Protective effect of polyphenol‐rich extract prepared from Malaysian cocoa (Theobroma cacao) on glucose levels and lipid profiles in streptozotocin‐induced diabetic rats

BACKGROUND: Cocoa beans are used for preparing cocoa liquor and cocoa powder, which are the main ingredients of cocoa‐based products. Previous studies have reported the health benefits of cocoa polyphenols in reducing the risk of cardiovascular diseases. However, there is no report on the efficacy of cocoa polyphenols on diabetes mellitus. Therefore this study was designed to evaluate the protective effect of cocoa polyphenol‐rich extract (CE) on glucose levels and lipid profiles in streptozotocin (STZ)‐induced diabetic rats. Male Sprague‐Dawley rats were divided into diabetic control, diabetic CE and diabetic glibenclamide groups. RESULTS: Three different dosages of CE (10, 20 and 30 mg per 100 g body weight) were administered orally once a day for 1 week before STZ injection and for 3 weeks thereafter. The results showed that CE could normalise the body weight loss caused by STZ. In the 20 mg CE‐pretreated group there was a 143% increase in plasma glucose levels, compared with a 226% increase in diabetic control rats. CE could also normalise total cholesterol, triglycerides and high‐density lipoprotein cholesterol at the end of the experiment compared with the baseline. CONCLUSION: The present study suggests that pretreatment with CE from roasted cocoa beans could prevent the development of diabetes induced by STZ injection in rats. Copyright © 2008 Society of Chemical Industry     

Intermittent administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and prevents pancreatic exhaustion in diabetic mice

We previously demonstrated that repetitive administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and energy expenditure in obese diabetic db/db mice. However, we have not evaluated in detail the effect of single or intermittent BDNF administration on glucose metabolism in a diabetic animal model. The objectives of this study were to examine the dose-response effect and dosing interval of BDNF administration in db/db mice and to evaluate the effect of intermittent BDNF administration on pancreatic function in db/db mice. We evaluated the dose-response effect of BDNF by single administration in db/db mice. First, single administration of BDNF greater than 70 mg/kg significantly reduced blood glucose concentration one day after administered, and the BDNF effect was maintained for 6 d. Next, the effects of BDNF administered twice a week at 4, 10, 25, and 62.5 mg/kg on blood glucose concentration, and the effects of BDNF administered once a week at 10, 20, 30, 50, and 70 mg/kg on blood glucose concentration were examined in db/db mice. In the intermittent treatment studies, BDNF dose-dependently ameliorated glucose metabolism by not only the twice-a-week administration but also the once-a-week administration. Lastly, because BDNF reduces the food intake of obese hyperphagic diabetic mice, the effects of BDNF administered once or twice a week on the blood glucose concentration and plasma and pancreatic insulin concentrations in db/db mice were compared with those of the vehicle under pair-fed conditions. Under pair-fed conditions, the intermittent administration of BDNF (25 mg/kg, twice a week, or 50 mg/kg, once a week) significantly reduced the blood glucose concentration and increased the plasma and pancreatic insulin concentrations compared with those in the pair-fed vehicle-treated db/db mice. This indicates that the prolonged hypoglycemic effect of BDNF is not simply due to the reduction of food intake. In conclusion, we demonstrated that the intermittent administration of BDNF ameliorates glucose metabolism and prevents pancreatic exhaustion in obese diabetic mice. These findings indicate that BDNF may have potential as a unique hypoglycemic agent for the treatment of diabetes at a fundamental level with good patient compliance.     

