title: Activation of Nrf2/HO-1signaling pathway involves the anti-inflammatory activity of magnolol in Porphyromonas gingivalis lipopolysaccharide-stimulated mouse RAW 264.7 macrophages.
abstract: Magnolol isolated from Magnolia officinalis, a Chinese medical herb, exhibits an anti-inflammatory activity and a protective effect against periodontitis. The inflammation caused by lipopolysaccharide (LPS) from Porphyromonas gingivalis (P. gingivalis) has been considered a key inducer in the development of periodontitis. In this study, we investigated whether magnolol inhibits P. gingivalis LPS-evoked inflammatory responses in RAW 264.7 macrophages and the involvement of heme oxygenase-1 (HO-1). Magnolol significantly activated p38 MAPK, Nrf-2/HO-1 cascade and reactive oxygen species (ROS) formation. Notably, the Nrf-2 activation and HO-1 induction by magnolol were greatly diminished by blocking p38 MAPK activity and ROS production. Furthermore, in P. gingivalis LPS-stimulated macrophages, magnolol treatment remarkably inhibited the inflammatory responses evidenced by suppression of pro-inflammatory cytokine, prostaglandin E2, nitrite formation, and the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as NF-κB activation accompanied by a significant elevation of Nrf-2 nuclear translocation and HO-1 expression/activity. However, inhibiting HO-1 activity with tin protoporphyrin IX markedly reversed the anti-inflammatory effects of magnolol. Collectively, these findings provide a novel mechanism by which magnolol inhibits P. gingivalis LPS-induced inflammation in macrophages is at least partly mediated by HO-1 activation, and thereby promoting its clinical use in periodontitis.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Sheng-Hua
authors.initials: SH
authors.lastname: Lu
authors.affiliation: School of Medicine, Tzu Chi University, Taiwan; Department of Radiation Oncology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Hsu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan; Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; China Medical University Hospital, China Medical University, Taichung, Taiwan. Electronic address: tcchou48@mail.tcu.edu.tw.
authors.forename: Tz-Chong
authors.initials: TC
authors.lastname: Chou
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D017705:Lignans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000187:drug effects / Q000378:metabolism*; D016966:Porphyromonas gingivalis / Q000737:chemistry*; D011524:Protoporphyrins / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D016207:Cytokines; D017705:Lignans; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C005498:magnolol; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Heme oxygenase-1; Inflammation; Lipopolysaccharide; Magnolol; Porphyromonas gingivalis