Antidiabetic effect of Streblus asper in streptozotocin-induced diabetic rats

Context: In the Indian traditional system of medicine, Streblus asper Lour (Moraceae) is prescribed for the treatment of diabetes mellitus.

Objective: In the present study, α-amyrin acetate isolated from S. asper, and the petroleum ether extract of S. asper stem bark (PESA) was screened for their antidiabetic properties in streptozotocin (STZ)-induced diabetic rats.

Materials and methods: Successive Soxhlet extraction of the dried stem bark with petroleum ether and then with ethanol (95%) yielded petroleum ether and ethanol extracts, respectively, which were concentrated under reduced pressure. Hyperglycemia was induced in rats by STZ (50?mg/kg, b.w.). Twenty-four hours after STZ induction, respective groups of diabetic rats received PESA (100, 250 and 500?mg/kg, b.w.) and α-amyrin acetate (25, 50 and 75?mg/kg, b.w.) respectively, orally daily for 15 days. Glibenclamide (0.5?mg/kg, orally) served as a reference. Blood glucose levels were measured on every 5th day during the 15 days of treatment. The serum lipid profiles and biochemical parameters, viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), insulin and glycosylated hemoglobin level, were measured.

Results: PESA significantly (p < 0.01) normalized blood-glucose levels and serum biochemical parameters as compared with those of STZ controls. α-Amyrin acetate (75?mg/kg, b.w.) exhibited maximum glucose lowering effect (71.10%) in diabetic rats compared to the other dose (25, 50?mg/kg) at the end of the study. The protective effect was further confirmed by histopathological examination of the liver.

Conclusion: PESA and α-amyrin acetate demonstrated remarkable antidiabetic activity in STZ-induced diabetic rats.     

桑叶提取物对腹腔蛋黄致高血脂小鼠模型的影响研究

目的观察桑叶提取物的降血脂疗效。方法ICR小鼠随机分为6组。分别为正常对照组、高脂模型组、辛伐他汀组、桑叶提取物低剂量组、中剂量组和高剂量组．一次性腹腔注射75％蛋黄乳剂造成高脂血症模型,灌胃给药连续10天。测定小鼠血清中胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）及丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性。结果桑叶提取物中、高剂量均能降低高血脂小鼠血清TC、TG含量。升高HDL—C含量。高剂量还能降低血清中MDA含量．升高SOD活性。结论桑叶提取物能调节体内血脂、脂蛋白、氧化产物及抗氧化物酶水平．具有降血脂疗效。     

格列本脲对GK大鼠心肌的保护作用实验研究

<正>糖尿病心肌病(diabetic cardiomyopathy,DCM)指由糖尿病引起心脏微血管病变、心肌代谢紊乱和心肌纤维化等所致的心肌广泛结构异常的一种疾病状态[1]。近年来的研究发现,血管紧张素(Ang-Ⅱ)增多、游离脂肪酸(IFFA)在DCM的发病中起着重要的作用。     

杜仲叶绿原酸提取物对大鼠的减肥作用机制

目的研究杜仲叶绿原酸提取物(CAEF)减肥作用的可能机制。方法SD大鼠40只禁食不禁水,用高脂乳剂分别与CAEF(含量20.0%,42.4%)或奥利司他灌胃3天,收集粪便,测定其中所含的总脂量、胆固醇和胆汁酸排出量,据其值评价各药物对肠道吸收脂肪及对肠道酯酶抑制的影响。结果 42.4%CAEF可显著升高粪便中总脂质、胆固醇和胆汁酸含量,且强于奥利司他(P<0.05)。结论 CAEF通过抑制胰脂肪酶活性抑制脂肪吸收,促进胆固醇和胆汁酸的排出,这可能是其减肥的作用机制。     

Antidiabetic effect of garlic oil but not diallyl disulfide in rats with streptozotocin-induced diabetes.

We investigated the effects of garlic oil and diallyl disulfide (DADS) on glycemic control and renal function in rats with streptozotocin-induced diabetes. Rats received by gavage garlic oil (100 mg/kg body wt) or DADS (40 or 80 mg/kg body wt) every other day until 16 weeks after the induction of diabetes. The control rats were treated with corn oil only. Neither garlic oil nor DADS significantly affected fasting blood glucose concentrations throughout the investigation period. Garlic oil did not affect oral glucose tolerance in diabetes acutely but significantly improved oral glucose tolerance at 4, 8, 12, and 16 weeks and significantly ameliorated proteinuria at the end of 16 weeks. DADS did not significantly affect oral glucose tolerance or renal function. Diabetic rats fed 80 mg DADS/kg body wt had a significantly lower rate of body weight gain and a significantly lower ratio of muscle weight to body weight than did vehicle-treated diabetic rats. In conclusion, long-term treatment of diabetes with garlic oil can improve oral glucose tolerance and renal function in diabetes but not through the action of DADS. High doses of DADS may further complicate the metabolic disturbances in diabetes.     

