Erythrocyte redox status in streptozotocin diabetic rats: effect of Casearia esculenta root extract

The present study was aimed to investigate the effect of Casearia esculenta root extract on erythrocyte lipid peroxidation and to assess the status of antioxidants in red blood cells of streptozotocin (STZ) diabetic rats. The study showed a significant elevation (p < 0.05) of erythrocyte thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation and significant reduction (p < 0.05) in reduced glutathione (GSH), ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the STZ diabetic rats. The study also observed significant reduction in membrane cholesterol and phospholipid content in STZ diabetic rats. By oral administration of C. esculenta (200 and 300 mg/kg body wt.) for 45 days to the diabetic rats these values approached almost normal levels. A dose of 300 mg/kg body weight C. esculenta extract showed better antioxidant effects than 200 mg/kg body weight.     

Effect of Casearia esculenta root extract on blood glucose and plasma antioxidant status in streptozotocin diabetic rats

Our preliminary study shows that an oral administration of an aqueous extract of Casearia esculenta, an indigenous antidiabetic plant popularly used in South India for diabetes mellitus, lowers blood glucose level under normal and glucose load conditions, and in streptozotocin (STZ)-induced diabetes in rats. The study was further undertaken to evaluate the antioxidant potential of C. esculenta in STZ diabetic rats. Oral administration of C. esculenta root extract at doses of 200 and 300 mg/kg for 45 days resulted in significant reduction in plasma thiobarbituric acid reactive substances (TBARS), hydroperoxide and ceruloplasmin and a significant elevation in plasma reduced glutathione (GSH), ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E). The study indicates that C. esculenta root extract at doses of 200 and 300 mg/kg restored all the antioxidant parameters to near normal value.     

Influence of Casearia esculenta root extract on protein metabolism and marker enzymes in streptozotocin-induced diabetic rats

The present study investigated the possible protective effects of Casearia esculenta root extract on certain biochemical markers in streptozotocin (STZ)-induced diabetes in rats. STZ treatment (50 mg/kg, ip) caused a hyperglycemic state, that led to various physiological and biochemical alterations. Blood levels of glucose, urea, uric acid and creatinine, plasma levels of albumin and albumin/globulin ratio and the activities of diagnostic marker enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gamma-glutamyltranspeptidase (gamma-GT) in plasma, liver and kidney were markedly altered in STZ diabetic rats. Oral administration of C. esculenta (200 and 300 mg/kg) for 45 days restored all these biochemical parameters to near normal levels. Thus, the present results have shown that C. esculenta root extract has the antihyperglycemic effect and consequently may alleviate liver and renal damage associated with STZ-induced diabetes in rats.     

Hypolipidaemic effect of Casearia esculenta root extracts in streptozotocin-induced diabetic rats

The hypolipidaemic effect of an aqueous extract of Casearia esculenta root, an indigenous antidiabetic medicine popularly used in rural South India was investigated. Administration of the extract of C. esculenta (200 and 300 mg/kg body wt.) for 45 days resulted in significant reduction in serum and tissue cholesterol, phospholipids, free fatty acids and triglycerides in streptozotocin (STZ) diabetic rats. In addition to that, significant (p < 0.05) decrease in high density lipoprotein (HDL) whereas significant increase (p < 0.05) in low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were observed in STZ diabetic rats, which was normalized after 45 days of C. esculenta root extract treatment. The root extract at dose of 300 mg/kg body wt. showed much significant hypolipidaemic effects than the dose of 200 mg/kg body weight.     

Antihyperglycaemic effect of Casearia esculenta root extracts in streptozotocin-induced diabetic rats

The present study was carried out to evaluate the antihyperglycaemic effect of Casearia esculenta root extract and to study the activities of liver hexokinase and gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase in liver and kidney of normal and streptozotocin-induced diabetic rats. Oral administration of aqueous extract of root (300 mg/kg body weight) for 45 days resulted in a significant reduction in blood glucose from 250.79 +/- 12.65 to 135.70 +/- 8.90 and in a decrease in the activities of glucose-6-phosphatase and fructose-1,6-bishosphatase and an increase in the activity of liver hexokinase. However, in the case of 200 mg/kg body weight of extract, less activity was observed. The study clearly shows that the root extract of C. esculenta possesses potent antihyperglycaemic activity but weaker than that of glibenclamide.     

