucleus. The inhibitory activity of saurolactam on the activation of NF-kappaB was confirmed by a NF-kappaB luciferase reporter gene assay. In conclusion, we propose that the in vitro anti-inflammatory activity of saurolactam is produced by blocking ERK/MAP kinase and NF-kappaB activation.
Lee
Su-Ui
SU
Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, Yuseong-gu, Daejeon, South Korea.
Choi
Yeon Hee
YH
Kim
Young Sup
YS
Min
Yong Ki
YK
Rhee
Myungchull
M
Kim
Seong Hwan
SH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D017930:Genes, Reporter / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D054833:Isoindoles / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D032134:Saururaceae / Q000737:chemistry; D015398:Signal Transduction / Q000502:physiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016207:Cytokines; D018836:Inflammation Mediators; D054833:Isoindoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C549632:saurolactam; D009569:Nitric Oxide; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone