Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum

The hypoglycemic and hypolipidemic effects of Lycium barbarum fruit water decoction, crude polysaccharide extracts (crude LBP), and purified polysaccharide fractions (LBP-X) in alloxan-induced diabetic or hyperlipidemic rabbits were investigated through designed sequential trials and by measuring blood glucose and serum lipid parameters. Total antioxidant capacity was also assessed using trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC) assay. It was found that the three Lycium barbarum fruit extracts/fractions could significantly reduce blood glucose levels and serum total cholesterol (TC) and triglyceride (TG) concentrations and at same time markedly increase high density lipoprotein cholesterol (HDL-c) levels after 10 days treatment in tested rabbits, indicating that there were substantial hypoglycemic and hypolipidemic effects. Hypoglycemic effect of LBP-X was more significant than those of water decoction and crude LBP, but its hypolipidemic effect seemed to be weaker. Total antioxidant capacity assay showed that all three Lycium barbarum extracts/fractions possessed antioxidant activity. However, water and methanolc fruit extracts and crude polysaccharide extracts exhibited stronger antioxidant activity than purified polysaccharide fractions because crude extracts were identified to be rich in antioxidants (e.g., carotenoids, riboflavin, ascorbic acid, thiamine, nicotinic acid). Lycium barbarum polysaccharides (glycocojugates), containing several monosaccharides and 17 amino acids, were major bioactive constituents of hypoglycemic effect. Both polysaccharides and vitamin antioxidants from Lycium barbarum fruits were possible active principles of hypolipidemic effect.     

Hypoglycemic effects of the wood of Taxus yunnanensis on streptozotocin-induced diabetic rats and its active components

Hypoglycemic effects of the H(2)O and MeOH extracts of the wood of Taxus yunnanensis were examined in streptozotocin (STZ)-induced diabetic rats. The H(2)O extract significantly lowered the fasting blood glucose level by 33.7% at a 100mg/kg dose on intraperitoneal administration. From the active H(2)O extract of the wood, three lignans, i.e., isotaxiresinol (1), secoisolariciresinol (2) and taxiresinol (3), were isolated as major components. These lignans were further tested for their hypoglycemic effects on the same experimental model. At a dose of 100mg/kg (i.p.), isotaxiresinol (1) reduced the fasting blood glucose level of diabetic rats by 34.5%, while secoisolariciresinol (2) and taxiresinol (3) reduced by 33.4% and 20.9%, respectively. The blood glucose lowering effects of 1 and 2 were stronger than the mixture of tolbutamide (200mg/kg) and buformin (1mg/kg) used as a positive control, which lowered fasting blood glucose level by 24.0%.     

Hypoglycemic benefit and potential mechanism of a polysaccharide from Hericium erinaceus in streptozotoxin-induced diabetic rats

In this study, the hypoglycemic effect and possible mechanism of a polysaccharide, HEP-C, isolated from the fruit body of Hericium erinaceus were evaluated in streptozotoxin (STZ)-induced diabetic rats. Compared with the untreated STZ-induced diabetic rats, the supplements with HEP-C (150 and 300 mg/kg body weight [BW]) could significantly and dose-dependently relieve BW loss and organ injures, reduce fasting blood glucose, enhance glucose tolerance, alleviate hepatic function and serum lipid metabolism, elevate antioxidant enzyme activities, and suppress lipid peroxidation, which contributed to its potent hypoglycemic benefit. Liver histopathological observation revealed that HEP-C could effectively attenuate the deteriorated hepatic lesions in STZ-induced diabetic rats. HEP-C with potent hypoglycemic effect positively mediated glycogen synthesis by activating the phosphatidylinositol-3-kinase/protein kinase B signaling pathway. In summary, these results suggested that HEP-C, as a new dietary functional food or therapeutic agent, exhibited great potential for the prevention and treatment of diabetes mellitus and its complications.     