Hypoglycemic effect of extract of Hericium erinaceus

Recent studies have determined that many types of mushroom (eg Hericium spp), may have important physiological functions in humans, including antioxidant activities, the regulation of blood lipid levels and reduction of blood glucose levels. In this study, a methanol extract of the fruiting bodies of Hericium erinaceus was adsorbed on silica gel columns and eluted using polarity gradients of chloroform/ethyl acetate/acetone/methanol. The major components of the extract were D ‐threitol, D ‐arabinitol and palmitic acid identified by their chromatographic profiles and spectroscopic characteristics. The methanol extract of H erinaceus was concentrated to remove solvent yielding a residue (referred to as HEM) which was added to the diet. The hypoglycemic effects of feeding HEM to streptozotocin‐induced diabetic rats were studied. Polydipsia was stronger in induced diabetic rats not fed HEM than in those receiving HEM. Rats fed with HEM had significantly lower elevation rates of blood glucose level than those not fed with HEM. The effects on blood glucose, serum triglyceride and total cholesterol levels were more significant in the rats fed daily with HEM at doses of 100 mg kg^?1 body weight (bw) rather than 20 mg kg^?1 bw (p < 0.05). Copyright © 2004 Society of Chemical Industry     

Long-term high animal protein diet reduces body weight gain and insulin secretion in diet-induced obese rats

BACKGROUND: The effects of a high protein diet on insulin secretion and glucose metabolism have been quite controversial. The aim of this study was to evaluate the effects of long‐term isocaloric high animal protein intake on insulin secretion in diet‐induced obese rats. RESULTS: After the experimental period (24 weeks), the high‐fat diet‐induced obese rats that were fed isocaloric high‐protein diets (HP) had lower body weight gain (P < 0.01) and lower visceral fat (P < 0.05) than normal protein (NP) rats. Fasting plasma glucagon‐like peptide‐1 (GLP‐1) was also reduced significantly (P < 0.05), as well as serum insulin levels at 5 min and 10 min by intravenous insulin releasing test. In addition, insulin mRNA and pancreatic duodenal homeodomain‐1 (PDX‐1), GLP‐1 protein expression were both markedly lower in HP rats (P < 0.05), while PDX‐1 mRNA in HP rats had no difference from NP rats. CONCLUSION: These results suggest that long‐term isocaloric high animal protein intake reduces the acute insulin response in obese rats and the decrease of insulin is associated with both reduced weight gain and inhibition of PDX‐1 expression. GLP‐1 might be a negative feedback for the balance of energy metabolism secondary to changes of body weight and visceral fat. Copyright © 2012 Society of Chemical Industry     

Cocoa‐rich diet attenuates beta cell mass loss and function in young Zucker diabetic fatty rats by preventing oxidative stress and beta cell apoptosis

We have recently shown that cocoa flavanols may have anti‐diabetic potential by promoting survival and function of pancreatic beta‐cells in vitro. In this work, we investigated if a cocoa‐rich diet is able to preserve beta‐cell mass and function in an animal model of type 2 diabetes and the mechanisms involved. Our results showed that cocoa feeding during the prediabetic state attenuates hyperglycaemia, reduces insulin resistant, and increases beta cell mass and function in obese Zucker diabetic rats. At the molecular level, cocoa‐rich diet prevented beta‐cell apoptosis by increasing the levels of Bcl‐xL and decreasing Bax levels and caspase‐3 activity. Cocoa diet enhanced the activity of endogenous antioxidant defenses, mainly glutathione peroxidase, preventing thus oxidative injury induced by the pre‐diabetic condition and leading to apoptosis prevention. These findings provide the first in vivo evidence that a cocoa‐rich diet may delay the loss of functional beta‐cell mass and delay the progression of diabetes by preventing oxidative stress and beta‐cell apoptosis.     

