Itch is a common sensory experience that is prevalent in patients with inflammatory skin diseases, as well as in those with systemic and neuropathic conditions. In patients with these conditions, itch is often severe and significantly affects quality of life. Itch is encoded by 2 major neuronal pathways: histaminergic (in acute itch) and nonhistaminergic (in chronic itch). In the majority of cases, crosstalk existing between keratinocytes, the immune system, and nonhistaminergic sensory nerves is responsible for the pathophysiology of chronic itch. This review provides an overview of the current understanding of the molecular, neural, and immune mechanisms of itch: beginning in the skin, proceeding to the spinal cord, and eventually ascending to the brain, where itch is processed. A growing understanding of the mechanisms of chronic itch is expanding, as is our pipeline of more targeted topical and systemic therapies. Our therapeutic armamentarium for treating chronic itch has expanded in the last 5 years, with developments of topical and systemic treatments targeting the neural and immune systems.

Obesity is a serious health problem, and its prevention is promoted through life style including diet and exercise. In this study, we investigated the suppressive effects of tea catechin on the differentiation of 3T3-L1 preadipocytes to adipocytes. (-)-Catechin 3-gallate (CG), (-)-epigallocatechin (EGC), (-)-epicatechin 3-gallate, and (-)-epigallocatechin 3-gallate at 5 muM suppressed intracellular lipid accumulation. The suppressive effects of CG and EGC were stronger than the others, and CG and EGC also suppressed the activity of glycerol-3-phosphate dehydrogenase as a differentiation marker. These catechins inhibited the expression of peroxisome proliferator-activated receptor (PPAR) gamma2 and CCAAT/enhancer-binding protein (C/EBP) alpha, both of which act as key transcription factors at an early stage of differentiation, followed by the expression of glucose transporter (GLUT) 4 at a later stage. In addition, the catechins did not affect the phosphorylation status of the insulin signal pathway. Thus, catechin suppressed adipocyte differentiation accompanied by the down-regulation of PPARgamma2, C/EBPalpha, and GLUT4. These results suggest that tea catechin prevents obesity through the suppression of adipocyte differentiation.

The pharmacokinetics of dietary fucoxanthin, one of the xanthophylls in brown sea algae, is little understood. In the present study, mice were orally administered fucoxanthin, and the distribution and accumulation of fucoxanthin and its metabolites fucoxanthinol and amarouciaxanthin A were measured in the plasma, erythrocytes, liver, lung, kidney, heart, spleen and adipose tissue. In a single oral administration of 160 nmol fucoxanthin, fucoxanthinol and amarouciaxanthin A were detectable in all specimens tested in the present study, but fucoxanthin was not. The time at maximum concentration (T max ) of these metabolites in adipose tissue was 24 h, while the T max in the others was 4 h. The area under the curve to infinity (AUC 1 ) of fucoxanthinol in the liver was the highest value (4680 nmol/g £ h) among the tissues tested in the present study, while the AUC 1 of amarouciaxanthin A in adipose tissue was the highest value (4630 nmol/g £ h). In daily oral administration of 160 nmol fucoxanthin for 1 week, fucoxanthin was also detectable in the tissues even at a low concentration. The amount of fucoxanthinol was 123 nmol/g in the heart and 85·2 nmol/g in the liver. Amarouciaxanthin A in the adipose tissue was distributed at a concentration of 97·5 nmol/g. These results demonstrate that dietary fucoxanthin accumulates in the heart and liver as fucoxanthinol and in adipose tissue as amarouciaxanthin A. Fucoxanthin: Fucoxanthinol: Amarouciaxanthin A: MiceBrown algae are a traditional foodstuff of East Asians, and an epidemiological study (1) has shown that the consumption of brown sea algae is associated with a low risk of breast cancer. Brown alga powders or extracts have been reported to suppress chemical-induced carcinogenesis in animals (2 -5) . Fucoxanthin is one of the xanthophylls found in brown algae such as kombu (Laminaria japonica), hijiki (Sargassum fusiforme) and wakame (Undaria pinnatifida) (6) . The oral administration of fucoxanthin prevented carcinogenesis in several animal models (7,8) . Recent studies with cancer cell lines have suggested that the suppressive effect is due to the inhibitory effect of fucoxanthin on cell proliferation through the induction of apoptosis (9,10) and cell cycle arrest (11) . In addition to these activities, the compound also has anti-inflammatory and anti-obesity activities (12,13) . Interestingly, a recent study showed that dietary fucoxanthin stimulates the expression of uncoupling protein 1 in the mitochondria of white adipose tissue and facilitates the consumption of fats in rats (14) . Thus, fucoxanthin has various physiological activities and contributes to the beneficial effects of brown algae.Many studies (15 -20) have reported the metabolism of hydrocarbon carotenoids such as a-carotene and b-carotene; these carotenoids are absorbed in the small intestine and then converted to vitamin A. However, information on the metabolism of non-provitamin A-type carotenoids is insufficient to explain their bioavailability and safety, although some xanthophylls such as a...

