蒺藜皂苷对大鼠小肠α-葡萄糖苷酶的抑制作用

目的:研究蒺藜皂苷(STT)对大鼠小肠α-葡萄糖苷酶的抑制作用及对餐后血糖水平的影响。方法:提取大鼠小肠α-葡萄糖苷酶,测定STT对其活性的抑制作用;一次性灌胃蔗糖(2 g.kg^-1)或葡萄糖(2 g.kg^-1),同时灌胃STT(100 mg.kg^-1),测定60 min后血糖水平的变化;每天一次性灌胃STT(100 mg.kg^-1),连续14 d,测定小肠α-葡萄糖苷酶活性以及灌胃蔗糖(2 g.kg^-1)60 min后血糖水平的变化。结果:0.1,1,10 mg.mL^-1的STT能够显著抑制α-葡萄糖苷酶的体外活性(P<0.001),抑制率分别为(20.83±1.66)%,(43.73±2.39)%和(52.62±2.69)%;STT显著抑制大鼠一次性灌胃蔗糖60 min后血糖水平的升高(P<0.01),变化幅度为对照的(52.61±6.24)%,但对灌胃葡萄糖没有作用;连续灌胃STT 14 d后,α-葡萄糖苷酶活性显著低于对照(P<0.05),为对照的(58.17±3.24)%,灌胃蔗糖60 min后血糖变化幅度为对照的(69.50±4.28)%(P<0.05)。结论:STT抑制大鼠餐后血糖水平的升高,是由其对小肠α-葡萄糖苷酶的抑制作用实现的。     

alpha-Glucosidase inhibitory activity of the methanolic extract from Tournefortia hartwegiana: an anti-hyperglycemic agent

Tournefortia hartwegiana is a Mexican medicinal plant that is used for the treatment of diabetes, diarrhea and kidney pain. In a previous investigation, the methanolic extract of Tournefortia hartwegiana (METh) showed significant hypoglycemic and anti-diabetic properties on normoglycemic and alloxanized rats. In this context, the purpose of the present study was to establish one of the possible modes of action of METh to induce anti-diabetic activity. METh (310mg/kg) effect on alpha-glucosidase activity was investigated. METh intragastric administration was conducted to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.05) by the extract after substrates administration. On the other hand, METh inhibited alpha-glucosidase activity in vitro, in a concentration-dependent manner (IC(50) of 3.16mg/mL). These results suggest that METh might exert its anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the post-prandial increase of blood glucose. On the other hand, the bio-guided fractionation of this extract led to the isolation of: beta-sitosterol (1), stigmasterol (2), lupeol (3), ursolic acid (4), oleanolic acid (5), saccharose (6) and myo-inositol (7), using various chromatographic techniques.     

绿茶提取物对糖尿病大鼠糖耐量的影响及机制研究

目的　研究绿茶提取物对糖尿病大鼠糖耐量的影响及其机制。方法　给糖尿病大鼠口服蔗糖或淀粉和绿茶提取物后 ,观察绿茶提取物对糖尿病大鼠糖耐量的影响 ,并用比色法测定绿茶提取物对α-葡萄糖苷酶 (EC 3.2 .1.2 0 )和α -淀粉酶 (EC 3.2 .1.1)的抑制活性。结果　绿茶提取物可明显改善蔗糖或淀粉负荷糖尿病大鼠的血糖水平。在糖尿病相关酶的抑制试验中 ,绿茶提取物显示有较强的α -葡萄糖苷酶抑制活性 ,其α -葡萄糖苷酶的半抑制浓度(IC50 )值为 0 .13g/L ;绿茶提取物对α-淀粉酶的抑制活性则较弱 ,浓度为 1g/L时 ,其对α -淀粉酶的抑制率为 2 1%。结论　绿茶提取物能够降低糖尿病大鼠糖负荷血糖 ,可能由其对α -葡萄糖苷酶和α -淀粉酶的抑制作用所致     

Insulin releasing and alpha-glucosidase inhibitory activity of ethyl acetate fraction of Acorus calamus in vitro and in vivo

Ethnopharmacological relevance

The radix of Acorus calamus L. (AC) is widely used in the therapy of diabetes in traditional folk medicine of America and Indonesia, and we previously reported the insulin sensitizing activity of the ethyl acetate fraction of AC (ACE).

Aim of the study

To investigate the insulin releasing and alpha-glucosidase inhibitory activity of ACE in vitro and in vivo.

