Hypoglycemic Activity In Rats Research Articles

Formulation of novel niosomal repaglinide chewable tablets using coprocessed excipients: in vitro characterization, optimization and enhanced hypoglycemic activity in rats

Repaglinide (RPG), a monotherapy insulin secretagogue used to treat diabetes mellitus-type II yet, it suffers from poor water solubility and variable bioavailability (∼ 50%) due to hepatic first pass metabolism. In this study, 2FI I-Optimal statistical design was employed to encapsulate RPG into niosomal formulations using cholesterol,span 60 and peceolTM. The optimized niosomal formulation (ONF) showed particle size 306.60 ± 84.00 nm, zeta potential −38.60 ± 1.20 mV, polydispersity index 0.48 ± 0.05 and entrapment efficiency 92.00 ± 2.60%. ONF showed > 65% RPG release that lasted for 3.5 h, and significantly higher sustained release compared to Novonorm® tablets after 6 h (p < 0.0001). TEM for ONF showed spherical vesicles with dark core and light-colored lipid bilayer membrane. RPG peaks disappeared in FTIR confirming successful RPG entrapment. To eliminate dysphagia associating conventional oral tablets, chewable tablets loaded with ONF were prepared using coprocessed excipients; Pharmaburst® 500, F-melt® and Prosolv® ODT. Tablets showed friability <1%, hardness 3.9 ± 0.423-4.7 ± 0.410 Kg, thickness 4.1 ± 0.045-4.4 ± 0.017 mm and acceptable weight.All tablets showed robust RPG release at 30 min compared to Novonorm® tablets. At 6h, chewable tablets containing only Pharmaburst® 500 and F-melt® showed sustained and significantly increased RPG release compared to Novonorm® tablets (p < 0.05). Pharmaburst® 500 and F-melt® tablets showed rapid in vivo hypoglycemic effect with 5 and 3.5 fold significant reduction in blood glucose compared to Novonorm® tablets (p < 0.05) at 30 min. Also, at 6h the same tablets showed 1.5 and 1.3 fold significant extended reduction in blood glucose compared to the same market product (p < 0.05). It could be concluded that chewable tablets loaded with RPG ONF represent promising novel oral drug delivery systems for diabetic patients suffering from dysphagia.

PRONIOSOMAL GEL MEDIATED TRANSDERMAL DELIVERY OF GLIBENCLAMIDE AND ATENOLOL COMBINATION: EXVIVO AND PHARMACODYNAMIC STUDIES

Objective: The objective of the present work was to develop an optimized dosage form for treating comorbidity in combination and evaluate it for its pharmacodynamic performance in male Wistar albino rats.&#x0D; Methods: Transdermal proniosomal gel for Combination of Glibenclamide (GLB) and Atenolol (ATN) was developed and optimized by Box Behnken design. This optimized combinational proniosomal gel (OCPG), which was selected by a point prediction method, was evaluated for its ex vivo, skin irritation studies and pharmacodynamic activities of both drugs in rats in comparison with its oral therapy.&#x0D; Results: The ex-vivo permeation behavior through different skins was studied and the findings were also confirmed by the values of the steady-state flux (Jss). The OCPG observed an increase of more than twice in the cumulative amount of impregnated drugs compared to pure drug films. The study on skin irritation revealed the non-irritability of the developed OCPG applied. OCPG significantly showed sustained hypoglycemic activity in rats (p&lt;0.001), when compared to orally treat animals up to 24 h. Systolic blood pressure (SBP) lowering effect of OCPG was found to be significant (p&lt;0.02), when compared to orally treat rats up to 24 h. However, the reduction was slow and sustained in the case of OPCG where a significant response was observed in the performed studies.&#x0D; Conclusion: Overall, the results show that controlled release GLB and ATN proniosomes offer a useful and promising transdermal delivery system. Henceforth this may be an achievement in treating the diabetic hypertensive patient.

Pharmacokinetics, Tissue Distribution, and Excretion Study of Cajanonic Acid A in Rats by UPLC-MS/MS.

