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.
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Authors | Sheng-Hua Lu, Wen-Lin Hsu, Tso-Hsiao Chen, Tz-Chong Chou |
Journal | International immunopharmacology
(Int Immunopharmacol)
Vol. 29
Issue 2
Pg. 770-778
(Dec 2015)
ISSN: 1878-1705 [Electronic] Netherlands |
PMID | 26388191
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 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
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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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