罗格列酮对糖尿病肾病大鼠肾脏的保护作用

目的 探讨罗格列酮对糖尿病肾病(DN)大鼠肾脏的保护作用.方法 单次腹腔注射链脲佐菌素(STZ)诱导糖尿病大鼠模型,将糖尿病大鼠随机分为糖尿病肾病组(DN组,6只)和罗格列酮组(R组,8只),以正常大鼠(N组,6只)作对照.干预8周后,观察各组大鼠尿蛋白、血糖、血脂、血尿素氮(BUN)、血肌酐(SCr)变化;用免疫组化及实时荧光定量PCR分析肾脏环氧化酶-2(COX-2)、过氧化物酶增殖体激活受体γ(PPARγ)的表达.结果 DN组尿蛋白、BUN、SCr、肾脏COX-2蛋白及mRNA水平均较N组明显升高,PPARγ蛋白表达下调;而R组大鼠上述各项检测指标明显逆转;24-h尿蛋白定量分别与COX-2蛋白及mRNA水平呈显著正相关.DN组血糖、血脂均显著高于N组,罗格列酮治疗后上述指标无明显变化.结论 罗格列酮可能通过PPAR途径下调DN大鼠肾脏COX-2表达,发挥不依赖糖脂代谢的直接肾保护作用.     

Hypoglycemic effect of aqueous extract of Ammi visnaga in normal and streptozotocin-induced diabetic rats

The effect of the aqueous extract of Ammi visnaga (Apiaceae) on blood glucose levels was investigated in fasting normal and streptozotocin-induced diabetic rats after single and repeated oral administration. The aqueous extract of Ammi visnaga (AV) at a dose of 20 mg/kg significantly reduced blood glucose in normal rats six hours after a single oral administration (P < 0.005) and nine days after repeated oral administration (P < 0.05). This hypoglycemic effect is more pronounced in streptozotocin (STZ) diabetic rats (P < 0.001). Acute toxicity (LD50) and general behavioural effects of an aqueous extract of AV fruits was studied in mice. The LD50 of intraperitoneal (i.p.) and oral administration was 3.6 and 10.1 g/kg, respectively. These findings suggest that the aqueous extract of AV possess significant hypoglycemic effect in both normal and STZ diabetic rats and support, therefore, its claimed clinical use by the Moroccan population.     

罗布麻提取物对STZ糖尿病大鼠肾损害的防护作用

本文探讨了罗布麻提取物 (AV) 对STZ大鼠糖尿病肾脏损害的防护作用及部分作用机制。采用链脲佐菌素 (STZ) 诱导大鼠糖尿病模型方法, 观察8周时大鼠血糖、肾功能、氧化应激等指标以及经AV治疗后的变化。结果显示, 糖尿病大鼠的血糖、血尿素氮、24 h尿蛋白含量、尿量、肾脏肥大指数、肾皮质MDA含量显著升高; 肾皮质SOD、GSH活性显著降低。AV干预治疗组的上述指标得到改善, 具有显著性差异。实验结果表明, AV对STZ大鼠糖尿病肾功能有明显的防护作用, 其作用可能与抑制肾脏氧化应激作用有关。     

Antihyperglycemic effect of andrographolide in streptozotocin-induced diabetic rats

The antihyperglycemic action of andrographolide, an active principle in the leaves of Andrographis paniculata (Burm. f.) Nees, was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). Oral treatment of andrographolide decreased the plasma glucose concentrations of STZ-diabetic rats in a dose-dependent manner. Similar treatment with andrographolide also decreased the plasma glucose in normal rats and the maximal effect was more marked than that in STZ-diabetic rats. Andrographolide at the effective dose (1.5 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. In the isolated soleus muscle of STZ-diabetic rats, andrographolide enhanced the uptake of radioactive glucose in a concentration-dependent manner. Moreover, the mRNA and protein levels of the subtype 4 form of the glucose transporter (GLUT4) in soleus muscle were increased after repeated intravenous administration of andrographolide in STZ-diabetic rats for 3 days. These results suggest that andrographolide can increase the glucose utilization to lower plasma glucose in diabetic rats lacking insulin.     