水芹黄酮的抗糖尿病作用(英文)

目的:研究水芹黄酮(OjF)的抗糖尿病作用。方法:给小鼠尾静脉注射四氧嘧啶90mg·kg~(-1),造成高血糖动物模型。用自动生化分析仪测定血糖、血脂和胰淀粉酶。放免法测定血清胰岛素。光镜下观察胰腺和胰岛的组织学变化。结果:一次ig OjF 200mg·kg~(-1)后0.5-6h,可使正常动物血糖降低。重复给药10天,OjF 200mg·kg~(-1)和400mg·kg~(-1)均使四氧嘧啶糖尿病动物血糖明显降低(P<0.05,P<0.01)。并促进正常动物及高血糖动物胰岛素释放。OjF还能明显降低血清甘油三酯(P<0.01)及升高糖尿病动物降低的胰淀粉酶水平(P<0.01)。组织学观察OjF治疗组胰岛损伤的变化与对照组相似,但程度较轻。结论:OjF具有降低血糖和甘油三酯作用,并对胰腺损伤有一定的拮抗作用。OjF降血糖作用主要是由于促进了胰岛B细胞释放胰岛素。     

Antidiabetic activity of Bauhinia forficata extracts in alloxan-diabetic rats

The antidiabetic activity of aqueous, ethanolic and hexanic extracts of Bauhinia forficata was investigated in a model of alloxan-induced diabetes in rats. The biochemical parameters studied were: plasma glucose, serum triglycerides, cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL). Extracts were administered daily for 7 d at doses of 200 and 400 mg/kg, p.o., 48 h after alloxan injection (60 mg/kg, i.v.). The alloxan-diabetic rats showed significant reductions in plasma glucose, triglycerides, total cholesterol and HDL-cholesterol after treatment with the extracts and glibenclamide (used as standard) as compared to the diabetic controls. Levels of LDL were not altered. In conclusion, our results showed that the plant extracts when administered by gavage may reduce glucose, triglycerides, total cholesterol and HDL-cholesterol levels. These results suggest the validity of the clinical use of B. forficata in the treatment of diabetes mellitus type II.     

Antidiabetic effect of glycyrrhizin in genetically diabetic KK-Ay mice

We, previously demonstrated that one shot administration of glycyrrhizin (Grz) reduced the postprandial blood glucose rise, using Std ddY mice. Subsequently, we evaluated the effects of long-term Grz treatment (2.7, 4.1 g/kg diet) on diabetic symptoms using genetically non-insulin dependent diabetic model mice (KK-Ay). Male KK-Ay mice were divided into 3 groups: the control group, 0.27% Grz diet (2.7 g of Grz/kg diet) group and 0.41% Grz diet (4.1 g of Grz/kg diet) group. The elevation of blood glucose concentration was almost entirely suppressed in mice fed the 0.41% Grz diet 7 weeks after the beginning of test feeding, although it was not suppressed in mice fed the control diet or the 0.27% Grz diet. Water intake in the control and 0.27% Grz diet groups increased gradually, whereas, this was not true in the 0.41% Grz diet group. Grz treatment significantly lowered blood insulin level. Throughout the experiment, Grz did not affect the food intake or body weight among the three groups. The mice fed the 0.41% Grz diet also improved their tolerance to oral glucose loading 9 weeks after the beginning of test feeding. This study shows that Grz has an antidiabetic effect in noninsulin-dependent diabetes model mice.     

Antidiabetic effect of T-1095, an inhibitor of Na(+)-glucose cotransporter, in neonatally streptozotocin-treated rats

