Xanthoangelol and 4-hydroxyderrcin suppress obesity-induced inflammatory responses

Obesity (Silver Spring). 2016 Nov;24(11):2351-2360. doi: 10.1002/oby.21611. Epub 2016 Sep 13.

Abstract

Objective: Obesity-induced inflammation plays a pivotal role in the pathogenesis of insulin resistance and type 2 diabetes. Xanthoangelol (XA) and 4-hydroxyderrcin (4-HD), phytochemicals extracted from Angelica keiskei, have been reported to possess various biological properties. Whether XA and 4-HD alleviate obesity-induced inflammation and inflammation-induced adipocyte dysfunction was investigated.

Methods: For the in vitro study, a co-culture system composed of macrophages and adipocytes and macrophages stimulated with conditioned medium derived from fully differentiated adipocytes was conducted. For the in vivo study, mice were fed a high-fat diet supplemented with XA for 14 weeks.

Results: XA and 4-HD suppressed inflammatory factors in co-culture system. Moreover, treatment of RAW macrophages with XA and 4-HD moderated the suppression of uncoupling protein 1 promoter activity and gene expression in C3H10T1/2 adipocytes, which was induced by conditioned medium derived from LPS-stimulated RAW macrophages. Also, XA and 4-HD inhibited c-Jun N-terminal kinase phosphorylation, nuclear factor-κB, and activator protein 1, the last two being transcription activators in activated macrophages. Furthermore, in mice fed the high-fat diet, XA reduced inflammatory factors within the white adipose tissue.

Conclusions: These results suggest that XA and 4-HD might be promising phytochemicals to suppress obesity-induced inflammation and inflammation-induced adipocyte dysfunction.

MeSH terms

  • Adipocytes / drug effects
  • Angelica / chemistry*
  • Animals
  • Cell Differentiation / drug effects
  • Chalcone / analogs & derivatives*
  • Chalcone / pharmacology
  • Coculture Techniques
  • Culture Media, Conditioned
  • Diet, High-Fat
  • Inflammation / drug therapy
  • Inflammation / etiology
  • JNK Mitogen-Activated Protein Kinases / drug effects
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / drug effects
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / physiopathology
  • Phosphorylation / drug effects
  • Phytotherapy*
  • Plant Extracts / pharmacology*
  • Transcription Factor AP-1 / drug effects

Substances

  • Culture Media, Conditioned
  • NF-kappa B
  • Plant Extracts
  • Transcription Factor AP-1
  • 4-hydroxyderricin
  • Chalcone
  • xanthoangelol
  • JNK Mitogen-Activated Protein Kinases