Renoprotective effect of berberine on type 2 diabetic nephropathy in rats

Inflammation, fibrosis, and lipid disorder are essential promoters in the pathogenesis of diabetic kidney injury in diabetes mellitus type 2. Berberine (BBR) has been reported to have beneficial effects on diabetic nephropathy, but its action mechanism is still unclear. The present study was designed to elucidate the therapeutic mechanism of BBR in a type 2 diabetic nephropathy rat model induced by a high‐fat diet and low‐dose streptozotocin injection. The diabetic rats were treated with or without BBR by gavage for 20 weeks and examined by serology, 24‐h albuminuria, histology, immunohistochemistry, and molecular analyses. Results showed that treatment with BBR significantly reduced serum levels of blood glucose and lipids, inhibited urinary excretion of albumin, and attenuated renal histological injuries in diabetic rats. Berberine treatment also inhibited renal inflammation, which was associated with inactivation of nuclear factor kappa‐light‐chain‐enhancer of activated B‐cell signalling. As a result, the upregulation of pro‐inflammatory cytokines (interleukin‐1β, tumour necrosis factor‐α) and chemokine (monocyte chemotactic protein‐1) was blocked. In addition, BBR treatment also inactivated transforming growth factor‐β/Smad3 signalling and suppressed renal fibrosis, including expression of fibronectin, collagen I, and collagen IV. The present study reveals that BBR is a therapeutic agent for attenuating type 2 diabetic nephropathy by inhibiting nuclear factor kappa‐light‐chain‐enhancer of activated B cell‐driven renal inflammation and transforming growth factor‐β/Smad3 signalling pathway.     

Hypoglycaemic effect of Melothria heterophylla in streptozotocin-induced diabetic rats

Context: In the Indian traditional system of medicine, Melothria heterophylla (Lour.) Cogn., (Cucurbitaceae) is prescribed for the treatment of diabetes mellitus. Objective: In the present study, the antidiabetic effect of ethanol extract of Melothria heterophylla (EEMH), and its active isolated constituents were investigated in streptozotocin (STZ)-induced diabetic Swiss albino rats. Method: Successive Soxhlet extraction of the dried total aerial parts with petroleum ether for defatting and then with ethanol (95%) to obtain ethanol extract, which was concentrated under reduced pressure. Hyperglycemia was induced in rats by STZ (50 mg/kg, body weight). Twenty-four hours after STZ induction, respective groups of diabetic rats received EEMH (200 and 400 mg/kg, body weight), gallic acid (GA) (2 and 4 mg/kg, body weight), and rutin (RU) (2 and 4 mg/kg, body weight), respectively, orally daily for 15 days. Glibenclamide (0.5 mg/kg, orally) served as reference. Blood glucose levels and change in body weight were measured on every 5(th) day during 15 days of treatment. Biochemical parameters, viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and serum insulin, were measured. Results: EEMH and its active constituents significantly (p < 0.01) normalized blood glucose levels and serum biochemical parameters as compared to those of STZ controls. Both GA (4 mg/kg) and RU (4 mg/kg) exhibited maximum glucose lowering effect (69.1 and 66.7%, respectively) in diabetic rats compared to the other dose (2 mg/kg) at the end of the study. EEMH, gallic acid and RU also showed significant increase in serum insulin, and body weight of STZ-induced diabetic rats. Conclusion: Therefore, ethanol extract of Melothria heterophylla, GA and RU demonstrated remarkable antidiabetic activity in STZ-induced diabetic rats.     

吡格列酮对糖尿病大鼠肾脏的保护作用及其机制探讨

目的观察吡格列酮对糖尿病大鼠肾脏的保护作用并探讨其机制。方法采用链脲佐菌素(STZ)诱导糖尿病模型。24只大鼠随机分为正常对照组(NC组)、糖尿病组(DM组)、吡格列酮干预组(3mg·kg-1·d-1,DT组),每组8只。12周末,测定各组相关生化指标。运用比色法检测肾皮质中丙二醛(MDA)的含量、铜锌超氧化物歧化酶(Cu-ZnSOD)及过氧化氢酶(CAT)的活性。同时留取肾标本作电镜观察。结果与NC组相比,DM组和DT组血糖、胆固醇、甘油三酯、血清胰岛素、C肽、尿素氮、血肌酐、肾重/体重和24h尿蛋白定量差异有统计学意义。DM组与NC组比较,肾皮质Cu-ZnSOD、CAT活性明显降低(P<0.01),MDA含量明显增加(P<0.01)。DT组与DM组比较,血糖、胆固醇、甘油三酯、血清胰岛素、C肽、尿素氮、血肌酐差异无统计学意义(P>0.05),肾重/体重和24h尿蛋白定量明显降低(P<0.05);肾皮质CAT和Cu-ZnSOD活性增加(P<0.05),肾皮质MDA含量降低(P<0.05)。结论吡格列酮对糖尿病大鼠肾脏有保护作用且此作用不依赖其降糖、降脂机制,可能与吡格列酮的抗氧化机制有关。     

Hypoglycaemic effect of Melothria heterophylla in streptozotocin-induced diabetic rats

Context: In the Indian traditional system of medicine, Melothria heterophylla (Lour.) Cogn., (Cucurbitaceae) is prescribed for the treatment of diabetes mellitus.

Objective: In the present study, the antidiabetic effect of ethanol extract of Melothria heterophylla (EEMH), and its active isolated constituents were investigated in streptozotocin (STZ)-induced diabetic Swiss albino rats.