Pollen Typhae total flavone improves insulin resistance in high-fat diet and low-dose streptozotocin-induced type 2 diabetic rats

Pollen Typhae total flavone (PTF), the extract from Pollen Typhae, is reported to enhance glucose uptake in C2C12 myotubes in vitro, but the convincing evidence is lacking in vivo. In this study, PTF ameliorated insulin resistance and dyslipidemia, but failed to significantly increase body weight in type 2 diabetic rats induced by high-fat diet and low-dose streptozotocin.     

Modulatory effects of one polysaccharide from Acanthopanax senticosus in alloxan-induced diabetic mice

One water-soluble polysaccharide ASP was purified from Acanthopanax senticosus and its physicochemical properties were confirmed by the combination of chemical and instrumental analysis. ASP administered orally at three doses (100, 200 and 400 mg/kg body weight) could significantly decrease the concentration of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) cholesterol levels except for high density lipoprotein (HDL) cholesterol level and the relative ratio (HDL/TC) in alloxan-induced diabetic mice, compared with the diabetic controls without drug treatment, comparable with that of diabetic mice treated with metformin. Furthermore, ASP could obviously increase the body weight and serum insulin level and reduce the fasting blood glucose (FBG) levels, especially at dose of 200 mg/kg. The data demonstrated ASP at the certain did often exhibit the optimal protective effect in alloxan-induced diabetic mice. It is promising that ASP may serve as a drug candidate or a healthcare food for diabetic therapy or protection.     

Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis

Catalpol, an iridoid glycoside, exists in the root of Radix Rehmanniae. Some studies have shown that catalpol has a remarkable hypoglycemic effect in the streptozotocin- induced diabetic model, but the underlying mechanism for this effect has not been fully elucidated. Because mito- chondrial dysfunction plays a vital role in the pathology of diabetes and because improving mitochondrial function may offer a new approach for the treatment of diabetes, this study was designed. Catalpol was orally administered together with metformin to high-fat diet/streptozotocin （HFD/STZ）-induced diabetic mice daily for 4 weeks. Body weight （BW）, fasting blood glucose （FBG） level, and glucose disposal （IPGTT） were measured during or after the treatment. The results showed a dose-dependent re- duction of FBG level with no apparent changes in BW through four successive weeks of catalpol administration. Catalpol treatment substantially reduced serum total chol- esterol and triglyceride levels in the diabetic mice. In add- ition, catalpol efficiently increased mitochondrial ATP production and reversed the decrease of mitochondrial membrane potential and mtDNA copy number in skeletal muscle tissue. Furthermore, catalpol （200 mg/kg） rescued mitochondrial ultrastructure in skeletal muscle, as detected with transmission electron microscopy. The relative mRNA level of peroxisome proliferator-activated receptor gamma co-activator 1 （PGC1） α was significantly decreased in muscle tissue of diabetic mice, while this effect was reversed by catalpol. resulting in a dose-dependent up-regulation. Taken together, we found that catalpol was capable of lowering FBG level via improving mitochondrial function in skeletal musde of HFD/STZ-induced diabetic mice.     

Renoprotective effects of berberine and its possible molecular mechanisms in combination of high-fat diet and low-dose streptozotocin-induced diabetic rats

Berberine (BBR), an effective compound of Chinese traditional herbal medicine, has preventive effects on diabetes and its complications. In this study, we investigated the therapeutic effects and underlying molecular mechanisms of BBR in rats with high-fat diet and streptozotocin (STZ)-induced diabetic nephropathy model. BBR (50, 100, 200 mg/kg/d) were orally administered to male Sprague–Dawley rats after STZ injection and conducted for 8 weeks. Renal damage was evaluated by kidney weight to body weight ratio (KW/BW), urine microalbumin (UMAlb), urine protein for 24 h (UP24 h), urine creatinine (UCr), and histological examination. Type IV collagen and transforming growth factor-beta1 (TGF-β₁) were detected by immunohistochemistry and ultrastructure of glomeruli was observed. Fasting blood glucose (FBG),serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-c), low-density lipoprotein-cholesterol (LDL-c) in serum and G protein-coupled receptor kinases (GRKs), cAMP in kidney were measured. Remarkable renal damage, hyperglycemia and hyperlipidemia were observed in DN rats. BBR could restore renal functional parameters, suppress alterations in histological and ultrastructural changes in the kidney tissues, improve glucose and lipid metabolism disorders, and increase cAMP levels compared with those of DN model group. Furthermore, BBR down-regulated total protein expression of GRK2, GRK3 and up-regulated expression of GRK6 of renal cortex in DN rats, but had a slight effects on GRK4 and GRK5. These studies demonstrate, for the first time, that BBR exerts renoprotection in high-fat diet and STZ-induced DN rats by modulating the proteins expression of GRKs in G protein- AC-cAMP signaling pathway.     

Hypoglycemic and hypolipidemic effects of alcoholic extract of Tribulus alatus in streptozotocin-induced diabetic rats: a comparative study with T. terrestris (Caltrop)

The extracts of both T. alatus and T. terrestris significantly decrease fasting glucose level in diabetic rats. After 4 and 6 hr, T. alatus extract showed significant reduction in glucose level as compared to T. terrestris. After 3 weeks of treatment with T. alatus extract, glucose level was significantly decreased to the normal level. Both the extracts also caused a significant decrease in the levels of glycosylated hemoglobin, total cholesterol, triglycerides and LDL-cholesterol. The percent of reduction in rats treated with T. alatus extract was significantly higher than that of the rats treated with T. terrestris. The results indicate that alcoholic extract of T. alatus possesses hypoglycemic activity in type-1 model of diabetes.     

Hypoglycemic and hypolipidemic effects of aqueous extract of Arachis hypogaea in normal and alloxan-induced diabetic rats.

The hypoglycemic and hypolipidemic effect of aqueous extract of Arachis hypogaea was investigated in normal and alloxan-induced diabetic rats. The extract caused a significant (P < 0.05) decrease of fasting blood glucose of both normal and alloxan-induced diabetic rats from 102.60 +/- 1.65 mg/dl to 88.79 +/- 0.94 mg/dl for normal and 189.0 +/- 30.79 mg/dl to 107.55 +/- 1.54 mg/dl for alloxan-induced diabetic rats. The extract also caused a significant (P < 0.05) decrease in serum triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol in both normal and alloxan-induced diabetic rats.     

Views on high-fat diet linked insulin resistance

Insulin resistance is linked to impaired cell metabolism and survival in the peripheral tissues, as well as increased oxidative stress and activated inflammatory responses. Chronic High fat diet insulin resistant to exposure results in liver damage, impaired glucose homeostasis, hyperinsulinemia, late pancreatic-cell failure to generate insulin due to cell exhaustion, and subsequent hyperglycaemia, all of which are hallmarks of Type 2 Diabetes Mellitus (T2DM). Therefore, it is of intrest to document a short review on the impact of a high-fat diet with insulin resistance.     

Oral glycine administration attenuates diabetic complications in streptozotocin-induced diabetic rats

Diabetes mellitus is a disease characterized by impaired glucose metabolism that leads to retinopathy, brain micro-infarcts and other complications. We have previously shown that oral glycine administration to diabetic rats inhibits non-enzymatic glycation of hemoglobin and diminishes renal damage. In this work, we evaluated the capacity of the amino acid glycine (1% w/v, 130 mM) to attenuate diabetic complications in streptozotocin (STZ)-induced diabetic Wistar rats and compared them with non-treated or taurine-treated (0.5% w/v, 40 mM) diabetic rats. Glycine-treated diabetic rats showed an important diminution in the percentage of animals with opacity in lens and microaneurysms in the eyes. Interestingly, there was a diminished expression of O-acetyl sialic acid in brain vessels compared with untreated diabetic rats (P<0.05). Additionally, peripheral blood mononuclear cells isolated from glycine-treated diabetic rats showed a better proliferative response to PHA or ConA than those obtained from non-treated diabetic rats (P<0.05). Glycine-treated rats had a less intense corporal weight loss in comparison with non-treated animals. Our results suggest that administration of glycine attenuates the diabetic complications in the STZ-induced diabetic rat model, probably due to inhibition of the non-enzymatic glycation process.     

Antioxidant and vascular effects of gliclazide in type 2 diabetic rats fed high-fat diet

Diabetes mellitus is characterized by oxidative stress, which in turn determines endothelial dysfunction. Gliclazide is a sulphonylurea antidiabetic drug with antioxidant effects due to its azabicyclo-octyl ring. It has been reported to potentially protect the vasculature through improvements in plasma lipid levels and platelet function. We hypothesized that gliclazide has a beneficial effect on endothelial function in Goto-Kakizaki rats (GK), an animal model of type 2 diabetes fed an atherogenic diet for 4 months. We evaluated the influence of gliclazide on both metabolic and oxidative status and NO-mediated vasodilation. GKAD rats showed increased oxidative stress and impaired endothelium-dependent vasodilation. GKAD rats treated with gliclazide showed increased sensitivity to NO-mediated vasodilation, a significant decrease in fasting glycemia and insulinemia, and a significant decrease in systemic oxidative stress. In conclusion, our results suggest that gliclazide treatment improves NO-mediated vasodilation in diabetic GK rats with dyslipidemia probably due to its antioxidant effects, although we cannot rule out substantial benefits due to a reduction in fasting blood glucose. The availability of a compound that simultaneously decreases hyperglycemia, hyperinsulinemia, and inhibits oxidative stress is a promising therapeutic candidate for the prevention of vascular complications of diabetes.     

Hypoglycemic and antihyperglycemic activity of Syzygium alternifolium (Wt.) Walp. seed extracts in normal and diabetic rats

Aqueous, ethanolic and hexane fractions of Syzygium alternifolium seeds were prepared and given different doses of these extracts individually to different batches of rats (both normal and alloxan diabetic rats) after an overnight fast. The blood glucose levels were measured at 0, 1, 3, 5 and 7 hours after the treatment. The aqueous extract of Syzygium alternifolium at a dosage of 0.75 g/kg b.w. is showing maximum blood glucose lowering effect in both normal and alloxan diabetic rats. The ethanol and hexane fractions are also showing hypoglycemic and antihyperglycemic activity, but the effect is significantly less than that of aqueous extract. The antihyperglycemic activity of Syzygium alternifolium seed was compared with the treatment of Glibenclamide.     

Hypoglycemic activity of inorganic constitutents in Eugenia jambolana seed on streptozotocin-induced diabetes in rats

Medicinal herbs used in indigenous medicines for the management of diabetes mellitus contain both organic and inorganic constituents. Some of these inorganic trace elements possess antidiabetic properties, which accounts for the activity of medicinal herbs. The aim of this study was to analyze the inorganic trace elements present in Eugenia jambolana seeds and to evaluate the hypoglycemic activity of the inorganic part of E. jambolana seeds on streptozotocin-induced diabetes. The seeds of E. jambolana seeds were reduced to ash and the inorganic elements present were assayed. The hypoglycemic efficacy of the inorganic part was tested by the glucose tolerance test on streptozotocin-induced diabetes. Elements such as zinc, chromium, vanadium, potassium, and sodium, possessing hypoglycemic activity, were present in the seed. The E. jambolana seed ashtreated diabetic rats exhibited normoglycemia and better glucose tolerance. The conclusion that the inorganic constituents might play a important role in the antidiabetic nature E. jambolana seeds was reached.     

