4-hydroxyderricin and Obesity

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

Topics: Adipocytes; Angelica; Animals; Cell Differentiation; Chalcone; Coculture Techniques; Culture Media, Conditioned; Diet, High-Fat; Inflammation; JNK Mitogen-Activated Protein Kinases; Macrophages; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Obesity; Phosphorylation; Phytotherapy; Plant Extracts; Transcription Factor AP-1