Young-In Kwon

Phenolic-linked variation in strawberry cultivars for potential dietary management of hyperglycemia and related complications of hypertension

Fruit extracts of different strawberry cultivars were evaluated for their potential to contribute to the dietary management of hyperglycemia-linked to type 2 diabetes and related hypertension. In vitro inhibition of alpha-amylase, alpha-glucosidase, and angiotensin-1-converting enzyme (ACE) activity was evaluated using fruit extracts and correlated to phenolic content and antioxidant activity. There were significant differences between cultivars in both phenolic-linked antioxidant activity and inhibitory activity for the targeted disease relevant enzymes. Honeoye, Idea, and Jewel cultivars exhibited moderate alpha-amylase inhibition. Strawberry cultivars, in general, exhibited uniform alpha-glucosidase inhibition with Ovation having the highest inhibitory activity. Water extracts of Jewel and Ovation cultivars had moderate ACE inhibition compared to low inhibition observed in other cultivars. Strawberry cultivars with combined inhibitory potential against alpha-glucosidase and ACE and with moderate or low alpha-amylase inhibitory potential could be targeted for potential management of hyperglycemia-linked type 2 diabetes and related complication of hypertension.

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.

Protective mechanism of quercetin and rutin on 2,2'-azobis(2-amidinopropane)dihydrochloride or Cu2+-induced oxidative stress in HepG2 cells.

Protective effects of quercetin and rutin against oxidative stress were evaluated using in vitro and intracellular antioxidant assay. Quercetin showed higher peroxyl and hydroxyl radical-scavenging activity in a dose-dependent manner than did rutin in oxygen-radical absorbance capacity (ORAC). At 10 and 100 μM, quercetin had higher metal-chelating activity than rutin carrying rutinose at position C-3 and was also more efficient than rutin in reducing intracellular oxidative stress caused by peroxyl radicals and Cu(2+). The protective activities of 10 and 100 μM quercetin against Cu(2+)-induced intracellular oxidation were 13.8% and 44.8%, respectively. Rutin showed no protective activity against Cu(2+)-induced oxidative stress. Quercetin showed significantly lower intracellular Cu(2+)-chelating activity than did 1,10-phenanthroline but offered greater protection from Cu(2+)-induced oxidative stress. Thus, quercetin may diffuse through the cell membrane more efficiently than rutin because quercetin does not carry rutinose, is hydrophilic, and reduces Cu(2+)-induced oxidative stress by scavenging radicals instead of chelating with metal ions.

Rhodiola-induced inhibition of adipogenesis involves antioxidant enzyme response associated with pentose phosphate pathway.

The aim of this study was to investigate whether Rhodiola crenulata extract and tyrosol, a major bioactive phenolic compound present in Rhodiola, change the activities of endogenous antioxidant enzyme response (AER) and energy pathways linked to proline‐mediated pentose phosphate pathway (PPP) during adipogenesis. Treatment with Rhodiola extracts inhibited the activities of proline dehydrogenase (PDH) and glucose‐6‐phosphate dehydrogenase (G6PDH) as well as lipid accumulation and reactive oxygen species (ROS) production. The inhibition of PDH and G6PDH activities by Rhodiola likely prevented proline oxidation required for critical ATP generation that is coupled to AER via the PPP, leading to inhibition of adipogenesis. Rhodiola extracts dose‐dependently increased superoxide dismutase (SOD) activity, resulting in a reduced ROS level during adipogenesis. Moreover, the effects of tyrosol, a major bioactive compound in Rhodiola species, were directly correlated with all observed effects by Rhodiola extracts. These results indicate that the antiadipogenic effects of Rhodiola extracts can be attributed to a phenolic tyrosol that may potentially disrupt proline‐mediated energy generation and AER via PPP, resulting in the suppression of adipogenesis and lipid accumulation. This further provides a biochemical rationale to identify the roles of phenolics that modulate the cellular redox environment and therefore have relevance for obesity management. Copyright

The reduction effect of low molecular weight chitosan oligosaccharide (GO2KA1) on postprandial blood glucose levels in healthy individuals

The effects of chitosan-oligosaccharide (GO2KA1) on postprandial blood glucose levels in adults with normal blood glucose levels were investigated. Postprandial blood glucose levels were measured at 30, 60, 90, and 120 min after sucrose administration with and without 500 mg of GO2KA1. GO2KA1 administration reduced the area under the blood glucose-time curve (AUC) and the blood glucose peak (Cmax) values while the time of peak plasma concentration of blood glucose (Tmax) value was significantly (p<0.05) increased, compared to controls. GO2KA1 reduced postprandial blood glucose level increases via slower absorption of glucose in the small intestine based on carbohydrate hydrolyzing enzyme inhibition.