3-(Benzo[b]furan-5-yl)-2', 6'-dihydroxy-4'-methylpropiophenone-2'-O-(6-O-methoxycarbonyl)-bet a-D -glucopyranoside (T-1095) is a derivative of phlorizin, a potent inhibitor of Na(+)-glucose cotransporters. We determined the antidiabetic effect of T-1095 in neonatally streptozotocin-treated diabetic rats. Orally administered T-1095 is metabolized to an active form, 3-(benzo[b]furan-5-yl)-2', 6'-dihydroxy-4'-methylpropiophenone-2'-O-beta-D-glucopyranoside (T-1095A), which inhibits renal Na(+)-glucose cotransporters as potently as phlorizin in vitro. A single oral administration of T-1095 (30 and 100 mg/kg, p.o.) markedly lowered blood glucose levels with a concomitant increase in urinary glucose excretion; whereas the effect on blood glucose levels in non-diabetic rats was minimal. Continuous administration of T-1095 to diabetic rats for 6 weeks (0.1% in diet) improved not only hyperglycemia, but also the elevation of plasma free fatty acid and plasma ketone body levels. In addition, oral glucose tolerance testing clearly illustrated the improvement of glucose tolerance and insulin secretion with T-1095. In fact, amelioration of impaired insulin sensitivity in diabetic rats was demonstrated by the increase of whole-body and skeletal-muscle insulin-mediated glucose utilization with normalization of muscle glucose transporter (GLUT)4 content, and decrease of the hepatic glucose production rate. Consequently, polyuria and glucosuria were also improved in the T-1095-treated group. Therefore, T-1095 has a therapeutic potential as a means of ameliorating abnormal glucose metabolism via diminished glucose toxicity.     

Antidiabetic effect of chronic administration of JTT-608, a new hypoglycemic agent,in diabetic Goto-Kakizaki rats

We investigated the chronic effect of a new antidiabetic agent, trans-4-(methylcyclohexyl)-4-oxobutyric acid (JTT-608), in Goto-Kakizaki rats, a genetic model of non-obese type II diabetes mellitus. The rats were fed a liquid meal, three times a day, for 12 weeks. The rats were treated orally with JTT-608 (10-100 mg/kg) 10 min before each meal. Fasting blood glucose, triglyceride and hemoglobin A1c levels were reduced by JTT-608 at all dose levels during the experimental period. Blood glucagon-like peptide-1 level with 100 mg/kg JTT-608 increased at the end of the treatment period. JTT-608 (30-100 mg/kg) reduced urinary protein levels after administration for 5-12 weeks. In Goto-Kakizaki rats showing slight diabetic renal lesions, pathological examination revealed that JTT-608 reduced the incidence of vacuolation in renal tubules. JTT-608 (30-100 mg/kg) ameliorated the reduced motor nerve conduction velocities observed in the Goto-Kakizaki rats after administration for 12 weeks. We conclude that chronic administration of JTT-608 produces good blood glucose control and gradually arrests the development of diabetic neuropathy and nephropathy.     

Antidiabetic and antihiperlipidemic effect of Andrographis paniculata (Burm. f.) Nees and andrographolide in high-fructose-fat-fed rats

Objectives:

Andrographis paniculata (Burm. f.) Nees originates from India and grows widely in many areas in Southeast Asian countries. Andrographis paniculata (Burm. f.) Nees has shown an antidiabetic effect in type 1 DM rats. The present study investigates the purified extract of the plant and its active compound andrographolide for antidiabetic and antihyperlipidemic effects in high-fructose-fat-fed rats, a model of type 2 DM rats.

Materials and Methods:

Hyperglycemia in rats was induced by high-fructose-fat diet containing 36% fructose, 15% lard, and 5% egg yolks in 0.36 g/200 gb.wt. 55 days. The rats were treated with the extract or test compound on the 50^th day. Antidiabetic activity was measured by estimating mainly the pre– and postprandial blood glucose levels and other parameters such as cholesterol, LDL, triglyceride, and body weight.

Results:

The purified extract and andrographolide significantly (P<0.05) decreased the levels of blood glucose, triglyceride, and LDL compared to controls. However, no changes were observed in serum cholesterol and rat body weight. Metformin also showed similar effects on these parameters.

Conclusions:

Andrographis paniculata (Burm. f.) Nees or its active compound andrographolide showed hypoglycemic and hypolipidemic effects in high-fat-fructose-fed rat.KEY WORDS: Andrographis paniculata (Burm. f.) Nees, andrographolide, diabetes, fructose, hyperlipidemia     

Antidiabetic and antioxidant activity of Swietenia mahagoni in streptozotocin-induced diabetic rats

Context: Swietenia mahagoni L. Jacq. (Meliaceae) is a medium to large evergreen tree native to Southern Florida, Cuba, The Bahamas, Hispaniola, and Jamaica.

Objective: To evaluate the antidiabetic and antioxidant potential of S. mahagoni bark.

Materials and methods: In the present study, the antidiabetic activity of the methanol extract of S. mahagoni (MESM) bark in streptozotocin (STZ; 65?mg/kg body weight)-induced diabetic rats was evaluated. Glibenclamide (0.5?mg/kg; orally) was taken as the reference drug. The blood glucose levels and body weights were measured every 5th day over a period of 15 days. Antioxidant effects were assayed in diabetic rats by estimating thiobarbituric acid reactive substances (TBARS), glutathione (GSH), and catalase (CAT) levels.

