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

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.

• Authors: 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
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 155 Issue 1 Pg. 154-64 (Aug 08 2014) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 24858059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• 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

Topics

• Anti-Inflammatory Agents (isolation & purification, 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, pathology)
• Medicine, East Asian Traditional (methods)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Reactive Oxygen Species (metabolism)