Materials and methods

Insulin releasing and alpha-glucosidase inhibitory effects of different fractions from AC were detected in vitro using HIT-T15 cell line and alpha-glucosidase enzyme. Furthermore, effects of ACE orally on serum glucose were detected in fasted and glucose/amylum challenged normal mice.

Results

AC and ACE increased insulin secretion in HIT-T15 cells as gliclazide did. As in vivo results, ACE (400 and 800 mg/kg) significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2 g/kg glucose loading in normal mice. In addition, ACE as a mixed-type inhibitor inhibited alpha-glucosidase activity in vitro with an IC₅₀ of 0.41 μg/ml, and 100 mg/kg of it clearly reduced the increase of blood glucose levels after 5 g/kg amylum loading in normal mice.

Conclusions

Apart from its insulin sensitizing effect, ACE may have hypoglycemic effects via mechanisms of insulin releasing and alpha-glucosidase inhibition, and thus improves postprandial hyperglycemia and cardiovascular complications.     

蛇菰乙醇提取物降血糖作用的实验研究

目的：探讨蛇菰95%乙醇提取物(SHG)的降血糖作用及其机制。方法：以四氧嘧啶诱导雄性ICR小鼠形成糖尿病模型。用葡萄糖氧化酶法测定血糖浓度,用同位素放射免疫法测定血清胰岛素浓度。给动物口服SHG相当于生药20,30 g·kg^-1体重连续7～10 d,以动物不禁食和禁食2.5 h的血糖水平和口服葡萄糖负荷后的血糖水平,观察SHG对机体血糖及糖耐量的影响；以腹腔注射葡萄糖负荷后的血糖和血胰岛素水平,评价SHG对机体高血糖诱导血胰岛素水平的影响；以口服蔗糖耐量和口服淀粉耐量评价药物对糖吸收的影响。结果：SHG可显著降低正常和糖尿病小鼠的餐后血糖和空腹血糖水平。动物口服蔗糖和口服淀粉耐量实验中,SHG可明显降低并后移蔗糖或淀粉负荷后的血糖峰值,减少血糖-时间曲线下面积(AUC)。动物口服葡萄糖耐量实验中,SHG可显著降低葡萄糖负荷后血糖的峰值,减少AUC。在正常小鼠腹腔注射葡萄糖耐量实验中,SHG组平均血糖上升百分数明显低于对照组,但血胰岛素水平与对照组无明显差异。结论：SHG显著降低正常和糖尿病小鼠的餐后血糖和空腹血糖、改善葡萄糖耐量。SHG控制血糖作用的机制可能与抑制肠道α-葡萄糖苷酶和增强体内葡萄糖代谢有关。     

Effects of Lythrum salicaria in normoglycemic rats

Several extracts from stem and flower of Lythrum salicaria were evaluated for their hypoglycemic activity in rats. Results indicate that ether extracts from stem or flowers at a dose equivalent to 10 g/kg of crude plant material caused a significant reduction in blood glucose 4 h after oral administration and that this effect was associated with an increase of circulating insulin. The effects of extracts on lipid and carbohydrate metabolism were also studied.     

Inhibition of postprandial hyperglycaemia by oolong tea extract (OTE)

Oolong tea extract (OTE) was found to inhibit sucrase from the small intestine and α-amylase. The IC₅₀ values were 0.25 mg/mL and 5.0 mg/mL respectively. The effect of OTE on postprandial hyperglycaemia was investigated in vivo in rats loaded with sucrose, maltose, soluble starch or glucose. OTE suppressed the increase of blood glucose levels in sucrose-, maltose- and glucose-loaded rats, but not in soluble starch-loaded rats. From these results it was assumed that orally administered OTE inhibits intestinal glycosidases, especially sucrase, thereby deterring the digestion of certain amounts of sucrose or maltose, and also inhibits glucose absorption partially, leading eventually to a reduction in blood glucose levels.     

Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats

Postprandial hyperglycemia plays an important role in the development of type 2 diabetes and has been proposed as an independent risk factor for cardiovascular diseases. The flowering part of Punica granatum Linn. (Punicaceae) (PGF) has been recommended in Unani literature as a remedy for diabetes. We investigated the effect and action mechanism of a methanolic extract from PGF on hyperglycemia in vivo and in vitro. Oral administration of PGF extract markedly lowered plasma glucose levels in non-fasted Zucker diabetic fatty rats (a genetic model of obesity and type 2 diabetes), whereas it had little effect in the fasted animals, suggesting it affected postprandial hyperglycemia in type 2 diabetes. In support of this conclusion the extract was found to markedly inhibit the increase of plasma glucose levels after sucrose loading, but not after glucose loading in mice, and it had no effect on glucose levels in normal mice. In vitro, PGF extract demonstrated a potent inhibitory effect on alpha-glucosidase activity (IC50: 1.8 microg/ml). The inhibition is dependent on the concentration of enzyme and substrate, as well as on the length of pretreatment with the enzyme. These findings strongly suggest that PGF extract improves postprandial hyperglycemia in type 2 diabetes and obesity, at least in part, by inhibiting intestinal alpha-glucosidase activity.     

