Pheophorbide A from Gelidium amansii improves postprandial hyperglycemia in diabetic mice through α-glucosidase inhibition.

This study was designed to determine the inhibitory effects of pheophorbide A on carbohydrate digesting enzymes and its ability to improve postprandial hyperglycemia in streptozotocin (STZ)-induced diabetic mice. Pheophorbide A caused noticeable inhibitory effects on α-glucosidase and α-amylase, with half-maximal inhibitory concentrations (IC50 ) of 80.65 ± 5.90 and 76.48 ± 6.31 µM, respectively. The pheophorbide-mediated inhibition of α-glucosidase and α-amylase was significantly more effective than that of the positive control, acarbose. The increase in postprandial blood glucose levels was more significantly suppressed in the pheophorbide A group than in the control group of STZ-induced diabetic mice. In addition, the area under the curve was decreased by pheophorbide A intake in STZ-induced diabetic mice. Our results suggested that pheophorbide A may help to improve postprandial hyperglycemia by inhibiting the activity of carbohydrate digesting enzymes.

Gelidium amansii extract ameliorates obesity by down-regulating adipogenic transcription factors in diet-induced obese mice.

BACKGROUND/OBJECTIVES: In this study, we investigated whether Gelidium amansii extract (GAE) ameliorates obesity in diet-induced obese (DIO) mice. MATERIALS/METHODS: The mice were maintained on a high-fat diet (HD) for 5 weeks to generate the DIO mouse model. And then mice fed HD plus 0.5% (GAE1), 1% (GAE2) or 2% (GAE3) for 8 weeks. RESULTS: After the experimental period, GAE-supplemented groups were significantly lower than the HD group in body weight gain and liver weight. GAE supplemented groups were significantly lower than the HD group in both epididymal and mesenteric adipose tissue mass. The plasma leptin level was significantly higher in the HD group than in GAE-supplemented groups. The leptin level of HD+GAE3 group was significantly lower than that of the HD+conjugated linoleic acid (CLA) group. In contrast, plasma adiponectin level of the HD group was significantly lower than those of HD+GAE2 and HD+GAE3 groups. The expression levels of adipogenic proteins such as fatty acid synthase, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer binding protein α in the GAE supplemented groups were significantly decreased than those in HD group, respectively. In addition, the expression levels of HD+GAE2 and HD+GAE3 groups are significantly decreased compared to those of HD+CLA group. On the contrary, the expression levels of hormone-sensitive lipase and phospho-AMP-activated protein kinase, proteins associated with lipolysis, were significantly increased in the GAE supplemented groups compared to those in the HD group. HD+GAE3 group showed the highest level among the GAE supplemented groups. CONCLUSIONS: These results suggested that GAE supplementation stimulated the expressions of lipid metabolic factors and reduced weight gain in HD-fed C57BL/6J obese mice.

Effect of diphlorethohydroxycarmalol isolated from Ishige okamurae on apoptosis in 3 T3-L1 preadipocytes.

Obesity is an important issue in the world of public health and preventive medicine. Inhibition of proliferation of preadipocytes plays an important role in proposed antiobesity mechanisms. In this study, we investigated the effect of diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae on the apoptotic pathway. The results showed that DPHC inhibited population growth in 3 T3-L1 preadipocytes as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometric analysis of 3 T3-L1 preadipocytes showed that the number of early and late apoptotic cells increases in a dose-dependent manner after exposure to DPHC, while the number of normal cells was reduced. Our findings indicate that the induction of apoptosis in 3 T3-L1 preadipocytes by DPHC is mediated through the activation of caspase-3, Bax, and caspase-9, and then through the cleavage of poly(ADP-ribose) polymerase and the down-regulation of Bcl-2. The data also indicated that treatment with DPHC inhibits histone deacetylase activity in 3 T3-L1 preadipocytes. These results show that DPHC efficiently induces apoptosis in 3 T3-L1 preadipocytes.

Ishige okamurae ameliorates hyperglycemia and insulin resistance in C57BL/KsJ-db/db mice.

We investigated the effect of Ishige okamurae extract on blood glucose level and insulin resistance in C57BL/-KsJ-db/db mice. We administered a standard AIN-93G diet with or without IOE to the animals for 6 weeks. After 6 weeks, blood glucose level was improved and blood glycosylated hemoglobin levels were lowered in sample group mice as compared to those in the diabetic control group mice. Hyperinsulinemia was reduced in the I. okamurae extract group mice with type 2 diabetes. With regard to hepatic glucose metabolic enzyme activities, glucokinase activity was enhanced in the IOE group mice, while glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the IOE group mice were significantly lowered than those in the diabetic control group mice. In addition, the hepatic glycogen content was elevated in the IOE group as compared to that in the diabetic control group. The homeostatic index of insulin resistance was lower in the I. okamurae extract group mice than in the diabetic control group mice. These results suggest that a dietary supplement of I. okamurae extract lowers the blood glucose level by altering the hepatic glucose metabolic enzyme activities and improves insulin resistance.

Diphlorethohydroxycarmalol isolated from Ishige okamurae, a brown algae, a potent alpha-glucosidase and alpha-amylase inhibitor, alleviates postprandial hyperglycemia in diabetic mice.

This study was designed to investigate whether diphlorethohydroxycarmalol (DPHC) may inhibit alpha-glucosidase and alpha-amylase activities, and alleviate postprandial hyperglycemia in streptozotocin-induced diabetic mice. DPHC isolated from Ishige okamurae, a brown algae, evidenced prominent inhibitory effect against alpha-glucosidase and alpha-amylase. The IC(50) values of DPHC against alpha-glucosidase and alpha-amylase were 0.16 and 0.53 mM, respectively, which evidenced the higher activities than that of acarbose. DPHC did not exert any cytotoxic effect in human umbilical vein endothelial cells (HUVECs) at various concentrations (from 0.49 to 3.91 mM). The increase of postprandial blood glucose levels were significantly suppressed in the DPHC-administered group than those in the streptozotocin-induced diabetic or normal mice. Moreover, the area under curve (AUC) was significantly reduced via DPHC administration (2022 versus 2210 mmol x min/l) in the diabetic mice as well as it delays absorption of dietary carbohydrates. Therefore, these result indicated that DPHC might be a potent inhibitor for alpha-glucosidase and alpha-amylase.