Suppression of blood glucose level by a new fermented tea obtained by tea‐rolling processing of loquat (Eriobotrya japonica) and green tea leaves in disaccharide‐loaded Sprague‐Dawley rats

BACKGROUND: In the field of food science, much interest has been focused on the development of alternative medicinal foods with the ability to regulate excess blood glucose level (BGL) rise. The authors have successfully developed a new fermented tea product (LG tea) by co‐fermentation of loquat (Eriobotrya japonica) leaf and summer‐harvested green tea leaf. The objective of this study was to examine the acute suppression effect of LG tea on BGL rise in disaccharide‐loaded Sprague‐Dawley (SD) rats and to evaluate its possible usage as an antidiabetic functional food material. RESULTS: As a result of single oral administration of hot water extract of LG tea (50 mg kg^?1) to maltose‐loaded SD rats, BGL at 30 min was significantly decreased by 23.8% (P < 0.01) compared with the control. A corresponding reduction in serum insulin secretion was also observed. The ED₅₀ value of LG tea (50.7 mg kg^?1) was estimated to be about 16‐fold higher than that of the therapeutic drug acarbose (3.1 mg kg^?1). CONCLUSION: No significant change in BGL was observed when sucrose or glucose was administered, suggesting that the suppression effect of LG tea was achieved by maltase inhibition, not by sucrase inhibition or glucose transport inhibition at the intestinal membrane. Copyright © 2010 Society of Chemical Industry     

Antihyperlipidaemic effect of Aegle marmelos fruit extract in streptozotocin‐induced diabetes in rats

The present study determines the effect of an aqueous extract of Aegle marmelos fruits on serum and tissue lipids in experimental diabetes. Albino Wistar rats were rendered diabetic by intraperitoneal administration of streptozotocin (45 mg kg^?1). Serum and tissue lipids such as total cholesterol, triglycerides, free fatty acids and phospholipids were elevated in diabetic rats. Oral administration of A marmelos fruit extract at doses of 125 and 250 mg kg^?1 to diabetic rats twice daily for 1 month led to a significant lowering of these lipids in diabetic rats. The effect exerted by the fruit extract at a dose of 250 mg kg^?1 was greater than that of the dose of 125 mg kg^?1 or of glibenclamide (300 µg kg^?1). The results of this study demonstrate that an aqueous A marmelos fruit extract exhibits an antihyperlipidaemic effect in streptozotocin‐induced diabetic rats. Copyright © 2004 Society of Chemical Industry     

Limonia fruit as a food supplement to regulate fluoride‐induced hyperglycaemia and hyperlipidaemia

BACKGROUND: Limonia fruit pulp is edible and used in a number of food preparations. This fruit is also used as a folk medicine to treat various ailments and reportedly possesses antihyperglycaemic and antihyperlipidaemic activities. The purpose of the present study was to examine the potential of Limonia acidissima L. (LA) fruit pulp in regulating the carbohydrate and lipid profiles in fluoride‐exposed rats. RESULTS: Exposure to fluoride (100 mg l^?1 NaF) resulted in significant increases in plasma and hepatic carbohydrate and lipid profiles. Administration of LA fruit powder (2.5, 5 and 10 g kg^?1) in the diet for 4 weeks resulted in significant decreases in plasma glucose and lipid profiles and hepatic glucose‐6‐phosphatase activity and significant increases in hepatic glycogen content and hexokinase activity and plasma high‐density lipoprotein cholesterol. Phytochemical analysis of the LA fruit pulp revealed the presence of fibres, phytosterols, saponins, polyphenols, flavonoids and ascorbic acid. CONCLUSION: Consumption of LA fruit pulp is beneficial in controlling hyperglycaemia and hyperlipidaemia in fluoride‐induced toxicity. Since fibres, phytosterols, saponins, polyphenols, flavonoids and total ascorbic acid are known to influence both carbohydrate and lipid metabolisms, the decline in carbohydrate and lipid levels in LA‐administered fluoride‐exposed rats could be attributed to the phytoconstituents of the fruit. Copyright © 2012 Society of Chemical Industry     

Hypoglycaemic role of Cucurbita ficifolia (Cucurbitaceae) fruit extract in streptozotocin‐induced diabetic rats

