Antiobesity effect of baicalin involves the modulations of proadipogenic and antiadipogenic regulators of the adipogenesis pathway

Abstract

In this study, the antiobesity effects of baicalin, 5,6-dihydroxyflavone-7-glucuronic acid, were characterized using an in vitro system of adipogenesis, i.e. fat cell formation. Baicalin-treatment of 3T3-L1 preadipocytes was shown to inhibit triglyceride accumulation and lipid droplet formation during induced adipogenesis. Microarray analyses showed that baicalin modulated the expression of genes located in pathways such as adipogenesis, cholesterol biosynthesis, focal adhesion and others. In the adipogenesis pathway, treatment with baicalin significantly down-regulated terminal differentiation markers of adipocytes including fatty acid binding protein 4. The effects of baicalin on the core part of the adipogenesis pathway, however, were paradoxical; the expression levels of CCAAT/enhancer binding protein (C/EBP)beta and C/EBPdelta were up-regulated, while the expression levels of the peroxisome proliferator-activated receptor (PPAR)gamma and C/EBPalpha were down-regulated. The antiadipogenic mechanisms of baicalin can be explained by its effects on the upstream part of adipogenesis pathway; baicalin not only up-regulates the antiadipogenic regulators, C/EBPgamma, C/EBP homologous protein and Kruppel-like factor (KLF)2, but also down-regulates the proadipogenic regulator, KLF15. The overall effects of baicalin on these upstream regulators of adipogenesis were antiadipogenic, resulting in the down-regulation of downstream genes and the inhibition of cellular fat accumulation.

Negative Regulation of Adipogenesis by Kaempferol, a Component of <i>Rhizoma Polygonati falcatum</i> in 3T3-L1 Cells

“…Natural flavonoids, found in various plants and herbal medicines, up-or down-regulate differentiation of 3T3-L1 preadipocytes and gene expression involved in adipogenesis. [24][25][26][27][28] In our study, we found that the flavonoid kaempferol is potent in repressing both lipid accumulation and expression of adipogenic markers. Kaempferol is found in many medical plants, such as Gingko biloba (Gb), Pinus densiflora SIEB.…”

Shikonin inhibits adipogenesis by modulation of the WNT/β-catenin pathway

“…Recently, much interest has been focused on the discovery of safe and effective natural products capable of regulating adipogenesis and fat accumulation (Hassan et al, 2007;Lee et al, 2009;Saito et al, 2008;Zhang et al, 2009). In our previous study, we demonstrated that shikonin, a natural compound isolated from Lithospermun erythrorhizon Sieb.…”

Cineromycin B isolated from Streptomyces cinerochromogenes inhibits adipocyte differentiation of 3T3-L1 cells via Krüppel-like factors 2 and 3

“…Moreover, polymethoxyflavonoids and sakuranetin isolated from Kaempferia parviflora and Smallanthus fruticosus, respectively, enhanced adipocyte differentiation via GATA-2 mRNA expression [26,27]. Platycodin D from Platycodon grandiflorus and baicalin from Scutellaria baicalensis have been reported to inhibit adipogenesis via upregulating KLF2 and via upregulating KLF2 and downregulating KLF15 mRNA levels, respectively; mRNA levels were measured at 2-7 days after induction [28,29]. These reports indicated that some members of the GATA and KLF families are key regulators of adipocyte differentiation at an early stage (~2 days after induction).…”