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Tenuigenin exhibits anti-inflammatory activity via inhibiting MAPK and NF-κB and inducing Nrf2/HO-1 signaling in macrophages
- Source :
- Foodfunction. 7(1)
- Publication Year :
- 2015
-
Abstract
- Tenuigenin (TNG), isolated from the root of the Chinese herb Polygala tenuifolia, possesses various biological and pharmacological activities, including anti-oxidation and anti-inflammation activities. In this study, we aimed to further investigate whether its anti-inflammatory activity is associated with the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our results showed that TNG treatment dramatically reduced prostaglandin E2 (PGE2) and NO production, decreased iNOS and COX-2 gene expression, inhibited JNK1/2, ERK1/2, p38 and NF-κB (p65) phosphorylation, and blocked IκBα phosphorylation and degradation. Further studies revealed that TNG dramatically up-regulated heme oxygenase (HO)-1 and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, which was related to the induction of Nrf2 nuclear translocation and decreased Keap1 protein expression. Additionally, treatment with JNK1/2, ERK1/2 or p38 inhibitors had no effect on the TNG-induced HO-1 protein expression. Furthermore, the LPS-induced iNOS and COX-2 expression levels were inhibited by TNG, which was partially reversed by the HO-1-siRNA and HO-1 inhibitors. Together, these results showed that TNG's anti-inflammatory activity is related to the inhibition of iNOS and COX-2 expression via down-regulation of the MAPK and NF-κB, and up-regulation of the Nrf2/HO-1 signaling pathways.
- Subjects :
- 0301 basic medicine
MAPK/ERK pathway
Lipopolysaccharides
Polygala
Metalloporphyrins
NF-E2-Related Factor 2
p38 mitogen-activated protein kinases
Anti-Inflammatory Agents
Nitric Oxide Synthase Type II
Protoporphyrins
Bioinformatics
03 medical and health sciences
chemistry.chemical_compound
Mice
Medicine
Animals
RNA, Small Interfering
Adaptor Proteins, Signal Transducing
Mitogen-Activated Protein Kinase Kinases
Kelch-Like ECH-Associated Protein 1
biology
business.industry
Macrophages
NF-kappa B
Membrane Proteins
NF-κB
General Medicine
Molecular biology
Nitric oxide synthase
Heme oxygenase
IκBα
Cytoskeletal Proteins
030104 developmental biology
RAW 264.7 Cells
chemistry
Gene Expression Regulation
Cyclooxygenase 2
biology.protein
Phosphorylation
Signal transduction
business
Heme Oxygenase-1
Food Science
Drugs, Chinese Herbal
Signal Transduction
Subjects
Details
- ISSN :
- 2042650X
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Foodfunction
- Accession number :
- edsair.doi.dedup.....0f2de140276038815c054c38783b96ea