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Several types of coumarins have been isolated from Peucedanum japonicum Thunb (PJT) and we previously reported the anti-obesity activity of pteryxin (PTX), as an active compound of PJT. However, during our research, we identified another variety of PJT, which does not contain any PTX. Here, we prepared concentrates from the two varieties of PJT and demonstrated that dietary PJT concentrates both with and without PTX significantly decreased the relative weights of white adipose tissue (WAT) and mRNA levels of lipogenic genes in epididymal WAT. Furthermore, we compared the inhibitory effects of dihydropyranocoumarins of PJT on lipid accumulation of differentiated 3T3-L1 adipocytes. All of the dihydropyranocoumarins used in this study significantly inhibited lipid accumulation and lipogenic-related gene expressions in 3T3-L1 adipocytes. However, the magnitudes of the effects were distinctly different. The present study demonstrated that several dihydropyranocoumarins in PJT possess anti-obesity activities, which mainly act by inhibiting lipogenesis in adipocytes.

Cirsium brevicaule A. GRAY is a wild perennial herb, and its roots (CbR) have traditionally been used as both food and medicine on the Japanese islands of Okinawa and Amami. The present study evaluated the antiadipogenic effect of CbR using mouse embryonic fibroblast cell line 3T3-L1 from JCRB cell bank. Dried CbR powder was serially extracted with solvents of various polarities, and these crude extracts were tested for antiadipogenic activity. Treatment with the methanol extract of CbR showed a significant suppression of lipid accumulation in 3T3-L1 cells. Methanol extract of CbR was then fractionated and subjected to further activity analyses. The phenylpropanoid glycosidic molecule syringin was identified as an active compound. Syringin dose dependently suppressed lipid accumulation of 3T3-L1 cells without cytotoxicity, and significantly reduced the expressions of peroxisome proliferator-activated receptor gamma, the master regulator of adipogenesis, and other differentiation markers. It was demonstrated that syringin effectively enhanced the phosphorylation of the AMP-activated protein kinase and acetyl-CoA carboxylase. These results indicate that syringin attenuates adipocyte differentiation, adipogenesis, and promotes lipid metabolism, thus, syringin may potentially serve as a therapeutic candidate for treatment of obesity.

Background The leaves of Cirsium brevicaule A. GRAY (CL) significantly decreased hepatic lipid accumulation and the expression of fatty acid synthase gene ( FASN ) in mice. Purpose We aimed to purify and identify the active compound(s) from CL and determine the inhibitory mechanism of expression of FASN . Methods We purified monogalactosyldiacylglycerol (MGDG) from extracts of CL (CL-MGDG) and showed that it was the active CL component through analyses of its effects on the expression of genes of human breast cancer cell line, SKBR-3. Results The content and fatty acid composition of CL-MGDG are distinctly different from those of other vegetable-derived MGDGs. Treatment of SKBR-3 cells with MGDG decreased the level of FASN mRNA as well as the levels of mRNA encoding other protein involved in lipogenesis. Further, MGDG treatments significantly inhibited luciferase activities of constructs containing liver X receptor response element in FASN promoter region without altering the levels of mRNA encoding transcription factors. MGDG and the FASN inhibitor C75 decreased the viabilities of SKBR-3 cells in a concentration-dependent manner. CL-MGDG more potently inhibited cell viability than a commercial MGDG preparation. Conclusions CL represents a good source of glycoglycerolipids with potential as functional ingredients of food.