Modulating role of 'Saptarangi' (Casearia esculenta) on membrane bound ATPase in streptozotocin diabetic rats

We have studied the activities of adenosine triphosphatase (Na+/K+ATPase, Mg2+ATPase, Ca2+ATPase and Total ATPase) in erythrocyte, liver, kidney and cardiac tissues of control and Casearia esculenta treated streptozotocin (STZ) diabetic rats. The activity of Na+/K+ATPase plays a central role in the regulation of intra and extra cellular homeostasis and alteration of this transport system is thought to be linked to several complications of diabetes mellitus. An Mg2+ dependent ATPase activity is responsible for controlling the energy requiring process in cells whereas Ca2+ATPase is responsible for the signal transduction pathways and membrane fluidity. Activities of these enzymes were significantly altered (p < 0.05) in STZ diabetic rats. Oral administration of C. esculenta root extract for a period of 45 days resulted in significant (p < 0.05) reversal of these enzymes' activities to near normal. Thus the results suggest that C. esculenta protects the membrane integrity and functional status in STZ diabetic rats.     

Influence of 3-hydroxymethyl xylitol,a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root,on glycoprotein components in streptozotocin-diabetic rats

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on antihyperglycemic, antioxidants, antihyperlipidemic, and protein metabolism and kidney marker enzymes was investigated, and its effect was shown previously. In this study, we investigated the effect of 3-HMX on plasma and tissue glycoproteins in streptozotocin-diabetic rats. Animals were divided into five groups viz., control group, 3-HMX (40 mg/kg of body weight) treated group, diabetic group, diabetic+3-HMX (40 mg/kg of body weight), and diabetic+glibenclamide (600 μg/kg of body weight). 3-HMX was administered orally at a dose of 40 mg/kg of body weight for 45 days. The study shows significant increases in the level of sialic acid except kidney and elevated levels of hexose, hexosamine, and fucose in the liver and kidney of diabetic rats, and the treatment with 3-HMX and glibenclamide showed reversal of these parameters toward normalcy. Thus, the study indicates that 3-HMX possesses a significant beneficial effect on glycoprotein components.     

Influence of 3-hydroxymethyl xylitol, a novel antidiabetic compound isolated from Casearia esculenta (Roxb.) root, on glycoprotein components in streptozotocin-diabetic rats

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound, 3-hydroxymethyl xylitol (3-HMX), has been isolated, and its optimum dose has been determined in a short duration study and patented. In addition, the long-term effect of 3-HMX in type 2 diabetic rats on antihyperglycemic, antioxidants, antihyperlipidemic, and protein metabolism and kidney marker enzymes was investigated, and its effect was shown previously. In this study, we investigated the effect of 3-HMX on plasma and tissue glycoproteins in streptozotocin-diabetic rats. Animals were divided into five groups viz., control group, 3-HMX (40 mg/kg of body weight) treated group, diabetic group, diabetic+3-HMX (40 mg/kg of body weight), and diabetic+glibenclamide (600 μg/kg of body weight). 3-HMX was administered orally at a dose of 40 mg/kg of body weight for 45 days. The study shows significant increases in the level of sialic acid except kidney and elevated levels of hexose, hexosamine, and fucose in the liver and kidney of diabetic rats, and the treatment with 3-HMX and glibenclamide showed reversal of these parameters toward normalcy. Thus, the study indicates that 3-HMX possesses a significant beneficial effect on glycoprotein components.     

A novel compound from Casearia esculenta (Roxb.) root and its effect on carbohydrate metabolism in streptozotocin-diabetic rats

Casearia esculenta root (Roxb.) is widely used in traditional system of medicine to treat diabetes in India. An active compound 3-hydroxymethyl xylitol (3-HMX) has been isolated and its optimum dose has been determined in a short duration study and patented. In the present study, the long-term effect of 3-HMX in type 2 diabetic rats has been investigated. An optimum dose of 3-HMX (40 mg/kg body weight) was orally administered for 45 days to streptozotocin-diabetic rats for the assessment of glucose, insulin, hemoglobin (Hb), glycated hemoglobin (HbA(1c)), hepatic glycogen, and activities of carbohydrate metabolizing enzymes, such as glucokinase, glucose 6-phosphatase, fructose 1,6-bisphosphatase and glucose-6-phosphate dehydrogenase and hepatic marker enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT) in normal and streptozotocin-diabetic rats. 3-HMX at 40 mg dose produced similar effects on all biochemical parameters studied as that of glibenclamide, a standard drug. Histological study of pancreas also confirmed the biochemical findings. These results indicate that 3-hydroxymethyl xylitol, the compound from C. esculenta, possesses antihyperglycemic effect on long-term treatment also.     

