Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ANTIDIABETICS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 865 records · Page 48Linked to original sources
PubMed1998

Antidiabetic principles of natural medicines. II. Aldose reductase and alpha-glucosidase inhibitors from Brazilian natural medicine, the leaves of Myrcia multiflora DC. (Myrtaceae): structures of myrciacitrins I and II and myrciaphenones A and B.

The methanolic extract and ethyl acetate-soluble portion from a Brazilian natural medicine, the leaves of Myrcia multiflora DC., which has been used as a specific medicine against diabetes, were found to show inhibitory activities on aldose reductase and alpha-glucosidase and on the increase of serum glucose level in sucrose-loaded rats and in alloxan-induced diabetic mice. From the ethyl acetate-soluble portion, new flavanone glucosides, myrciacitrins I and II, and new acetophenone glucosides, myrciaphenones A and B, were isolated together with several known compounds such as five flavonol glycosides, myricitrin, mearnsitrin, quercitrin, desmanthin-1, and guaijaverin. The structures of new compounds were determined on the basis of physicochemical and chemical evidence. The principal components of this natural medicine including new glucosides, myrciacitrin I and myrciaphenone B, were found to show potent inhibitory activities on aldose reductase and alpha-glucosidase.

Acetophenones↗
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↗
PubMed1998

Na(+)-glucose cotransporter inhibitors as antidiabetic agents. III. Synthesis and pharmacological properties of 4'-dehydroxyphlorizin derivatives modified at the OH groups of the glucose moiety.

To overcome hydrolysis by beta-glucosidase present in the digestive tract, the OH groups on the glucose moiety of the 4'-dehydroxyphlorizin derivatives (1, 2, 3) were modified with various kinds of patterns, and then the effects of the modified compounds on urinary glucose excretion were evaluated in rats. Among them, triacetyl (9), 2,3-O-diacetyl (17), 6-O-methoxycarbonyl (34), 4-O-methoxycarbonyl (38), and 2-O-acetyl (41) derivatives showed more potent effect than the parent compound 2 by oral administration (p.o.). The stabilities of the compounds 34, 38, and 41 against beta-glucosidase were higher than that of 2. The increase in oral activity was found to correlate with the enhancement of the stability against beta-glucosidase.

Animals↗
PubMed1998

Na(+)-glucose cotransporter inhibitors as antidiabetic agents. II. Synthesis and structure-activity relationships of 4'-dehydroxyphlorizin derivatives.

A novel series of 4'-dehydroxyphlorizin derivatives was synthesized and the effects of these compounds on urinary glucose excretion were evaluated in rats. There was a strict structural requirement for activity. Introduction of a small substituent or a flat ring at the 3- and/or the 4-position on the A ring was permissible, but any change at the bridge part between the A and B rings or in the sugar moiety resulted in complete loss of activity. The 6'-OH group on the B ring was also necessary, and even small structural modifications of the 6'-OH group reduced the activity considerably. Among the compounds synthesized, the 5-benzofuryl derivative 25 was the most potent and was selected as a new lead for further structure-activity relationship investigations.

Animals↗
PubMed1999

Antidiabetic principles of natural medicines. IV. Aldose reductase and qlpha-glucosidase inhibitors from the roots of Salacia oblonga Wall. (Celastraceae): structure of a new friedelane-type triterpene, kotalagenin 16-acetate.

The aqueous methanolic extract of an Indian natural medicine, the roots of Salacia oblonga Wall. (Celastraceae), was found to show inhibitory activity on the increase in serum glucose level in sucrose- and maltose-loaded rats. The water-soluble and ethyl acetate-soluble portions from the aqueous methanolic extract showed inhibitory activities on alpha-glucosidase and aldose reductase, respectively. From the water-soluble portion, potent alpha-glucosidase inhibitors, salacinol and kotalanol, were isolated, together with nine sugar related components, while a new friedelane-type triterpene, kotalagenin 16-acetate, was isolated from the ethyl acetate-soluble portion along with known diterpenes and triterpenes. The structure of kotalagenin 16-acetate was elucidated on the basis of physicochemical evidence. Principal components from this natural medicine were examined in terms of inhibitory activity on aldose reductase, and the diterpene and triterpene constituents, including the new kotalagenin 16-acetate, were found to be responsible components for the inhibitory activity on aldose reductase.

Aldehyde Reductase↗
PubMed2002

Antidiabetic principles of natural medicines. V. Aldose reductase inhibitors from Myrcia multiflora DC. (2): Structures of myrciacitrins III, IV, and V.

Following the characterization of myrciacitrins I and II and myrciaphenones A and B, three new flavanone glucosides, myrciacitrins III, IV, and V, were isolated from the leaves of Brazilian Myrcia multiflora. The structures of new myrciacitrins were elucidated on the basis of physicochemical and chemical evidence. Myrciacitrins were found to show potent inhibitory activity on aldose reductase.

Aldehyde Reductase↗
PubMed2003

Studies on non-thiazolidinedione antidiabetic agents. 2. Novel oxyiminoalkanoic acid derivatives as potent glucose and lipid lowering agents.

