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Artemisia herba alba has been widely used in Iraqi folk medicine for the treatment of diabetes mellitus. Oral administration of an aqueous extract (0.39 g/kg) of the aerial parts of this plant to normoglycemic and to alloxan-diabetic rabbits produced significant hypoglycemic activity, which was consistent and time-dependent.
The hypoglycemic activity of several seaweed extracts on rabbits was studied. Ethanol extracts of Laminaria ochroleuca, Saccorhiza polyschides and Fucus vesiculosus were administered orally to normal animals and their effects on glycemia and triglyceridemia evaluated. Crude polysaccharides and protein solutions from Himanthalia elongata and Codium tomentosum were also assayed. Polysaccharides and proteins from H. elongata caused a significant reduction in blood glucose 8 h after intravenous administration. A case of 5 mg/kg of crude polysaccharide lowered glycemia about 18% in normal rabbits and by about 50% in alloxan-diabetic animals, while the protein solution lowered glycemia in diabetic rabbits by about 30%.
Bassic acid, an unsaturated triterpene acid isolated from an ethanol extract of Bumelia sartorum rootbark, elicited significant hypoglycemic activity in alloxan-diabetic rats and altered the pattern of glucose tolerance in these animals. In addition, bassic acid treatment increased significantly the glucose uptake process and glycogen synthesis in isolated rat diaphragm. Bassic acid treatment increased plasma insulin levels significantly in alloxan-diabetic rats. It is suggested that the hypoglycemia activity of bassic acid may be mediated through enhanced secretion of insulin from the pancreatic beta-cells.
Molecular structures of 10 metabolites, which were isolated from urine (M1-M8) or bile (M9 and M10) after administration of AY4166 (N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine), a novel amino acid derivative with hypoglycemic activity, have been elucidated by mass spectrometry and nuclear magnetic resonance. Four of these (M1, M2, M3 and M8) were determined to be hydroxyl derivatives of AY4166, two (M9 and M10) were carboxylate derivatives via oxidization of M2 and M3, three (M4, M5 and M6) were glucronic acid conjugates and the other (M7) was a dehydro derivative. The estimated structures for M1, M2, M3, M7, M8, M9 and M10 were confirmed by the coincidence of the retention time of HPLC, MS and 1H NMR spectra between the isolated metabolites and authentic synthesized substances. For three glucronic acid conjugates, M4, M5 and M6, structural confirmation was performed by a selective enzymatic digestion with beta-glucronidase. M1 and M2/3 were about 5-6 and 3 times less potent than AY4166, respectively, and M7 was almost as potent as AY4166.
BACKGROUND: Oral hypoglycemic agents (OHAs) are an important component in the management of type 2 diabetes mellitus (DM). Large-scale studies have demonstrated that tight glycemic control with such agents can reduce the frequency and severity of long-term DM-related complications. OBJECTIVES: The main goal of this study was to examine the impact of depression on utilization patterns of OHAs in patients newly diagnosed with type 2 DM. A secondary objective was to estimate the impact of depression on discontinuation and modification of pharmacotherapy for DM in these patients. METHODS: Patients newly diagnosed with type 2 DM during a 3-year period (1998-2000) were identified from a Medicaid claims database. Presence of preexisting depression was determined on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. The patient cohort was followed up until they received their first prescription for an OHA (1998-2001); this date was treated as the index date for the study. Utilization patterns (ie, discontinuation, augmentation, switching, non-modification) for OHAs were computed for a 12-month follow-up period after the index date. A multivariate framework was used to estimate the impact of depression on utilization patterns, controlling for confounders such as demographics, comorbidity, provider interaction, drug regimen complexity, and DM severity. RESULTS: A total of 1237 newly diagnosed type 2 DM patients were identified (depressed, n=446; nondepressed, n=791). A higher number of depressed patients (23.32%) switched or augmented therapy compared with nondepressed patients (16.18%). Also, a higher fraction of depressed patients (39.46%) discontinued OHA therapy compared with nondepressed patients (32.87%). Results of a multinomial logistic regression indicated that, controlling for covariates, patients with depression were 1.72 times more likely to switch (P=0.046) and 1.89 times more likely to augment therapy (P=0.004) compared with nondepressed patients. Logistic regression analysis also indicated that, controlling for confounding covariates, patients with depression were 1.72 times more likely to modify initial OHA therapy compared with patients without depression (P=0.003). CONCLUSION: Depression was significantly associated with utilization patterns of OHAs in these patients newly diagnosed with type 2 DM, thus possibly affecting their disease management.