Results and discussion: Oral administration of MESM at the doses of 25 and 50?mg/kg b.w. resulted in a significant (p?<?0.001) reduction in blood glucose levels in diabetic rats. Body weights were significantly (p?<?0.001) reduced in STZ-induced diabetic rats when compared to normal rats, while the extract significantly restored body weight. The present study was further undertaken to evaluate the antioxidant activity of MESM in STZ-induced diabetic rats. Decreased levels of TBARS and increased levels of GSH and CAT activity indicated a reduction in free radical formation in tissues such as the liver and kidney of diabetic rats.

Conclusion: These findings showed the significant hypoglycemic and antioxidant activity of the extract (MESM) in diabetic rats.     

自发性糖尿病GK 大鼠糖尿病周围神经病变模型的建立

摘要： 目的 通过高脂饲养 GK 大鼠建立一种符合人类糖尿病周围神经病变 （DPN） 发病特点, 又操作简单的 DPN 大鼠模型。方法 7~8 周龄 SPF 级雄性自发性 2 型糖尿病 GK 大鼠 30 只, 喂养高脂饲料造模。另取 30 只 SPF 级正常 Wistar 大鼠作为正常组, 喂养普通饲料。每周监测动物血糖、 体质量、 饮水量、 饲料量。分别于干预 8 周、 12 周、 16 周后检测血清糖化血红蛋白、 坐骨神经传导速度, 取对侧坐骨神经做 HE 染色, TUNEL 染色计算细胞凋亡指数。结果 随着造模时间延长, GK 大鼠逐渐出现多饮、 多食、 生长迟缓等表现。与正常组相比, 造模 12 周及 16 周的大鼠血糖、 糖化血红蛋白升高 （P < 0.01）, 感觉神经传导速度降低 （P < 0.01）, 运动神经传导速度有一定下降趋势（12 周 P < 0.05, 16 周 P > 0.05）, 坐骨神经病理形态及雪旺细胞凋亡情况均提示 DPN 的形成, 并与正常大鼠形成鲜明对照 （凋亡指数 P < 0.01）。结论 长期高脂饲料喂养的 GK 大鼠是 DPN 研究的良好模型, 12 周是较为成熟且经济的造模时间。     

Antidiabetic effect of plumbagin isolated from Plumbago zeylanica L. root and its effect on GLUT4 translocation in streptozotocin-induced diabetic rats

Plumbago zeylanica L. root is widely used in Indian medicine to treat diabetes mellitus. The aim of the present investigation was to evaluate the antidiabetic effects of plumbagin isolated from P. zeylanica L. root and its effect on GLUT4 translocation in STZ-induced diabetic rats. Plumbagin (15 and 30 mg/kg b wt) was orally administered to STZ-induced diabetic rats for 28 days. An oral glucose tolerance test was performed on 21st day. The effect of plumbagin on body weight, blood glucose, plasma insulin, total protein, urea, creatinine, liver glycogen, plasma enzymes (SGOT, SGPT and ALP) and carbohydrate metabolism enzymes (glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase) were investigated. GLUT4 mRNA and protein expression in skeletal muscles were also studied. Plumbagin significantly reduced the blood glucose and significantly altered all other biochemical parameters to near normal. Further, plumbagin increased the activity of hexokinase and decreased the activities of glucose-6-phosphatase and fructose-1,6-bisphosphatase significantly in treated diabetic rats. Enhanced GLUT4 mRNA and protein expression were observed in diabetic rats after treatment with plumbagin. The results indicated that plumbagin enhanced GLUT4 translocation and contributed to glucose homeostasis. It could be further probed for use as a drug to treat diabetes.     

Antidiabetic effects of chitosan oligosaccharides in neonatal streptozotocin-induced noninsulin-dependent diabetes mellitus in rats

The antidiabetic effect of chitosan oligosaccharide (COS) was investigated in neonatal streptozotocin (STZ)-induced noninsulin-dependent diabetes mellitus rats. The fasting glucose level was reduced by about 19% in diabetic rats after treatment with 0.3% COS. Glucose tolerance was lower in the diabetic group compared with the normal group. After diabetic rats had been treated with 0.3% COS for 4 weeks, glucose tolerance increased significantly versus the diabetic control group, and glucose-inducible insulin expression increased significantly. In addition, fed-triglyceride (TG) levels in diabetic rats drinking 0.3% COS were reduced by 49% compared with those in diabetic control rats. The cholesterol levels of animals treated with COS were reduced by about 10% in fed or fasting conditions versus the corresponding controls, although the difference was not statistically significant. It was found that COS has a TG-lowering effect in diabetic rats, and that COS reduces signs of diabetic cardiomyopathy such as vacuolation of mitochondria and the separation and degeneration of myofibrils. In conclusion, these results indicate that COS can be used as an antidiabetic agent because it increases glucose tolerance and insulin secretion and decreases TG.     