Cajanonic acid A (CAA), a prenylated stilbene derivative extracted from the leaves of pigeon pea (Cajanus cajan), has been reported to possess inhibitory activity on the peroxisome proliferator-activated receptor gamma (PPARγ) and protein tyrosine phosphatase 1B (PTP1B). Its hypoglycemic activity in rats is comparable to that of the approved antidiabetic agent rosiglitazone. Therefore, CAA is a potential candidate for the treatment of type 2 diabetes and a lead compound for the discovery of novel hypoglycemic drugs. To achieve a thorough understanding of the biological behavior of CAA in vivo, our current study was designed to investigate the pharmacokinetics, bioavailability, distribution, and excretion of CAA in rats by UPLC-MS/MS. Chromatographic separation was performed on BEHC18 column (2.1 mm × 50 mm, 1.7 µm). Quantification was performed under the negative ion mode by using single reaction monitoring (SRM) of the transitions of m/z 353.14 → 309.11 for CAA and m/z 269.86 → 224.11 for genistein, respectively. Standard calibration curve showed excellent linearity (r2 > 0.99) within the range of 2 - 800 ng/mL. The accuracies and precisions were within the acceptance limits (all < 20%). CAA was quickly absorbed into bloodstream and distributed rapidly and widely to various tissues. The excretion ratio of CAA in the 3 main pathways via bile, feces, and urine was only 5.17%. These results indicate that CAA was quickly and thoroughly metabolized in vivo and excreted mainly as metabolites.

Effect of Fermentation Time of Kombucha Tea on Its Hypoglycaemic Activity in Rats

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia. Functional food, such as kombucha tea, is widely used as complementary treatment for type 2 diabetes mellitus. Kombucha tea is made through fermentation process of green or black tea using a microbial kombucha consortium (Acetobacter xylinum and several types of yeast). The aim of this study was to evaluate the effect of fermentation time of kombucha tea on its hypoglycaemic activity in rats. The green tea (Camellia sinensis) was fermented with kombucha consortium for 8, 14, and 21 days. Evaluation of hypoglycaemic activity was conducted using glucose tolerance test method. First, fasting blood glucose levels in rats were measured after 16 hours fasting. Hyperglycaemic condition was induced by administering glucose 2 g/0.2 kg body weight. Blood glucose levels were measured again after 30 minutes. Subsequently, 5.5 ml of kombucha tea in various fermentation time was orally administered. Blood glucose levels were measured at 30, 60, 90, 120, 150 and 180 minutes after kombucha tea administration. The results revealed the average reduction of blood glucose were 18.16%, 33.64%, and 19.88% by kombucha tea fermented for 8, 14, and 21 days, respectively. In conclusion, kombucha tea fermented for 14 days is potential to be developed as a hypoglycaemic agent. Keywords: fermentation time, glucose level, hypoglycaemia, kombucha tea

Lead generation and optimization of novel GPR119 agonists with a spirocyclic cyclohexane structure

We describe here the generation of a lead compound and its optimization studies that led to the identification of a novel GPR119 agonist. Based on a spirocyclic cyclohexane structure reported in our previous work, we identified compound 8 as a lead compound, being guided by ligand-lipophilicity efficiency (LLE), which linked potency and lipophilicity. Subsequent optimization studies of 8 for improvement of solubility afforded representative 21. Compound 21 had no inhibitory activity against six CYP isoforms and showed favorable pharmacokinetic properties and hypoglycemic activity in rats.

Antihyperglycemic Activity and Phytochemical Screening of &amp;lt;i&amp;gt;Khaya Senegalensis&amp;lt;/i&amp;gt; (Meliaceae) in Wistar Rats

The aim of this study was to identify the chemical group, evaluate an acute toxicity study and analyze the effect of aqueous extract Khaya senegalensis (Meliaceae), on experimentally induced hyperglycemic condition in rats. The phytochemical study of the aqueous extract of Khaya senegalensis revealed the presence of active secondary metabolic compounds such as flavonoids, polyphenols, catechol tannins, quinones, saponins, sterols and terpenes. The stem bark of Khaya senegalensis was used for acute toxicity study by gavage in Swiss mice. The aqueous extract of Khaya senegalensis (AEKS) at the dose of 35±5 mg/kg administrated by gavage showed that all the mice treated were living after 24 hours. The lethal dose obtained by intraperitoneal administration with graded doses to the mice was 1778 mg/kg. This extract could be non-toxic. The study of AEKS activity on blood glucose in rats showed a significant (p <0.01) the concentration of glucose in the serum of the treated rats with the AEKS (96.2 ± 30 mg/dl) and Glibenclamide (92.4±10 mg/dL), compared to glucose concentrations in the serum of hyperglycemic rats (197.1 ± 50 mg/dl). Thus, the study showed hypoglycemic activity of aqueous extract of Khaya senegalensis. In conclusion, the administration of AEKS causes hypoglycemic activity in rats given oral glucose load. Hypoglycemia this is due to the presence of active chemical groups in the extract of this plant, such as flavonoids, catechin tannins, polyphenols, quinones, sterols and terpenes. These results confirm the therapeutic indication in traditional medicine Khaya senegalensis in the treatment of diabetic disease.