Cucurbita ficifolia is commonly used as an antidiabetic and antihyperglycaemic agent in Asia. However, the mechanisms of antidiabetic action of the plant remain to be clarified. This study was undertaken to investigate the effects of C. ficifolia fruit extract on blood plasma, plasma insulin level, lipid peroxidation and number of β cells in normal and streptozotocin (STZ)‐induced diabetic rats. The results indicated that feeding with C. ficifolia fruit extract caused reduction in STZ‐induced hyperglycaemia while increase plasma insulin level in STZ diabetic rats, and markedly reduced the STZ‐induced lipid peroxidation in pancreas of the rats. Further there was a significant increase in the number of β cells in C. ficifolia‐treated animals when compared with untreated diabetics, however, their number was still less than that obtained for normal rats, indicating the mode of protection of C. ficifolia fruit extract on pancreatic β cells. The present study thus confirms a hypoglycaemic effect of C. ficifolia fruit extract and suggests that oral feeding of C. ficifolia fruit extract may have a role in the renewal of β cells in STZ diabetic rats or, alternatively, may permit the recovery of partially destroyed β cells. Our results provide some documentation to define the role and mode of action of C. ficifolia fruit extract in its potential and promising use in treating diabetes. Copyright © 2007 Society of Chemical Industry     

Anti-diabetic effect of the soybean extract fermented by Bacillus subtilis MORI in db/db mice

This study investigated the effects of soy bean extract fermented by Bacillus subtilis MORI (BTD-1) on blood glucose, hemoglobin A1c (HbA1c), plasma insulin, and pancreatic β islets in db/db mice. The BTD-1 (500 mg/kg) group showed significantly lower fasting blood glucose level (p<0.01) and postprandial 2 h blood glucose level (p<0.01) compared with the db control group. The BTD-1 (500 mg/kg) group showed significantly lower HbA1c level compared with the db control group (p<0.01). After 8 weeks of BTD-1 administration, the pancreatic islet architecture was preserved and the immunofluorescent intensities of insulin in BTD-1 (500mg/kg) group apparently increased compared to in the db control group. Plasma insulin levels were found to be significantly higher in the BTD-1 (500 mg/kg) group than in the db control group (p<0.05). In summary, our results suggest that BTD-1 has an anti-diabetes effect in a non-insulin dependent diabetes mellitus mouse model.     

Comparison of the anti‐obesity and hypocholesterolaemic effects of single Lactobacillus casei strain Shirota and probiotic cocktail

This study compared the efficacy of Lactobacillus casei strain Shirota (LAB13) and a probiotic cocktail for their anti‐obesity and other lipid profile modulating effects. Diet‐induced obese rats were supplemented with two different probiotics which are LAB13 (1 × 10⁹ CFU day^?1 per rat) and cocktail of five bacterial strains (1 × 10⁹ CFU day^?1 per rat) for 12 weeks. Comparative data on weight gain, energy intake, liver weight, subcutaneous fat, total fat weights, total cholesterol and leptin levels in both treatment groups showed significant reduction in probiotic‐treated groups compared to the obese control group. Both probiotics have the anti‐obesity and hypocholesterolaemic effects and are able to reduce body weight and fats via reduction in energy intake. Only LAB13 was able to reduce the level of triglyceride significantly. Therefore, the LAB13 is equally effective compared to the probiotic cocktail in weight reduction. LAB13 is more effective in improving lipid profile which is a common medical complication of obesity.     

Evaluation of in vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats

Effect of Ganoderma lucidum polysaccharides treatment on blood glucose, serum insulin level, lipid peroxidation, nonenzymic and enzymic antioxidants in the plasma and liver of streptozotocin (STZ)-induced diabetic rats was studied. Adult male rats of Wistar strain, weighing 195 to 250 g, were randomized into control and experimental groups. Experiment group rats were induced diabetes by administration of STZ (45 mg/kg b.wt.) intraperitoneally. The diabetic rats were treated with G. lucidum polysaccharides (60, 120, 180 mg/kg b.wt.) dissolved in 15% dimethyl sulphoxide (DMSO) for 30 days. The normal control rats were treated with 15% DMSO for 30 days. Streptozotocin treatment elevated the levels of lipid peroxidation markers (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes), and reduced nonenzymic antioxidants (vitamin C and reduced glutathione, vitamin E) levels, and enzymic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) activities in the plasma and liver of untreated diabetic control rats. Decreased level of serum insulin and increased level of blood glucose (BG) were observed in the plasma of untreated diabetic control rats. G. lucidum polysaccharides treatment significantly and dose-dependently increased nonenzymic and enzymic antioxidants, serum insulin level and reduced lipid peroxidation, blood glucose levels in STZ-diabetic rats. From the present study, it can be concluded that G. lucidum polysaccharides can be considered as a potent antioxidant.     