Beneficial effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats

Context: Olive oil is the major source of tyrosol which is a natural phenolic antioxidant. Olive oil constitutes a major component of the Mediterranean diet that is linked to a reduced incidence of chronic diseases.

Objective: This study evaluates the effects of tyrosol on altered glycoprotein components in streptozotocin-induced diabetic rats.

Materials and methods: Diabetes mellitus was induced in male Wistar rats by streptozotocin (40?mg/kg body weight). These rats were administered tyrosol (20?mg/kg body weight) and glibenclamide (600?μg/kg body weight) orally daily for 45?days. Plasma glucose, plasma insulin, glycoprotein components such as hexose, hexosamine, sialic acid and fucose in the plasma, liver and kidney, and histopathogy of tissues were analyzed.

Results: Diabetic rats revealed significant (p?p?p?in vitro study revealed the antioxidant effect of tyrosol.

Discussion and conclusions: Thus, tyrosol protects streptozotocin-induced diabetic rats from the altered glycoprotein components. Further, this study can be extrapolated to humans.     

Antioxidative and hypolipidemic efficacy of alcoholic seed extract of Swietenia macrophylla in streptozotocin diabetic rats

The present study was designed to examine the antioxidative potential and antihyperlipidemic activity of Swietenia macrophylla in streptozotocin diabetic rats. The experimental groups were rendered diabetic by intraperitoneal injection of a single dose of streptozotocin (STZ; 40 mg/kg body weight, BW). Rats with glucose levels >200 mg/dL were considered diabetic and were divided into five groups. Three groups of diabetic animals were orally administered daily with seed extract (SME) at a dosage of 50, 100 and 200 mg/kg BW. One group of STZ rats was treated as diabetic control and another group orally administered 600 μg/kg BW glibenclamide daily. Repeated daily oral administration of S. macrophylla significantly reduced blood glucose levels after 45 days of treatment. The lipid peroxidation products such as thiobarbituric acid reactive substances and lipid hydroperoxides of SME treated rats decreased in the plasma, liver and kidney. Glutathione peroxidase, superoxide dismutase and catalase activity were significantly increased in SME treated rats. Antioxidants such as reduced glutathione level in the plasma, liver and kidney and vitamins C and E levels in the plasma increased in SME treated rats. Total cholesterol, triglycerides, phospholipids and free fatty acids and lipoproteins levels increased. Altered lipid profile of treated rats lead to normality with treatment of S. macrophylla. Thus, our results indicate that the administration of 100 mg/kg BW SME restores near normal blood glucose, redox status and lipid profile in STZ-diabetic rats.     

不同剂量和不同给药次数的链脲霉素对大鼠胰岛的影响

目的研究不同剂量和不同给药次数的链脲霉素(STZ)诱发胰岛炎和损害α、β细胞的程度。方法将Wistar大鼠分成6组对照组;A组STZ50mg·kg-1·d-11次给药;B组STZ50mg·kg-1·d-连续2d给药;C组STZ50mg·kg-1·d-1连续3d给药;D组STZ30mg·kg-1·d-1连续5d给药;E组STZ80mg·kg-1·d-11次给药。观察各组大鼠的体重和末梢血糖变化,择期摘取大鼠的胰腺制作成组织切片,进行HE,Azan和免疫组织化学染色,并在光学显微镜下进行组织学比较。结果与对照组相比,各组大鼠的胰腺均存在明显的胰岛炎,D组胰岛的炎细胞浸润、空洞形成和组织纤维化较其他各组显著严重,各组残留胰岛数量、胰岛平均面积、β细胞面积和β细胞面积胰岛平均面积之比均显著减少,尤其是C、D和E组最明显;相反,各组的α细胞面积和α细胞面积胰岛平均面积之比因α细胞的显露而显著增大。结论STZ可同时诱发化学性胰岛炎和自身免疫性胰岛炎,破坏α细胞和β细胞,使胰岛出现空洞形成和组织纤维化。STZ80mg·kg-1·d-11次给药可造成最严重的胰岛损害。     