No abstract

A system for assessing the anti-inflammatory effect of food factors was developed by establishing a co-culture system with intestinal epithelial Caco-2 cells (apical side) and macrophage RAW264.7 cells (basolateral side). In this system, the stimulation of RAW264.7 cells with lipopolysaccharide was followed by a decrease in transepithelial electrical resistance, which is a marker of the integrity of the Caco-2 monolayer and an increase in TNF-alpha production from RAW264.7 cells and IL-8 mRNA expression in Caco-2 cells. Treatment with anti-TNF-alpha antibodies or budesonide suppressed in increase in TNF-alpha production and IL-8 mRNA expression. These results indicated that this co-culture model could imitate the gut inflammation in vivo. In addition, fucoidan, sulphated polysaccharides from brown algae, was employed as a candidate of evolution and added to the apical side of this model. Fucoidan suppressed IL-8 gene expression through a reduction in TNF-alpha production from RAW264.7 cells stimulated with lipopolysaccharide.

To investigate mechanisms of the anti-obesity actions of green tea in vivo, rats were given green tea instead of drinking water for 3 weeks. It was confirmed that green tea reduced adipose tissue weight without any change in body weight, other tissue weights, and food and water intakes. Green tea also significantly reduced the plasma levels of cholesterols and free fatty acids. Certain catechins existed in the plasma at 0.24 microM under our experimental conditions, though most of them existed as conjugated forms. For mechanisms of the anti-obesity actions, green tea significantly reduced glucose uptake accompanied by a decrease in translocation of glucose transporter 4 (GLUT4) in adipose tissue, while it significantly stimulated the glucose uptake with GLUT4 translocation in skeletal muscle. Moreover, green tea suppressed the expression of peroxisome proliferator-activated receptor gamma and the activation of sterol regulatory element binding protein-1 in adipose tissue. In conclusion, green tea modulates the glucose uptake system in adipose tissue and skeletal muscle and suppresses the expression and/or activation of adipogenesis-related transcription factors, as the possible mechanisms of its anti-obesity actions.

No abstract

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. It is unknown whether β-1,3;1,6-glucan can induce immune suppressive effects. Here, we study intestinal anti-inflammatory activity of Lentinula edodes-derived β-1,3;1,6-glucan, which is known as lentinan. Dextran sulfate sodium (DSS)-induced colitis mice were used to elucidate effects of lentinan in vivo. In the cellular level assessment, lentinan was added into a co-culture model consisting of intestinal epithelial Caco-2 cells and LPS-stimulated macrophage RAW264.7 cells. Ligated intestinal loop assay was performed for assessing effects of lentinan on intestinal epithelial cells (IECs) in vivo. Oral administration of lentinan (100 µg/mouse) significantly ameliorated DSS-induced colitis in body weight loss, shortening of colon lengths, histological score, and inflammatory cytokine mRNA expression in inflamed tissues. Lentinan reduced interleukin (IL)-8 mRNA expression and nuclear factor (NF)-κB activation in Caco-2 cells without decreasing of tumor necrosis factor (TNF)-α production from RAW264.7 cells. Flow cytometric analysis revealed that surface levels of TNF receptor (TNFR) 1 were decreased by lentinan treatment. A clathrin-mediated endocytosis inhibitor, monodansylcadaverine, canceled lentinan inhibition of IL-8 mRNA expression. Moreover, lentinan inhibited TNFR1 expression in Caco-2 cells in both protein and mRNA level. Lentinan also inhibited TNFR1 mRNA expression in mouse IECs. These results suggest that lentinan exhibits intestinal anti-inflammatory activity through inhibition of IL-8 mRNA expression associated with the inhibition of NF-κB activation which is triggered by TNFR1 endocytosis and lowering of their expression in IECs. Lentinan may be effective for the treatment of gut inflammation including IBD.