Xanthohumol inhibits IL-12 production and reduces chronic allergic contact dermatitis.
Xanthohumol (XN) and its related compounds were evaluated for their effects on modulating the production of interleukin (IL)-12, the most important factor driving T helper 1 immune responses. XN showed the strongest inhibitory effect on IL-12 production in macrophages stimulated by lipopolysaccharide (LPS) or LPS/interferon-gamma. Xanthohumol 4'-O-beta-D-glucopyranoside (XNG) inhibited IL-12 production less effectively than XN. Isoxanthohumol and 8-prenylnaringenin showed comparatively lower inhibitory effects on IL-12 production than XNG. (2S)-5-methoxy-8-prenylnaringenin 7-O-beta-D-glucopyranoside did not exert any effect on IL-12 production. We then tested how these compounds affected NF-kappaB binding activity to the kappaB site in the nucleus. The compounds inhibited kappaB binding in macrophages with the same potency order as IL-12 inhibition. Furthermore, we investigated whether XN, which showed the most effective reduction of IL-12 production, attenuated skin inflammation. Chronic allergic contact dermatitis, an experimental model for psoriasis, was used to determine the anti-inflammatory effects of XN in vivo. XN treatment reduced the degree of ear thickening induced by oxazolone. Taken together, XN might be effective as an anti-inflammatory agent to reduce skin inflammation by inhibiting IL-12 production.
College of Pharmacy & Research Institute of Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.
Young-Chang
YC
Cho
Sung-Kyun
SK
You
Hyun Jung
HJ
Kim
Cheong-Weon
CW
Cho
Ik-Soo
IS
Lee
Bok Yun
BY
Kang
D000818:Animals; D002478:Cells, Cultured; D002908:Chronic Disease; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D010081:Oxazolone / Q000008:administration & dosage; D011427:Propiophenones / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D011485:Protein Binding; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology
D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011427:Propiophenones; D010081:Oxazolone; D018664:Interleukin-12; D007371:Interferon-gamma; C104536:xanthohumol