IL-4 receptor α in non-lipid rafts is the target molecule of strictinin in inhibiting STAT6 activation.

Strictinin has been shown to suppress interleukin (IL)-4-induced signal transducer and activator of transcription (STAT)-6 phosphorylation, which is a critical event for IgE class switching. However, it is unclear how strictinin inhibits STAT6 activation. Strictinin inhibited STAT6 phosphorylation by suppressing IL-4 receptor α (IL-4Rα) activation. Strictinin was bound to the cell surface and only localized in non-lipid raft fraction of the cells where IL-4Rα was also located. In addition, strictinin directly bound to IL-4Rα and inhibited binding of IL-4 to IL-4Rα. These results suggest that IL-4Rα locating in non-lipid raft region is a target molecule for strictinin in inhibiting STAT6 activation.

Saturated fatty acid attenuates anti-obesity effect of green tea.

Green tea and its major polyphenol epigallocatechin-3-O-gallate (EGCG) have suppressive effect on dietary obesity. However, it remains unsolved what type of diet on which they exhibit high or low anti-obesity effect. In the present study, we investigated whether anti-obesity effect of green tea differs depending on composition of fats or fatty acids that consist high-fat (HF) diet in mouse model. Green tea extract (GTE) intake dramatically suppressed weight gain and fat accumulation induced by olive oil-based HF diet, whereas the effects on those induced by beef tallow-based HF diet were weak. GTE also effectively suppressed obesity induced by unsaturated fatty acid-enriched HF diet with the stronger effect compared with that induced by saturated fatty acid-enriched HF diet. These differences would be associated with the increasing action of GTE on expression of PPARδ signaling pathway-related genes in the white adipose tissue. Expressions of genes relating to EGCG signaling pathway that is critical for exhibition of physiological effects of EGCG were also associated with the different effects of GTE. Here, we show that anti-obesity effect of GTE differs depending on types of fats or fatty acids that consist HF diet and could be attenuated by saturated fatty acid.

1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose increases a population of T regulatory cells and inhibits IgE production in ovalbumin-sensitized mice.

1,2,3,4,6-penta-O-galloyl-ß-D-glucopyranose (PGG) is a gallotannin isolated from various plants. In a previous study, it was reported that PGG suppressed interleukin (IL)-4 induced signal pathway in B cell which is indispensable for immunoglobulin E (IgE) production. However, the suppressive effect of PGG on IgE production in allergen-sensitized mice remains unclear. Therefore, the aim of this study was to investigate the inhibitory effect of PGG on IgE production in ovalbumin (OVA)-sensitized mice. Mice orally administered PGG showed a decrease in total and OVA-specific IgE levels in serum. Oral administration of PGG strongly suppressed production of type 2 T helper (IL-4 and IL-13), type 1 T helper (IFN-γ), and pro-inflammatory cytokines (TNF-α and IL-6), but not anti-inflammatory cytokine (IL-10) from splenocytes of OVA-sensitized mice against OVA re-stimulation. A population of T regulatory (Treg) cells with immunosuppressive properties was increased in mesenteric lymph nodes and spleen of PGG-fed mice. PGG administration not only reduced expression levels of eotaxin, tissue inhibitors of metalloproteinases-1, and TNF-α, which assisted with IgE production, but also increased the expression of insulin-like growth factor binding protein-3 which inhibits IgE production. Additionally, PGG increased the levels of Treg cell-inducing factors such as IL-2, IL-10 and platelet factor-4 in serum. These data suggest that the inhibitory effect of PGG on IgE production could be partially caused by increasing a population of Treg cells in conjunction with Treg-inducing factors.

In situ label-free visualization of orally dosed strictinin within mouse kidney by MALDI-MS imaging.

Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is a powerful technique for visualizing the distribution of a wide range of biomolecules within tissue sections. However, methodology for visualizing a bioactive ellagitannin has not yet been established. This paper presents a novel in situ label-free MALDI-MSI technique for visualizing the distribution of strictinin, a bioactive ellagitannin found in green tea, within mammalian kidney after oral dosing. Among nine representative matrix candidates, 1,5-diaminonaphthalene (1,5-DAN), harmane, and ferulic acid showed higher sensitivity to strictinin spotted onto a MALDI sample plate. Of these, 1,5-DAN enables visualization of a two-dimensional image of strictinin directly spotted on mouse kidney sections with the highest sensitivity. Furthermore, 1,5-DAN-based MALDI-MSI could detect the unique distribution of orally dosed strictinin within kidney sections. This in situ label-free imaging technique will contribute to the localization analysis of strictinin and its biological mechanisms.

Phosphodiesterase 5 inhibitor acts as a potent agent sensitizing acute myeloid leukemia cells to 67-kDa laminin receptor-dependent apoptosis.

(-)-Epigallocatechin-3-O-gallate (EGCG), a polyphenol in green tea, induces apoptosis in acute myeloid leukemia (AML) cells without affecting normal cells. In this study, we observed that cGMP acts as a cell death mediator of the EGCG-induced anti-AML effect through acid sphingomyelinase activation. EGCG activated the Akt/eNOS axis, a well-known mechanism in vascular cGMP upregulation. We also observed that a major cGMP negative regulator, phosphodiesterase 5, was overexpressed in AML cells, and PDE5 inhibitor, an anti-erectile dysfunction drug, synergistically enhanced the anti-AML effect of EGCG. This combination regimen killed AML cells via overexpressed 67-kDa laminin receptors.

Green tea extract containing a highly absorbent catechin prevents diet-induced lipid metabolism disorder.

We investigated the effects of extracts of Benifuuki (a tea cultivar that contains methylated catechins such as epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me)) in mice fed a high-fat/high-sucrose (HF/HS) diet. This tea cultivar was then compared with an extract of Yabukita (a popular tea cultivar that lacks methylated catechins). For 6 weeks, C57BL/6J mice were fed either HF/HS diet with or without tea extracts from tea cultivars, which contained almost identical ingredients except for methylated catechins (i.e., Yabukita (0.2% and 1%) or Benifuuki (0.2% and 1%) extract powders). Supplementation with Benifuuki 0.2% markedly lowered plasma levels of TG and NEFAs compared with mice supplemented with Yabukita 0.2%. The diet containing Benifuuki 1% decreased adipose tissue weights, liver TG, and expression of lipogenic genes in the liver. These results suggested that Benifuuki had much greater lipid-lowering effects than Yabukita. Taken together, these data suggest that methylated catechins direct the strong lipid-lowering activity of Benifuuki.