title: Biochanin A ameliorates the cytokine secretion profile of lipopolysaccharide-stimulated             macrophages by a PPARγ-dependent pathway.
abstract: The role of peroxisome proliferator-activated receptors (PPARs) as anti-inflammatory mediators has been established, and the fact that some isoflavones are dual agonists of PPARα/γ indicates the involvement of PPARα and/or PPARγ in the anti-inflammatory action of certain isoflavones. However, the dependency of isoflavones on PPARs in their anti-inflammatory action has not been demonstrated. Here, we report the dependency of an isoflavone biochanin A and the independency of another isoflavone genistein in relation to PPARγ to ameliorate the cytokine secretion profile of lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages. A total amount of 10 µmol/l of biochanin A or genistein significantly suppressed the secretion of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) in LPS-induced RAW264.7 cells, whereas another two isoflavones, formononectin and daidzein, only significantly suppressed the secretion of IL-6. Their anti-inflammatory efficiencies were not in correspondence with their PPARα/γ agonist activities. Inhibition of PPARγ activity by its antagonist GW9662 significantly reversed the anti-inflammatory effect of biochanin A but not genistein, which demonstrated the dependency of biochanin A and the independency of genistein on PPARγ in their anti-inflammatory actions. Meanwhile, the PPARγ-dependency of biochanin A was further confirmed by the result that the suppression of LPS-induced NF-κB activation by biochanin A was reversed following GW9662 co-treatment. Moreover, inhibition of PPARα activity by its antagonist MK886 did not significantly reverse the anti-inflammatory effects of biochanin A and genistein, indicating that their anti-inflammatory properties were PPARα-independent.
authors.affiliation: School of Life Sciences, Longyan University, Longyan 364000, PR China. qlongxin@tom.com
authors.forename: Longxin
authors.initials: L
authors.lastname: Qiu
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Lin
authors.forename: Yiping
authors.initials: Y
authors.lastname: Lin
authors.forename: Meicong
authors.initials: M
authors.lastname: Lin
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002460:Cell Line; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048789:Phytoestrogens / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D002722:Chlorobenzenes
chemical_list: D000813:Anilides; D016588:Anticarcinogenic Agents; D019833:Genistein; D007211:Indoles; D015850:Interleukin-6; D007529:Isoflavones; D008070:Lipopolysaccharides; D016859:Lipoxygenase Inhibitors; D016328:NF-kappa B; D047493:PPAR alpha; D047495:PPAR gamma; D048789:Phytoestrogens; D014409:Tumor Necrosis Factor-alpha; C457499:2-chloro-5-nitrobenzanilide; C060893:MK-886; D002722:Chlorobenzenes; C007768:formononetin; C004742:daidzein; C004541:biochanin A