We previously reported the synthesis and biological activity of novel substituted pyridines and purines having thiazolidinedione with hypoglycemic and hypolipidemic activities. We now report the synthesis and antidiabetic activity of novel substituted pyrimidines having thiazolidinedione moiety. These compounds (entry No. 5a-i, 10a-d and 16) were evaluated for their glucose and lipid lowering activity in KKA(y) mice. From the results, novel compounds, 5c and 5g, exhibited considerably more potent biological activity than that of the reference compounds, pioglitazone and rosiglitazone, respectively.
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 been shown to counteract insulin resistance in diabetic rodent models. However, it is not clear whether this compound has a significant effect on hyperlipidemia in vivo. Hyperlipidemia has been reported to be a risk factor for the early development of renal disease. The aim of this study is to examine the effects of chronic treatment with YM440 on hyperlipidemia and renal injury in obese Zucker fatty (ZF) rats. Treatment of 8-week-old ZF rats with YM440 (100 mg/kg/day) for 16 weeks decreased plasma triglyceride and cholesterol concentrations. YM440 markedly reduced the rate of progression of both albuminuria and proteinuria. YM440 normalized urinary N-acetyl-beta-D-glucosaminidase (NAG) activity, which is a marker for renal proximal tubular damage, and ameliorated the rise in systolic blood pressure compared to the vehicle control. YM440 also blocked the development of nephromegaly. Histological analyses revealed that both glomerular area expansion and tubular cast accumulation gradually lessened in YM440-treated ZF rats. Regression analyses between the plasma triglyceride levels and the renal parameters (urinary protein excretion and albumin excretion) indicated that the renal parameters correlated positively with the plasma triglyceride levels. In conclusion, the hypolipidemic effects of YM440 prevent renal injury in ZF rats. YM440 might be useful for preventing the early development of diabetic nephropathy in subjects with type 2 diabetes by ameliorating metabolic control problems.
In this study, three steroidal sapogenins (Delta3 diosgenin, diosgenin, and pennogenin) and the phytosterols, stigmasterol and beta-sitosterol were isolated from Jamaican bitter yam, Dioscorea polygonoides. Their effects on fasting blood glucose and intestinal amylase and ATPases in streptozotocin-induced diabetic rats were studied. The diabetic rats (fed supplemented and unsupplemented diets) lost weight significantly compared to the normal group. There was a significant increase in the activity of alpha-amylase in the proximal region of the small intestinal mucosa of diabetic rats fed sapogenin extract or commercial diosgenin. However, this did not result in increased fasting blood glucose. Instead, supplementation of the diet with bitter yam sapogenin extract significantly decreased fasting blood glucose compared to the diabetic group. Supplementation of the diet with bitter yam sapogenin extract or commercial diosgenin significantly reduced Na+-K+-ATPase activity in all three regions compared to the diabetic control group. Commercial diosgenin supplementation resulted in a significant increase in Ca2+ ATPase activity in proximal region compared to the diabetic control and bitter yam sapogenin extract groups. The effect of bitter yam sapogenin extract or commercial diosgenin on intestinal Na+-K+-ATPase activity could account for their hypoglycemic properties. However, there was adverse effect on the body weight.
The effect of different fractions of methanolic extract of Bauhinia candicans leaves were investigated on experimentally-induced diabetic rabbits. The crude extracts (8 mg/kg) showed hypoglycemic activity along with a reduced urinary glucose excretion. Among the fractions, the highest activity was exhibited by the butanolic fraction (fraction III). Moreover, fraction III reduced plasma glucose level also in normal, as well as, glucose loaded rabbits. These results suggest that B. candicans increases the peripheral metabolism of glucose.
The extract of the methanolic leaves of Bauhinia cheilandra (BC) was tested on glucose loaded and alloxan-induced diabetic rats. In both tests, the methanolic extract at doses of 300, 600, and 900 mg/kg, has shown a statistically significant and considerable hypoglycemic activity.