Method: Successive Soxhlet extraction of the dried total aerial parts with petroleum ether for defatting and then with ethanol (95%) to obtain ethanol extract, which was concentrated under reduced pressure. Hyperglycemia was induced in rats by STZ (50 mg/kg, body weight). Twenty-four hours after STZ induction, respective groups of diabetic rats received EEMH (200 and 400 mg/kg, body weight), gallic acid (GA) (2 and 4 mg/kg, body weight), and rutin (RU) (2 and 4 mg/kg, body weight), respectively, orally daily for 15 days. Glibenclamide (0.5 mg/kg, orally) served as reference. Blood glucose levels and change in body weight were measured on every 5^th day during 15 days of treatment. Biochemical parameters, viz., serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and serum insulin, were measured.

Results: EEMH and its active constituents significantly (p < 0.01) normalized blood glucose levels and serum biochemical parameters as compared to those of STZ controls. Both GA (4 mg/kg) and RU (4 mg/kg) exhibited maximum glucose lowering effect (69.1 and 66.7%, respectively) in diabetic rats compared to the other dose (2 mg/kg) at the end of the study. EEMH, gallic acid and RU also showed significant increase in serum insulin, and body weight of STZ-induced diabetic rats.

Conclusion: Therefore, ethanol extract of Melothria heterophylla, GA and RU demonstrated remarkable antidiabetic activity in STZ-induced diabetic rats.     

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.     

Ethanol extract of Butea monosperma bark modulates dyslipidemia in streptozotocin-induced diabetic rats

Context: Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus (DM). The availability of multiple lipid-lowering drugs and supplements provides new opportunities for patients to regulate lipid levels.

Objective: The present study was designed to evaluate the effect of Butea monosperma Lam. (Fabaceae) bark extract in diabetes-induced dyslipidemia.

Materials and methods: A daily dose of B. monosperma bark extract (BMBE, 500?mg/kg body weight) was given orally to streptozotocin (STZ)-induced diabetic rats for 60?d. Several indices such as blood glucose, insulin, glycosylated hemoglobin, TC, TG, high-density lipoprotein-cholesterol (HDL-C), apo A1, apo B, activities of lipogenic enzymes in tissues, liver function tests, and histopathology of liver were analyzed to assess the modulation of STZ-induced diabetic dyslipidemia by B. monosperma bark.

Results: BMBE significantly reduced blood glucose (40.79%) and increased plasma insulin (37.5%) levels in diabetic rats. Altered levels of serum lipids, lipoproteins, and activities of lipogenic enzymes in tissues were partially restored upon the administration of BMBE in diabetic rats. Liver function tests and histopathological examination revealed that consumption of BMBE at a dose of 500?mg/kg body weight had no toxic effects in experimental rats.

Conclusion: The findings suggest that BMBE supplementation could ameliorate dyslipidemia in DM.     

Hypoglycemic and antioxidant effects of Rheum franzenbachii extract in streptozotocin-induced diabetic rats

The hypoglycemic and antioxidant effects of ethanol extract from the roots and rhizomes of Rheum franzenbachii Münt. (Polygonaceae) were evaluated in streptozotocin-induced diabetic rats. Effects of repeated oral administration of ethanol extract (125, 250, and 500?mg/kg body weight) on the plasma glucose level (PGL), oral glucose tolerance test (OGTT), malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in diabetic rats were examined. It was found that administration of ethanol extract (125, 250, and 500?mg/kg) produced a significant fall in PGL, AUC, and MDA, while elevating the GSH levels and SOD and CAT activities in diabetic rats. The dose of 500?mg/kg was identified as the most effective dose, with a decrease of 65.8 and 44.0% in PGL and MDA, and elevation of 72.6, 75.0, and 51.5% in GSH level and SOD and CAT activities, respectively, after 14 days of ERF administration in diabetic rats. Moreover, the OGTT studies showed a maximum reduction in PGL and AUC. From the active extract of Rheum franzenbachii, two stilbenes, desoxyrhapontigenin (1) and desoxyrhaponticin (2), were isolated as major constituents. The present study concludes that the ethanol extract of roots and rhizomes from Rheum franzenbachii had significant hypoglycemic and antioxidant effects.     