Partially purified hexane phase (HP) of Peucedanum japonicum Thunb (PJT) was identified as an antiobesity candidate. However, the compound responsible for the antiobesity activity remained unknown. Thus, in this study we isolated the active compound, to determine the mechanisms related to antiobesity activity in vitro.The HP was fractionated, and the effect on the triacylglycerol (TG) content was evaluated in 3T3-L1 preadipocytes and HepG2 hepatocytes. On the basis of comprehensive spectroscopic analyses, the structure of the active compound was identified as pteryxin, a known compound in PJT. However, to our knowledge, its biological activities against obesity have not been reported previously. The dose-dependent effect on the TG content, and the gene expressions related to adipogenesis, fatty acid catabolism, energy expenditure, lipolysis, and lipogenesis due to pteryxin (10, 15, and 20 μg/mL) were examined in vitro.Pteryxin dose dependently suppressed TG content in both 3T3-L1 adipocytes (by 52.7%, 53.8%, and 57.4%, respectively; P0.05) and HepG2 hepatocytes (by 25.2%, 34.1%, and 27.4%, respectively; P0.05). Sterol regulatory element-binding protein-1 (SREBP-1c), fatty acid synthase (FASN), and acetyl-coenzyme A carboxylase-1 (ACC1) were down-regulated in pteryxin-treated 3T3-L1 adipocytes (by 18%, 36.1%, and 38.2%, P0.05) and HepG2 hepatocytes (by 72.3%, 62.9%, and 38.8%, respectively; P0.05). The adipocyte size marker gene, paternally expressed gene1/mesoderm specific transcript (MEST) was down-regulated (by 42.8%; P0.05), and hormone-sensitive lipase, a lipid catabolizing gene was up-regulated (by 15.1%; P0.05) in pteryxin-treated adipocytes. The uncoupling protein 2 (by 77.5%; P0.05) and adiponectin (by 76.3%; P0.05) were up-regulated due to pteryxin.Our study demonstrated that pteryxin in PJT plays the key role in regulating the lipid metabolism-related gene network and improving energy production in vitro. Thus, the results suggest pteryxin as a new natural compound to be used as an antiobesity drug in the pharmaceutical industry.

Background: Various flavonoids obtained from the genus Cirsium have been reported to exhibit beneficial effects on health. The present study evaluated the antiobesity effects of Cirsium brevicaule A. GRAY leaf (CL) by using 3T3-L1 cells and C57BL/6 mice that were fed a high-fat diet (HFD). Methods: Dried CL powder was serially extracted with solvents of various polarities, and these extracts were tested for antiadipogenic activity using 3T3-L1 adipocytes. Mice were fed experimental HFD supplemented with dried CL powder for 4 wk. Lipid levels and mRNA levels of genes related to lipid metabolism were determined in 3T3-L1 adipocytes and the white adipose tissue (WAT) and liver of mice fed on a HFD. Results: Treatment of 3T3-L1 adipocytes with a hexane extract of CL significantly reduced cellular lipid accumulation and expression of the fatty acid synthase (FASN) gene. Dietary CL reduced the serum levels of nonesterified fatty acids in HFD-fed mice. Significant decreases in subcutaneous WAT weight and associated FASN gene expression were observed in the mice fed the experimental CL diet. Dietary CL also reduced the hepatic lipid and\nserum levels of a hepatopathic indicator in the HFD-fed mice. A significant reduction in mRNA levels of FASN and HMG-CoA reductase were observed in the livers of the CL-diet group. Dietary CL, on the other hand, increased in the hepatic mRNA levels of genes related to β-oxidation, namely peroxisome proliferator-activated receptor α, calnitine palmitoyltrasferase 1A, and uncoupling protein 2. Expression of the insulin receptor gene was also significantly increased in the livers of mice-fed the CL diet. Conclusions: The present study therefore demonstrated that CL suppresses lipid accumulation in the WAT and liver partly through inhibiting mRNA levels of FASN gene and enhancing the lipolysis-related gene expression., 論文

Objective Crude ethanolic extract of Peucedanum japonicum Thunb (PJT) has been identified as an antiobesity and antidiabetic candidate. The aim of this study was to assess the mechanisms related to the antiobesity activity of partially purified PJT ethanol extract in vitro. Methods PJT ethanol extract (EE) was partitioned into hexane phase (HP) and residual water phase. The effect of PJT extracts on triacylglycerol (TG) content, lipid metabolism-related gene expression, and energy expenditure was assessed in vitro in 3T3-L1, HepG2, and C2C12 cells. Furthermore, the active components in PJT extracts were partially profiled by high-performance liquid chromatography (HPLC) analysis. Results The HP significantly down-regulated lipogenic gene expressions in hepatocytes, inhibited TG accumulation, and decreased the size of 3T3-L1 adipocytes. Moreover, the inhibition of lipid accumulation was at maximum during the adipocyte maturation stage. Furthermore, we found an increase in fat hydrolysis by HP in 3T3-L1. In C2C12 myotubes, the HP tended to enhance energy expenditure. HPLC analysis demonstrated that hydrophobic compounds available in the HP were responsible for antiobesity, which corresponded to the latter peaks on the HPLC chromatogram of EE. Conclusion Our study demonstrated that the HP plays a crucial role in regulating lipid metabolism-related gene expressions and energy expenditure in vitro. The results thus provide insight on the activity of HP involved in suppressing obesity and its chemical entities.