Inhibitory effect of total lignan from Fructus Arctii on aldose reductase

The potent inhibitory effect of the total lignan from the plant Fructus Arctii on aldose reductase was observed, suggesting its preventive potential on diabetic complications upon long term administration. Copyright © 2009 John Wiley & Sons, Ltd.     

The effects of hypoglycemia and weight loss of total lignans from Fructus Arctii in KKAy mice and its mechanisms of the activity

Fructus Arctii (great burdock achene) is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and is included in the Chinese pharmacopoeia. It has been reported that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. This study aimed to investigate antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous Type 2 diabetic rodent model that exhibits marked obesity. In this study, KKAy mice were gavaged once daily with solvents (0.5% sodium carboxymethyl cellulose), TLFA (250 and 125 mg/kg), or metformin (200 mg/kg) for 11 weeks, and C57BL/6J mice treated with saline solution (0.9%, w/v) were used as normal control. The results indicate that TLFA has dual effects of hypoglycemia and weight loss, and administration of TLFA in KKAy mice could decrease fasting blood glucose, glycated hemoglobin, and body weight; improve oral glucose tolerance; increase high density lipoprotein cholesterol; and decrease triglycerides and free fatty acid in mice serum. Its efficacy may associate with multiple mechanisms of action such as stimulation of insulin secretion, activation of phosphatidylinositol 3‐kinase/protein kinase B, and adenosine‐monophosphate‐activated protein kinase signaling pathway, decreasing leptin.     

Sedative and hypnotic activities of the ethanol fraction from Fructus Schisandrae in mice and rats

Fruits of Fructus Schisandrae have been used as medicine for the treatment for insomnia in traditional Chinese medicine. In the present research, the sedative and hypnotic activities of the ethanol fraction of Fructus Schisandrae fruit (SY3) were studied in mice and rats. In the open field test, SY3 (25, 50 and 100 mg/kg) significantly inhibited the motor activity of mice compared to the normal. Results also showed SY3 potentiated pentobarbital-induced sleep by not only increasing the number of falling asleep and prolonging sleeping time but also reducing sleep latency. Furthermore, sleep–wake stages of rats were evaluated by polytrophic recording for 3 h after treatment. The results demonstrated that SY3 at doses of 20, 40 and 80 mg/kg behaved remarkable action on sleep architecture of rats, which contain the increase of total sleeping time, the rate of deep slow wave sleep (SWS) and mean episode duration of deep SWS, and the decrease of the latency of deep SWS. Therefore, these results suggest that the ethanol fraction of Fructus Schisandrae fruit possesses potent sedative and hypnotic activity, which supported its therapeutic use for insomnia.     

鹰嘴豆总皂苷对2型糖尿病大鼠血糖及胰腺病理结构的影响

目的:观察鹰嘴豆总皂苷(TSCA)对2型糖尿病大鼠血糖及胰腺病理结构的影响。方法:高糖高脂饲料喂养加链脲佐菌素(STZ)腹腔注射建立2型糖尿病大鼠模型。将造模成功大鼠随机分为模型组和鹰嘴豆总皂苷治疗组,灌胃给药,另设正常对照组,给药2周后,检测空腹血糖值(FPG)、并对胰腺组织进行病理学观察。结果:与模型组相比,鹰嘴豆总皂苷各剂量组均可有效降低2型糖尿病大鼠的血糖,对损伤的胰岛有一定的修复作用。结论:鹰嘴豆总皂苷各剂量组可有效降低2型糖尿病大鼠空腹血糖,并改善损伤胰岛的病理结构。     

Comparison of the antidiabetic activity of Berberis lyceum root extract and berberine in alloxan-induced diabetic rats

Berberine has been shown to have hypoglycaemic activity in several in vitro and in vivo models, although the mechanism of action is not fully known. Berberis lyceum Royle root produces high concentrations of berberine, and in traditional medicine, the whole extract of this plant is used widely to treat diabetes. The antidiabetic activity of the ethanol root extract of Berberis lyceum was compared with pure berberine in normal and alloxan-diabetic rats using similar doses of each. The concentration of berberine in the extract was determined to be 80% dry weight with only trace amounts of other alkaloids present. The purpose of the study was to investigate the effects of berberine and a whole extract of Berberis lyceum on blood glucose and other parameters associated with diabetes, to compare the effects of the crude extract with those of pure berberine and thus validate its use as a therapeutic agent, and finally to identify any contribution of the other components of the extract to these effects. Oral administration of 50 mg/kg of Berberis extract and berberine to normal and experimental diabetic rats produced a significant (p < 0.05) reduction in blood glucose levels from days 3-7 days of treatment. Significant effects were also observed on the glucose tolerance, glycosylated haemoglobin, serum lipid profiles and body weight of experimental animals. Berberis extract and berberine demonstrated similar effects on all parameters measured, and although the extract was comparable in efficacy to berberine, it did not produce any effects additional to those shown by pure berberine. The results support the use of the extract in traditional medicine, and demonstrate that apart from being a highly cost-effective means of treating with berberine, the total extract does not appear to confer any additional benefits or disadvantages compared with the pure compound.     

Evaluation of hypoglycemic activity of total lignans from Fructus Arctii in the spontaneously diabetic Goto-Kakizaki rats

Ethnopharmacological relevance

Fructus Arctii, called “Niubangzi” in China (Great burdock achene in English), is a well-known Chinese Materia Medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions. Meanwhile it has been utilized extensively in a number of classical drug formulas as a major component for the treatment of noninsulin-dependent diabetes mellitus. It has also been reported recently that the clinical use of Fructus Arctii resulted in a satisfactory hypoglycemic effect in diabetic patients. The aim of this study was to investigate hypoglycemic activity of total lignans from Fructus Arctii (TLFA) in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and the mechanism of its hypoglycemic activity.

Materials and methods

Male GK rats and normal Wistar rats were used in this study, GK rats fed twice daily were given TLFA (300 mg/kg) or nateglinide (50 mg/kg) orally before each meal for 12 weeks. Besides common evaluation indexes of hypoglycemic activity such as blood glucose level, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters such as cholesterol (CHOL), triglycerides (TG), et al., in rat serum. The effects of TLFA on insulin secretion and pancreas tissue sections, the levels of serum glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), and the α-glucosidase inhibitory activity of TLFA in vitro were investigated.

Results

TLFA demonstrated stable and long-lasting hypoglycemic activity in GK rats and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. Both TLFA and nateglinide controlled the glycosylated hemoglobin levels of the experimental animals very well. Stimulation of insulin secretion was proved to be one of the hypoglycemic mechanism of TLFA, promoting the release of GLP-1 should be another one, and ɑ-glucosidase inhibitory activity of TLFA also contributes to its hypoglycemic activity. In this study, we didn't found that TLFA could effect the body weight of GK rats, which was also verified by the changes of biochemical parameters of blood in experimental rats.

Conclusion

The results of this study indicates that TLFA has significant hypoglycemic potential in GK rats, and it may be acting through stimulating insulin secretion, promoting the release of GLP-1, and decreasing intestinal absorption of glucose.     

桑椹多糖对实验性2型糖尿病大鼠血糖及血脂的影响

目的:观察桑椹多糖对链脲佐菌素(STZ)和高能量饲料诱发的2型糖尿病(T2DM)模型大鼠血糖、血脂的影响。方法:高糖高脂饲料喂养4周后,ip 30 mg·kg-1STZ建立T2DM大鼠模型,随机分为糖尿病模型对照组、桑椹多糖低剂量组(ig150 mg·kg-1·d-1)、中剂量组(ig 300 mg·kg-1·d-1)、高剂量组(ig 450 mg·kg-1·d-1)及罗格列酮治疗组(ig 4 mg·kg-1·d-1)。持续ig给药60 d后测空腹血糖(FBG)、血脂、糖化血红蛋白(HbAlc)、胰岛素(Ins)的含量。结果:桑椹多糖治疗组与模型组比较,FBG,HbAlc,甘油三酯(TG)、总胆固醇(TCH)及低密度脂蛋白(LDL)水平显著降低(P<0.05),高密度脂蛋白(HDL)和Ins水平显著升高(P<0.05)。结论:桑椹多糖能有效地降低T2DM模型大鼠的血糖,促进Ins分泌,调节血脂。     

桑椹多糖的结构表征及其对乙醇脱氢酶活性的影响研究

该实验采用回流法提取桑椹多糖,经脱蛋白及DEAE-Cellulose 52分离纯化得到4种多糖组分(中性多糖MFP-1,微酸性多糖MFP-2,酸性多糖MFP-3和MFP-4)。通过化学法和仪器分析法对各多糖组分进行理化性质测定和结构表征,并研究其对乙醇脱氢酶(ADH)活性的影响。结果表明,MFP-1,MFP-2,MFP-3和MFP-4中的多糖量分别为75.3%,83.7%,79.1%,74.3%,其平均相对分子质量分别为112.2,128.8,199.5,181.9 k Da。MFP-1主要含有半乳糖、葡萄糖、阿拉伯糖、鼠李糖、甘露糖(26.8∶20.4∶8.7∶5∶1);MFP-2主要含有阿拉伯糖、半乳糖、鼠李糖、葡萄糖、半乳糖醛酸(34.2∶38.2∶8∶17.5∶15.1);MFP-3主要含有半乳糖醛酸、半乳糖、葡萄糖、鼠李糖、阿拉伯糖(28.3∶22.6∶20.9∶18.6∶12.5);MFP-4主要含有葡萄糖、半乳糖、鼠李糖、半乳糖醛酸、阿拉伯糖、葡萄糖醛酸(47.4∶34.9∶36.1∶33.1∶19.9∶4.1)。红外光谱分析结果表明,MFP-1,MFP-2,MFP-3和MFP-4中均有多糖的特征吸收峰,其中MFP-3和MFP-4是以β苷键为主的吡喃型多糖。活性结果表明,4种多糖对ADH均有激活作用,其ADH激活能力顺序为:联苯双酯MFP-3MFP-1MFP-2硫普罗宁MFP-4,MFP-1,MFP-2和MFP-3对ADH的激活作用均大于阳性对照硫普罗宁,同时发现MFP-3对ADH的激活效果与阳性对照联苯双酯的激活效果相当,推测其与之连接的糖醛酸种类有关,这为桑椹多糖的"构-效"研究提供参考依据。     

总丹酚酸对小鼠和大鼠脑缺血再灌注损伤的保护作用

目的：观察总丹酚酸（Sal)对脑缺血再灌注损伤的保护作用。方法：采用小鼠和大鼠脑缺血再灌注模型。结果：在小鼠和大鼠全脑缺血再灌注模型上,Sal10,20mg/kg iv及Sal5,10mg/kgiv可显著提高脑组织乳酸脱氢酶（LDH）及超氧化物歧化酶（SOD）活性,明显降低丙二醛（MDA）含量。在大鼠局灶性脑缺血2h再灌注24h模型上,Sal5,10mg/kgiv可明显缩小梗死灶面积,改善神经功能缺损,并显著抑制缺血脑组织中LDH和SOD活性降低,减少MDA的地量产生。结论：Sal对小鼠和大鼠脑缺血再灌注损伤有显著保护作用,其机制与其抗氧自由基作用有关。     

玉竹对STZ诱导的1型糖尿病小鼠的降糖作用

目的:探讨玉竹对链脲佐菌素(STZ)诱导的1型糖尿病小鼠的降糖作用及其可能的作用机制。方法:采用多次小剂量STZ(mlD-STZ)腹腔注射的方法建立1型糖尿病小鼠模型。玉竹提取物8,4,2g/kg剂量组分别按相应剂量用玉竹提取物灌胃,糖尿病模型组和正常对照组用蒸馏水灌胃0.2ml/只,1次/d,共4周。每周剪尾取血1次,用快速血糖仪监测血糖变化。四周后将小鼠处死取胰腺做HE染色,光镜下观察胰腺病理学改变;采用酶联免疫分析(ELISA)法检测小鼠脾细胞上清液中IFN-γ和IL-4水平。结果:与糖尿病模型组相比,玉竹提取物8g/kg和4g/kg剂量组小鼠血糖明显降低(P<0.01)、胰岛炎程度明显缓解、脾细胞上清液中IFN-γ水平和IFN-γ/IL-4比值明显降低(P<0.05～0.01),而2g/kg剂量组小鼠上述指标变化不明显;各组小鼠脾细胞上清液中IL-4水平差异无统计学意义。结论:玉竹提取物能明显降低STZ诱导的1型糖尿病小鼠的血糖,其降糖机制可能与抑制1型糖尿病小鼠Th1细胞的极化程度,减轻细胞免疫功能对胰岛β细胞的破坏有关。     

草问荆总生物碱对小鼠脑单胺氧化酶-B活性的影响

目的 研究草问荆总生物碱(TAEP)对小鼠脑单胺氧化酶—B(MAO—B)活性的影响，揭示TAEP对中枢神经系统抑制作用的机制。方法 采用紫外分光光度法测定MAO—B的活性。结果 TAEP对小鼠脑MAO—B具有明显的激活作用，并具有对抗烟肼酰胺抑制小鼠脑MAO—B活性的作用。结论 TAEP是MAO—B的激动药，有单胺代谢作用，这可能是TAEP中枢抑制作用的作用机制之一。     

真武汤对肾纤维化大鼠血清和肾脏组织中SOD活力、MDA含量的影响

目的:单侧结扎左肾输尿管建立肾梗阻(unilateral ureteral obstruction,UUO)致肾纤维化模型,探讨真武汤对肾纤维化大鼠血清及肾脏组织中总超氧化物歧化酶(total superoxide dismutase,T-SOD)活力和丙二醛(maleic dialdehyde,MDA)含量的影响。方法:将大鼠随机分为5组,除正常对照组外,采用结扎左侧输尿管的方法建立肾纤维化模型。造模大鼠随机分为4组:模型组、氯沙坦钾组(20mg/kg.d)、真武汤低剂量组(2.1 g生药/kg.d)、真武汤高剂量组(9.8g生药/kg.d),给药28天后腹主动脉取血,检测血清及术侧肾脏组织匀浆液中T-SOD活力及MDA含量。结果 :相比于组织样本,血清中T-SOD活力及MDA含量变化幅度较小,但整体趋势一致:造模大鼠血清及肾脏组织中T-SOD活力和MDA含量较正常组均有所降低,经真武汤治疗后,T-SOD活力趋于正常,与空白对照组相比无显著差异;与模型组相比,真武汤治疗组大鼠肾脏组织中MDA含量上升,但与正常组仍存在一定差异。结论:真武汤可上调UUO大鼠血清及结扎肾脏组织中超氧化物歧化酶活力,对结扎导致的组织细胞损伤也有一定的缓解作用。     

泽泻水提物对正常及高血糖小鼠血糖的影响

泽泻水提物１０ｇ／ｋｇ及２０ｇ／ｋｇｉｇ２天，可使正常小鼠血糖明显降低。２０ｇ／ｋｇ治疗７天或预防给药３天均可使四氧嘧啶小鼠血糖明显降低     

榼藤子总皂苷抗糖尿病作用机制的初步研究

目的:探讨榼藤子总皂苷对2型糖尿病大鼠胰岛形态及骨骼肌PI3K通路相关蛋白表达的影响。方法:通过高脂饲料喂养结合注射小剂量链脲佐菌素(STZ)建立2型糖尿病大鼠模型。实验大鼠随机分为正常对照组、模型组、阳性对照组(二甲双胍,200 mg.kg-1)、榼藤子总皂苷低、高(25,50 mg.kg-1)剂量组。治疗3周后对各组大鼠胰腺HE染色病理切片胰岛形态、数目等进行观察比较,采用Western blot方法检测各组大鼠骨骼肌组织中胰岛素受体底物-1(IRS-1)、磷脂酰肌醇3激酶(PI3K)、蛋白酪氨酸磷酸酶-1B(PTP-1B)和葡萄糖转运子4(GLUT4)等蛋白的表达水平。结果:同模型组相比,榼藤子总皂苷各给药组胰腺组织病理切片均结构相对正常、胰泡细胞清晰可见、被膜结构完整,胰岛数目均接近于对照组;同时上述各给药组大鼠骨骼肌组织中IRS-1,PI3K和GLUT4蛋白表达水平均较模型组有所上调,PTP-1B蛋白表达水平均较模型组有所下调。结论:榼藤子总皂苷对2型糖尿病大鼠胰腺组织具有保护作用,并对骨骼肌组织中蛋白的异常表达具有干预作用。     

Hypoglycemic activity of Ailanthus excelsa leaves in normal and streptozotocin-induced diabetic rats

The hypoglycemic activity of a 70% methanol extract from the leaves of Ailanthus excelsa Roxb. (Simaroubaceae) was studied in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats. Oral administration of the extract at doses of 14, 70 and 350 mg/kg body weight caused no significant changes in fasting blood glucose levels of normal rats. In an oral glucose tolerance test, the extract produced a significant decrease in glycemia 90 min after the glucose pulse. Daily administration of A. excelsa extract for 60 days produced a significant hypoglycemic effect in diabetic animals. In addition, this treatment improved the altered renal function observed in diabetic control rats. This study suggests that Ailanthus leaf extract could be potentially useful for post-prandial hyperglycemia treatment.     

芪蓝糖脂宁胶囊对实验性糖尿病合并高脂血症大鼠糖、脂代谢的影响

目的:探讨芪蓝糖脂宁胶囊降糖、调脂的药理作用,为临床用药提供药效学基础。方法:采用高糖高脂饲料喂饲2个月,小剂量30mg·kg^-1一次性腹腔注射2%链脲佐菌素的方法复制糖尿病合并高脂血症大鼠模型,造模成功后,灌胃给药,观察血糖、血清脂质含量的变化,以及肝脏、胰腺组织病理学改变。结果:芪蓝糖脂宁胶囊能明显降低实验大鼠血糖及血清中总胆固醇、甘油三酯、低密度脂蛋白胆固醇的含量,升高高密度脂蛋白胆固醇的含量,改善肝脏、胰腺的病理损害。结论:芪蓝糖脂宁胶囊具有较好的降低血糖、调节血脂和改善肝脏、胰腺病理损害的作用。     

豁痰祛瘀颗粒对糖尿病大鼠耳蜗形态学干预效应研究

目的:观察豁痰祛瘀颗粒对链脲佐菌素致糖尿病大鼠糖代谢及对糖尿病大鼠早期耳蜗病理组织学的作用.方法:按55 mg·kg-1剂量一次性腹腔注射链脲佐菌素,造成糖尿病大鼠模型,以豁痰祛瘀颗粒治疗,并用都可喜为阳性对照组,观察各组大鼠的血糖、耳蜗病理组织学及超微结构的改变情况.结果:豁痰祛瘀颗粒能降低糖尿病大鼠升高的血糖,减轻糖尿病大鼠早期耳蜗基底膜、血管纹增厚程度,使稀疏的螺旋神经节细胞变致密.结论:豁痰祛瘀颗粒对糖尿病性大鼠模型具有较好的降糖作用,并通过改善受损的耳蜗组织病理学改变,达到治疗的目的.豁痰祛瘀颗粒改善耳蜗微血管病变可能是其改善听力下降的病理学基础.[关健词]豁痰祛瘀颗粒;糖尿病;血糖;耳蜗;病理组织学     

