Ganoderic acid C1 isolated from the anti-asthma formula, ASHMI™ suppresses TNF-α production by mouse macrophages and peripheral blood mononuclear cells from asthma patients

Changda Liu, Nan Yang, Ying Song, Lixin Wang, Jiachen Zi, Shuwei Zhang, David Dunkin, Paula Busse, David Weir, Jody Tversky, Rachel L. Miller, Joseph Goldfarb, Jixun Zhan, Xiu Min Li

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number3712
Pages (from-to)224-231
Number of pages8
JournalInternational immunopharmacology
Volume27
Issue number2
DOIs
StatePublished - Jul 18 2015

Keywords

  • ASHMITM
  • Asthma
  • Ganoderic acid C1
  • Ganoderma lucidum
  • Inflammation
  • Macrophages
  • PBMCs
  • Peripheral blood mononuclear cells
  • RAW 264.7 cells
  • TNF-α
  • Traditional Chinese medicines

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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