Inhibitory activity of Plantago major L. on angiotensin I-converting enzyme

Eight compounds were isolated from methanol extract of Plantago major L. leaves and investigated for their ability to inhibit angiotensin I-converting enzyme activity. Among them, compound 1 showed the most potent inhibition with rate of 28.06 ± 0.21% at a concentration of 100 μM. Compounds 2 and 8 exhibited weak activities. These results suggest that compound 1 might contribute to the ability of P. major to inhibit the activity of angiotensin I- converting enzyme.

Novel α-Glucosidase Inhibitors, CKD-711 and CKD-711a Produced by Streptomyces sp. CK-4416

New alpha-glucosidase inhibitors, CKD-711 and CKD-711a were produced from the fermentation broth of Streptomyces sp. CK-4416 which was isolated from a forest soil of Jeju Island, South Korea. CKD-711 and CKD-711a were purified by Dowex 50W-2X and Sephadex G-10 column chromatography. In in vitro studies, CKD-711 showed a potent inhibitory activity against a-glucosidase from mammalian, but less inhibition against a-amylase from microorganism and mammalian. CKD-711a showed a lower inhibitory activity than CKD-711.

Potential mechanism of kaempferol against Cu2+-induced oxidative stress through chelating activity and regulation of nuclear factorerythroid-2-related factor 2 signaling

Metal ions play important roles in various biological processes of living systems. However, the generation of reactive oxygen species (ROS) is also closely linked with the participation of redox-active metal ions such as copper, iron, chromium, and cobalt ions. Excessive production of ROS by redox-active metal ions can cause oxidative stress and further oxidative stress-related diseases. This study shows the results of the antioxidant activity of kaempferol in both ORACOH· and Cu2+-treated HepG2 cells. Preventive mechanism of kaempferol in Cu2+-treated HepG2 cells is also elucidated. These results suggest that both cellular Cu2+-chelating activity and expression of phase II detoxifying enzymes such as HO-1 and GSTA2 through activating Nrf2 are required for cellular antioxidant activity of kaempferol in Cu2+-treated HepG2 cells. Our findings provide the scientific evidence for the development of Nrf2 targeting dietary antioxidant to prevent oxidative stressrelated conditions.

Antidiabetic effect of chitosan oligosaccharide (GO2KA1) is mediated via inhibition of intestinal alpha‐glucosidase and glucose transporters and PPARγ expression

We have previously reported that administration of low molecular weight chitosan oligosaccharide (GO2KA1) significantly suppressed postprandial blood glucose rise with increased plasma adiponectin and HbA1c levels in animals and humans. However, the cellular mechanisms whereby GO2KA1 exerts antihyperglycemic effects still remain to be determined. Using intestinal Caco-2 cells and 3T3-L1 cells, here we show that GO2KA1 has dual modes of antidiabetic action by (1) inhibiting intestinal α-glucosidase as well as glucose transporters SGLT1 and GLUT2 that were distinct from the acarbose effect; (2) enhancing adipocyte differentiation, PPARγ expression and its target genes, such as FABP4, adiponectin, and GLUT4, whereas the effects were abolished by co-treatment with BADGE, a PPARγ antagonist. Moreover, GO2KA1 significantly increased glucose uptake, which was reduced in the presence of BADGE. Our data show that GO2KA1 may prevent hyperglycemia by inhibiting intestinal glucose digestion and transport and also enhance glucose uptake, at least in part, by upregulating adiponectin expression through PPARγ in adipocytes. These findings may provide potential molecular modes of action for the antidiabetic effects of chitosan oligosaccharide observed in clinical and animal studies.

Effects of long-term supplementation of policosanol on blood cholesterol/glucose levels and 3-hydroxy-3-methylglutaryl coenzyme a reductase activity in a rat model fed high cholesterol diets

Policosanol is a well-defined nutraceutical for the management of blood cholesterol levels. The present study examined (i) the effect of policosanol supplementation on blood cholesterol and glucose levels and (ii) changes in hepatic cholesterol biosynthesis using 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) activity in Wistar rats fed high cholesterol diets. The Wistar rats were assigned randomly to high-cholesterol diets (1.25% cholesterol) with or without policosanol (8.0 mg/kg body weight) for 6 weeks. Compared with the control group, dietary treatment with policosanol resulted in a significant decrease of blood cholesterol (p<0.01), blood glucose (p<0.01), triglyceride (p<0.001), and low density lipoprotein-cholesterol levels (p<0.01) and HMG-CoA reductase activity (p<0.001) in the liver. These results indicate that policosanol decreases blood cholesterol levels by suppressing cholesterol biosynthesis via decrease of HMG-CoA activity. Policosanol has the potential to be developed into an effective dietary strategy for both postprandial hyperglycemia and hypercholesterolemia.