title: Upregulation of heme oxygenase-1 via PI3K/Akt and Nrf-2 signaling pathways mediates the anti-inflammatory activity of Schisandrin in Porphyromonas gingivalis LPS-stimulated macrophages.
abstract: The lipopolysaccharide (LPS) of Porphyromonas gingivalis is thought to induce periodontitis. In this study, we isolated Schisandrin from the dried fruits of Schisandra chinensis and examined the anti-inflammatory effect of Schisandrin in macrophages stimulated with LPS from P. gingivalis. First, Schisandrin inhibited LPS-induced pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6. And Schisandrin suppressed the nuclear translocation and activity of NF-κB and phosphorylation of IκBα in LPS-stimulated RAW 264.7 cells. Next, the presence of a selective inhibitor of HO-1 (SnPP) and a siRNA specific for HO-1 inhibited Schisandrin-mediated anti-inflammatory activity. Furthermore, Schisandrin induced HO-1 expression of RAW 264.7 cells through Nrf-2, PI3K/Akt, and ERK activation. Therefore, these results suggest that the anti-inflammatory effects of Schisandrin on P. gingivalis LPS-stimulated RAW 264.7 cells may be due to a reduction of NF-κB activity and induction of the expression of HO-1, leading to TNF-α, IL-1β, and IL-6 down-regulation.
authors.affiliation: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.forename: Da Jung
authors.initials: DJ
authors.lastname: Park
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.forename: Younghee
authors.initials: Y
authors.lastname: Kim
authors.forename: Sun Gun
authors.initials: SG
authors.lastname: Kim
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Shon
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Choi
authors.forename: Sang-Joon
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D034242:Cyclooctanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011083:Polycyclic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016966:Porphyromonas gingivalis / Q000276:immunology*; D021381:Protein Transport / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D034242:Cyclooctanes; D018836:Inflammation Mediators; D017705:Lignans; D008070:Lipopolysaccharides; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D011083:Polycyclic Compounds; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C011105:schizandrin