Adipocyte dysfunction is strongly associated with the development of obesity, which is a major risk factor for many disorders including diabetes, hypertension, and heart disease. It is generally accepted that the regulation of adipogenesis or adipokines expression prevents obesity. In this study, we show that isorhamnetin inhibits adipocyte differentiation, as evidenced by reduced triglyceride (TG) accumulation and glycerol-3-phosphate dehydrogenase (GPDH) activity. At the molecular level, the mRNA expression levels of peroxidase proliferator-activated receptor-gamma (PPAR-gamma) and CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), which are the major adipogenic transcription factors, were markedly reduced by isorhamnetin. However, the mRNA levels of C/EBP-beta and -delta, the upstream regulators of PPAR-gamma and C/EBP-alpha, were not reduced by isorhamnetin. Moreover, the mRNA levels of PPAR-gamma target genes such as lipoprotein lipase (LPL), CD36, aP2, and liver X receptor-alpha (LXR-alpha) were downregulated by isorhamnetin. We also showed that isorhamnetin inhibits the expression and secretion of adiponectin, and the results of adiponectin promoter assays suggest the inhibition of PPAR-gamma expression as a possible mechanism underlying the isorhamnetin-mediated effects. Taken together, these results indicate that isorhamnetin inhibits adipogenesis through downregulation of PPAR-gamma and C/EBP-alpha.

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Androgen-inducible transforming growth factor beta (TGF-beta1) derived from dermal papilla cells (DPCs) is a catagen inducer that mediates hair growth suppression in androgenetic alopecia (AGA). In this study, a cell-based assay system was developed to monitor TGF-beta1 promoter activity and then used to evaluate the effects of activated TGF-beta1 promoter in human epidermal keratinocytes (HaCaT). To accomplish this, a pMetLuc-TGF-beta1 promoter plasmid that expresses the luciferase reporter gene in response to TGF-beta1 promoter activity was constructed. Treatment of HaCaT with dihydrotestosterone, which is known to be a primary factor of AGA, resulted in a concentration-dependent increase in TGF-beta1 promoter activity. However, treatment of HaCaT with the TGF-beta1 inhibitor, curcumin, resulted in a concentration-dependant decrease in TGF-beta1 expression. Subsequent use of this assay system to screen TGF-beta1 revealed that HaCaT that were treated with apigenin showed decreased levels of TGF-beta1 expression. In addition, treatment with apigenin also significantly increased the proliferation of both SV40T-DPCs (human DPCs) and HaCaT cells. Furthermore, apigenin stimulated the elongation of hair follicles in a rat vibrissa hair follicle organ culture. Taken together, these findings suggest that apigenin, which is known to have antioxidant, anti-inflammatory, and anti-tumor properties, stimulates hair growth through downregulation of the TGF-beta1 gene. In addition, these results suggest that this assay system could be used to quantitatively measure TGF-beta1 promoter activity in HaCaT, thereby facilitating the screening of agents promoting hair growth.