Antidiabetic properties of the alcoholic extract of Sphaeranthus indicus in streptozotocin-nicotinamide diabetic rats

We have investigated the possible antihyperglycaemic effects of Sphaeranthus indicus extract in rats rendered diabetic by nicotinamide (120 mgkg(-1) i.p.) and streptozotocin (STZ) (60 mgkg(-1) i.p). Fasting plasma glucose levels, serum insulin levels, serum lipid profiles, magnesium levels, glycosylated haemoglobin, changes in body weight and liver glycogen levels were evaluated in normal and diabetic rats. Oral administration of S. indicus for 15 days resulted in significant decrease in blood glucose levels and increases in hepatic glycogen and plasma insulin levels. Fasting normal rats treated with the alcoholic extract of S. indicus showed significant improvement in oral glucose tolerance test. Glibenclamide was used as a reference standard. The findings demonstrate that the alcoholic S. indicus extract may be useful in the treatment of diabetes.     

Inhibition of choroidal angiogenesis by calcium dobesilate in normal Wistar and diabetic GK rats

Calcium dobesilate reduces vascular endothelial growth factor (VEGF) over-expression in diabetic rat retina, but its effect on intraocular angiogenesis is unknown. Therefore, we tested calcium dobesilate for its in vitro and ex vivo effects on choroidal explant angiogenesis in spontaneously diabetic Goto-Kakizaki (GK) rats. Choroidal explants were cultured in gels of collagen. Budded microvessels numbers and VEGF formation were taken as markers of angiogenesis. Ex vivo studies were performed in GK rats orally given 100 mg/kg/day calcium dobesilate for 10 days. In vitro, calcium dobesilate dose- and time-dependently inhibited both microvessel formation and VEGF production, at concentrations >or=25 mug/ml (i.e. >or=60 microM), with complete inhibition at 100 microg/ml. Oral treatment of diabetic GK rats with calcium dobesilate induced a significant reduction of choroidal angiogenesis ex vivo (38.8% after 3 days of culture). In conclusion, calcium dobesilate inhibited choroidal explant angiogenesis both in vitro and ex vivo. This effect may be due, at least in part, to inhibition of VEGF production. Antiangiogenesis by calcium dobesilate can be involved in its therapeutic benefit in diabetic retinopathy.     

Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats

The present study was aimed to evaluate the hypoglycemic efficacy in an aqueous extract of seeds of two varieties, namely a country and a hybrid variety of Momordica charantia (MCSEt1 and MCSEt2) respectively in streptozotocin (STZ) induced diabetic rats. STZ-induced diabetic rats were treated with aqueous extracts of MCSEt1 and t2 for a period of 30 days. MCSEt1 and t2 extract treatment to diabetic rats resulted in a significant reduction in blood glucose, glycosylated hemoglobin, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and glycogen phosphorylase, and a concomitant increase in the levels of hemoglobin, glycogen and activities of hexokinase and glycogen synthase. These results clearly show the antidiabetic properties of Momordica charantia. Both the varieties showed safe and significant hypoglycemic effects which were more pronounced in MCSEt1 compared to MCSEt2 and glibenclamide.     

Antidiabetic activity of Croton klozchianus in rats and direct stimulation of insulin secretion in-vitro

Croton klozchianus is a relatively uninvestigated species with no pharmacological or phytochemical reports available, although it has been used clinically by Ayurvedic physicians to treat diabetes. We have investigated this use by studying the insulin secretion and antidiabetic activity of C. klozchianus. Treatment of diabetic rats with aerial parts of C. klozchianus extract (CK, 100 and 300 mg kg(-1) body weight) for three weeks showed significant reduction in blood glucose (45.8% after 14 days for 300 mg kg(-1)). C. klozchianus extract caused a significant concentration-dependent increase in insulin secretion (8-fold at 2 mg mL(-1) for cells challenged with 20 mM glucose) from MIN6 cells grown as monolayers and as pseudoislets, indicating that the antidiabetic activity may have been as a result of increased insulin secretion. It also had a role on the lipid profile of the rats by causing reduction in cholesterol and triglycerides and increasing high density lipoprotein significantly. The results obtained gave some scientific support to the traditional use of the plant as a treatment for diabetes.