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At least 649 records · Page 36Linked to original sources
PubMed1996

Bioactive saponins and glycosides. II. Senegae Radix. (2): Chemical structures, hypoglycemic activity, and ethanol absorption-inhibitory effect of E-senegasaponin c, Z-senegasaponin c, and Z-senegins II, III, and IV.

Following the characterization of E-senegasaponins a and b and Z-senegasaponins a and b, new bioactive saponins named E-senegasaponin c and Z-senegasaponin c were isolated from Senegae Radix, the root of Polygala senega L. var. latifolia TORREY et GRAY., together with Z-senegins II, III, and IV. The chemical structures of E and Z-senegasaponins c and Z-senegins II, III, and IV were elucidated on the basis of chemical and physicochemical evidence, and the geometrical isomeric structures of the 4"-methoxycinnamoyl and 3",4"-dimethoxycinnamoyl groups in these saponins were found to show tautomer-like behavior under irradiation with fluorescent lamps. E and Z-Senegasaponins c and E and Z-senegins II, III, and IV were found to exhibit hypoglycemic activity in the oral D-glucose tolerance test. (E) and (Z)-Senegins II also showed an inhibitory effect on alcohol absorption in rats.

Absorption↗
PubMed1996

Bioactive saponins and glycosides. III. Horse chestnut. (1): The structures, inhibitory effects on ethanol absorption, and hypoglycemic activity of escins Ia, Ib, IIa, IIb, and IIIa from the seeds of Aesculus hippocastanum L.

Five bioactive triterpene oligoglycosides named escins, Ia, Ib, IIa, IIb, and IIIa were isolated from the seeds of horse chestnut tree, Aesculus hippocastanum L. (Hippocastanaceae). The chemical structures of escins Ia, Ib, IIa, IIb, and IIIa were determine on the basis of chemical and physicochemical evidence, which included selective cleavage of the glucuronide linkage using photochemical reaction and lead tetraacetate decarboxylation reaction. Escins Ia, Ib, IIa, and IIb were found to exhibit an ethanol absorption-inhibitory effect and hypoglycemic activity in the oral glucose tolerance test in rats. Some structure-activity relationships are reported.

Animals↗
PubMed1996

New hypoglycemic constituents in "gymnemic acid" from Gymnema sylvestre.

Investigation of hypoglycemic activity of major saponin constituents from "gymnemic acid", a crude saponin fraction of G. sylvestre, exposed not only two new saponins, gymnemosides a (1) and b (2), but also gymnemoside b and gymnemic acid V (7) as active principles. Furthermore, an acetyl group linked 16- or 22-hydroxy group in 1 and 2 was found to migrate easily to primary 28-hydroxyl group, while acyl migration from 28-hydroxy group in 3 was little observed.

Animals↗
PubMed1997

Novel benzoxazole 2,4-thiazolidinediones as potent hypoglycemic agents. Synthesis and structure-activity relationships.

A new series of benzoxazole 2,4-thiazolidinediones was synthesized and evaluated for hypoglycemic activity in genetically obese and diabetic yellow KK mice. 2-Arylmethyl- and 2-(heteroarylmethyl)benzoxazole derivatives showed far more potent activity than known 2,4-thiazolidinedione derivatives such as ciglitazone, troglitazone and pioglitazone. A facile synthesis of benzoxazole 2,4-thiazolidinediones was also established using aminophenol 2,4-thiazolidinedione (11) as a key intermediate. Details of synthesis and structure-activity relationships for this series are described.

Animals↗
PubMed1998

Antidiabetic principles of natural medicines. III. Structure-related inhibitory activity and action mode of oleanolic acid glycosides on hypoglycemic activity.

We examined the structure-related activity of oleanolic acid glycosides with respect to their inhibitory effect on the increase in serum glucose in oral glucose-loaded rats and their mechanism of action using oleanolic acid 3-O-glucuronide and momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 3-O-glucuronide was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety reduced such activity. Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the increase in serum glucose in oral glucose-loaded rats, did not lower serum glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and also inhibit glucose uptake in the rat small intestine in vitro. These results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity. They exhibit their hypoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.

Administration, Oral↗
PubMed2001

Medicinal flowers. III. Marigold. (1): hypoglycemic, gastric emptying inhibitory, and gastroprotective principles and new oleanane-type triterpene oligoglycosides, calendasaponins A, B, C, and D, from Egyptian Calendula officinalis.

