Xanthoangelol and 4-hydroxyderrcin suppress obesity-induced inflammatory responses.
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.
Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Yongjia
Y
Li
Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.|Research Unit for Physiological Chemistry, Japan, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.
Tsuyoshi
T
Goto
Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Ryuma
R
Ikutani
Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Shan
S
Lin
Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.|Research Unit for Physiological Chemistry, Japan, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan.
Nobuyuki
N
Takahashi
Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Haruya
H
Takahashi
Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Kyoto, Japan.
Huei-Fen
HF
Jheng
Department of Food Science and Nutrition, University of Ulsan, Ulsan, South Korea.
Rina
R
Yu
Division of Pharmaceutics, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Masahiko
M
Taniguchi
Division of Pharmaceutics, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
Kimiye
K
Baba
Department of Bioscience, Fukui Prefectural University, Fukui, Japan.
Shigeru
S
Murakami
Division of Food Science and Biotechnology, Laboratory of Molecular Function of Food, Graduate School of Agriculture, Kyoto University, Kyoto, Japan. fat@kais.kyoto-u.ac.jp.|Research Unit for Physiological Chemistry, Japan, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto, Japan. fat@kais.kyoto-u.ac.jp.
Teruo
T
Kawada
D017667:Adipocytes / Q000187:drug effects; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D059305:Diet, High-Fat; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000187:drug effects; D009765:Obesity / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000187:drug effects
D017077:Culture Media, Conditioned; D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; C068243:4-hydroxyderricin; D002599:Chalcone; C068244:xanthoangelol; D048031:JNK Mitogen-Activated Protein Kinases