葡萄籽多酚对糖尿病大鼠的降血糖作用及其机制

目的：研究葡萄籽多酚对糖尿病大鼠的降血糖作用,并从胰岛细胞损伤及胰岛素表达的角度探讨其作用机 制。方法：以链脲佐菌素腹腔注射至雄性SD大鼠,建立Ⅱ型糖尿病大鼠模型,成模后随机分为模型组、阿卡波糖 阳性对照组和葡萄籽多酚组。通过为期8 周的葡萄籽多酚（50 mg/（kg·d）,以体质量计）干预,观察大鼠空腹血 糖水平、胰岛素水平、葡萄糖耐受性变化,并采用免疫组化法检测胰岛病变及胰岛素表达。结果：葡萄籽多酚可明 显降低糖尿病大鼠的空腹血糖水平（P＜0.05）,提高对葡萄糖的耐受性,促进胰岛素分泌,改善胰岛细胞损伤, 增加胰腺中胰岛素的表达（P＜0.05）,增加血清中超氧化物歧化酶的活力及降低丙二醛的含量（P＜0.05）。结 论：长期低剂量的葡萄籽多酚干预可以有效调节糖尿病大鼠的血糖水平。葡萄籽多酚通过修复胰岛损伤促进胰岛素 分泌降低空腹血糖水平,改善葡萄糖耐受程度,这一作用可能与其显著的体内抗氧化功效相关。     

Hydro‐ethanolic extract of cashew tree (Anacardium occidentale) nut and its principal compound,anacardic acid,stimulate glucose uptake in C2C12 muscle cells

Scope: Products of cashew tree (Anacardium occidentale) are used in traditional medicine for various ailments, including diabetes. Methods and results: The anti‐diabetic properties of cashew plant parts were studied using differentiated C2C12 myoblasts (myotubes) and rat liver mitochondria. Hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (AA), stimulated glucose transport into C2C12 myotubes in a concentration‐dependent manner. Extracts of other parts (leaves, bark and apple) of cashew plant were inactive. Significant synergistic effect on glucose uptake with insulin was noticed at 100 μg/mL CSE. CSE and AA caused activation of adenosine monophosphate‐activated protein kinase in C2C12 myotubes after 6 h of incubation. No significant effect was noticed on Akt and insulin receptor phosphorylation. Both CSE and AA exerted significant uncoupling of succinate‐stimulated respiration in rat liver mitochondria. Conclusion: Activation of adenosine monophosphate‐activated protein kinase by CSE and AA likely increases plasma membrane glucose transporters, resulting in elevated glucose uptake. In addition, the dysfunction of mitochondrial oxidative phosphorylation may enhance glycolysis and contribute to increased glucose uptake. These results collectively suggest that CSE may be a potential anti‐diabetic nutraceutical.     