Structures of steroidal alkaloid oligoglycosides, robeneosides A and B, and antidiabetogenic constituents from the Brazilian medicinal plant Solanum lycocarpum

In the course of our studies on antidiabetogenic compounds from natural medicines and medicinal foodstuffs, a methanolic extract of the fruits of Solanum lycocarpum showed an inhibitory effect on the increase of serum glucose levels in oral sucrose-loaded rats. Through bioassay-guided separation, three known steroidal alkaloid oligoglycosides, solamargine (1), solasonine (3), and 12-hydroxysolasonine (5), were isolated from the active fraction together with two new steroidal alkaloid oligoglycosides, robeneosides A (2) and B (4). The major constituents, solamargine (1) and solasonine (3), exhibited an inhibitory effect on the increase of serum glucose levels in oral sucrose-loaded rats. In addition, these compounds suppressed gastric emptying in mice. However, this methanolic extract from S. lycocarpum fruits did not have any effect on intestinal alpha-glucosidase (sucrase and maltase) in vitro. It was concluded that these steroidal alkaloid oligoglycosides, 1 and 3, inhibited the increase of rat serum glucose levels by suppressing the transfer of sucrose from the stomach to the small intestine.     

Alfa-glucosidase-inhibiting activity of some Mexican plants used in the treatment of type 2 diabetes

Type 2 diabetes is an endocrine disease, which accounts for 9% of deaths worldwide. The aim of oral therapy is to reach normoglycemia to prevent later complications. Among glucose-lowering medications, alpha-glucosidase inhibitors delay the absorption of ingested carbohydrates, reducing the postprandial glucose and insulin peaks. In the present study, we tested the butanolic extracts of four Mexican plants with respect to their alpha-glucosidase inhibition activity, without excluding other possible mechanisms of action. The plants Cecropia obtusifolia Bertol., Equisetum myriochaetum Schlecht & Cham, Acosmium panamense (Benth.) Yacolev and Malmea depressa (Baill) R.E. Fries are used in traditional medicine to treat type 2 diabetes. In previous studies, we have demonstrated these plants' hypoglycemic activity and determined the phytochemical composition of their extracts. Our results in n-STZ diabetic rats loaded with maltose showed that Malmea and Acosmium extracts decreased plasma glucose significantly from 30 min on resembling the effect of acarbose. Cecropia extract produced the highest reduction of plasma glucose, and at 90 min, the glucose level was lower than the fasting level, which suggests another mechanism of action. Equisetum did not exert any effect. In vitro assays of alpha-glucosidase activity showed an IC(50) of 14 microg/ml for Cecropia, 21 microg/ml for Malmea, and 109 microg/ml for Acosmium, which were lower than that of acarbose (128 microg/ml). Equisetum did not show any significant effect on this assay, either. These results contribute to understand the mechanism of action of these plants on glucose metabolism.     

Screening for antihyperglycaemic activity in several local herbs of Malaysia

Screening of aqueous extract of Phyllantus niruri (PL), Zingiber zerumbet (ZG), Eurycoma longifolia (TA-a and TA-b) and Andrographis paniculata (AP) to determine their blood glucose lowering effect were conducted in normoglycaemic and Streptozotocin-induced hyperglycaemic rats. Significant reduction in blood glucose level at 52.90% was shown when hyperglycaemic rats were treated with 50 mg/kg body weight (BW) aqueous extract of AP. This effect is enhanced when freeze-dried material was used, where 6.25 mg/kg BW gave 61.81% reduction in blood glucose level. In the administration of TA-a and TA-b, positive results in hyperglyacaemic rats were only obtained when 150 mg/kg BW of the aqueous extract was used. No significant reduction in blood glucose level were shown in hyperglycaemic rats treated with PL and ZG at all concentrations used (50, 100 and 150 mg/kg BW). In normoglycaemic rats, no significant reduction was noted when all the same extracts were used.     

Antihyperglycaemic effect of Mangifera indica in rat.

