Inhibition of the intestinal postprandial glucose transport by gallic acid and gallic acid derivatives.

Inhibition of glucose uptake in the intestine through sodium-dependent glucose transporter 1 (SGLT1) or glucose transporter 2 (GLUT2) may be beneficial in controlling postprandial blood glucose levels. Gallic acid and ten of its derivatives were identified in the active fractions of Terminalia chebula Retz. fructus immaturus, a popular edible plant fruit which has previously been associated with the inhibition of glucose uptake. Gallic acid derivatives (methyl gallate, ethyl gallate, pentyl gallate, 3,4,6-tri-O-galloyl-ß-d-glucose, and corilagin) showed good glucose transport inhibition with inhibitory rates of 72.1 ± 1.6%, 71.5 ± 1.4%, 79.9 ± 1.2%, 44.7 ± 1.2%, and 75.0 ± 0.7% at 5 mM d-glucose and/or 56.3 ± 2.3, 52.1 ± 3.2%, 70.2 ± 1.7%, 15.6 ± 1.6%, and 37.1 ± 0.8% at 25 mM d-glucose. However, only 3,4,6-tri-O-galloyl-ß-d-glucose and corilagin were confirmed GLUT2-specific inhibitors. Whilst some tea flavonoids demonstrated minimal glucose transport inhibition, their gallic acid derivatives strongly inhibited transport effect with GLUT2 specificity. This suggests that gallic acid structures are crucial for glucose transport inhibition. Plants, such as T. chebula, which contain high levels of gallic acid and its derivatives, show promise as natural functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels.

Homoisoflavonoids Are Potent Glucose Transporter 2 (GLUT2) Inhibitors: A Potential Mechanism for the Glucose-Lowering Properties of Polygonatum odoratum.

Foods of high carbohydrate content such as sucrose or starch increase postprandial blood glucose concentrations. The glucose absorption system in the intestine comprises two components: sodium-dependent glucose transporter-1 (SGLT1) and glucose transporter 2 (GLUT2). Here five sappanin-type (SAP) homoisoflavonoids were identified as novel potent GLUT2 inhibitors, with three of them isolated from the fibrous roots of Polygonatum odoratum (Mill.) Druce. SAP homoisolflavonoids had a stronger inhibitory effect on 25 mM glucose transport (41.6 ± 2.5, 50.5 ± 7.6, 47.5 ± 1.9, 42.6 ± 2.4, and 45.7 ± 4.1% for EA-1, EA-2, EA-3, MOA, and MOB) than flavonoids (19.3 ± 2.2, 11.5 ± 3.7, 16.4 ± 2.4, 5.3 ± 1.0, 3.7 ± 2.2, and 18.1 ± 2.4% for apigenin, luteolin, quercetin, naringenin, hesperetin, and genistein) and phloretin (28.1 ± 1.6%) at 15 µM. SAP homoisoflavonoids and SGLT1 inhibitors were found to synergistically inhibit the uptake of glucose using an in vitro model comprising Caco-2 cells. This observed new mechanism of the glucose-lowering action of P. odoratum suggests that SAP homoisoflavonoids and their combination with flavonoid monoglucosides show promise as naturally functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels.

Employing observational method for prospective data collection: A case study for analyzing diagnostic process and evaluating efficacy of TCM treatments for diabetes mellitus.

ETHNOPHARMACOLOGICAL RELEVANCE: With the mounting pandemic of glucose metabolism dysregulation and type 2 Diabetes Mellitus (T2DM), traditional medicine such as traditional Chinese medicine (TCM) recipes has been widely adopted as a part of therapeutic approach, especially in Asian countries. AIM OF THE STUDY: A novel approach, which is adopted from cohort studies from epidemiology has been applied to explore the clinical efficacy, as well as the herbal component selection of a variety of TCM formulations against T2DM. MATERIALS AND METHODS: In the current study, 98 newly diagnosed T2DM patients were recruited in two hospitals. Over a span of 4 weeks, the patients were treated by prescriptions of their individual TCM physicians. General TCM symptoms, blood glucose parameters, as well as general metabolic health biomarkers were evaluated over the therapy period. The pattern of which herbs were used, together with association between blood glucose level change and the use of herbs, were analyzed. RESULTS: TCM diabetic syndrome diagnosis was made by physicians based on symptoms, who prescribed herbal TCM medication afterwards for individual subjects. The results showed significant reduction in fasting and postmeal glucose levels, as well as insulin after the TCM treatment regimen as compared to baseline. As secondary endpoint, total triglyceride level decreased over the period of study as well. Kudzuvine root, Rhemannia root, Figwoot root, and Mulberry leaf were the top herbs associated with pronounced glucose reduction. CONCLUSIONS: In conclusion, an observational study on a cohort of patients receiving TCM therapy has shown good clinical outcome for T2DM patients receiving TCM treatments. Association analysis on herbal usage and clinical outcome suggested opportunity in constructing optimized formulation for superior efficacy with future studies at a larger scale.

Characterization of two homogalacturonan pectins with immunomodulatory activity from green tea.

Two natural homogalacturonan (HG) pectins (MW ca. 20 kDa) were isolated from green tea based on their immunomodulatory activity. The crude tea polysaccharides (TPS1 and TPS2) were obtained from green tea leaves by hot water extraction and followed by 40% and 70% ethanol precipitation, respectively. Two homogenous water soluble polysaccharides (TPS1-2a and TPS1-2b) were obtained from TPS1 after purification with gel permeation, which gave a higher phagocytic effect than TPS2. A combination of composition, methylation and configuration analyses, as well as NMR (nuclear magnetic resonance) spectroscopy revealed that TPS1-2a and TPS1-2b were homogalacturonan (HG) pectins consisting of a backbone of 1,4-linked α-D-galacturonic acid (GalA) residues with 28.4% and 26.1% of carboxyl groups as methyl ester, respectively. The immunological assay results demonstrated that TPS1-2, which consisted mainly of HG pectins, showed phagocytosis-enhancing activity in HL-60 cells.

Homogalacturonans from preinfused green tea: structural characterization and anticomplementary activity of their sulfated derivatives.

Two homogeneous water-soluble polysaccharides (TPSR4-2B and TPSR4-2C) were obtained from preinfused green tea. Their average molecular weights were estimated to be 41 kDa and 28 kDa, respectively. A combination of composition, methylation, and configuration analysis, as well as NMR spectroscopy, indicated that both TPSR4-2B and TPSR4-2C were poly-(1-4)-α-d-galactopyranosyluronic acid in which 30.5 ± 0.3% and 28.3 ± 0.5%, respectively, of uronic acid existed as methyl ester. Two sulfated derivatives (Sul-R4-2B and Sul-R4-2C) from TPSR4-2B and TPSR4-2C were prepared after sulfation with a 2:1 chlorosulfonic acid-pyridine ratio. The anticomplementary assay showed that Sul-R4-2B and Sul-R4-2C demonstrated a stronger inhibitory effect on the complement activation through the classic pathway, compared to that of heparin. Preliminary mechanism studies by using complement component depleted-sera indicated that both Sul-R4-2B and Sul-R4-2C selectively interact with C1q, C1r, C1s, C2, C5, and C9 but not with C3 and C4. The relationship between DS and the anticomplementary activity of sulfated derivatives of homogalacturonans showed that low sulfated derivatives of homogalacturonans also exhibited potent anticomplementary effect, which might greatly reduce the side effects related to heparin and oversulfated chondroitin sulfate, such as anticoagulant activity and allergic-type reaction. These results suggested that sulfated derivatives of homogalacturonans might be promising drug candidates for therapeutic complement inhibition.