title: Xanthii fructus inhibits inflammatory responses in LPS-stimulated RAW 264.7 macrophages through suppressing NF-κB and JNK/p38 MAPK.
abstract: BACKGROUND
  Xanthii fructus (XF) has long been used to treat a variety of inflammatory conditions in Korean traditional medicine, but the underlying mechanisms that could explain the anti-inflammatory actions of XF remain largely unknown.
  
  
  OBJECTIVE
  This study aimed to elucidate the anti-inflammatory effects of X. fructus (XF) and to examine its underlying molecular mechanisms in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages.
  
  
  METHODS
  The effect of XF on LPS-induced mRNA and protein expressions of inflammatory mediators and cytokines were determined. Moreover, the activation of the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways and the expression of heme oxygenase-1 (HO-1) were explored to elucidate the anti-inflammatory mechanisms.
  
  
  RESULTS
  XF significantly inhibited LPS-induced production of inflammatory mediators, interleukin-6 (IL-6), nitric oxide (NO), and prostaglandin E2 (PGE2), without any cytotoxicity. However, it did not affect tissue necrosis factor (TNF)-α or IL-1β production in LPS-stimulated RAW 264.7 cells. Expression levels of inducible nitric oxide synthase (iNOS) mRNA and protein were inhibited dose-dependently by XF in LPS-stimulated RAW 264.7 cells, but there were no changes in cyclooxygenase-2 (COX-2) mRNA and protein. XF significantly attenuated LPS-induced phosphorylation and degradation of inhibitory kappa Bα (IκBα) and consequently reduced the nuclear translocation of p65 NF-κB. Pretreatment with XF also strongly inhibited the LPS-induced phosphorylation of p38 kinase and JNK, whereas the phosphorylation of ERK1/2 was not affected. In addition, XF led to an increase in HO-1 expression.
  
  
  CONCLUSIONS
  Taken together, our findings support that XF inhibits LPS-induced inflammatory responses by blocking NF-κB activation, inhibiting JNK/p38 MAPK phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that it could be an attractive therapeutic candidate for various inflammatory diseases.
authors.affiliation: Acupuncture and Meridian Science Research Center, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Mijung
authors.initials: M
authors.lastname: Yeom
authors.affiliation: Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Min
authors.affiliation: Inuri Medical Group, Seoul 137-877, Republic of Korea.
authors.forename: Man Ki
authors.initials: MK
authors.lastname: Hwang
authors.affiliation: Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Hyuk-Sang
authors.initials: HS
authors.lastname: Jung
authors.affiliation: Department of Anatomy, College of Korean Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: youngjoos@khu.ac.kr.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Sohn
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005638:Fruit; D051547:Heme Oxygenase-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D031210:Xanthium; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D010936:Plant Extracts; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Inflammation; MAPKs; NF-κB; Xanthii fructus; Xanthium strumarium (Asteraceae); iNOS