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Zhang T.,Kobe University | Yamamoto N.,House Wellness Foods Corporation | Yamashita Y.,Kobe University | Ashida H.,Kobe University
Archives of Biochemistry and Biophysics | Year: 2014

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. © 2014 Elsevier Inc. All rights reserved.

Takahashi A.,Kyoto University | Yamamoto N.,House Wellness Foods Corporation | Murakami A.,Kyoto University
Life Sciences | Year: 2011

Aims: Overproduction of nitric oxide (NO) from inducible NO synthase (iNOS) plays many pivotal roles in various inflammatory diseases. In this study, we examined the effects of 6 flavonoids on lipopolysaccharide (LPS)-induced NO generation in macrophage (Mφ), and addressed molecular mechanisms of cardamonin. Main methods: Suppressive effects on NO generation in vitro were assayed in LPS-stimulated macrophages (Mφ). In vivo anti-inflammatory activity was evaluated with LPS-challenged ICR mice. Mechanistic analyses were done by ELISA, Western blot, RT-PCR, etc. Key findings: Cardamonin, a chalcone, exhibited pronounced suppressive activity, while pinocembrin, a counterpart flavanone, was much less active. Administration of cardamonin (0.02-2 mg/kg body weight) significantly decreased NOx concentrations in the sera from LPS-challenged ICR mice. This efficacy was superior to that of curcumin, a well-known anti-inflammatory agent present in turmeric. Cardamonin down-regulated iNOS mRNA expression and suppressed activation of STAT-1, but not nuclear factor kappaB, both of which are transcription factors for the iNOS gene in peritoneal Mφ of ICR mice. Interferon (IFN)-γ was identified as the major cytokine which mediates LPS-induced STAT-1 activation and resultant iNOS expression. Intriguingly, cardamonin suppressed the activation of not only STAT-1 but also STATs-2, 3 and 4. The involvement of the JAK/STATs pathway in NO generation was suggested because its specific inhibitor, AG490, decreased NO generation. Significance: Cardamonin was identified to be a unique phytochemical that targets the production of IFN- and thereby suppresses the STAT pathway for mitigating inflammation. © 2011 Elsevier Inc. All rights reserved.

Zhang T.,Kobe University | Yamamoto N.,House Wellness Foods Corporation | Ashida H.,Kobe University
Food and Function | Year: 2014

Excessive lipid accumulation in the liver has been proposed to cause hyperlipidemia, diabetes and fatty liver disease. 4-Hydroxyderricin (4HD), xanthoangelol (XAG), cardamonin (CAR) and flavokawain B (FKB) are chalcones that have exhibited various biological effects against obesity, inflammation, and diabetes; however, little is known about the inhibitory effects of these chalcones on fatty liver disease. In the present study, we investigated the ability of 4HD, XAG, CAR, and FKB to reduce lipid accumulation in hepatocytes. When HepG2 cells were treated with a mixture of fatty acids (FAs; palmitic acid:oleic acid = 1:2 ratio), significant lipid accumulation was observed. Under the same experimental conditions, addition of chalcones at 5 μM significantly suppressed the FA-induced lipid accumulation. We found that the expression of sterol regulatory element-binding protein-1 (SREBP-1), a key molecule involved in lipogenesis, was decreased in these chalcone-treated cells. We also found that these chalcones increased the expression of peroxisome proliferator-activated receptor α (PPARα), which is involved in FA oxidation. Moreover, these chalcones increased phosphorylation of AMP-activated protein kinase (AMPK) and liver kinase B1 (LKB1), upstream regulators of SREBP-1 and PPARα. We confirmed that an AMPK inhibitor, compound C, reversed chalcone-induced changes in SREBP-1 and PPARα expression in the HepG2 cells. Collectively, we found that 4HD, XAG, CAR, and XAG attenuated lipid accumulation through activation of the LKB1/AMPK signaling pathway in HepG2 cells. © 2014 the Partner Organisations.

House Wellness Foods Corporation | Date: 2015-06-08

A composition comprising (a) and (b), and a food or drink or a medicine comprising the composition, wherein (a) is at least a kind of polyphenols selected from the group consisting of a polyphenol containing 15 mass % or more of proanthocyanidin having a polymerization degree of 1 to 3, hesperidin, a hesperidin derivative, and hesperetin; and

House Wellness Foods Corporation | Date: 2011-01-14

A composition comprising (a) and (b), and a food or drink or a medicine comprising the composition, wherein

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