Biochanin�A ameliorates the cytokine secretion profile of lipopolysaccharide-stimulated macrophages by a PPARγ-dependent pathway

Abstract

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 antiinflammatory efficiencies were not in correspondence with their PPARα/γ agonist activities. Inhibition of PPARγ activity by its antagonist GW9662 significantly reversed the antiinflammatory 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.

Red clover extract exerts antidiabetic and hypolipidemic effects in db/db mice

“…Isoflavones like biochanin A and formononetin are reported to be potent agonists of PPARα (12,15,16). To determine the effects of red clover extract treatment on certain target genes of PPARα in the liver, we analyzed hepatic ACO, CPT-1, APOC3 and APOA5 mRNA expression in db/db diabetic mice.…”

“…In vitro studies have demonstrated that biochanin A, formononetin and genistein, three of the isoflavones from red clover are effective PPARγ agonists (12,15,16). In this study, we demonstrated that red clover extract treatment resulted in activation of known PPARγ-regulated genes in the liver in vivo .…”

Biochanin A protects lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation

“…Previous studies showed that biochanin A improved epithelial barrier function in CaCo-2 cells via inhibition of NF-κB phosphorylation [17]. Biochanin A was found to inhibit LPS-induced TNF-α and IL-6 production in macrophages [18]. Biochanin A also showed anti-proliferative and antiinflammatory activities through inhibition of NF-κB nuclear translocation [19].…”

Biochanin A inhibits lipopolysaccharide-induced inflammation in human umbilical vein endothelial cells

“…It has been shown that biochanin A exhibited broad spectrum anti-inflammatory effects [25]. Biochanin A was found to inhibit TNF-α and IL-6 production in LPS-stimulated macrophages [30]. Studies showed that biochanin A protected dopaminergic neurons against LPS-induced damage through inhibition of pro-inflammatory cytokine production [4].…”