The medicinal fungus Antrodia cinnamomea suppresses inflammation by inhibiting the NLRP3 inflammasome

Tsung-Teng Huang; Sian-Pu Wu; Kowit-Yu Chong; David M Ojcius; Yun-Fei Ko; Yi-Hui Wu; Cheng-Yeu Wu; Chia-Chen Lu; Jan Martel; John D Young; Hsin-Chih Lai

doi:10.1016/j.jep.2014.04.053

The medicinal fungus Antrodia cinnamomea suppresses inflammation by inhibiting the NLRP3 inflammasome

J Ethnopharmacol. 2014 Aug 8;155(1):154-64. doi: 10.1016/j.jep.2014.04.053. Epub 2014 May 20.

Authors

Tsung-Teng Huang¹, Sian-Pu Wu², Kowit-Yu Chong², David M Ojcius³, Yun-Fei Ko⁴, Yi-Hui Wu⁵, Cheng-Yeu Wu⁶, Chia-Chen Lu⁷, Jan Martel⁸, John D Young⁹, Hsin-Chih Lai¹⁰

Affiliations

¹ Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Laboratory of Nanomaterials, Chang Gung University, Taoyuan 333, Taiwan; Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan 333, Taiwan.
² Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
³ Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Department of Molecular Cell Biology and Health Sciences Research Institute, University of California, Merced, Merced, CA 95343, USA.
⁴ Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei 24301, Taiwan; Chang Gung Biotechnology Corporation, Taipei 10508, Taiwan.
⁵ Cancer Research Center, National Cheng Kung University Hospital, Tainan 704, Taiwan.
⁶ Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Laboratory of Nanomaterials, Chang Gung University, Taoyuan 333, Taiwan; Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan 333, Taiwan.
⁷ Department of Respiratory Therapy, Fu Jen Catholic University, Taipei 24205, Taiwan.
⁸ Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Laboratory of Nanomaterials, Chang Gung University, Taoyuan 333, Taiwan.
⁹ Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Laboratory of Nanomaterials, Chang Gung University, Taoyuan 333, Taiwan; Biochemical Engineering Research Center, Ming Chi University of Technology, Taipei 24301, Taiwan; Chang Gung Biotechnology Corporation, Taipei 10508, Taiwan; Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY 10021, USA. Electronic address: [email protected].
¹⁰ Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan 333, Taiwan; Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan 333, Taiwan. Electronic address: [email protected].

PMID: 24858059
DOI: 10.1016/j.jep.2014.04.053

Abstract

Ethnopharmacological relevance: Antrodia cinnamomea--a medicinal fungus that is indigenous to Taiwan--has been used as a health tonic by aboriginal tribes and the Asian population. Recent studies indicate that Antrodia cinnamomea extracts exhibit hepato-protective, anti-hypertensive, anti-oxidative, anti-inflammatory, immuno-modulatory, and anti-cancer effects on cultured cells and laboratory animals. This study aims to explore the anti-inflammatory activity of an Antrodia cinnamomea ethanol extract (ACEE) and elucidate its underlying mechanisms of action using lipopolysaccharide (LPS)-primed, ATP-stimulated human THP-1 macrophages.

Materials and methods: The effects of ACEE on cell viability were studied using the MTT assay. The expressions of genes, proteins, and pro-inflammatory cytokines were measured by quantitative real-time RT-PCR, Western blotting and ELISA, respectively. The ACEE was further investigated for its effects on reactive oxygen species (ROS) production using ROS detection kit.

Results: Our results showed that ACEE significantly inhibits ATP-induced secretion of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) by LPS-primed macrophages. ACEE also suppresses the transcription and activation of caspase-1, which is responsible for the cleavage and activation of IL-1β and IL-18. Of note, ACEE not only reduces expression of the inflammasome component NLRP3 and the purinergic receptor P2X7R but also inhibits ATP-induced ROS production and caspase-1 activation. Furthermore, the anti-inflammatory properties of ACEE correlate with reduced activation of the MAPK and NF-κB pathways.

Conclusion: The results of the present study indicate that Antrodia cinnamomea suppresses the secretion of IL-1β and IL-18 associated with inhibition of the NLRP3 inflammasome in macrophages. These findings suggest that ACEE may have therapeutic potential for the treatment of inflammatory diseases.

Keywords: Anti-inflammatory activity; Antrodia cinnamomea; Caspase-1; Inflammasome; NLRP3; Reactive oxygen species.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents / isolation & purification
Anti-Inflammatory Agents / pharmacology*
Antrodia / chemistry*
Carrier Proteins / metabolism
Caspase 1 / metabolism
Cell Line
Cell Survival / drug effects
Cytokines / metabolism
Humans
Inflammasomes / drug effects*
Inflammation / drug therapy*
Lipopolysaccharides / pharmacology
MAP Kinase Signaling System / drug effects
Macrophages / drug effects
Macrophages / pathology
Medicine, East Asian Traditional / methods
NF-kappa B / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein
Reactive Oxygen Species / metabolism

Substances

Anti-Inflammatory Agents
Carrier Proteins
Cytokines
Inflammasomes
Lipopolysaccharides
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3 protein, human
Reactive Oxygen Species
Caspase 1