Effect of flavonol glycoside in mulberry (Morus alba L.) leaf on glucose metabolism and oxidative stress in liver in diet‐induced obese mice

BACKGROUND: Mulberry therapies on type 2 diabetic patients or streptozotocin‐induced diabetic rats have been reported to improve fasting blood glucose levels. We investigated the effects of dietary consumption of mulberry‐leaf powder and purified quercetin 3‐(6‐malonylglucoside), the quantitatively major flavonol glycoside in mulberry leaves, on glucose and lipid metabolism in high‐fat diet‐induced obese mice. Male C57BL/6J mice aged 8 weeks were assigned to three groups (control, mulberry leaf powder (MLP), and quercetin 3‐(6‐malonylglucoside) (Q3MG)) and treated with their respective diets for 8 weeks. RESULTS: We found that dietary supplementation of 10 g MLP kg^?1 or 1 g Q3MG kg^?1 in high‐fat diet effectively suppressed blood glucose levels. We also noted increased expression of glycolysis‐related genes and suppression of thiobarbituric acid reactive substances concentrations in the liver of Q3MG group compared to control mice. CONCLUSION: Dietary consumption of Q3MG, the quantitatively major flavonol glycoside in mulberry leaves, improved hyperglycemia in obese mice and reduced oxidative stress in the liver. Copyright © 2010 Society of Chemical Industry     

The effect of leaf protein concentrate from red clover on plasma cholesterol level in rats

The effect of native and defatted leaf protein concentrate (LPC) from red clover on plasma cholesterol level in rats was studied. Fat-free casein was used as a control protein. The native LPC contained 212 g kg^?1 of ether extract and oleic acid (C_{18: 1}) was its main fatty acid. LPC protein was relatively poor in sulphur-containing amino acids. Each protein studied was given to rats with or without soya bean oil. It was found that total cholesterol level in plasma of rats fed with the oil-containing diets was higher than that of rats fed with the oil-free diets. Original fat present in the native LPC though rich in unsaturated fatty acids had no hypocholesterolaemic effect. LPC was hypocholesterolaemic compared with casein in diets not containing added soya bean oil, although the difference did not reach statistical significance.     

Arginine-rich coconut kernel diet influences nitric oxide synthase activity in alloxandiabetic rats

BACKGROUND: Coconut kernel protein (CKP) has been reported to contain significant amounts of L ‐arginine. Its potential effect on glucose homeostasis, possibly through the nitric oxide synthase (NO) pathway, was therefore investigated in alloxan‐induced diabetic rats. Diabetes was induced by a single intraperitoneal dose of alloxan (150 mg kg^?1 body weight). Experimental rats were grouped as follows: Group I, normal control; Group II, diabetic control; Group III, diabetic + CKP; Group IV, diabetic + L ‐arginine; Group V, diabetic + L ‐arginine + L ‐N^G‐Nitroarginine methyl ester (L ‐NAME). Purified CKP isolated from dried coconut kernel and L ‐arginine was administered to rats along with a semi‐synthetic diet for 45 days. L ‐NAME (0.5 mg kg^?1 body weight) was given to Group V animals. After the experimental period, serum glucose, insulin, activities of liver nitric oxide synthase and arginase, liver glycogen levels and histopathology of the pancreas were evaluated. RESULTS: Serum glucose, insulin and antioxidant enzyme activities and liver glycogen levels were found to be restored to basal levels in CKP‐fed rats. Decreased arginase and increased nitric oxide synthase (NOS) activities were found in CKP‐ and arginine‐fed rats. L ‐NAME treatment showed a partial effect on these parameters. Histopathology revealed that CKP and L ‐arginine feeding reduced the diabetes‐related pancreatic damage in treated rats compared to the diabetic control. CONCLUSION: The results observed in this study indicate that the potential antidiabetic activity of CKP may be through an arginine‐NO pathway leading to pancreatic beta cell regeneration. Copyright © 2012 Society of Chemical Industry     

Lemon balm extract causes potent antihyperglycemic and antihyperlipidemic effects in insulin‐resistant obese mice

