1. Academic Validation
  2. 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

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

  • Int Immunopharmacol. 2015 Aug;27(2):224-31. doi: 10.1016/j.intimp.2015.05.018.
Changda Liu 1 Nan Yang 1 Ying Song 1 Lixin Wang 2 Jiachen Zi 3 Shuwei Zhang 3 David Dunkin 4 Paula Busse 5 David Weir 6 Jody Tversky 7 Rachel L Miller 8 Joseph Goldfarb 9 Jixun Zhan 10 Xiu-Min Li 11
Affiliations

Affiliations

  • 1 Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai, NY 10029, United States.
  • 2 Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai, NY 10029, United States; Shanghai Municipal Hospital of Traditional Chinese Medicine affiliated with Shanghai TCM University, China.
  • 3 Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322, United States.
  • 4 Pediatric Gastroenterology, Pediatric Department, Icahn School of Medicine at Mount Sinai, NY 10029, United States.
  • 5 Immunology Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, NY 10029, United States.
  • 6 Division of Pulmonary, Critical Care Medicine, and Sleep Medicine , Mount Sinai Medical Center, NY 10029, United States.
  • 7 Division of Allergy & Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, MD 21224, United States.
  • 8 Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University, New York, NY, 10032, United States; Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Columbia University, New York, NY 10032, United States; Department of Environmental Health Sciences, Columbia University, New York, NY, 10032, United States.
  • 9 Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, NY, 10029, United States.
  • 10 Department of Biological Engineering, Utah State University, 4105 Old Main Hill, Logan, UT 84322, United States. Electronic address: jixun.zhan@usu.edu.
  • 11 Pediatric Allergy & Immunology, Icahn School of Medicine at Mount Sinai, NY 10029, United States. Electronic address: xiu-min.li@mssm.edu.
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.

Keywords

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

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