Anti-resorptive saurolactam exhibits in vitro anti-inflammatory activity via ERK-NF-kappa B signaling pathway

作者：Lee Su Ui; Choi Yeon Hee; Kim Young Sup; Min Yong Ki; Rhee Myungchull^*; Kim Seong Hwan

来源：International Immunopharmacology, 2010, 10(3): 298-303.

DOI：10.1016/j.intimp.2009.11.014

• Saurolactam
• Inflammation
• Extracellular signal-regulated kinase
• Mitogen-activated protein kinase
• Nuclear factor-kappa B

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 mu M) significantly inhibited the LPS-induced mRNA and protein expression levels of pro-inflammatory genes, including interleukin (IL)-1 beta, 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)-kappa B translocation into the nucleus. The inhibitory activity of saurolactam on the activation of NF-kappa B was confirmed by a NF-kappa B 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-kappa B activation.

• 出版日期2010-3