Over the last decades polyetiological metabolic diseases such as obesity and type 2 diabetes have emerged as a global epidemic. Efficient strategies for prevention and treatment include dietary intervention and the development of validated nutraceuticals. Safe extracts of edible plants provide a resource of structurally diverse molecules that can effectively interfere with multifactorial diseases. In this study, we describe the application of ethanolic lemon balm (Melissa officinalis) leaves extract for the treatment of insulin‐resistance and dyslipidemia in mice. We show that lemon balm extract (LBE) activates the peroxisome proliferator‐activated receptors (PPARs), which have key roles in the regulation of whole body glucose and lipid metabolism. Application of LBE (0.6 mg/mL) to human primary adipocytes resulted in specific peroxisome proliferator‐activated receptor target gene expression. LBE treatment of insulin‐resistant high‐fat diet‐fed C57BL/6 mice (200 mg/kg/day) for 6 weeks considerably reduced hyperglycemia and insulin resistance, plasma triacylglycerol, nonesterified fatty acids and LDL/VLDL cholesterol levels. Taken together, ethanolic lemon balm extract can potentially be used to prevent or concomitantly treat type 2 diabetes and associated disorders such as dyslipidemia and hypercholesterolemia.     

Growth inhibitory efficacy of lycopene and β-carotene against androgen-independent prostate tumor cells xenografted in nude mice

Scope : In this study, we evaluated the efficacy of lycopene against the growth of prostate cancer in vivo. Methods and results : Athymic nude mice were implanted subcutaneously with human androgen‐independent prostate carcinoma PC‐3 cells. They were supplemented with a low or a high dose of lycopene (4 and 16 mg/kg) and a single dose of β‐carotene (16 mg/kg) twice a week for 7 wk. At the end of the experiment, both lycopene and β‐carotene strongly inhibited the tumor growth, as evidenced by the decrease in tumor volume and tumor weight. High‐dosage lycopene and β‐carotene significantly decreased the expression of proliferating cell nuclear antigen in tumor tissues and increased the levels of insulin‐like growth factor‐binding protein‐3 in plasma. In addition, high‐dosage lycopene supplementation significantly decreased the vascular endothelial growth factor (VEGF) levels in plasma. In contrast, β‐carotene supplementation significantly increased the VEGF levels, as compared with tumor control group. Conclusion : Lycopene and β‐carotene supplementation suppressed the growth of prostate tumor cells, and the effects are likely associated with reduction of proliferation (attenuation of proliferating cell nuclear antigen expression) and with interference of the insulin‐like growth factor 1 signaling (increased plasma insulin‐like growth factor‐binding protein‐3 levels). Furthermore, the inhibition of VEGF by lycopene suggests that the antitumor mechanisms of lycopene also involve anti‐angiogenesis.     

Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice

We investigated the effect of curcumin on insulin resistance and glucose homeostasis in male C57BL/KsJ-db/db mice and their age-matched lean non-diabetic db/+ mice. Both db/+ and db/db mice were fed with or without curcumin (0.02%, wt/wt) for 6 wks. Curcumin significantly lowered blood glucose and HbA 1c levels, and it suppressed body weight loss in db/db mice. Curcumin improved homeostasis model assessment of insulin resistance and glucose tolerance, and elevated the plasma insulin level in db/db mice. Hepatic glucokinase activity was significantly higher in the curcumin-supplemented db/db group than in the db/db group, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly lower. In db/db mice, curcumin significantly lowered the hepatic activities of fatty acid synthase, beta-oxidation, 3-hydroxy-3-methylglutaryl coenzyme reductase, and acyl-CoA: cholesterol acyltransferase. Curcumin significantly lowered plasma free fatty acid, cholesterol, and triglyceride concentrations and increased the hepatic glycogen and skeletal muscle lipoprotein lipase in db/db mice. Curcumin normalized erythrocyte and hepatic antioxidant enzyme activities (superoxide dismutase, catalase, gluthathione peroxidase) in db/db mice that resulted in a significant reduction in lipid peroxidation. However, curcumin showed no effect on the blood glucose, plasma insulin, and glucose regulating enzyme activities in db/+ mice. These results suggest that curcumin seemed to be a potential glucose-lowering agent and antioxidant in type 2 diabetic db/db mice, but had no affect in non-diabetic db/+ mice.