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Geniposide suppresses LPS-induced nitric oxide, PGE2 and inflammatory cytokine by downregulating NF-κB, MAPK and AP-1 signaling pathways in macrophages
- Source :
- International immunopharmacology. 20(2)
- Publication Year :
- 2013
-
Abstract
- Inflammatory responses are important to host immune reactions, but uncontrolled inflammatory mediators may aid in the pathogenesis of other inflammatory diseases. Geniposide, an iridoid glycoside found in the herb gardenia, is believed to have broad-spectrum anti-inflammatory effects in murine models but its mechanism of action is unclear. We investigated the action of this compound in murine macrophages stimulated by lipopolysaccharide (LPS), as the stimulation of macrophages by LPS is known to induce inflammatory reactions. We determined the effect of geniposide on LPS-induced production of the inflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2), the mRNA and protein expression of the NO and PGE2 synthases, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively, and the mRNA and protein expression of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Furthermore, nuclear factor (NF)-κB, mitogen-activated protein kinase (MAPK) and activator protein (AP)-1 activity were assayed. To understand the action of geniposide on the NF-κB and MAPK pathways, we studied the effect of NF-κB and MAPK inhibitors on the LPS-induced production of NO, PGE2 and TNF-α. Our findings clearly showed that geniposide mainly exerts its anti-inflammatory effects by inhibiting the LPS-induced NF-κB, MAPK and AP-1 signaling pathways in macrophages, which subsequently reduces overexpression of the inducible enzymes iNOS and COX-2 and suppresses the expression and release of the inflammatory factors, TNF-α, IL-6, NO and PGE2. Thus, geniposide shows promise as a therapeutic agent in inflammatory diseases.
- Subjects :
- MAPK/ERK pathway
Lipopolysaccharides
Male
medicine.medical_specialty
Lipopolysaccharide
Pyridines
medicine.medical_treatment
Immunology
Anti-Inflammatory Agents
Nitric Oxide Synthase Type II
Inflammation
Mice, Inbred Strains
Biology
Pharmacology
Nitric Oxide
Dinoprostone
Nitric oxide
Cell Line
chemistry.chemical_compound
Mice
Internal medicine
Nitriles
medicine
Butadienes
Immunology and Allergy
Animals
Iridoids
Sulfones
Extracellular Signal-Regulated MAP Kinases
Interleukin-6
Tumor Necrosis Factor-alpha
Imidazoles
NF-kappa B
NF-κB
Gardenia
Nitric oxide synthase
Transcription Factor AP-1
Endocrinology
Cytokine
chemistry
Cyclooxygenase 2
biology.protein
Macrophages, Peritoneal
Tumor necrosis factor alpha
medicine.symptom
Inflammation Mediators
Signal Transduction
Subjects
Details
- ISSN :
- 18781705
- Volume :
- 20
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- International immunopharmacology
- Accession number :
- edsair.doi.dedup.....0f979ebcb350927c54eb4b5f84f7e398