Abstract |
The ethanol extract of the flower of P. vulgaris var. lilacina (EEPV) has been used traditionally as an antiinflammatory agent in many countries. Inducers of heme oxygenase-1 (HO-1) reduce high mobility group box 1 ( HMGB1), a late phase cytokine, in sepsis. Although EEPV has been used as an antiinflammatory agent, no report is available as to whether it modifies HMGB1 in sepsis due to HO-1 induction. It was found that EEPV increased HO-1 protein expression in RAW 264.7 cells, which was significantly inhibited by LY294002, but not PD98059, SB203580 or SP600125. In addition, EEPV activated NF-E2-related factor (Nrf2) to move from the cytosol to the nucleus, and EEPV-induced HO-1 and activation of ARE- luciferase activity were significantly reduced by siNrf2 transfection and LY294002 but not SB203508. EEPV also significantly inhibited NF-κB luciferase activity, and decreased both iNOS/NO and COX-2/ PGE(2) production in lipopolysaccharide (LPS)-stimulated macrophages which was reversed by siHO-1 RNA transfection. Importantly, EEPV inhibited HMGB1 release in LPS-activated macrophages in a PI3K-sensitive manner and reduced serum HMGB1 level and lung HMGB1 expression in cecal ligation and puncture (CLP)-induced septic mice. It is concluded that EEPV induces HO-1 expression through PI3K/Nrf2 signal pathways, which may be beneficial for the treatment of sepsis due to a reduction of HMGB1 release.
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Authors | Min Soo Jun, Hee Sook Kim, Young Min Kim, Hye Jung Kim, Eun Jung Park, Jae Heun Lee, Kang Ro Lee, Yeong Shik Kim, Ki Churl Chang |
Journal | Phytotherapy research : PTR
(Phytother Res)
Vol. 26
Issue 4
Pg. 605-12
(Apr 2012)
ISSN: 1099-1573 [Electronic] England |
PMID | 21971692
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 John Wiley & Sons, Ltd. |
Chemical References |
- Anthracenes
- Chromones
- Flavonoids
- HMGB1 Protein
- Imidazoles
- Lipopolysaccharides
- Membrane Proteins
- Morpholines
- NF-E2-Related Factor 2
- NF-kappa B
- Nfe2l2 protein, mouse
- Plant Extracts
- Pyridines
- pyrazolanthrone
- 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
- Ethanol
- Nitric Oxide Synthase Type II
- Nos2 protein, mouse
- Heme Oxygenase-1
- Hmox1 protein, mouse
- Ptgs2 protein, mouse
- Cyclooxygenase 2
- SB 203580
- 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
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Topics |
- Animals
- Anthracenes
(pharmacology)
- Cecum
(injuries, pathology)
- Cell Line
- Cell Survival
- Chromones
(pharmacology)
- Cyclooxygenase 2
(metabolism)
- Disease Models, Animal
- Drug Evaluation, Preclinical
- Enzyme Activation
- Enzyme Induction
- Ethanol
- Flavonoids
(pharmacology)
- Flowers
(chemistry)
- Genetic Vectors
- HMGB1 Protein
(antagonists & inhibitors, blood)
- Heme Oxygenase-1
(antagonists & inhibitors, metabolism)
- Imidazoles
(pharmacology)
- Lipopolysaccharides
(adverse effects)
- Lung
(pathology)
- Macrophages
(drug effects, enzymology)
- Male
- Membrane Proteins
(antagonists & inhibitors, metabolism)
- Mice
- Mice, Inbred BALB C
- Morpholines
(pharmacology)
- NF-E2-Related Factor 2
(metabolism)
- NF-kappa B
(metabolism)
- Nitric Oxide Synthase Type II
(antagonists & inhibitors, metabolism)
- Plant Extracts
(pharmacology)
- Protein Transport
- Prunella
(chemistry)
- Pyridines
(pharmacology)
- Sepsis
(pathology)
- Signal Transduction
- Transfection
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