title: Sofalcone, an anti-ulcer chalcone derivative, suppresses inflammatory crosstalk between macrophages and adipocytes and adipocyte differentiation: implication of heme-oxygenase-1 induction.
abstract: Sofalcone, 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone, has been used as an anti-ulcer agent, although its precise molecular mechanism has not been completely understood. In the current study, we tested the effects of sofalcone on the inflammatory crosstalk between macrophages and adipocytes and on the differentiation of pre-adipocytes. We found that sofalcone has a strong suppressive effect on the production of nitric oxide (NO), tumor necrosis factor (TNF)alpha, and monocyte chemoattractant protein (MCP)-1 in the culture medium of a coculture system containing RAW264.7 macrophages and 3T3-F442A adipocytes stimulated with lipopolysaccharide (LPS). The suppressive effect of sofalcone on NO production was attenuated by treatment with tin-protoporphyrin (SnPP), a heme-oxygenase (HO)-1 inhibitor. Western blotting analysis showed that sofalcone increased HO-1 expression in both 3T3-F442A mature adipocytes and undifferentiated fibroblasts. Sofalcone also inhibited the differentiation of 3T3-F442A pre-adipocytes into adipocytes, which was restored by SnPP treatment. These results suggest that sofalcone has preferable properties for obesity or metabolic syndrome.
authors.affiliation: Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Seito
authors.initials: S
authors.lastname: Nakamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Onda
authors.forename: Tomoya
authors.initials: T
authors.lastname: Tazaki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000378:metabolism; D018920:Coculture Techniques; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D011524:Protoporphyrins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000897:Anti-Ulcer Agents; C491768:Ccl2 protein, mouse; D047188:Chalcones; D018932:Chemokine CCL2; D008665:Metalloporphyrins; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; C035032:sofalcone; D009569:Nitric Oxide; C032628:tin protoporphyrin IX; D051547:Heme Oxygenase-1