氯沙坦对实验性糖尿病大鼠肾脏功能的保护作用

目的 :探讨氯沙坦对糖尿病肾病肾脏功能的保护作用。方法 :制作糖尿病大鼠模型 ,分成 3组 ,每组 15只 ,糖尿病治疗组给予氯沙坦灌胃 ,糖尿病组和正常对照组均给予等量生理盐水灌胃。分别于实验的wk 1,2 ,4取材 ,测定血糖、血肌酐、尿清蛋白、尿肌酐、尿α1 微球蛋白排泄率和血浆内皮素(ET)水平。结果 :糖尿病组大鼠出现血糖升高、肌酐清除率下降、尿清蛋白和尿α1 微球蛋白排泄率升高 ,与正常对照组相比差异有非常显著和显著意义(P <0 .0 1或P <0 .0 5 ) ,血浆ET水平升高 ,wk 2时与正常对照组间差异有非常显著意义 ;肌酐清除率、尿清蛋白和尿α1 微球蛋白排泄率等指标 ,治疗组与糖尿病组比较差异均有显著或非常显著意义。结论 :动物实验证实氯沙坦可减轻糖尿病肾病的肾功能损害 ,改善肾功能 ,具有肾脏保护作用     

Protective effect of aged garlic extract on the small intestinal damage of rats induced by methotrexate administration.

The methotrexate (MTX) administration to rats causes the damage of small intestine. The small intestinal damage was evaluated by measuring the intestinal permeability of the poorly absorbable compound, fluorescein isothiocyanate (FITC)-labeled dextran (average molecular weight, 4,400) (FD-4) using the in vitro everted intestine technique and by determining the FD-4 that appeared in plasma using the in situ closed loop intestine technique. The MTX administration to rats fed with the standard laboratory diet increased the small intestinal permeability of FD-4 due to the damage of the small intestine. Interestingly, the permeability of FD-4, when MTX was administered to rats fed with the aged garlic extract containing diet, was depressed almost to the level of control rats without the MTX treatment. The present study showed that the aged garlic extract protected the small intestine from the damage induced by the action of MTX on the crypt cells.     

Antioxidant effect of Aloe vera gel extract in streptozotocin-induced diabetes in rats

In the present study, an attempt has been made to evaluate the presence of antioxidant property in the alcoholic extract of Aloe vera leaf gel. Oral administration of Aloe vera gel extract at a concentration of 300 mg/kg to diabetic rats significantly decreased the levels of blood glucose, glycosylated hemoglobin and increased hemoglobin. The increased levels of lipid peroxidation and hydroperoxides in tissues of diabetic rats were reverted back to near normal levels after the treatment with gel extract. The extract treatment also resulted in a significant increase in reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase in the liver and kidney of diabetic rats. These results clearly show the antioxidant property of Aloe vera gel extract. The extract was also more effective than glibenclamide in restoring the values of these parameters.     

Hypoglycaemic and anti-oxidant activity of Salacia oblonga Wall. extract in streptozotocin-induced diabetic rats

The petroleum ether extract of the root bark of S. oblonga Wall. (Celastraceae) (SOB) was studied in streptozotocin (STZ) diabetic rats and anti-lipid peroxidative activity of the same was studied in the cardiac tissue. SOB prevented significantly the streptozotocin-induced hyperglycaemia and hypoinsulinaemia. It also produced a significant decrease in peroxidation products viz. thiobarbituric acid reactive substances (P < 0.001), conjugated dienes (P < 0.05), hydroperoxides (P < 0.001). The activity of antioxidant enzymes such as superoxide dismutase (P < 0.001), catalase (P < 0.001), GSHPxase and GSSGRase was found to be increased in the heart tissue of diabetic animals treated with SOB. These results suggest that S. oblonga root bark extract possesses anti-diabetic and anti-oxidative activity in streptozotocin-diabetic rats.     

Antihyperglycemic effect of constituents from Hintonia standleyana in streptozotocin-induced diabetic rats

An extract (100 mg/kg) of the stem bark of Hintonia standleyana caused a significant decrease in blood glucose levels in both normal and streptozotocin (STZ)-diabetic rats when compared with vehicle-treated groups (p < 0.05). From the active extract, 3- O- beta- D-glucopyranosyl-23,24-dihydrocucurbitacin F ( 1), 5- O-beta- D-glucopyranosyl-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin ( 2) and 5- O-[ beta- D-apiofuranosyl-(1-->6)- beta- D-glucopyranosyl]-7-methoxy-3',4'-dihydroxy-4-phenylcoumarin ( 3) were isolated. Coumarin 3 is a new natural product and was identified by spectroscopic methods. Compounds 1 and 3 did not decrease blood glucose levels in normal rats. However, in two different long-term subacute experiments, using animals with a developing diabetes condition and with STZ-induced diabetes, both compounds at daily doses of 10 mg/kg (developing diabetes condition) or 30 mg/kg (STZ-induced diabetes condition) provoked a significant antihyperglycemic activity (p < 0.05). Furthermore, compound 3 restored normal blood glucose levels in STZ-induced diabetic rats. In all cases, the groups treated with the active principles and the extract showed less body weight lost than the glibenclamide-treated and diabetic control groups (p < 0.05). These results showed that the antihyperglycemic active principles of H. standleyana are both 4-phenylcoumarins and cucurbitacin glycosides.     

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.     

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.