The leaves of Mangifera indica are used as an antidiabetic agent in Nigerian folk medicine. To determine whether or not there is a scientific basis for this use, the effect of the aqueous extract of the leaves on blood glucose level was assessed in normoglycaemic, glucose - induced hyperglycaemic and streptozotocin (STZ)-induced diabetic rats. The aqueous extract given orally (1 g/kg) did not alter the blood glucose levels in either normoglycaemic or STZ-induced diabetic rats. In glucose - induced hyperglycaemia, however, antidiabetic activity was seen when the extract and glucose were administered simultaneously and also when the extract was given to the rats 60 min before the glucose. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity. This action may be due to an intestinal reduction of the absorption of glucose. However, other different mechanisms of action cannot be excluded.     

桃胶多糖降糖机制研究

目的:研究桃胶多糖降低糖尿病大鼠血糖的可能机制。方法:采用水提、梯度醇沉的方法提取3种桃胶多糖,小剂量四氧嘧啶+高糖饲料复制糖尿病模型,桃胶多糖按4 g(/kg.d)晚上灌胃,阿卡波糖作为对照2周后,测定空腹血糖、胰岛素(Ins)、C肽、餐后2 h血糖;分别予淀粉、蔗糖、麦芽糖混合桃胶多糖灌胃后测定0、10、30、60、90、120 min血糖水平。结果:桃胶多糖不能被消化酶分解;与模型组相比,3种桃胶多糖均能降低糖尿病大鼠空腹及餐后血糖水平(P<0.05),Ins及C肽差异无统计学意义(P>0.05);3种分子量桃胶多糖降糖效果差异无统计学意义(P>0.05);与对照组相比桃胶多糖能延缓餐后血糖升高水平。结论:桃胶多糖降糖机制可能与抑制消化酶活性,延缓葡萄糖吸收相关。     

Hypoglycemic effects of aqueous extract of Rhizoma Polygonati Odorati in mice and rats

Water soluble extract of Rhizoma Polygonati Odorati (RPO) was studied for its hypoglycemic effect in diabetic mice and rats. Results showed that RPO significantly lowered hyperglycemia caused by starch loading in both normal and diabetic mice. Four week's administration with RPO reduced fasting blood glucose, decreased glycosylated hemoglobin (GHb), and improved the glucose tolerance in diabetic mice. In diabetic rats complicated with hyperlipemia, RPO prevented and reduced both hyperglycemia and hypertriglyceridemia. The results support the view that RPO may influence glucose or carbohydrate metabolism of diabetic animals in many ways including inhibiting the activity of alpha-glucosidase in digestive canal, and improving the metabolism of glucose and triglyceride.     

Hypoglycemic effect of Rehmannia glutinosa oligosaccharide in hyperglycemic and alloxan-induced diabetic rats and its mechanism

The hypoglycemic and anti-diabetic effect of Rehmannia glutinosa oligosaccharide (ROS) in glucose-induced hyperglycemic and alloxan-induced diabetic rats and its mechanism was investigated in this paper. It was found that pretreatment of ROS in normal rats with 100 mg/kg for 3 days, i.p., induced a partial prevention of hyperglycemia caused by glucose (2g/kg, i.p.), while when hyperglycemia was induced in adrenalectomized (ADX) rats, the preventive effect of ROS on hyperglycemia was lost. In alloxan-induced diabetic rats, ROS (100 mg/kg for 15 days, i.p.) showed a significant decrease in blood glucose level and hepatic glucose-6-phosphatase activity with an increase in hepatic glycogen content. Furthermore, ROS raised plasma insulin level and lowered plasma corticosterone level in alloxan-induced diabetic rats. The results indicated that oligosaccharide of Rehmannia glutinosa Libosch. exerted a significant hypoglycemic effect in normal and alloxan-induced diabetic rats. The regulatory mechanism of ROS on glucose metabolism was adrenal dependent and had a close relation with the neuroendocrine system.     