The aim of this study was to develop a microemulsion formulation providing an improved efficacy of orally administered insulin. The microemulsions were prepared using Labrafil M 1944 CS, Phospholipon 90 G (lecithin), absolute alcohol and bi-distilled water. The microemulsions of recombinant human (rh)-insulin and aqueous solution (200 IU/kg) were administered intragastrically by a canulla to diabetic and non-diabetic rats. Aprotinin (2500 KIU/g) was added as the enzyme inhibitor to the formulation. Upon the administration of intragastric rh-insulin solution (IS) to non-diabetic rats, the plasma glucose and insulin levels were not changed significantly. Therefore, the hypoglycemic effect caused by subcutaneous rh-insulin solution (SC), microemulsion containing rh-insulin (IME) and microemulsion containing rh-insulin and aprotinin (IMEA) were analyzed in diabetic rats. The area above the plasma glucose levels time curves (AAC), minimum glucose concentration (Cmin) and time to Cmin (tmin) were derived from the plasma glucose profiles. IME and IMEA caused approximately 30% decrease in plasma glucose levels. The decrease in the plasma glucose levels continued after the 90th min. The highest AAC value was obtained when IMEA was administered to rats. The maximum plasma insulin concentration (Cmax), time to reach Cmax (tmax), terminal half-life (t(1/2)), area under the plasma concentration-time curve (AUC), mean residence time (MRT) and elimination rate constant (k(el)) values were also calculated. It was observed that t(1/2) values varied between 0.53 and 1.31h. No significant difference could be found between the pharmacokinetic parameters of the IME and IMEA administered groups. Addition of aprotinin to the microemulsion containing rh-insulin increased bioavailability when compared to those not containing it, although the difference is not significant.
Biodegradable microparticles were prepared with alginate by the piezoelectric ejection process, and lectin (wheat germ agglutinin, WGA) was conjugated to alginate microparticles to take advantage of the protective effects of alginate microparticles and the mucoadhesive properties of WGA for improved oral delivery of insulin. Their specific interaction with model mucin was determined by pig mucin (PM) immobilized surface plasmon resonance (SPR) biosensor and in vitro adsorption studies. The hypoglycemic effects of alginate and WGA-conjugated alginate microparticles were examined after oral administration in streptozotocin-induced diabetic rats. The alginate microparticles were fabricated by ejecting alginate/insulin solution into 0.1 M CaCl2 solution through a nozzle actuated by the piezoelectric transducer. The WGA was conjugated to alginate microparticles by activating hydroxyl groups with carbonyldiimidazole (CDI). The affinity constant (K(A)) of alginate-WGA microparticles from the SPR data (K(A)=5.455 g(-1) L) was about nine times greater than alginate microparticles (K(A)=0.628 g(-1) L). In vitro experiments in the mucin solution showed that the conjugated WGA enhanced the interaction about three times. In vivo studies with diabetic rats showed that the blood glucose level of SPF rats was lowest when alginate-WGA microparticles were orally administered. Larger K(A) of alginate-WGA microparticles resulted in larger glucose change (%) from base level. Still, it is not clear whether the transport of insulin through the intestinal mucous membrane was influenced by the increase of residence time at intestinal membrane through the specific adsorption of WGA-conjugated microparticles. However, it is concluded that alginate-WGA microparticles enhance the intestinal absorption of insulin sufficient to drop the glucose level of blood.
The seed powder of Datura metel was tested for its hypoglycemic activity in normal and alloxan-induced diabetic rats. Graded doses (25, 50 and 75 mg/kg, p.o.) of the seed powder when given to both normal and diabetic rats produced significant reduction in blood glucose at the 8 h. The effect was found to be dose dependent with all treatments at the doses administered.
Cogniauxia podoleana Baillon (Cucurbitaceae family) leaves are used in Congolese traditional medicine for the treatment of diabetes mellitus. Based on an increasing number of reports on blood glucose level reduction associated with some saponins and flavonoids isolated from medicinal plants, the hypoglycemic and antihyperglycemic effects of flavonoid and saponin fractions were investigated. Saponin fractions were obtained by the fractionation of aqueous extract of leaves using benzene and ethyl acetate. Flavonoid fraction was isolated from the aqueous phase obtained after the settling of benzene-aqueous extract mixture by means of diethyl ether. The diethyl ether fraction (100mg/kg) reduced the blood glucose levels in 40.0% 3h after oral administration to normal rats. In contrast, the oral administration of benzene and ethyl acetate fractions at a dose of 100mg/kg to normal rats did not decrease the blood glucose levels. The diethyl ether fraction at a dose of 50mg/kg was found to reduce the increase of blood glucose levels in 29.4 and 44.5%, respectively, 3 and 4h after oral administration to alloxan-induced diabetic rats, whereas at a dose of 100mg/kg, it decreased the levels of hyperglycemia in 41.4 and 70.4%, respectively, after 3 and 4h. These data confirm the antidiabetic activity of the leaves of Cogniauxia podoleana Baillon in Congolese traditional medicine for diabetes mellitus treatment. However, it was important to note that the antihyperglycemic action could not be attributed to the presence of flavonoids; contamination is detected (amino acids, carbohydrates and other compounds) in the diethyl ether fraction containing flavonoids.
