title: Schizonepeta tenuifolia ethanol extract exerts anti-inflammatory activity through the inhibition of TLR4 signaling in lipopolysaccharide-stimulated macrophage cells.
abstract: Inflammatory diseases remain the leading cause of mortality worldwide in both men and women. Schizonepeta tenuifolia (ST) exerts a wide range of physiological activities and has been found to possess beneficial efficacies against inflammation-related diseases; however, the molecular mechanisms underlying this anti-inflammatory activity remain to be elucidated. We investigated the molecular basis for the downregulation of toll-like receptor 4 (TLR4) signal transduction by ST ethanol extract in lipopolysaccharide (LPS)-stimulated macrophages. In this study, ST ethanol extract (100 μg/mL) did not induce cell cytotoxicity and was used in all the following experiments. Treatment of LPS-stimulated macrophages with ST ethanol extract resulted in a significant decrease in cyclooxygenase-2 and prostaglandin E2 levels, and inducible nitric oxide synthase-mediated NO production. LPS-induced expression of cell surface molecules (CD80 and CD86) and production of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β, and IL-6) were inhibited by ST ethanol extract. Further, we also found that the anti-inflammatory activities of ST ethanol extract was caused by inhibition of LPS-induced activation of mitogen-activated protein kinases, such as extracellular signal-regulated kinase 1/2 and p38, and the translocation of nuclear factor κB through TLR4 in macrophages. Thus, ST ethanol extract may possess novel and potent therapeutic efficacy for the treatment of inflammatory disease.
authors.affiliation: Department of Food Science and Biotechnology, Woosong University , Daejeon, Republic of Korea.
authors.forename: Myung-Woo
authors.initials: MW
authors.lastname: Byun
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D019686:Lamiaceae / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010936:Plant Extracts; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone