六味地黄加味胶囊对糖尿病肾病大鼠肾脏蛋白激酶C活性及结缔组织生长因子的影响

目的观察六味地黄加味胶囊对糖尿病肾病(DN)大鼠肾脏的保护作用,对肾脏蛋白激酶C(PKC)活性及结缔组织生长因子(CTGF)表达的影响。方法ip链脲佐菌素(STZ)建立大鼠DN模型,模型成功后随机分为5组:对照组、模型组、洛汀新组、六味地黄加味胶囊组、洛汀新与六味地黄加味胶囊合用组,药物干预12周后,透射电镜观察各组大鼠肾脏超微结构,免疫组织化学法检查肾皮质CTGF表达,检测相对肾质量、血糖、尿白蛋白排泄率(UPER)、血肌酐(SCr)、尿肌酐(UCr)、内生肌酐清除率(CCr)、肾脏PKC活性等。结果DN大鼠肾脏胶原沉积明显,相对肾质量、血糖、UPER、CCr、肾脏PKC活性、肾皮质CTGF表达等显著升高,洛汀新、六味地黄加味胶囊及两药合用均可降低肾脏PKC活性和肾皮质CTGF的表达,改善DN大鼠蛋白尿、肾功能,减轻肾脏胶原沉积,两药合用能更显著降低肾脏PKC活性、肾皮质CTGF的表达,降低蛋白尿和改善肾功能作用更强。结论洛汀新、六味地黄加味胶囊及两药合用均能保护DN大鼠肾脏,且两药合用较单用洛汀新作用更强。     

茱萸丸对大鼠实验性2型糖尿病的治疗作用

目的:观察茱萸丸对实验性2型糖尿病大鼠降糖、降脂等作用的影响。方法:Wistar大鼠110只,随机抽取50只作为正常大鼠实验组,其余60只为糖尿病大鼠组。糖尿病组以高脂饲料诱导加链脲佐菌素(STZ)30 mg.kg-1 ip建立2型糖尿病模型,7 d后选取成模大鼠50只。50只正常大鼠和50只糖尿病大鼠各自按随机数字表法分为正常组(0.9%生理盐水)、模型组(0.9%生理盐水)、药物组(盐酸二甲双胍0.2 g.kg-1)、茱萸丸组(低、中、高剂量组分别为0.75,1.5,3 g.kg-1),每组10只。连续ig给药2周后,观察各组大鼠体重、血糖、血脂的变化。结果:茱萸丸对实验性2型糖尿病大鼠血糖有明显降低作用(P<0.01),对正常大鼠血糖无明显变化;能明显改善糖尿病大鼠的血脂(P<0.01),明显降低大鼠TC,TG,对糖尿病大鼠治疗后期的体重减轻起到延缓的作用(P<0.01)。结论:茱萸丸能降低糖尿病大鼠的血糖,改善糖尿病大鼠的血脂和体重。     

Antihyperglycemic effects of baicalin on streptozotocin – nicotinamide induced diabetic rats

The aim of the study was to investigate the effects of baicalin on blood glucose, insulin and cytokine levels. Rat diabetes was induced by intraperitoneal (i.p.) injection of nicotinamide and streptozotocin. Diabetic rats were dosed with i.p. baicalin or oral metformin daily for 8 days. Blood glucose, insulin and hepatic glycogen were determined using conventional methods. The activity of hepatic hexokinase was determined using a coupled assay with glucose‐6‐phosphate dehydrogenase. Serum levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α) and adiponectin were measured by enzyme‐linked immunosorbent assay. Administration of baicalin at 50 or 100 mg/kg significantly decreased plasma glucose levels in a dose dependent manner. The serum insulin level was not increased by baicalin treatment. Administration of baicalin at a high dose (100 mg/kg) resulted in a significant increase of liver glycogen content and a reduction of serum TNF‐α. The activity of hepatic hexokinase was significantly increased after dosing baicalin at 25, 50 or 10 mg/kg. Administration of baicalin (50 or 10 mg/kg) or metformin (10 mg/kg) significantly alleviated the morphological injury to the pancreas caused by STZ. The possible mechanisms contributing to the hypoglycemic effect include increasing the hepatic glycogen content and glycolysis, and reducing the serum levels of TNF‐α. Copyright © 2010 John Wiley & Sons, Ltd.     

甲福明和水飞蓟素对抗D-半乳糖诱导大鼠糖耐量减退作用的比较

目的 研究甲福明(metforin)和水飞蓟素(silymarin)对D-半乳糖(D-gal)诱导大鼠糖耐量减退(impaired glucose tolerance,IGT)的影响.方法 以ip D-gal 150mg·kg-1,qd×56d诱导胰岛素抵抗(insulin resistanse,R),IGT大鼠模型,测其空腹血糖(fasting blood glucose,FBG)和口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)后2h血糖(2-hours blood glucose,2h BG)含量;并观察甲福明和水飞蓟素对病鼠FBG及OGTT后2hBG的效应.结果 正常对照组、甲福明和水飞蓟素组与模型组比较,FBG均未见明显影响,差异未见显著性(P＞0.05);而OGTT后2hBG,模型组明显高于正常对照组(P＜0.01)说明D-gal致大鼠IGT模型成立;甲福明和水飞蓟素均能抑制OGTT后2h BG的升高,差异均有高度显著性(P＜0.01),FBG与OGTT后2h BG间差值降低,差异均有高度显著性(P＜0.01),说明各药均能改善D-gal所致IR模型大鼠的IGT.结论 D-gal可诱导以IGT为表现的IR,其机制可能与D-gal诱导蛋白非酶糖基化-氧化应激-自由基损伤作用和直接干扰糖、脂代谢有关;甲福明和水飞蓟素均能改善D-gal诱导IR大鼠的糖耐量.     

Mangiferin prevents diabetic nephropathy progression in streptozotocin‐induced diabetic rats

Diabetic nephropathy is one of the most severe diabetic microangiopathies and accounting for approximately one‐third of all cases of end‐stage renal disease. In the present study, we investigated the effect of mangiferin, a polyphenol from Anemarrhena asphodeloides Bge. or Mangifera indica L., on diabetic nephropathy and the possible mechanisms by using a developed diabetic nephropathy rat model and cultured rat mesangial cells. Serum‐advanced glycation end‐products level, malonaldehyde level, sorbitol concentration of red blood cell, 24 h albuminuria excretion were significantly decreased, whereas activity of serum superoxide dismutase and glutathione peroxidase and creatinine clearance rate were increased by mangiferin. Blood glucose level remained unaffected. Mangiferin significantly inhibited glomerular extracellular matrix expansion and accumulation and transforming growth factor‐beta 1 overexpression in glomeruli of diabetic nephropathy rats. Moreover, mangiferin was observed to inhibit proliferation of mesangial cells induced by high glucose and the overexpression of collagen type IV of mesangial cells induced by advanced glycation end products. In summary, mangiferin could significantly prevent progression of diabetic nephropathy and improve renal function. Copyright © 2009 John Wiley & Sons, Ltd.     

Murraya paniculata (L.) (Orange Jasmine): Potential Nutraceuticals with Ameliorative Effect in Alloxan‐Induced Diabetic Rats

Orange jasmine, Murraya paniculata (Rutaceae), is a plant from India widely used in folk medicine as antinociceptive, antiinflammatory, and antioxidant. Although oral hypoglycemic agents and insulin are the mainstays of treatment of diabetes mellitus (DM), there is a significant demand for new natural products to reduce the development of diabetic complications. Alloxan‐induced diabetic rats were treated for 60 days with a hydroalcoholic extract of M. paniculata (MPE), at doses of 100, 200, and 400 mg/kg. MPE decreased glycemia and also cholesterol and triglyceride levels, starting 1 week after treatments, as compared with the same group before treatments. Glucose values were reduced toward normality after 1 week of treatment. MPE hypoglycemic effects were potentiated by glibenclamide and metformin. MPE also decreased fructosamine and glycated hemoglobin values. MPE reduced diabetes‐induced morphological alterations of the kidney, pancreas, and liver. MPE acts similarly to glibenclamide and metformin, and its glucose‐lowering action is partly a consequence of ATP‐sensitive K⁺ channel inhibition. MPE may be a potential therapeutic alternative for the treatment of diabetes and its complications. Copyright © 2017 John Wiley & Sons, Ltd.     

The Effects of Pycnogenol® as Add‐on Drug to Metformin Therapy in Diabetic Rats

The progression of diabetes mellitus leads in time to the development of serious cardiovascular complications. Pycnogenol® (PYC) belongs to strong antioxidants that may interfere with different pathways playing an important role in diseases associated with oxidative stress. Metformin (MET), commonly used antidiabetic drug, has cardio‐protective effects via activation of AMP kinase (AMPK). In our study, we examined the effects of PYC as add‐on drug to metformin therapy in streptozotocin (STZ)‐induced diabetic rats. Our results revealed that both used agents, PYC and MET, showed improvement of blood glucose levels, vascular reactivity, left ventricular hypertrophy, expression of AMPK, glucose transporter 4 (GLUT4) and calcium/calmodulin‐dependent protein kinase II (CaMKII) in left ventricle of the hearts. However, the combination of these interventions has failed to possess higher efficacy. Copyright © 2016 John Wiley & Sons, Ltd.     

Amelioration of metformin‐induced hypothyroidism by Withania somnifera and Bauhinia purpurea extracts in Type 2 diabetic mice

An investigation was carried out to reveal the possible ameliorative role of two plant extracts on an antidiabetic drug‐induced hypothyroidism in Type 2 diabetic animals. Dexamethasone (1.0 mg/kg, i.m.) administration caused hyperglycemia with a parallel increase in renal lipid peroxidation (LPO), relative risk ratio (RR), and the concentrations of serum insulin; total cholesterol (TC); low‐density lipoprotein cholesterol (LDL‐C); very low‐density lipoprotein cholesterol (VLDL‐C) and triglycerides (TG). It decreased serum triiodothyronine (T₃), thyroxine (T₄) and high‐density lipoprotein cholesterol (HDL‐C) levels as well as renal superoxide dismutase (SOD); catalase (CAT) and reduced glutathione (GSH) content. Administration with metformin (150 mg/kg, orally) to diabetic animals further reduced circulating T₄ level and caused severe hypothyroidism. It also reduced renal LPO, RR, serum concentrations of insulin; glucose and LDL‐C with a parallel increase in cellular antioxidants. While oral administration with either Withania somnifera (1.4 g/kg) or Bauhinia purpurea (2.5 mg/kg) extract along with dexamethasone and metformin elevated the concentrations of circulating T₃ and T₄ to euthyroid level. The plant extracts also corrected RR ratio and serum concentration of lipids. The findings of the present study, for the first time, reveal that the evaluated plant extracts have a potential to ameliorate metformin‐induced hypothyroidism in Type 2 diabetic subjects. Copyright © 2009 John Wiley & Sons, Ltd.     

Antidiabetic Properties and Mechanism of Action of Orthosiphon stamineus Benth Bioactive Sub-fraction in Streptozotocin-induced Diabetic Rats

Orthosiphon stamineus is a popular folk medicine widely used to treat many diseases including diabetes. Previous studies have shown that the sub-fraction of chloroform extract was able to inhibit the rise of blood glucose levels in a glucose tolerance test. This study was carried out to evaluate the chronic effect and possible mechanism of action of the bioactive chloroform sub-fraction of O. stamineus using streptozotocin-induced diabetic rats and in vitro methods. Administration of the chloroform extract sub-fraction 2 (C?2-b) at a dose of 1 g/kg twice daily on diabetic rats for 14 days showed a significant lowering (p < 0.05) of the final blood glucose level compared to the pretreatment level. However, there were no significant differences in the plasma insulin levels post-treatment compared to the pretreatment levels for all doses of C?2-b. Conversely, C?2-b at a concentration of 2 mg/mL significantly increased (p < 0.001) the glucose uptake by the rat diaphragm muscle. The increase in glucose uptake was also shown when the muscle was incubated in a solution containing 1 IU/mL of insulin or 1 mg/mL of metformin. Furthermore, the effect of this sub-fraction on glucose absorption in the everted rat jejunum showed that C?2-b at concentrations of 0.5 mg/mL, 1 mg/mL and, 2 mg/mL significantly reduced the glucose absorption of the jejunum (p < 0.05–0.001). Similarly, the absorption of glucose was also inhibited by 1 mg/mL and 2 mg/mL of metformin (p < 0.001). These results suggest that the effect of C?2-b may be due to extra-pancreatic mechanisms. There was no evidence that the plant extract stimulated the release of insulin in order to lower the blood glucose level.     

Modulatory Effects of Quercetin and Rutin on the Activity,Expression and Inducibility of CYP1A1 in Intestinal HCT‐8 Cells

Flavonoids, plant secondary metabolites present in fruits and vegetables, show antioxidant and anti‐tumorigenic effects in vitro, but their poor absorption from gastrointestinal tract limits their systemic efficacy in humans. On the other hand, flavonoids could protect intestinal cells against carcinogens by their potential to inhibit the enzymes metabolizing pre‐carcinogenic compounds (e.g. CYP1A) to reactive ones. This work was designed to test the effect of quercetin (the most abundant flavonoid) and rutin (the most abundant glycosidic form) on the activity, expression and inducibility of CYP1A in intestinal HCT–8 cells. CYP1A enzymatic activity was measured by ethoxyresorufin‐O‐deethylase (EROD) activity, CYP1A protein expression was detected by western blotting. The effect of flavonoids on viability of cells was examined by neutral red uptake test. No cytotoxic effect of flavonoids up to 50 μM concentration was observed. Quercetin significantly inhibited EROD activity in the cells, where CYP1A had been preinduced by β‐naphthoflavone and methylcholanthrene, and it also significantly reduced the CYP1A induction mediated by these model inducers. The effect of rutin was substantially weaker and mostly insignificant in all conducted experiments. The results suggest that quercetin may have a potential to limit the CYP1A‐mediated activation of pre‐carcinogens in intestinal cells. Copyright © 2013 John Wiley & Sons, Ltd.     

Effect of Arctiin on Glomerular Filtration Barrier Damage in STZ‐Induced Diabetic Nephropathy Rats

Diabetic nephropathy (DN) is the major life‐threatening complication of diabetes. Abnormal permeability of glomerular basement membrane plays an important role in DN pathogenesis. This study was performed to assess the effect of arctiin, the lignan constituent from Arctium lappa L., on metabolic profile and aggravation of renal lesions in a rat model of streptozotocin (STZ)‐induced DN. STZ‐induced diabetic rats were treated with arctiin at the dosage of 60 or 40 mg/kg/day via intraperitoneal injection for 8 weeks. Blood glucose and 24‐h urinary albumin content were measured, and kidney histopathological changes were monitored. RT‐PCR and immunohistochemistry were used to detect the mRNA and protein levels of nephrin, podocin and heparanase (HPSE) in the kidney cortex of rats, respectively. Treatment with arctiin significantly decreased the levels of 24‐h urinary albumin, prevented the sclerosis of glomeruli and effectively restored the glomerular filtration barrier damage by up‐regulating the expression of nephrin and podocin and down‐regulating HPSE level. Our studies suggest that arctiin might be beneficial for DN. The effects of arctiin on attenuating albuminuria and glomerulosclerosis are possibly mediated by regulating the expression of nephrin and podocin and HPSE in STZ‐induced diabetic rats. Copyright © 2012 John Wiley & Sons, Ltd.     

益肾活血胶囊对糖耐量低减大鼠的血糖及空腹血清胰岛素水平的影响

目的：研究益肾活血胶囊（yishenhuoxue capsule,YSHXC）、二甲双胍（metformin,met）对D-半乳糖（D-galactose,D-gal）诱导大鼠糖耐量减退（Impaired Glucose Tolerance,IGT）的影响。方法：以ip D-gal 150mg kg-1,qd×56d诱导胰岛素抵抗（insulin resistance,IR）,IGT大鼠模型,测其空腹血糖（fasting blood glucose,FBG）和口服葡萄糖耐量试验（Oral Glucose Tolerancetest,OGTT）后2h血糖（2-hours Blood Glucose,2h BG）含量及空腹血清胰岛素水平（fasting serum insulin,FINS）;并观察YSHXC2个剂量、met对病鼠FBG、2h BG及FINS的效应。结果：正常对照组、YSHXC 2个剂量和met与模型组相比较,FBG均未见明显影响,差异未见显著性（P〉0.05）;而OGTT后2hBG,模型组明显高于正常对照组（P〈0.01）,说明D-gal致大鼠IGT模型成立;YSHXC 2个剂量和met均能抑制OGTT后2h BG的升高,差异均有高度显著性（P〈0.01）,FBG与OGTT后2H BG间差值降低,差异均有高度显著性（P〈0.01）,同时YSHXC 2个剂量同模型组相比均降低了病鼠的FINS水平,差异均有高度显著性（P〈0.01）,说明各药均能改善D-gal致IR模型大鼠的IGT。结论：D-gal可诱导以IGT为表现的IR,其机制可能与D-gal诱导蛋白非酶糖基化-氧化应激-自由基损伤作用和直接干扰糖脂代谢有关;益肾活血胶囊与met一样,能改善D-gal诱导IR大鼠的糖耐量以及由糖耐量低减所引起的高胰岛素血症。     

施今墨对药配方对2型糖尿病大鼠氧化应激的影响

目的 观察施今墨对药配方对2型糖尿病大鼠血糖、游离脂肪酸(FFA)和氧化应激的影响,初步探讨其作用机制.方法 随机选取6只Wistar大鼠作为正常组,余44只采用高脂高糖饲养+腹腔注射链脲佐菌素(35 mg/kg)方法制备2型糖尿病大鼠模型,将造模成功大鼠随机分为模型组、二甲双胍组及施今墨对药配方高、中、低剂量组,二甲...     

丹参注射剂体内外对糖尿病状态下肾小管AT1表达的影响

目的探究丹参注射剂体内外对糖尿病状态下肾小管AT1表达的影响。方法采用高糖培养基培养NRK-52E,Western blot检测AT1蛋白表达。高糖高脂联合STZ建立糖尿病大鼠模型,大鼠随机分为正常组、模型组、氯沙坦组(20 mg/kg)、丹参注射液组(2 mL/kg),腹腔注射丹参注射剂,1次/d,给药6周。BCA法检测尿蛋白水平、自动生化仪分析检测血尿素氮(BUN)和血清肌酐(Scr)水平,HE染色观察肾脏结构,IHC和Western blot检测AT1蛋白表达。结果丹参注射液可以抑制高糖环境下NRK-52E和糖尿病大鼠肾小管AT1表达的上调(P<0.05,P<0.01),改善糖尿病大鼠24 h尿蛋白排泄(P<0.01),降低血尿素氮(BUN)和血清肌酐(Scr)水平(P<0.01),减轻糖尿病大鼠肾小管病变。结论丹参注射液对糖尿病肾病改善作用可能与抑制AT1表达及改善肾素-血管紧张素系统有关。     

3‐O‐Acetyloleanolic Acid Induces Apoptosis in Human Colon Carcinoma Hct‐116 Cells

The cytotoxic effect of 3‐O‐acetyloleanolic acid, an oleanolic acid derivative isolated from the seeds of Vigna sinensis K., was investigated in human colon carcinoma HCT‐116 cells. 3‐O‐acetyloleanolic acid dose‐dependently inhibited the viability of HCT‐116 cells. Apoptosis was characterized by detection of cell surface annexin V and sub‐G1 apoptotic cell populations. The number of immunostained cells with annexin V‐FITC was increased after treatment with 3‐O‐acetyloleanolic acid. The sub‐G1 cell population was also increased. Expression of TRAIL‐mediated apoptosis signaling‐related death receptor DR5 was increased in 3‐O‐acetyloleanolic acid‐treated HCT‐116 cells. Activation of caspase‐8 and caspase‐3, critical mediators of extrinsic apoptosis signaling, was also increased by 3‐O‐acetyloleanolic acid. The results indicate that 3‐O‐acetyloleanolic acid induces apoptosis in HCT‐116 cells mediated by an extrinsic apoptosis signaling cascade via up‐regulation of DR5. Copyright © 2012 John Wiley & Sons, Ltd.     

Effects of three different doses of a fruit extract of Terminalia chebula on metabolic components of metabolic syndrome,in a rat model

There is documented evidence of the use of Terminalia chebula for various ailments in the Ayurvedic literature. The extract has been shown to possess glucose lowering activity and to improve insulin sensitivity in animal models of type 2 diabetes mellitus. The present study was carried out to study the dose response relationship of this extract in a rat model of metabolic syndrome. Six groups of rats were fed a high fructose diet (HFD) for a period of 20 days to induce metabolic syndrome. Three doses of fruit extract of T. chebula 50, 100 and 200 mg/kg were administered orally and pioglitazone 2.7 mg/kg was used as a positive control. Blood samples were collected at days 0, 20 and 40 from the tail vein. Systolic blood pressure (SBP) was measured using the tail cuff method and an oral glucose tolerance test (OGTT) was done on the day of blood collection. Administration of HFD for 20 days significantly increased fasting blood glucose (FBG), SBP and the area under the curve of OGTT. On day 40 the FBG in the 50, 100 and 200 mg/kg group was 97.33 ± 5.82 (NS), 86.83 ± 5.08 (p = 0.038) and 85.67 ± 6.74 (p = 0.15), respectively. These results show that the fruit extract of T. chebula exerts a significant and dose‐dependent glucose lowering effect in the rat model of metabolic syndrome. Copyright © 2009 John Wiley & Sons, Ltd.     

复方黄连胶囊对大鼠糖尿病肾病及血液流变学异常的干预作用

目的 探讨复方黄连胶囊(CRCC)对大鼠糖尿病肾病(DN)及血液流变学异常的干预作用.方法 以链脲佐菌素(STZ)复制早期DN大鼠模型,动物分为对照组、模型组、3个CRCC(1.09、2.18、4.36 g/kg)治疗组、消渴丸治疗组,30 d后检测空腹血糖(FBG)、尿素氮(BUN)、肌酐(Scr)、胰岛素(INS)、尿蛋白(Upro)及血液流变学;光镜和电镜观察肾组织形态学和超微结构的改变.结果 与模型组比较,CRCC治疗组糖尿病大鼠FBG、BUN、Scr及Upro水平降低,INS升高;全血黏度、血浆黏度、红细胞聚集指数(AI)、红细胞刚性指数(IR)和纤维蛋白原的量(fib)降低,红细胞压积(HCT)和红细胞变形指数(IED)无变化;肾组织形态学异常和超微结构病变改善.结论 CRCC对早期DN大鼠微血管病变具有明显的干预作用.延缓慢性病理进展,但不能阻断DN,其机制可能与改善血液流变学有关.     

金钗石斛生物总碱对糖尿病大鼠血糖及肝脏组织IRS-2 mRNA，IGF-1 mRNA表达的影响

目的:研究金钗石斛生物总碱(Dendrobium nobile Lindl.alkaloids,DNLA)对糖尿病大鼠血糖及肝脏组织胰岛素受体底物2(IRS-2)mRNA、胰岛素样生长因子1(IGF-1)mRNA表达的影响。方法:雄性SD大鼠高脂、高糖饲料喂养大鼠6周后,1次ip链脲佐菌素(STZ)40 mg·kg-1诱导糖尿病大鼠模型。糖尿病大鼠随机分为模型组,二甲双胍组(二甲双胍100 mg·kg-1)和DNLA 20,40,80 mg·kg-1组。另设正常对照组予基础饲料喂养。给药组每日ig给药1次,连续4周,正常组及模型组ig给予等体积的双蒸水。检测大鼠空腹血糖(FPG)空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR),Real time RTPCR检测大鼠肝脏组织中IRS-2 mRNA,IGF-1 mRNA表达。结果:与正常组比较,模型组FPG,FINS,HOMA-IR明显升高(P<0.05);与模型组比较,二甲双胍组、DNLA 40,80 mg·kg-1组FPG,FINS,HOMA-IR显著降低(P<0.05);与正常组比较,模型组肝脏组织中IRS-2 mRNA,IGF-1 mRNA表达明显减少(P<0.05);与模型组比较,二甲双胍组、DNLA 40,80mg·kg-1组肝脏组织中IRS-2 mRNA,IGF-1 mRNA表达明显增加。结论:DNLA能降低糖尿病大鼠血糖,其机制可能与其上调肝脏组织IRS-2 mRNA,IGF-1 mRNA表达,减轻胰岛素抵抗有关。