The hypoglycemic activity of the flavonoids rich fraction of 70% alcohol extract of the Egyptian Morus alba root bark (MRBF-3) was evaluated after its oral administration to streptozotocin-induced diabetic rats. Diabetes was induced by injection of 60 mg kg(-1) i.p. The administration of MRBF-3 to streptozotocin (STZ)-diabetic rats for 10 days in a dose of 200 and 400 mg kg(-1)day(-1) was not significant. However, administration of MRBF-3 for 10 days (600 mg kg(-1)day(-1)) significantly reduced the amount of the glucose from control level (379+/-9 mg/dl) to a lower level (155+/-8 mg/dl) and significantly increased the insulin level from control (10.8+/-0.3 microU/ml) to a high level (15.6+/-0.3 microU/ml). The measurement of produced lipid peroxides (expressed as the amount of thiobarbituric acid (TBA) reactive substance, nmol TBARS/ml serum) indicated antiperoxidative activity of MRBF-3. The oral administration of MRBF-3 to STZ-diabetic rats significantly decreased the lipid peroxides from 6.3+/-0.8 to 5.1+/-0.7 nmol TBARS/ml serum. The phytochemical investigation of MRBF-3 resulted in the isolation of four hydrophobic flavonoids with one or two isoprenoid groups (log P=5-9): morusin, cyclomorusin, neocyclomorusin, and kuwanon E, a 2-arylbenzofuran, moracin M, and two triterpenes, betulinic acid and methyl ursolate. The data obtained from this study revealed that MRBF-3 may protect pancreatic beta cells from degeneration and diminish lipid peroxidation. However, this is the first biological screening of the Egyptian Morus alba root bark; further future merit studies including clinical study will be necessary in order to confirm the results obtained from this study.
The claimed hypoglycemic activities of Paronychia argentea Lam. (Caryophyllaceae) and Teucrium polium L. (Labiatae), two traditionally widely used medicinal plants in Jordan were evaluated using normoglycemic and alloxan induced hyperglycemic rabbits by intranasal administration of the plant crude extracts (10%) in a vehicle containing 5% (w/w) Pluronic F127. No significant difference was observed between the extract treated and non-treated control animals receiving only water.
There is a general lack of adequate methods to quantitatively assess the importance of specific medicinal plants in a culture. In Mexico like in many other countries type 2 diabetes is an increasing health problem and the use of medicinal plants to treat this disease is widespread. In the present study we propose a mathematical tool for analysing ethnopharmacological field data, with the ultimate aim to select species with most prominent impact on a community to treat a single disease. Using this tool in a Yucatec Mayan community we demonstrate that Malmea depressa (Baill.) R.E. Fr. and Cecropia peltata L. are culturally most salient hypoglycemic plants in this community.
The hypoglycemic activity of fermented mushroom of Coprinus comatus rich in vanadium (CCRV) was studied in this paper. Alloxan and adrenalin induced hyperglycemic mice were used in the study. The blood glucose and the HbA1c of the mice were analyzed, respectively. At the same time, the sugar tolerance of the normal mice was also determined. After the mice were administered (ig) with CCRV, the blood glucose and the HbA1c of alloxan-induced hyperglycemic mice decreased (p < 0.05, p < 0.01), ascension of blood glucose induced by adrenalin was inhibited (p < 0.01) and the sugar tolerance of the normal mice was improved. Also, the body weight of the alloxan-induced hyperglycemic mice was increased gradually. In the fermented mushroom of C. comatus, vanadium at lower doses in combination with C. comatus, induced significant decreases of the blood glucose and HbA1c levels in hyperglycemic mice.