Effects of diet and exercise on metabolic disturbances in high-fat diet-fed mice

Consumption of a high-fat diet (HFD) is associated with white adipose tissue (WAT) inflammation, which contributes to key components of the metabolic syndrome, including insulin resistance (IR) and hepatic steatosis (HS). To determine the differential effects of exercise training (EX), low-fat diet (LFD), and their combination on WAT inflammation, Balb/cByJ male mice (n = 34) were fed an HFD for 12 wks before they were randomized into one of four intervention groups: HFD-EX, LFD-EX, HFD-sedentary (SED), or LFD-SED. EX mice performed 12 wks of exercise training on a motorized treadmill (1 h/d, 5 d/wk, 12 m/min, 5% grade, 65% VO₂ max), while SED mice remained sedentary in their home cages. WAT gene expression of adipokines was assessed using rt-PCR. IR was measured using HOMA-IR, and HS via hepatic triglyceride content. EX significantly reduced (53%) WAT gene expression of MCP-1, and LFD significantly reduced (50%) WAT gene expression of the macrophage specific marker, F4/80 as well as the adipocytokine IL-1ra (25%). EX independently improved IR, while both EX and LFD improved HS. These findings suggest that both diet and exercise have unique beneficial effects on WAT inflammatory markers and the mechanism by which each treatment improves metabolic complications associated with chronic consumption of an HFD may be different.     

Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats

Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.     

Impact of curcumin treatment on diabetic albino rats

The current study was aimed to study the effect of curcumin on the expression levels of brain glucose transporter 1 protein (GLUT1) and femoral muscle glucose transporter 4 protein (GLUT4), in addition to study its possible therapeutic role in ameliorating insulin resistance and the metabolic disturbance in the obese and type 2 diabetic male albino Wistar rat model. Diabetes was induced by a high-fat (HF) diet with low dose streptozotocin (STZ). Curcumin was administered intragastrically for 8 weeks (80 mg/kg BW/day). The HF-diet group developed obesity, hyperglycemia, hyperinsulinemia, reduced liver glycogen content with significant dyslipidemia. In the diabetic control group, hyperglycemia and insulin resistance high calculated homeostasis model assessment (HOMA-IR-index score) were pronounced, with reductions in liver and muscle glycogen contents, concomitant with dyslipidemia and significantly elevated malondialdehyde levels in liver and pancreas. GLUT1 and GLUT4 were down-regulated in the obese and the diabetic control groups, respectively. Curcumin, showed glucose-lowering effect and decreased insulin resistance, dyslipidemia and malondialdehyde levels in both tissues, it increased liver & muscle glycogen contents, compared to the diabetic control. Curcumin significantly up-regulated GLUT4 gene expression, compared to the diabetic control group. In conclusions, these results indicate a therapeutic role of curcumin in improving the diabetic status, obesity and enhancing the expression of GLUT4 gene.     

Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits

Patients with diabetes mellitus are likely to develop certain complication such as retinopathy, nephropathy and neuropathy as a result of oxidative stress and overwhelming free radicals. Treatment of diabetic patients with antioxidant may be of advantage in attenuating these complications. Oleuropein, the active constituent of olive leaf (Olea europaea), has been endowed with many beneficial and health promoting properties mostly linked to its antioxidant activity. This study aimed to evaluate the significance of supplementation of oleuropein in reducing oxidative stress and hyperglycemia in alloxan-induced diabetic rabbits. After induction of diabetes, a significant rise in plasma and erythrocyte malondialdehyde (MDA) and blood glucose as well as alteration in enzymatic and non-enzymatic antioxidants was observed in all diabetic animals. During 16 weeks of treatment of diabetic rabbits with 20 mg/kg body weight of oleuropein the levels of MDA along with blood glucose and most of the enzymatic and non-enzymatic antioxidants were significantly restored to establish values that were not different from normal control rabbits. Untreated diabetic rabbits on the other hand demonstrated persistent alterations in the oxidative stress marker MDA, blood glucose and the antioxidant parameters. These results demonstrate that oleuropein may be of advantage in inhibiting hyperglycemia and oxidative stress induced by diabetes and suggest that administration of oleuropein may be helpful in the prevention of diabetic complications associated with oxidative stress.