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Ganoderic acid C1 isolated from the Anti-asthma Formula, ASHMITM suppresses TNF-α production by mouse macrophages and peripheral blood mononuclear cells from asthma patients
- Publication Year :
- 2015
-
Abstract
- Asthma is a heterogeneous airway inflammatory disease, which is associated with Th2 cytokine-driven inflammation and non-Th2, TNF-α mediated inflammation. Unlike Th2 mediated inflammation, TNF-α mediated asthma inflammation is generally insensitive to inhaled corticosteroids (ICS). ASHMITM, aqueous extract of three medicinal herbs-Ganoderma lucidum (G. lucidum), Sophora flavescens Ait (S. flavescens) and Glycyrrhiza uralensis Fischer (G. uralensis), showed a high safety profile and was clinically beneficial in asthma patients. It also suppresses both Th2 and TNF-α associated inflammation in murine asthma models. We previously determined that G. uralensis flavonoids are the key active compounds responsible for ASHMITM suppression of Th2 mediated inflammation. Until now, there are limited studies on anti-TNF-α compounds presented in ASHMITM. The objective of this study was to isolate and identify TNF-α inhibitory compounds in ASHMITM. Here we report that G. lucidum, but not the other two herbal extracts, S. flavescens or G. uralensis inhibited TNF-α production by murine macrophages; and that the methylene chloride (MC)-triterpenoid-enriched fraction, but not the polysaccharide-enriched fraction, contained the inhibitory compounds. Of the 15 triterpenoids isolated from the MC fraction, only ganoderic acid C1 (GAC1) significantly reduced TNF-α production by murine macrophages (RAW 264.7 cells) and peripheral blood mononuclear cells (PBMCs) from asthma patients. Inhibition was associated with down-regulation of NF-κB expression, and partial suppression of MAPK and AP-1 signaling pathways. Ganoderic acid C1 may have potential for treating TNF-α mediated inflammation in asthma and other inflammatory diseases.
- Subjects :
- Male
Reishi
Immunology
Inflammation
Apoptosis
Pharmacology
Peripheral blood mononuclear cell
Anti-asthmatic Agent
Article
Cell Line
chemistry.chemical_compound
Mice
medicine
Immunology and Allergy
Animals
Humans
Glycyrrhiza uralensis
Anti-Asthmatic Agents
Cells, Cultured
Cell Proliferation
Sophora flavescens
biology
business.industry
Tumor Necrosis Factor-alpha
Macrophages
Ganoderic acid
NF-kappa B
biology.organism_classification
Asthma
Triterpenes
Transcription Factor AP-1
chemistry
Leukocytes, Mononuclear
Tumor necrosis factor alpha
Female
medicine.symptom
Mitogen-Activated Protein Kinases
business
Sophora
Drugs, Chinese Herbal
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....c300f85b67ff23bd065d82c6d7aed5fc