Presentation1.PDF

<p>Diabetes mellitus is one of a major worldwide concerns, regulated by either defects in secretion or action of insulin, or both. Insulin signaling down-regulation has been related with over activity of protein tyrosine phosphatase 1B (PTP1B) enzyme, which has been a promising target for the treatment of diabetes mellitus. Herein, activity guided separation of methanol extract (95%) of Dodonaea viscosa aerial parts afforded nine (1-9) polyphenolic compounds, all of them were identified through spectroscopic data including 2D NMR and HREIMS. Subsequently, their PTP1B inhibitory potentials were evaluated, in which all of the isolates exhibited significant dose-dependent inhibition with IC₅₀ 13.5–57.9 μM. Among them, viscosol (4) was found to be the most potent compound having IC₅₀ 13.5 μM. In order to unveil the mechanistic behavior, detailed kinetic study was carried out, in which compound 4 was observed as a reversible, and mixed type I inhibitor of PTP1B with inhibitory constant (K_i) value of 4.6 μM. Furthermore, we annotated the major metabolites through HPLC-DAD-ESI/MS analysis, in which compounds 3, 6, 7, and 9 were found to be the most abundant metabolites in D. viscosa extract.</p

Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from <i>Paulownia tomentosa</i>

<p>Protein tyrosine phosphatase 1B (PTP1B) and α<b>-</b>glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of <i>Paulownia tomentosa</i> fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (<b>1–8</b>) displaying dual inhibition of PTP1B and α<b>-</b>glucosidase. The isolated compounds were identified as flavanones (<b>1–5</b>) and dihydroflavonols (<b>6–8</b>). Inhibitory potencies of these compounds varied accordingly, but most of the compounds were highly effective against PTP1B (IC₅₀ = 1.9–8.2 μM) than α<b>-</b>glucosidase (IC₅₀ = 2.2–78.9 μM). Mimulone (<b>1</b>) was the most effective against PTP1B with IC₅₀ = 1.9 μM, whereas 6-geranyl-3,3′,5,5′,7-pentahydroxy-4′-methoxyflavane (<b>8</b>) displayed potent inhibition against α<b>-</b>glucosidase (IC₅₀ = 2.2 μM). All inhibitors showed mixed type Ι inhibition toward PTP1B, and were noncompetitive inhibitors of α-glucosidase. This mixed type behavior against PTP1B was fully demonstrated by showing a decrease in <i>V</i>_max, an increase of <i>K</i>_m, and <i>K</i>_ik/<i>K</i>_iv ratio ranging between 2.66 and 3.69.</p

Ethylene Induced a High Accumulation of Dietary Isoflavones and Expression of Isoflavonoid Biosynthetic Genes in Soybean (<i>Glycine max</i>) Leaves

Dietary isoflavones, daidzein and genistein are of huge interest in the nutraceutical field due to their practical application to postmenopause complications. This study is the first report an efficient method to prepare isoflavone rich soybean leaves (soyleaves) which is an edible food stuff in Asian countries. The preharvest treatment of ethylene highly stimulated the level of isoflavone in soyleaves. Annotation and quantification of metabolites were determined by UPLC-Q-TOF-MS and HPLC. Phenolic metabolites of soyleaves are mostly kaempferol glycosides, but not dietary isoflavones. The accumulated isoflavones by ethylene treatment were determined to be daidzin <b>1</b>, genistin <b>2</b>, malonyldaidzin <b>3</b> and malonylgenistin <b>4</b>, which were easily hydrolyzed to daidzein and genistein by β-glucosidase. Total content of dietary isoflavones was increased up to 13854 μg/g. The most suitable condition was estimated to be 250 μg/g ethylene or 200 μg/g ethephon (ethylene donor) treatment at the R3 growth stage. The ratio of daidzein and genistein glycosides was approximately 5 to 3. The accumulated isoflavonoid biosynthesis pathway genes were identified within the transcriptome of soyleaves tissues at 1 day after treatment of ethephon. The quantitative RT-PCR analysis of these genes indicated significantly higher expression of <i>CHS, CHI, IFS, HID, IF7GT</i>, and <i>IF7MaT</i> compared to control leaves. These findings suggest that ethylene activates a set of structural genes involved in isoflavonoid biosynthesis, thereby leading to enhanced production of isoflavones in soybean plants