The chalcones cardamonin and flavokawain B inhibit the differentiation of preadipocytes to adipocytes by activating ERK

Aim We searched for polyphenols capable of inhibiting the lipid accumulation in 3T3-L1 cells, and investigated the mechanisms of two effective chalcones cardamonin and flavokawain B on differentiation of preadipocytes. Method and results We treated 3T3-L1 cells with a panel of 46 polyphenols and measured intracellular lipid accumulation by Sudan II staining. Four of them, including cardamonin and flavokawain B, inhibited lipid accumulation. In the further study, cardamonin and flavokawain B inhibited lipid accumulation by downregulating the expression of CCAAT/enhancer binding protein (C/EBP)-β, C/EBPα, and peroxisome proliferator-activated receptor-γ (PPARγ) at both mRNA and protein levels. Cardamonin and flavokawain B also increased phosphorylation of extracellular signal-regulated kinase (ERK) in the early phase of adipocyte differentiation. PD98059, an ERK inhibitor, restored C/EBPβ, PPARγ expression and intracellular lipid accumulation in adipocytes. Moreover, cardamonin and flavokawain B also modulated the secretion of C-reactive protein, dipeptidyl peptidase IV, interleukin-6, tumor necrosis factor-α and fibroblast growth factor-21 in mature adipocytes. Conclusions These results indicate that ERK activation and consequent downregulation of adipocyte-specific transcription factors are involved in the inhibitory effects of the chalcones cardamonin and flavokawain B on adipocyte differentiation. Moreover, cardamonin and flavokawain B are able to modulate secretion of adipokines in mature adipocytes.