Inhibitory Effect of Tangeretin and Cardamonin on Human Intestinal SGLT1 Activity In Vitro and Blood Glucose Levels in Mice In Vivo

Rapid postprandial blood glucose elevation can cause lifestyle-related diseases, such as type II diabetes. The absorption of food-derived glucose is primarily mediated by sodium/glucose cotransporter 1 (SGLT1). Moderate SGLT1 inhibition can help attenuate postprandial blood glucose elevation and prevent lifestyle-related diseases. In this study, we established a CHO cell line stably expressing human SGLT1 and examined the effects of phytochemicals on SGLT1 activity. Among the 50 phytochemicals assessed, tangeretin and cardamonin inhibited SGLT1 activity. Tangeretin and cardamonin did not affect the uptake of L-leucine, L-glutamate, and glycyl-sarcosine. Tangeretin, but not cardamonin, inhibited fructose uptake, suggesting that the inhibitory effect of tangeretin was specific to the monosaccharide transporter, whereas that of cardamonin was specific to SGLT1. Kinetic analysis suggested that the suppression of SGLT1 activity by tangeretin was associated with a reduction in Vmax and an increase in Km, whereas suppression by cardamonin was associated with a reduction in Vmax and no change in Km. Oral glucose tolerance tests in mice showed that tangeretin and cardamonin significantly suppressed the rapid increase in blood glucose levels. In conclusion, tangeretin and cardamonin were shown to inhibit SGLT1 activity in vitro and lower blood glucose level in vivo.

The Effects of Gold Kiwifruit Intake Timing with or without Pericarp on Postprandial Blood Glucose Level

The purpose of this study was to examine how gold kiwifruit pericarp (pericarp is defined as the skin of the fruit) consumption and the timing thereof affect the postprandial blood glucose profile. The study was conducted on ten healthy volunteers (six men and four women). According to our results, the simultaneous intake of gold kiwifruit with bread and the prior intake of gold kiwifruit evidently suppressed the postprandial blood glucose elevation compared with exclusive bread intake. There was no significant difference in postprandial blood glucose changes between the ingestion of gold kiwifruit pericarp and pulp and that of gold kiwifruit pulp only. The highest postprandial blood glucose elevation was suppressed by 27.6% and the area under the blood glucose elevation curve by 29.3%, even with the exclusive ingestion of gold kiwifruit pulp. We predicted that the ingestion of both the pericarp and pulp of gold kiwifruit would reduce the postprandial blood glucose elevation to a greater extent than that of gold kiwifruit pulp only; however, there was no significant difference between the two. These results indicate that gold kiwifruit consumption significantly suppresses the postprandial blood glucose elevation regardless of pericarp presence or absence and the timing of ingestion.

Suppressive effect of a single dose of monoglucosyl rutin on postprandial blood glucose elevation: A randomized, placebo-controlled, double-blind crossover study

Objective: This study aimed to investigate the suppressive effect of a single dose of water-soluble α- glycosylated rutin (monoglucosyl rutin; MR) on postprandial blood glucose elevation in healthy subjects with relatively high fasting blood glucose levels.Methods: This randomized, placebo-controlled, double-blind crossover study enrolled 34 healthy Japanese adult subjects with relatively high fasting blood glucose levels. The study period ran from November 13, 2019, to March 19, 2020. All subjects were randomly allocated to either sequence A or sequence B (n = 17 per group) using a computerized random number generator. The washout period was at least one week between periods I and II. In period I, the subjects took either MR or placebo tablets. In period II, subjects took different tablets from the ones they had taken in period I. We evaluated their blood glucose and insulin levels after glucose loading (150 g of cooked rice). The incremental area under the curve (IAUC) of the postprandial blood glucose level was determined as the primary outcome. The blood glucose and insulin levels at maximum (maximum blood concentration; Cmax), each measurement point, and IAUC of the blood insulin level after glucose loading were the secondary outcomes.Results: Out of 33 subjects, 16 in sequence A (11 men and 5 women, 54.5 ± 9.8 years) and 17 in sequence B (9 men and 8 women, 58.8 ± 9.4 years) were analyzed as a per-protocol dataset. The glucose IAUC after MR consumption was significantly lower than that of the placebo (P = 0.034). Results of the other outcomes were not observed with significant treatment effects. There were no adverse events attributable to the test foods.Conclusions: We suggest that MR has a suppressive effect on the elevation of postprandial blood glucose in healthy adults with relatively high fasting blood glucose levels.Trial registration: UMIN-CTR: UMIN000038515. Foundation: Toyo Sugar Refining Co., Ltd.Keywords: monoglucosyl rutin, blood glucose level, incremental area under the curve, α-amylase, α-glucosidase, crossover study

