title: Oryeongsan inhibits LPS-induced production of inflammatory mediators via blockade of the NF-kappaB, MAPK pathways and leads to HO-1 induction in macrophage cells.
abstract: BACKGROUND
  Oryeongsan (OR) is an herbal medication used in east-Asian traditional medicine to treat dysuresia, such as urinary frequency, hematuria, and dysuria due to renal disease and chronic nephritis. Recent studies showed that protective effect against acute gastric mucosal injury and an inhibitory effect on the renin-angiotensin-aldosterone pathway of OR. However, its effect on inflammation still remains unknown. In this study, to provide insight into the biological effects of OR, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in the RAW 264.7 macrophage cells.
  
  
  METHODS
  We investigated the pharmacological and biological effects of OR on the production of pro-inflammatory cytokines, inflammatory mediators, and related products through Enzyme-linked immunosorbent assay (ELISA), reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Also, we examined the activation and suppression of nuclear factor (NF)-kappaB and mitogen-activated protein kinases (MAPKs) pathways in LPS-stimulated macrophages via Western blot analysis in order to explore inhibitory mechanism of OR.
  
  
  RESULTS
  OR had anti-inflammatory effects by inhibiting the production of nitric oxide (NO), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1 beta. In addition, it strongly suppressed cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), NO synthesizing enzymes. It also induced heme oxygenase (HO)-1 expression and inhibited NF-kappaB signaling pathway activation and phosphorylation of MAPKs.
  
  
  CONCLUSIONS
  We further demonstrate the anti-inflammatory effects and inhibitory mechanism of OR in LPS-stimulated macrophages for the first time. OR contains strong anti-inflammatory activity and affects various mechanism pathways including NF-kappaB, MAPKs and HO-1. Our results suggest that OR has potential value to be developed as an inflammatory therapeutic agent from a natural substance.
authors.forename: You-Chang
authors.initials: YC
authors.lastname: Oh
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Jeong
authors.forename: Jeong-Ho
authors.initials: JH
authors.lastname: Ha
authors.affiliation: Korean Medicine (KM)-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, Yuseong, Republic of Korea. wkcho@kiom.re.kr.
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Cho
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D010936:Plant Extracts; C443861:wulingsan; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D020928:Mitogen-Activated Protein Kinases