title: Anti-inflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1.
abstract: OBJECTIVE
  Although apigenin exhibits various biological effects, its anti-inflammatory role in the periodontal field remains unknown. We examined the anti-inflammatory effects of apigenin and the underlying mechanism in nicotine- and lipopolysaccharide (LPS)-stimulated human periodontal ligament (hPDL) cells.
  
  
  METHODS
  Western blotting was used to examine the effect of apigenin (10-40 microM) on the LPS- and nicotine-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and heme oxygenase-1 (HO-1), as well as the phosphorylation of mitogen-activated protein kinases (MAPKs), in hPDL cells. Pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE2), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-12 were monitored using Griess reagents and ELISA.
  
  
  RESULTS
  Incubation of hPDL cells with apigenin decreased LPS- and nicotine-induced HO-1 protein expression and activity. Apigenin significantly inhibited the nicotine- and LPS-induced production of NO, PGE2, IL-1beta, TNF-alpha, IL-6, and IL-12, and the upregulation of iNOS and COX-2 in hPDL cells. Hemin, a selective HO-1 inducer, reversed the apigenin-mediated suppression of nicotine- and LPS-induced NO, PGE2 and cytokine production. Treatment with inhibitors of the phosphoinositide 3-kinase, MAPKs, p38, and JNK, as well as a protein kinase C inhibitor, blocked the anti-inflammatory effects of apigenin in nicotine- and LPS-treated cells.
  
  
  CONCLUSIONS
  Apigenin possesses anti-inflammatory activity in hPDL cells and works through a novel mechanism involving the action of HO-1. Thus, apigenin may have potential benefits as a host modulatory agent in the prevention and treatment of periodontal disease associated with smoking and dental plaque.
authors.affiliation: Zoonosis Research Center, Wonkwang University, Iksan, South Korea.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.forename: Seoung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Seong-Nyum
authors.initials: SN
authors.lastname: Jeong
authors.forename: Youn-Chul
authors.initials: YC
authors.lastname: Kim
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology*; D002461:Cell Line, Transformed; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003773:Dental Plaque / Q000150:complications; D015232:Dinoprostone / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism; D009569:Nitric Oxide / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010510:Periodontal Diseases / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology*; D010513:Periodontal Ligament / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D009538:Nicotine; D006427:Hemin; D047310:Apigenin; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D015232:Dinoprostone