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Curcumin, a polyphenol found in the rhizomes of Curcuma longa, improves obesity-associated inflammation and diabetes in obese mice. Curcumin also suppresses adipocyte differentiation, although the underlying mechanism remains unclear. Here, we used 3T3-L1 cells to investigate the details of the mechanism underlying the anti-adipogenic effects of curcumin. Curcumin inhibited mitogen-activated protein kinase (MAPK) (ERK, JNK, and p38) phosphorylation that was associated with differentiation of 3T3-L1 cells into adipocytes. During differentiation, curcumin also restored nuclear translocation of the integral Wnt signaling component beta-catenin in a dose-dependent manner. In parallel, curcumin reduced differentiation-stimulated expression of CK1alpha, GSK-3beta, and Axin, components of the destruction complex targeting beta-catenin. Accordingly, quantitative PCR analysis revealed that curcumin inhibited the mRNA expression of AP2 (mature adipocyte marker) and increased the mRNA expression of Wnt10b, Fz2 (Wnt direct receptor), and LRP5 (Wnt coreceptor). Curcumin also increased mRNA levels of c-Myc and cyclin D1, well-known Wnt targets. These results suggest that the Wnt signaling pathway participates in curcumin-induced suppression of adipogenesis in 3T3-L1 cells.

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In this study, we assessed the relationships between the structure and estrogenicity of flavonoid derivatives. We evaluated estrogenicity via yeast transactivation assays, E-screen assays, and ER binding assays. Genistein and coumestrol in the yeast transactivation assay and biochanin A, genistein, and equol in the E-screen assay, have been shown to have profound estrogenic activities. Flavonoids, with the exception of biochanin A and daidzein, exhibit more profound selectivity for ER beta than for ER alpha. We compared several flavonoids in terms of estrogenicity, as well as relatively small structural differences including the position of the phenol ring and hydroxy groups, the substitution of hydroxy groups or methoxy groups, the opening of the phenol ring; glycitein vs. 4',6,7-trihydroxyisoflavone, biochanin A vs. genistein, apigenin vs. genistein, 7,4'-dihydroxyflavone vs. isoliquiritigenin. A quantitative structure-activity relationship study design was utilized to develop model equations for the estrogenic activities of flavonoid derivatives. The prediction of estrogenicity with regard to ER alpha shows a positive correlation with MW and AlogP, and a negative correlation with Apol and Area (r2 = 0.89 and q2 = 0.83). The prediction of estrogenicity with regard to ER beta reveals a positive correlation with the AlogP and Hbond acceptors, and a negative correlation with RadOfGyration (r2 = 0.77 and q2 = 0.72).

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