Insulin sensitizing property of Indigofera mysorensis extract

Indigofera mysorens is a shrub used for its antidiabetic activity in rural India. Here, we elucidate the antidiabetic potential of Indigofera mysorensis extract. Ethanolic extract of the whole shrub of Indigofera (EEI) at 300 mg/kg for 10 days, produced a 63% reduction in plasma glucose, 41% reduction in plasma triglyceride and 77% reduction in plasma insulin levels in insulin resistant db/db mice, which is better than insulin sensitizer, troglitazone (400 mg/kg). EEI unlike sulphonylureas failed to show any acute hypoglycemic effect in normoglycemic Swiss albino mice (SAM). Even in a chronic study (10 days) in SAM, EEI (300 mg/kg) like insulin sensitizers showed no effect on plasma glucose, but an 81% reduction in plasma insulin levels. When challenged with 3 gm/kg sucrose, SAM treated with EEI (300 mg/kg, 7 days) failed to show any effect on the absorption of sugar, whereas standard drug, acarbose (10 mg/kg) showed 52% reduction in the area under the plasma glucose curve. EEI failed to show any significant transactivation of PPARgamma, a proposed target of synthetic insulin sensitizers. Taken together, our data indicate that the antidiabetic effect of the ethanolic extract of Indigofera is due to its insulin sensitizing property and is clearly different from that of sulfonylurea or acarbose.     

香椿总黄酮降血糖作用的实验研究

目的:研究香椿总黄酮(TSTF)对糖尿病小鼠动物模型的降血糖作用.方法:将四氧嘧啶用NS配成0.02 g/ml,按200 mg/kg注射到小鼠腹腔;连续2 d用葡萄糖灌胃(2 g/kg),早晚各一次,以葡萄糖氧化酶法测空腹血糖,大于11.00 mmol/L为造模成功小鼠.将入选小鼠随机分为模型组、TSTF低、高剂量组(0.06、0.12 g/kg)、降糖灵组(0.10 g/kg),另取20只正常小鼠为对照组(蒸馏水),灌胃1次/d,连续15 d,第16 d用葡萄糖氧化酶法测空腹血糖.结果:TSTF组四氧嘧啶小鼠血糖显著降低.结论:TSTF对四氧嘧啶所敛糖尿病模型小鼠有降血糖作用.     

Hypoglycaemic effect of Musa sapientum L. in alloxan-induced diabetic rats

Musa sapientum L. ('Ney Poovan') commonly known as 'banana' is mainly used in Indian folk medicine for the treatment of diabetes mellitus. Oral administration of 0.15, 0.20 and 0.25 g/kg of chloroform extract of the Musa sapientum flowers (MSFEt) for 30 days resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in total haemoglobin, but in the case of 0.25 g/kg the effect was highly significant. It also prevents decrease in body weight. Oral glucose tolerance test was also performed in experimental diabetic rats in which there was a significant improvement in glucose tolerance in animals treated with MSFEt and the effect was compared with glibenclamide. Thus the study shows that MSFEt has hypoglycaemic action.     

Hypoglycaemic activity of Scopariadulcis L. extract in alloxan induced hyperglycaemic rats

Scoparia dulcis L. commonly known as 'Sweet Broomweed' is widely used in Indian folk medicine for the treatment of diabetes mellitus. Oral administration of 0.15, 0.30 and 0.45 g/kg body weight of the aqueous extract of the Scoparia dulcis leaves (SLEt) for 45 days resulted in a significant reduction in blood glucose, glycosylated haemoglobin and an increase in total haemoglobin but in the case of 0.45 g/kg body weight the effect was highly significant. The aqueous extract also prevented a decrease in the body weight. An oral glucose tolerance test was also performed in experimental diabetic rats, in which there was a significant improvement in glucose tolerance in animals treated with SLEt and the effect was comparable to that of glibenclamide.     

Improving effects of the extracts from Eugenia uniflora on hyperglycemia and hypertriglyceridemia in mice

EtOH (70%) extracts from the leaves of Eugenia uniflora were separated into six fractions with different polarity and molecular size, i.e. NP-1-NP-6. In an oral glucose tolerance test, NP-1 and 4 inhibited the increase in plasma glucose level. However, in an intraperitoneal glucose tolerance test, such an inhibitory effect was not seen. Thus, the effects of NP-1 and 4 were apparently due to the inhibition of glucose absorption from the intestine. In a sucrose tolerance test, all fractions inhibited the increase in plasma glucose level. In an oral corn oil tolerance test, NP-3 and 4 showed an inhibitory effect on the increase in plasma triglycerides level. On the other hand, NP-3, 4, 5 and 6 inhibited maltase and sucrase activities and all fractions except for NP-1 showed an inhibitory effect on lipase activity dose-dependently. The inhibition of the increase in plasma glucose level by NP-3, 4, 5 and 6 in the oral sucrose tolerance test and the inhibition of the increase in plasma triglycerides by NP-3 and 4 in the oral corn oil tolerance test were apparently due to the inhibition of the decomposition of carbohydrates and fats in the intestine, respectively.