Effect of an aqueous extract of Scoparia dulcis on plasma and tissue glycoproteins in streptozotocin induced diabetic rats

The influence of Scoparia dulcis, a traditionally used plant for the treatment of diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement in glycoprotein levels. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia dulcis plant was administered orally for 6 weeks. The effect of the Scoparia dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins studied was in comparison to glibenclamide. The levels of blood glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin diabetic rats. Oral administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to decreased levels of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that Scoparia dulcis possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect.     

Kidney drug metabolizing activities in streptozotocin diabetic rats

• 1.1. Streptozotocin-induced diabetes produced significant changes on the drug metabolizing enzyme machinery of rat kidney microsomes.
• 2.2. It reduced the cytochrome P-450 content by 30%, this effect being reversed by insulin therapy.
• 3.3. Total androstenedione oxidative metabolism was increased 2.5-fold and insulin treatment partially antagonized this activation.
• 4.4. Total testosterone hydroxylase activities were not modified by diabetes nor by insulin but the formation of 2α OH testosterone and 6β OH testosterone were distinct in diabetes or insulin treated diabetic rats.
• 5.5. Only UDP-glucuronyltransferase activity for PNP was found in kidney microsomes. Diabetes determined a lower UDPGT substrate efficiency not reversed by insulin therapy.

     

Effect of Scoparia dulcis extract on insulin receptors in streptozotocin induced diabetic rats: studies on insulin binding to erythrocytes

We investigated the insulin-receptor-binding effect of Scoparia dulcis plant extract in streptozotocin (STZ)-induced male Wistar rats, using circulating erythrocytes (ER) as a model system. An aqueous extract of S dulcis plant (SPEt) (200 mg/kg body weight) was administered orally. We measured blood levels of glucose and plasma insulin and the binding of insulin to cell-membrane ER receptors. Glibenclamide was used as standard reference drug. The mean specific binding of insulin to ER was significantly lower in diabetic control rats (DC) (55.0 +/- 2.8%) than in SPEt-treated (70.0 +/- 3.5%)- and glibenclamide-treated (65.0 +/- 3.3%) diabetic rats, resulting in a significant decrease in plasma insulin. Scatchard plot analysis demonstrated that the decrease in insulin binding was accounted for by a lower number of insulin receptor sites per cell in DC rats when compared with SPEt- and glibenclamide-treated rats. High-affinity (Kd1), low-affinity (Kd2), and kinetic analysis revealed an increase in the average receptor affinity in ER from SPEt and glibenclamide treated diabetic rats having 2.5 +/- 0.15 x 10(10) M(-1) (Kd1); 17.0 +/- 1.0 x 10(-8) M(-1) (Kd2), and 2.0 +/- 0.1 x 10(-10) M(-1) (Kd1); 12.3 +/- 0.9 x 10(-8) M(-1) (Kd2) compared with 1.0 +/- 0.08 x 10(-10) M(-1) (Kd1); 2.7 +/- 0.25 x 10(-8) M(-1) (Kd2) in DC rats. The results suggest an acute alteration in the number of insulin receptors on ER membranes in STZ-induced diabetic rats. Treatment with SPEt and glibenclamide significantly improved specific insulin binding, with receptor number and affinity binding (p < 0.001) reaching almost normal non-diabetic levels. The data presented here show that SPEt and glibenclamide increase total ER membrane insulin binding sites with a concomitant significant increase in plasma insulin.     