The methanolic extract and its 1-butanol-soluble fraction from the flowers of Calendula officinalis were found to show a hypoglycemic effect, inhibitory activity of gastric emptying, and gastroprotective effect. From the 1-butanol-soluble fraction, four new triterpene oligoglycosides, calendasaponins A, B, C, and D, were isolated, together with eight known saponins, seven known flavonol glycosides, and a known sesquiterpene glucoside. Their structures were elucidated on the basis of chemical and physicochemical evidence. The principal saponin constituents, glycosides A, B, C, D, and F, exhibited potent inhibitory effects on an increase in serum glucose levels in glucose-loaded rats, gastric emptying in mice, and ethanol- and indomethacin-induced gastric lesions in rats. Some structure-activity relationships are discussed.

Animals↗
PubMed1997

[Studies on compounds with antioxidant activity--development of hypoglycemic agents, troglitazone (CS-045)].

An interest in compounds having both the quenching activity of the active oxygen species (antioxidant activity) and hypoglycemic and/or hypolipidemic activities significantly increases in the field of angiopathic disease, especially in the elderly. We studied hindered phenols in order to find biologically active compounds having the above activities. As a result, several compounds, such as 1,3-benzoxathioles, phenoxypentanoic acids, phenoxypentanols, 2-chloro-3-phenylpropionic acids, and thiazolidines, were found. Among these compounds, a thiazolidine, troglitazone, (CS-045), 1, showed desired biological properties both in vitro and in vivo without causing any increase in liver weight, and so was developed as a new type of antidiabetic agent. In this review, the structural design and the biological activities including antioxidant activities are described.

Animals↗
PubMed2003

Optimum hypoglycemic therapy can improve coronary flow velocity reserve in diabetic patients: demonstration by transthoracic doppler echocardiography.

The purpose of this study was to determine whether the elimination or the alleviation of hyperglycemia would improve coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). CFVR was measured by TTDE in the left anterior descending coronary artery in 49 poorly controlled diabetic patients before and after antidiabetic treatment and 15 well controlled diabetic patients also underwent the same measurements. The fasting blood glucose level in the poorly controlled patients reduced from 270 +/-106 mg/dl to 116+/-39 mg/dl at 20+/-15 days after the intensive treatment. Although baseline coronary flow velocity (CFV) did not change between the 2 measurements (19.9+/-6.9 cm/s vs 19.0+/-5.4 cm/s, p=NS), the hyperemic CFV increased significantly after the treatment (47.3+/-13.4 cm/s vs 55.4+/-13.2 cm/s, p<0.001). Thus, the CFVR improved significantly after the treatment (2.47+/-0.55 vs 2.98+/-0.56, p<0.001). Although there was minimal improvement in the control group (2.37+/-0.38 vs 2.50+/-0.37, p<0.05), the improvement in CFVR was significantly greater in the poorly controlled patients with intensive treatment (0.51+/-0.33 vs 0.12+/-0.19, p<0.001) than that in the control group. These results suggest that optimal hypoglycemic therapy is important to improve the CFVR in poorly controlled diabetic patients.

Aged↗
PubMed1989

The oral hypoglycemic activity of 2,5-dioxamide derivatives of 1,3,4-thiadiazole.

Dioxamide derivatives of 1,3,4-thiadiazole, synthesized earlier by Oke (1986), were screened for hypoglycemic activity. Alloxan-induced diabetic albino rats were used in the study. The structure-activity relationship of the dioxamide derivatives of 1,3,4-thiadiazole is discussed. The study shows that the dioxamide derivatives of 1,3,4-thiadiazole are more potent and of longer duration of action when compared with the oxamide derivatives of 1,3,4-thiadiazole, which were previously reported by Oke and Cherynk (1981).

Administration, Oral↗
PubMed1996

A rapid- and short-acting hypoglycemic agent KAD-1229 improves post-prandial hyperglycemia and diabetic complications in streptozotocin-induced non-insulin-dependent diabetes mellitus rats.

We investigated therapeutic effects of a rapid- and short-acting non-sulfonylurea hypoglycemic agent, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate dihydrate (KAD-1229), on streptozotocin (STZ)-induced non-insulin-dependent diabetes mellitus (NIDDM) rats. The effects exerted by KAD-1229 on the post-prandial plasma glucose rise in STZ-induced mild NIDDM (mNIDDM) rats were different from those of sulfonylureas. When KAD-1229 with liquid meal (10 kcal/kg) was given to the mNIDDM rats, the plasma glucose migration was similar to that of normal healthy rats. On the contrary, glibenclamide had little or no effect on the plasma glucose rise 0.5-1 hr after oral administration, and its effect was only evident 2-5 hr after dosing. Tolbutamide showed similar hypoglycemia to that induced by glibenclamide at 2-5 hr with insufficient efficacy at 0.5 hr. Gliclazide sufficiently suppressed the level of post-prandial plasma glucose. However, its complete inhibition of post-prandial plasma glucose was associated with the extra-hypoglycemia 1-5 hr after oral administration. We also tested the efficacy of KAD-1229 in more severe STZ-induced NIDDM (sNIDDM) rats to elucidate the effects of the drug on the long-term glycemic controls and diabetic complications. When the sNIDDM rats were treated with 10 mg/kg KAD-1229 twice a day for about 17 weeks, increases in fasting plasma glucose and hemoglobin A1c were inhibited. Furthermore, treatment with KAD-1229 suppressed the development of microalbuminuria and cortical cataract. We conclude that the rapid- and short-acting insulinotropic agent KAD-1229 is able to improve the deterioration in the glycemic controls and inhibit the development of diabetic complications in STZ-induced NIDDM rats.

Albuminuria↗
PubMed2006

The novel hypoglycemic agent YM440 improves hepatic insulin resistance in obese Zucker fatty rats.

The novel hypoglycemic agent YM440 ((Z)-1,4-bis{4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl] phenoxy}but-2-ene) is a ligand of the peroxisome proliferator-activated receptor (PPAR) gamma. YM440 has unique pharmacological profiles both in vitro and in vivo, but, it is not clear whether the compound has a significant effect on hepatic or peripheral insulin response throughout the body. The aim of this study is to examine the effects of YM440 on hepatic and peripheral insulin resistance in Zucker fatty (ZF) rats using the euglycemic-hyperinsulinaemic clamp technique. Treatment of ZF rats with YM440 (300 mg/kg per day) for 2 weeks significantly decreased plasma concentrations of glucose and insulin without inducing obesity. YM440 caused a 2-fold increase in the glucose infusion rate during euglycemic clamping compared with the vehicle control. YM440 also decreased the percent change in hepatic glucose production rate caused by intravenous insulin infusion in ZF rats. YM440 had no significant effect on the glucose disposal rate. These results indicate that YM440 ameliorates hepatic, but not peripheral insulin resistance in ZF rats. These findings strongly suggest that the main target organ of YM440 is the liver, unlike other PPARgamma agonist.

Algorithms↗
PubMed1996

Hypoglycemic effect of extracts from Lagerstroemia speciosa L. leaves in genetically diabetic KK-AY mice.

The hypoglycemic effects of Lagerstroemia speciosa L., known by the Tagalog name of banaba in the Phillipines, were studied using hereditary diabetic mice (Type II, KK-AY/Ta Jcl). The mice were fed a test diet containing 5% of the hot-water extract (HWE) from banaba leaves, 3% of the water eluent of the partial fraction unadsorbed onto HP-20 resin of HWE (HPWE), and 2% of the methanol eluent of the partial fraction adsorbed onto HP-20 resin of it (HPME) for a feeding period of 5 weeks. The elevation of blood plasma glucose level in non-insulin dependent diabetic mice fed the cellulose as control (CEL) diet were almost entirely suppressed by addition of either HWE or HPME in place of cellulose in the CEL diet. Water intakes were inclined to increase gradually in the group fed either CEL or HPWE, but lower in the mice fed either HWE or HPME than in the animals given either CEL or HPME. The level of serum insulin and the amount of urinary excreted glucose were also lowered in mice fed HWE. Plasma total cholesterol level was also lowered in mice fed the either HWE or HPME. It is suggested that HWE, especially HPME, obtained from banaba leaves have beneficial effects on control of the level of plasma glucose in non-insulin dependent diabetes mellitus.

Animals↗
PubMed2002

Hypoglycemic effect of a Lentinus edodes exo-polymer produced from a submerged mycelial culture.

The hypoglycemic effect of an exo-polymer produced from a submerged mycelial culture of Lentinus edodes was investigated in streptozotocin-induced diabetic rats. The administration of the exo-polymer (200 mg/kg BW) reduced the plasma glucose level by as much as 21.5%, and increased plasma insulin by 22.1% as compared to the control group. It also lowered the plasma total cholesterol and triglyceride levels by 25.1 and 44.5%, respectively. Gel chromatography of the exo-polymer revealed a single peak which is likely to have been a glycoprotein with a molecular weight of 52 kDa and was found to contain 83.5% carbohydrate and 16.5% protein. The Sugar and amino acid compositions of the exo-polymer were analyzed in detail.

Administration, Oral↗
PubMed2006

Enhanced hypoglycemic activity following intratracheal administration of insulin microcrystal suspension with injection adjuvant.

The pulmonary route appears to be the most attractive alternative for non-invasive systemic delivery of insulin. We have shown the feasibility of insulin microcrystals as a long-acting formulation for pulmonary delivery. In this study, we examined the effects of adjuvant for pulmonary formulations of insulin, such as protamine, zinc, and glycerol. In an in vivo experiment with rats, only zinc enhanced the hypoglycemic effect of insulin microcrystals, with 17% of minimum reductions in blood glucose (%MRBG) and a 44% decrement in the blood glucose level (D%9h).

Adjuvants, Pharmaceutic↗
PubMed2006

Depression in patients with type 2 diabetes: impact on adherence to oral hypoglycemic agents.

BACKGROUND: Adherence to oral hypoglycemic agents (OHAs) is important for adequate glycemic control and prevention of future complications in patients with type 2 diabetes. OBJECTIVE: To examine the impact of depression on adherence to OHAs in patients newly diagnosed with type 2 diabetes. METHODS: Patients newly diagnosed with type 2 diabetes during a 4 year period were identified from a Medicaid claims database. Presence of preexisting depression was determined on the basis of ICD-9-CM codes. Adherence to OHAs was computed using prescription refill data for a 12 month follow-up period from the date of the index OHA prescription. Two separate adherence indices (Medication Possession Ratio-1 [MPR-1], Medication Possession Ratio-2 [MPR-2]) were computed. The impact of depression on adherence was assessed after controlling for confounders such as demographics, comorbidity, provider interaction, complexity of regimen, and diabetes severity. RESULTS: A total of 1326 newly diagnosed patients with type 2 diabetes were identified (depressed = 471; nondepressed = 855). Results of the study indicated that patients with depression had significantly lower adherence (MPR-1 86%; MPR-2 66%) to OHAs compared with patients without depression (MPR-1 89%; MPR-2 73%). Multivariate results indicated that depression was a significant predictor of adherence, with depressed patients being 3-6% less adherent to OHAs than nondepressed patients, after controlling for confounding factors. CONCLUSIONS: Depression significantly impacts adherence to OHAs in patients with type 2 diabetes. The study results imply that depression screening and treatment need to be included in the protocol for management of patients with type 2 diabetes.

Administration, Oral↗
PubMed2004

Hypoglycemic and antihyperglycemic effect of Semecarpus anacardium Linn in normal and streptozotocin-induced diabetic rats.

The effect of ethanolic extract of dried nuts of Semecarpus anacardium on blood glucose was investigated in both normal (hypoglycemic) and streptozotocin-induced diabetic (antihyperglycemic) rats. The blood glucose levels were measured at 0, 1, 2 and 3 h after the treatment. The ethanolic extract of S. anacardium (100 mg/kg) reduced the blood glucose of normal rats from 85.83 +/- 1.55 to 65.83 +/- 2.20 mg/dl, 3 h after oral administration of the extract (p < 0.05). It also significantly lowered blood glucose levels in streptozotocin-induced diabetic rats from 335.33 +/- 4.90 to 132.17 +/- 4.49 mg/dl, 3 h after oral administration of the extract (p < 0.05). The antihyperglycemic activity of S. anacardium was compared with tolbutamide, a sulfonyl urea derivative used in diabetes mellitus.

Animals↗
PubMed1980

Syntheses and hypoglycemic activities of ethyl esters and various amides of omega-guanidino fatty acids with medium chain length.

The omega-guanidino fatty acids C6-C12 were prepared by amidination of the corresponding omega-amino acids. omega-Amino acids C7-C10 which are not available commercially, were obtained by use of Hofmann degradation of the next higher dicarboxylic monoamid monoethyl esters. For use in biological tests, the omega-guanidino fatty acids were converted into ethyl esters, dimethylamides, sometimes also into methyl- or diethylamides. In isolated fat cells these compounds inhibit glucose oxidation. The inhibition increases with increasing chain length. For example, glucose oxidation (control 100%) is diminished by the dimethylamides of 9-guanidinononanoic acid to 70%, of 10-guanidinodecanoic acid to 62%, of 11-guanidinoundecanoic acid to 17% and of 12-guanidinododecanoic acid to 12%. The same compounds -- except the ethyl esters--depress the blood glucose levels in mice after intraperitoneal injection. Blood glucose levels between 30 and 10 mg/100 ml are reached and convulsions are observed. In the mice fall test, ca. 15-30 min post inj., the mice fall down; the blood glucose values of the fallen mice are hypoglycemic. The toxicity of the compounds examined is remarkably high; lethal dose per mouse (20 g) is 3-5 mg for the dimethylamides. It is obvious that a relationship exists between the inhibition of glucose oxidation in adipocytes and the depression of blood glucose level. The stronger the inhibition, the stronger the blood glucose lowering effect.

Adipose Tissue↗