Kyoung-Soo Ha

In Vitro and in Vivo Anti-Hyperglycemic Effects of Omija (Schizandra chinensis) Fruit

The entrocytes of the small intestine can only absorb monosaccharides such as glucose and fructose from our diet. The intestinal absorption of dietary carbohydrates such as maltose and sucrose is carried out by a group of α-glucosidases. Inhibition of these enzymes can significantly decrease the postprandial increase of blood glucose level after a mixed carbohydrate diet. Therefore, the inhibitory activity of Omija (Schizandra chinensis) extract against rat intestinal α-glucosidase and porcine pancreatic α-amylase were investigated in vitro and in vivo. The in vitro inhibitory activities of water extract of Omija pulp/skin (OPE) on α-glucosidase and α-amylase were potent when compared to Omija seeds extract (OSE). The postprandial blood glucose lowering effect of Omija extracts was compared to a known type 2 diabetes drug (Acarbose), a strong α-glucosidase inhibitor in the Sprague-Dawley (SD) rat model. In rats fed on sucrose, OPE significantly reduced the blood glucose increase after sucrose loading. Furthermore, the oxygen radical absorbance capacity (ORAC) of OSE and OPE was evaluated. OPE had higher peroxyl radical absorbing activity than OSE. These results suggest that Omija, which has high ORAC value with α-glucosidase inhibitory activity and blood glucose lowering effect, could be physiologically useful for treatment of diabetes, although clinical trials are needed.

Molecular Weight Dependent Glucose Lowering Effect of Low Molecular Weight Chitosan Oligosaccharide (GO2KA1) on Postprandial Blood Glucose Level in SD Rats Model

This research investigated the effect of enzymatically digested low molecular weight (MW) chitosan oligosaccharide on type 2 diabetes prevention. Three different chitosan oligosaccharide samples with varying MW were evaluated in vitro for inhibition of rat small intestinal α-glucosidase and porcine pancreatic α-amylase (GO2KA1; <1000 Da, GO2KA2; 1000–10,000 Da, GO2KA3; MW > 10,000 Da). The in vitro results showed that all tested samples had similar rat α-glucosidase inhibitory and porcine α-amylase inhibitory activity. Based on these observations, we decided to further investigate the effect of all three samples at a dose of 0.1 g/kg, on reducing postprandial blood glucose levels in Sprague-Dawley (SD) rat model after sucrose loading test. In the animal trial, all tested samples had postprandial blood glucose reduction effect, when compared to control, however GO2KA1 supplementation had the strongest effect. The glucose peak (Cmax) for GO2KA1 and control was 152 mg/dL and 193 mg/dL, respectively. The area under the blood glucose-time curve (AUC) for GO2KA1 and control was 262 h mg/dL and 305 h mg/dL, respectively. Furthermore, the time of peak plasma concentration of blood glucose (Tmax) for GO2KA1 was significantly delayed (0.9 h) compared to control (0.5 h). These results suggest that GO2KA1 could have a beneficial effect for blood glucose management relevant to diabetes prevention in normal and pre-diabetic individuals. The suggested mechanism of action is via inhibition of the carbohydrate hydrolysis enzyme α-glucosidase and since GO2KA1 (MW < 1000 Da) had higher in vivo effect, we hypothesize that it is more readily absorbed and might exert further biological effect once it is absorbed in the blood stream, relevant to blood glucose management.

In Vitro and In Vivo Antihyperglycemic Effect of 2 Amadori Rearrangement Compounds, Arginyl-Fructose and Arginyl-Fructosyl-Glucose

During the heat processing of raw ginseng to produce red ginseng, amino acid derivatives such as arginyl-fructose (AF) and arginyl-fructosyl-glucose (AFG) are formed at high levels, through amadori rearrangement, the early step of Maillard reaction, from arginine and glucose or maltose, respectively. However, very limited information is available about the effect of the structural difference between AF and AFG on various biological activities. This is the first report of the mode of action and effect of AF and AFG on the type 2 diabetes management related inhibition of postprandial hyperglycemia in vitro and in animal model. In our previous study, standards AF and AFG were chemically synthesized and in this study their inhibitory activities against rat intestinal α-glucosidases and porcine pancreatic α-amylase were investigated in vitro. The IC(50) value of the in vitro inhibitory activity of AF and AFG on rat intestinal sucrase was high and in similar levels (6.40 and 6.20 mM, respectively). Additionally, a mild pancreatic α-amylase inhibitory activity was observed, with IC(50) values 36.30 and 37.60 mM for AF and AFG, respectively. The effect of AF and AFG on the postprandial blood glucose increase after meal was investigated in Sprague Dawley rats fed on starch or sucrose meals. Both amadori compounds significantly reduced the postprandial blood glucose levels after starch or sucrose loading. These results indicate that AF and AFG, Maillard reaction products, may have antidiabetic effect by suppressing carbohydrate absorption in the gastrointestinal level, and thereby reducing the postprandial increase of blood glucose.