红景天苷对链脲佐菌素所致糖尿病大鼠肝脏的保护作用

目的研究红景天苷对链脲佐菌素所致糖尿病大鼠肝脏的保护作用.方法一次性ip链脲佐菌素(60 mg/kg)制备糖尿病大鼠模型,取造模成功的糖尿病大鼠80只,按血糖水平随机分为模型组,红景天苷25、50、100 mg/kg组以及盐酸二甲双胍(25 mg/kg)组,每组16只;另取同龄正常饲养大鼠16只作为对照组.ip给药治疗,1次/d,疗程为12周.分别于0、4、8、12周测定各组大鼠血糖水平.治疗12周后,测定各组大鼠体质量和肝脏指数;检测血清中转氨酶(ALT、AST)、碱性磷酸酶(ALP)活性;测定肝脏组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和丙二醛(MDA)含量;并通过HE染色观察肝脏组织病理学改变.结果与模型组比较,红景天苷50、100 mg/kg组大鼠血糖水平显著降低(P<0.05、0.01),肝脏指数显著降低、体质量显著增高(P<0.05、0.01),血清中ALP活性明显降低(P<0.01),肝脏组织中SOD、CAT活性显著升高(P<0.05、0.01);红景天苷25、50、100 mg/kg组大鼠血清中转氨酶(ALT、AST)活性和肝组织中MDA含量显著降低(P<0.05、0.01);红景天苷组大鼠肝组织病理形态学改变程度明显减轻.结论 红景天苷对链脲佐菌素所致糖尿病大鼠肝脏具有剂量相关性的保护作用,其作用机制可能与红景天苷能够有效改善抗氧化酶系统活性、降低氧化应激损伤,从而改善肝功能有关.     

Therapeutic effect of green tea extract on advanced glycation and cross-linking of collagen in the aorta of streptozotocin diabetic rats

1. The therapeutic effect of green tea extract (GTE) on the aortic collagen content and its characteristics were investigated in streptozotocin diabetic rats. 2. Diabetes was induced in rats by a single intra peritoneal injection of streptozotocin (60 mg/kg bodyweight). Six weeks after diabetes induction, GTE was administered orally for four weeks (300 mg/kg bodyweight daily). Systolic blood pressure, blood glucose, anti-oxidant status, collagen content, extent of glycation, collagen linked fluorescence and aortic collagen solubility pattern were determined in experimental rats. 3. At the end of the experimental period, there was a significant increase in the systolic blood pressure and blood glucose in diabetic rats. The lipid peroxides increased whereas glutathione and vitamin C levels were decreased in the serum of diabetic rats. The collagen content, extent of glycation, the advanced glycation end products (AGEs) and degree of cross-linking were increased in the aorta of diabetic rats. 4. The oral administration of GTE to diabetic rats significantly reduced the systolic blood pressure and blood glucose. The level of lipid peroxides reduced and the content of glutathione and vitamin C increased in the serum of GTE treated diabetic rats. Green tea extract also impede the accumulation of aortic collagen, extent of glycation, formation of AGEs and cross-linking of collagen in diabetic rats. The antihyperglycemic, anti-oxidant and antiglycating effects of GTE ascribed for these beneficial effects. In conclusion, green tea may have therapeutic effect in the treatment of cardiovascular complications characterized by increased AGE accumulation and protein cross-linking associated with diabetes.     

Effect of green tea extract on advanced glycation and cross-linking of tail tendon collagen in streptozotocin induced diabetic rats.

Diabetes leads to modification of collagen such as advanced glycation and cross-linking which play an important role in the pathogenesis of diabetes mellitus. We have investigated the effect of green tea on modification of collagen in streptozotocin (60 mg/kg body weight) induced diabetic rats. To investigate the therapeutic effect of green tea, treatment was begun six weeks after the onset of diabetes and green tea extract (300 mg/kg body weight) was given orally for 4 weeks. The collagen content, extent of advanced glycation, advanced glycation end products (AGE) and cross-linking of tail tendon collagen were investigated. Green tea reduced the tail tendon collagen content which increased in diabetic rats. Accelerated advanced glycation and AGE in diabetic animals, as detected by Ehrlich's-positive material and collagen linked fluorescence respectively were reduced significantly by green tea. The solubility of tail tendon collagen decreased significantly in diabetic rats indicating a remarkable increase in the cross-linking, whereas green tea increases the solubility of collagen in diabetic rats. The present study reveals that green tea is effective in reducing the modification of tail tendon collagen in diabetic rats. Thus green tea may have a therapeutic effect in the treatment of glycation induced complications of diabetes.