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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.
AuthorsSheng-Hua Lu, Wen-Lin Hsu, Tso-Hsiao Chen, Tz-Chong Chou
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 29 Issue 2 Pg. 770-778 (Dec 2015) ISSN: 1878-1705 [Electronic] Netherlands
PMID26388191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Biphenyl Compounds
  • Cytokines
  • Lignans
  • Lipopolysaccharides
  • Metalloporphyrins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Protoporphyrins
  • Reactive Oxygen Species
  • magnolol
  • tin protoporphyrin IX
  • Heme Oxygenase-1
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
  • Biphenyl Compounds (antagonists & inhibitors, pharmacology)
  • Cytokines (biosynthesis)
  • Enzyme Activation (drug effects)
  • Heme Oxygenase-1 (antagonists & inhibitors, drug effects, metabolism)
  • Lignans (antagonists & inhibitors, pharmacology)
  • Lipopolysaccharides (antagonists & inhibitors, pharmacology)
  • Metalloporphyrins (pharmacology)
  • Mice
  • NF-E2-Related Factor 2 (drug effects, metabolism)
  • Porphyromonas gingivalis (chemistry)
  • Protoporphyrins (pharmacology)
  • RAW 264.7 Cells
  • Reactive Oxygen Species (metabolism)
  • Signal Transduction (drug effects)
  • p38 Mitogen-Activated Protein Kinases (drug effects)

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