Selected tea and tea pomace extracts inhibit intestinal α-glucosidase activity in vitro and postprandial hyperglycemia in vivo.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by postprandial hyperglycemia, which is an early defect of T2DM and thus a primary target for anti-diabetic drugs. A therapeutic approach is to inhibit intestinal α-glucosidase, the key enzyme for dietary carbohydrate digestion, resulting in delayed rate of glucose absorption. Although tea extracts have been reported to have anti-diabetic effects, the potential bioactivity of tea pomace, the main bio waste of tea beverage processing, is largely unknown. We evaluated the anti-diabetic effects of three selected tea water extracts (TWE) and tea pomace extracts (TPE) by determining the relative potency of extracts on rat intestinal α-glucosidase activity in vitro as well as hypoglycemic effects in vivo. Green, oolong, and black tea bags were extracted in hot water and the remaining tea pomace were dried and further extracted in 70% ethanol. The extracts were determined for intestinal rat α-glucosidases activity, radical scavenging activity, and total phenolic content. The postprandial glucose-lowering effects of TWE and TPE of green and black tea were assessed in male Sprague-Dawley (SD) rats and compared to acarbose, a known pharmacological α-glucosidase inhibitor. The IC50 values of all three tea extracts against mammalian α-glucosidase were lower or similar in TPE groups than those of TWE groups. TWE and TPE of green tea exhibited the highest inhibitory effects against α-glucosidase activity with the IC50 of 2.04 ± 0.31 and 1.95 ± 0.37 mg/mL respectively. Among the specific enzymes tested, the IC50 values for TWE (0.16 ± 0.01 mg/mL) and TPE (0.13 ± 0.01 mg/mL) of green tea against sucrase activity were the lowest compared to those on maltase and glucoamylase activities. In the animal study, the blood glucose level at 30 min after oral intake (0.5 g/kg body wt) of TPE and TWE of both green and black tea was significantly reduced compared to the control in sucrose-loaded SD rats. The TPE of all three teas had significantly higher phenolic content than those of the TWE groups, which correlated strongly with the DPPH radical scavenging activity. This is the first report of tea pomace extract significantly inhibits intestinal α-glucosidase, resulting in delayed glucose absorption and thereby suppressed postprandial hyperglycemia. Our data suggest that tea pomace-derived bioactives may have great potential for further development as nutraceutical products and the reuse of otherwise biowaste as valuable bioresources for the industry.

Effect of long-term dietary arginyl-fructose (AF) on hyperglycemia and HbA1c in diabetic db/db mice.

We have previously reported that Amadori compounds exert anti-diabetic effects by lowering sucrose-induced hyperglycemia in normal Sprague-Dawley rats. In the present study we extended our recent findings to evaluate whether α-glucosidase inhibitor arginyl-fructose (AF) lowers blood glucose level in diabetic db/db mice, a genetic model for type 2 diabetes. The db/db mice were randomly assigned to high-carbohydrate diets (66.1% corn starch) with and without AF (4% in the diet) for 6 weeks. Changes in body weight, blood glucose level, and food intake were measured daily for 42 days. Dietary supplementation of AF resulted in a significant decrease of blood glucose level (p < 0.001) and body weight (p < 0.001). The level of HbA1c, a better indicator of plasma glucose concentration over prolonged periods of time, was also significantly decreased for 6-week period (p < 0.001). Dietary treatment of acarbose® (0.04% in diet), a positive control, also significantly alleviated the level of blood glucose, HbA1c, and body weight. These results indicate that AF Maillard reaction product improves postprandial hyperglycemia by suppressing glucose absorption as well as decreasing HbA1c level.

Effect of supplementation of low-molecular-weight chitosan oligosaccharide, GO2KA1, on postprandial blood glucose levels in healthy individuals following bread consumption

The effect of chitosan oligosaccharide (GO2KA1) administration on postprandial blood glucose levels of subjects with normal blood glucose levels was evaluated following bread consumption. Postprandial blood glucose levels were determined for 2 h after bread ingestion with or without 500 mg of GO2KA1. GO2KA1 significantly lowered the mean, maximum, and minimum levels of postprandial blood glucose at 30 min after the meal. Postprandial blood glucose levels were decreased by about 25% (from 155.11±13.06 to 138.50±13.59, p<0.01) at 30 min when compared to control. Furthermore, we observed that the area under the concentration-time curve (AUCt) was decreased by about 6% (from 255.46±15.43 to 240.15±14.22, p<0.05) and the peak concentration of blood glucose (Cmax) was decreased by about 11% (from 157.94±10.90 to 140.61±12.52, p<0.01) when compared to control. However, postprandial the time to reach Cmax (Tmax) levels were the same as those found in control. Our findings suggest that GO2KA1 limits the increase in postprandial blood glucose levels following bread consumption.