A plant kavalactone desmethoxyyangonin prevents inflammation and fulminant hepatitis in mice.

Abstract

Alpinia pricei Hayata is a Formosan plant which has been popularly used as nutraceutical or folk medicine for inflammation and various disorders. An active compound of the plant rhizomes, desmethoxyyangonin (DMY), was identified in this study for its novel effect against endotoxin lipopolysaccharide (LPS)-stimulated inflammation in murine macrophages and LPS/D-galactosamine (LPS/D-GalN)-induced fulminant hepatitis in mice. DMY was observed to significantly inhibit proliferation and activation of T cells ex vivo and the activity of several pro-inflammatory mediators in vitro. DMY also protected LPS/D-GalN-induced acute hepatic damages in mice through inhibiting aminotransferases activities and infiltrations of inflammatory macrophages, neutrophils and pathogenic T cells into the liver tissues. In addition, pretreatment with DMY significantly improved the survival rate of LPS/D-GalN-treated mice to 90% (9/10), compared to LPS/D-GalN-treated group (40%, 4/10). UPLC/MS platform-based comparative metabolomics approach was used to explore the serum metabolic profile in fulminant hepatic failure (FHF) mice with or without the DMY pretreatment. The results showed that LPS/D-GalN-induced hepatic damage is likely through perturbing amino acid metabolism, which leads to decreased pyruvate formation via catalysis of aminotransferases, and DMY treatment can prevent to a certain degree of these alterations in metabolic network in mouse caused by LPS/D-GalN. Mechanistic investigation demonstrated that DMY protects LPS or LPS/D-GalN-induced damages in cell or liver tissues mainly through de-regulating IKK/NFκB and Jak2/STAT3 signaling pathways. This report provides evidence-based knowledge to support the rationale for the use of A. pricei root extract in anti-inflammation and also its new function as hepatoprotetive agent against fulminant hepatitis.

• Authors: Tsui-Wei Chou, Jia-Hua Feng, Chi-Chang Huang, Ya-Wen Cheng, Shih-Chang Chien, Sheng-Yang Wang, Lie-Fen Shyur
• Journal: PloS one (PLoS One) Vol. 8 Issue 10 Pg. e77626 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 24143247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Lipopolysaccharides
• Pyrones
• STAT3 Transcription Factor
• desmethoxyyangonin
• Nitric Oxide
• Galactosamine
• Nitric Oxide Synthase Type II

Topics

• Animals
• Cell Line
• Cytoprotection (drug effects)
• Galactosamine (pharmacology)
• Gene Expression Regulation, Enzymologic (drug effects)
• Hepatitis (etiology, immunology, metabolism, prevention & control)
• Inflammation (chemically induced, prevention & control)
• Interleukin-6 (biosynthesis)
• Kava (chemistry)
• Lipopolysaccharides (pharmacology)
• Liver (cytology, drug effects, immunology, metabolism)
• Macrophages (drug effects, immunology, metabolism)
• Male
• Metabolomics
• Mice
• Mice, Inbred ICR
• Multivariate Analysis
• Neutrophils (drug effects, immunology)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type II (genetics)
• Phosphorylation (drug effects)
• Pyrones (pharmacology)
• STAT3 Transcription Factor (metabolism)