沙棘籽渣黄酮对更年期大鼠血脂及体内抗氧化系统的影响

目的：观察沙棘籽渣黄酮对更年期大鼠血脂及抗氧化能力的影响。方法：以11～15月龄SD大鼠为更年期模型,应用尼尔雌醇和3种剂量的沙棘籽渣黄酮进行灌胃给药,对照组以等体积蒸馏水灌胃。连续给药13周,观察沙棘籽渣黄酮对更年期大鼠血脂及血清和肝脏组织的总抗氧化能力、超氧化物歧化酶和丙二醛的水平。结果：更年期大鼠经灌胃给予沙棘籽渣黄酮后,血清胆固醇水平显著降低（P<0.01）；对血清和肝脏组织的总抗氧化能力、超氧化物歧化酶活性均有提高（P<0.05）,同时降低肝脏组织的丙二醛含量（P<0.01）。结论：沙棘籽渣黄酮可改善更年期大鼠的血脂代谢,并且增强其抗氧化能力。     

山楂总黄酮对复合因素致大鼠脂肪肝模型脂质代谢与低密度脂蛋白受体表达的影响

目的 研究山楂总黄酮对复合因素致大鼠脂肪肝模型脂质代谢与低密度脂蛋白受体(LDL-R)表达的影响.方法 采用复合因素致大鼠脂肪肝动物模型.造模成功后将动物随机分成6组,分别ig给予山楂总黄酮0.3、0.6、1.2 g/kg,东宝甘泰0.6g/kg,模型组和对照组每天ig给予等体积生理盐水.造模后、给药期间、末次给药后分别检测血清内氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(AKP)活性,以及三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)水平;末次给药后检测血液流变学指标和肝组织匀浆TG和TC水平,同时取肝左叶分别用于病理检查观察显微结构变化,RT-PCR和免疫组化检测LDL-R mRNA和蛋白表达.结果 山楂总黄酮作用于复合因素致脂肪肝大鼠模型,其血清中脂质、肝TC和肝TG与模型组比较有显著性降低;血清ALT、AST和AKP活性与模型组比较有显著性降低;山楂总黄酮能明显降低全血黏度(高切和低切)、红细胞聚集指数、红细胞压积以及明显增加红细胞变形指数;病理组织学检查显示,各给药组脂肪变性和炎症反应程度较模型组均有一定的减轻.RT-PCR和免疫组化结果显示,模型组大鼠肝组织LDL-R mRNA和蛋白表达与对照组比较显著降低(P＜0.05).山楂总黄酮和东宝甘泰对复合因素致脂肪肝模型大鼠肝组织LDL-RmRNA和蛋白表达降低有明显抑制作用.结论 山楂总黄酮可能通过调节脂肪代谢、改善肝脏功能和增加LDL-R mRNA和蛋白的表达,起到治疗大鼠脂肪肝的作用.     

山楂叶总黄酮对糖尿病小鼠糖脂代谢的影响

目的研究山楂叶总黄酮对糖尿病小鼠血糖和血脂等生化指标的影响。方法采用四氧嘧啶(45mg/kg)尾iv建立糖尿病小鼠模型,并ig不同剂量的山楂叶总黄酮,给药30d后用生化方法检测相关指标。结果山楂叶总黄酮可明显降低糖尿病小鼠血清中血糖、总胆固醇(TC)、甘油三酯(TG)、丙二醛(MDA)、果糖胺(FA)、山梨醇和大脑脂褐质水平(P<0.01),升高血清高密度脂蛋白-胆固醇(HDL-C)水平(P<0.05),呈剂量效应关系,对由糖尿病引起的肝脏组织脂肪积累有一定的清除作用。结论山楂叶总黄酮具有显著降低糖尿病小鼠血糖和血脂的作用,并对糖尿病并发症和肝脏组织脂肪积累具有一定的防治作用。