We previously reported that (Z)-2-(4-[(5-methyl-2-phenyl-1, 3-oxazol-4-yl)methoxy]benzyloxyimino)-2-(4-phenoxyphenyl)acetic acid (3) showed potent glucose and lipid lowering effects in genetically obese and diabetic mice, KKA(y). This compound also showed transcriptional activity for peroxisome proliferator-activated receptor (PPAR)-gamma. We expanded on the structure-activity relationships of oxyiminoalkanoic acid derivatives based on this transcriptional activity (in vitro). Insertion of a carbon chain between the imino carbon and the carboxyl moiety of (Z)-2-(4-[(5-methyl-2-phenyl-1, 3-oxazol-4-yl)methoxy]benzyloxyimino)-2-phenylacetic acid (2) resulted in a marked increase in transcriptional activity at PPARgamma. In vivo potencies of synthesized compounds, which showed strong functional activity at PPARgamma, were tested using KKA(y) mice. Among these compounds, (E)-4-(4-[(5-methyl-2-phenyl-1, 3-oxazol-4-yl)methoxy]benzyloxyimino)-4-phenylbutyric acid (27) exhibited marked glucose and lipid lowering activity while showing no significant body weight gain. Compound (27) (TAK-559) showed favorable pharmacokinetic properties with good absorption and duration, and was considered as an attractive candidate for further evaluation.

Alkenes↗
PubMed2004

Studies on non-thiazolidinedione antidiabetic agents. 3. Preparation and biological activity of the metabolites of TAK-559.

Preparation and biological activity of the metabolites of the potent antihyperglycemic and antihyperlipidemic agent, (E)-4-(4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzyloxyimino)-4-phenylbutyric acid (TAK-559) (1), were investigated. Metabolites M-I (2), M-II (3), M-III (4) and M-IV (5) were synthesized and their biological activities were evaluated by in vitro and in vivo experiments. Compounds 2-4 activate human peroxisome proliferator-activated receptor gamma one (hPPARgamma1) and hPPARalpha, but their activities are weaker than those of TAK-559 (1). Compound 5 only activates hPPARgamma1 weakly. TAK-559 (1) showed potent in vivo plasma glucose and triglyceride lowering activities in Wistar fatty rats after intraperitoneal administration, while its metabolites (2-5) showed comparatively weak activities.

Animals↗
PubMed2006

Momordica charantia constituents and antidiabetic screening of the isolated major compounds.

Bioguided fractionation of the methanol extract of Momordica charantia dried gourds led to the isolation of three new cucurbitane triterpenoids (1-3), together with eight known compounds (4-11). The aglycone of momordicoside I was isolated from the ether soluble fraction in a high amount. The structures of the metabolites were established on the basis of one and two dimensional NMR spectroscopic evidence, X-ray analysis, and comparison with the reported data in the literature. A number of phytochemicals have been isolated from Momordica charantia but the constituents responsible for the hypoglycaemic/antihyperglycaemic activities have not been determined. Therefore, in order to evaluate the contribution of the cucurbitane triterpenoids of the ether fraction of M. charantia methanol extract to in vivo anti-diabetic effects, the major compounds, 5beta,19-epoxy-3beta,25-dihydroxycucurbita-6,23(E)-diene (4), and 3beta,7beta,25-trihydroxycucurbita-5,23(E)-dien-19-al (5) have been tested and have shown blood hypoglycaemic effects in the diabetes-induced male ddY mice strain at 400 mg/kg. The two aglycones of charantin did not show any hypoglycaemic effects. Our finding is the first demonstration that major pure cucurbutanoid compounds of M. charantia have in vivo hypoglycaemic effects.

Animals↗
PubMed2003

Antidiabetic effect of Lactobacillus GG in streptozotocin-induced diabetic rats.

Neonatally streptozotocin-induced diabetic (n-STZ) rats were given food containing Lactobacillus GG cells (GG) or a control diet (control), from 9 to 18 weeks of age. The GG cells significantly lowered the blood hemoglobin A(1C) (HbA(1C)) level and improved glucose tolerance in n-STZ rats (p<0.05). In the GG group, the serum insulin level at 30 min after glucose loading was significantly higher than in the control group (p<0.05).

Animals↗
PubMed2000

The thiazolidinediones: a new class of antidiabetic agents.

Insulin resistance is a fundamental feature of type 2 diabetes and is strongly associated with metabolic disorders which predict increased cardiovascular risk, including hypertension and dyslipidaemia. A new class of insulin-sensitizing agents, the thiazolidinediones, reduce insulin resistance and improve glycaemia both as monotherapy and in combination with sulphonylureas or metformin.

Blood Glucose↗
PubMed1995

A study of effect of CS-045, a new antidiabetic drug, on hypertension in spontaneously hypertensive rat.

Several lines of evidence have suggested that insulin resistance may play an important role in the pathogenesis of hypertension. CS-045 is a new hypoglycemic drug by which improves insulin sensitivity in peripheral tissues. We assessed the effect of CS-045 on hypertension in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) as a control. At 20 weeks of age, the treatment with CS-045 was started by being mixed with chow pellets in the proportion of 0.2% (w/w) and continued for 6 weeks. Nonfasting plasma glucose levels were not changed in either strain of rats treated with CS-045, but plasma insulin levels decreased in SHR 4 and 5 weeks after the start of CS-045 therapy. Blood pressure increased with age in SHR without treatment, but CS-045 decreased blood pressure only 4 and 6 weeks after the treatment. These findings suggest that insulin resistance is not strongly associated with the pathogenesis of hypertension in SHR.

Animals↗