Skin-related enzyme inhibitory activity by hydrolyzable polyphenols in water chestnut (Trapa natans) husk

ABSTRACT Water chestnut is a floating leaf plant native to Asia and Europe. Its fruit has long been used as an edible and herbal medicine. Water chestnut contains many polyphenols and its consumption can prevent lifestyle-related diseases because it has a suppressive effect on postprandial blood glucose elevation; however, its suitability as a cosmetic material is unknown. Therefore, this study aimed at investigating the antiaging effect of polyphenols contained in the husk of the devil water chestnut (Trapa natans). Six hydrolyzable polyphenols—1,6-di-O-galloyl-β-d-glucopyranose, 1,2,6-tri-O-galloyl-β-d-glucopyranose, 1,6-di-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucopyranose (nobotanin D), eugeniin, 1,2,3,6-tetra-O-galloyl-β-d-glucopyranose, and trapain—were collected and isolated from the water chestnut husk. These polyphenols showed high antioxidant and antiglycation activities. In addition, inhibitory activities against hyaluronidase, elastase, and collagenase were observed. Especially, eugeniin and trapain, which have many gallic acids and a hexahydroxy-biphenyl group, showed high inhibitory activities. Thus, the polyphenols in water chestnut are beneficial for antiaging effects.

Liver-expressed antimicrobial peptide 2 antagonizes the effect of ghrelin in rodents

Ghrelin, a stomach-derived peptide, promotes feeding and growth hormone (GH) secretion. A recent study identified liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inhibitor of ghrelin-induced GH secretion, but the effect of LEAP2 in the brain remained unknown. In this study, we showed that intracerebroventricular (i.c.v.) administration of LEAP2 to rats suppressed central ghrelin functions including Fos expression in the hypothalamic nuclei, promotion of food intake, blood glucose elevation, and body temperature reduction. LEAP2 did not inhibit neuropeptide Y (NPY)-induced food intake or des-acyl ghrelin-induced reduction in body temperature, indicating that the inhibitory effects of LEAP2 were specific for GHSR. Plasma LEAP2 levels varied according to feeding status and seemed to be dependent on the hepatic Leap2 expression. Furthermore, ghrelin suppressed the expression of hepatic Leap2 via AMPK activation. Together, these results reveal that LEAP2 inhibits central ghrelin functions and crosstalk between liver and stomach.

Suppressive Effect of the α-Amylase Inhibitor Albumin from Buckwheat (Fagopyrum esculentum Moench) on Postprandial Hyperglycaemia

Inhibiting starch hydrolysis into sugar could reduce postprandial blood glucose elevation and contribute to diabetes prevention. Here, both buckwheat and wheat albumin that inhibited mammalian α-amylase in vitro suppressed blood glucose level elevation after starch loading in vivo, but it had no effect after glucose loading. In contrast to the non-competitive inhibition of wheat α-amylase inhibitor, buckwheat albumin acted in a competitive manner. Although buckwheat α-amylase inhibitor was readily hydrolysed by digestive enzymes, the hydrolysate retained inhibitory activity. Together with its thermal stability, this suggests its potential use in functional foods that prevent diabetes.

Preventive Effect of Flavonol Derivatives Abundant Sanglan Tea on Long-Term High-Fat-Diet-Induced Obesity Complications in C57BL/6 Mice

Sanglan Tea (SLT) is a Chinese medicine-based formulation that is consumed as a health drink for the effective management of obesity-associated complications. However, its chemical components and mechanism of action in the prevention of hepatic steatosis and obesity-related impairments have been uncertain. In this study, we aimed to unveil the chemical profile of SLT and to explore its preventive mechanism in high-fat-diet-induced non-alcoholic fatty liver disease (NAFLD) and obesity-related consequences in C57BL/6 mice. Ultrahigh-performance liquid chromatography (UHPLC) coupled to a quadrupole-orbitrap high-resolution mass spectrometry (MS) analysis of SLT indicated that analogs of quercetin and kaempferol are major compounds of flavonoids in SLT. A dietary supplement of SLT efficiently managed the blood glucose elevation, retained the serum total cholesterol (TC), LDL-cholesterol (LDL-C), and triglyceride (TG) levels, as well as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity, and reduced the fat storage in the liver induced by a high-fat diet. The underlying mechanism of this preventive effect is hypothesized to be related to the inhibition of over-expression of lipogenesis and adipogenesis-related genes. Overall, this study suggests that SLT, being rich in quercetin and kaempferol analogs, could be a potential food supplement for the prevention of high-fat-diet-induced NAFLD and obesity-related complications.