Розробка способу отримання стабільних субстанцій для функціональних харчових продуктів на основі порошку кореневих бульб якона (Smallanthus sonchifolius Poepp. &amp; Endl.) та дослідження їхньої цукрознижувальної активності у щурів

Розробка способу отримання стабільних субстанцій для функціональних харчових продуктів на основі порошку кореневих бульб якона (Smallanthus sonchifolius Poepp. &amp; Endl.) та дослідження їхньої цукрознижувальної активності у щурів

Pharmacological and Genotoxic Properties of Polyphenolic Extracts of Cedrela odorata L. and Juglans regia L. Barks in Rodents.

Evaluation of the phenolic compounds and antioxidant activity of Cedrela odorata L. and Juglans regia L. bark extracts was performed in vitro. Juglans regia showed greater extract concentration and higher antioxidant activity. Hypoglycemic activity in rats was assessed by generating a glucose tolerance curve and determining the area under the curve (AUC). Diabetes was later induced by an injection with streptozotocin (65 mg/kg of b.w.) and confirmed after 24 hours. The extract was administered (200 mg/kg b.w.) over 10 days, and blood glucose was monitored and compared with a control group. The glucose AUC showed a hypoglycemic effect of J. regia and C. odorata in normal rats. Both extracts reduced hepatic lipid peroxidation in diabetic rats. Polyphenolic extracts reduced cholesterol levels in a hypercholesterolemic mouse model and decreased hepatic lipid peroxidation. Polyphenolic extract doses of 100 and 200 mg/kg b.w. were administered alone or with cyclophosphamide (CPA) 50 mg/kg ip, which was used as a positive control. Analyses were performed using leukocytes in a comet assay after 4 and 24 h of treatment. Genotoxic effects were evaluated by the comet assay, which showed that while J. regia extract had no effect, C. odorata extract induced slight damage at 200 mg/kg, with the formation of type 0 and 1 comets.

The flavonoid content and antiproliferative, hypoglycaemic, anti-inflammatory and free radical scavenging activities of Annona dioica St. Hill

BackgroundAnnona dioica St. Hill (Annonacaeae) is a Brazilian plant used in folk medicine for the treatment of several types of rheumatisms and diarrhoea. The focus of this work was to evaluate the in vitro antiproliferative and antioxidant activity and the in vivo hypoglycaemic and anti-inflammatory activity of A. dioica and identify the principal constituents of this plant.MethodsThe crude methanol extract (EAD) and hexane (HF), chloroform (CF), ethyl acetate (EAF) and hydromethanol fractions (HMF) were evaluated for free radical scavenging activity using the DPPH assay. The EAD and EAF were assayed for hypoglycaemic activity in rats. The EAD was tested in an antiproliferation assay and for anti-inflammatory effects in paw oedema, in addition to myeloperoxidase activity induced by carrageenan (Cg) in mice. The EAF was assayed using chromatographic methods.ResultsThe fractionation of the EAF through chromatographic methods identified derivatives of the flavonoids quercetin and kaempferol. Among all the tested fractions, the ethyl acetate and hydromethanol fractions were the most potent, exhibiting an IC50 of 8.53 and 10.57 μg/mL, respectively, which is comparable to that of the commercial antioxidant butylated hydroxytoluene (BHT). The oral administration of the EAD (100 mg/kg) and EAF (15 mg/kg) inhibited the increase of glucose levels, resulting in a hypoglycaemic effect. The EAD (30 to 300 mg/kg) exhibited an anti-oedematogenic effect in Cg-induced paw oedema in a time- and dose-dependent manner. The results showed a reduction of MPO activity by A. dioica 6 h after the induction of paw oedema at all doses tested with maximal inhibition at 300 mg/kg.ConclusionsOur results reveal for the first time that compounds contained in the A. dioica leaves exert anti-inflammatory, hypoglycaemic, antiproliferative, and antioxidant effects. The antioxidant activity may be associated with the presence of flavonoids.

Oral Hypoglycemic Activity of Culinary-Medicinal Mushrooms Pleurotus ostreatus and P. cystidiosus (Higher Basidiomycetes) in Normal and Alloxan-Induced Diabetic Wistar Rats

This study investigates the oral hypoglycemic activity of Pleurotus ostreatus (P.o.) and P. cystidiosus (P.c.) mushrooms on normal and alloxan-induced diabetic Wistar rats. Different doses (250, 500, 750, 1000, and 1250 mg/kg/body weight) of suspensions of freeze-dried and powdered (SFDP) P.o. and P.c. were administered to normal rats, and postprandial serum glucose levels were measured. Optimal time of activity was investigated using the dose 500 mg/kg. Hypoglycemic effect of a single dose of SFDP P.o. and P.c. (500 mg/kg) were investigated using diabetic male and female rats at different stages of estrous cycle and compared with metformin and glibenclamide. Chronic hypoglycemic activity of SFDP P.o. and P.c. (500 mg/kg) was studied using serum glucose levels and glycosylated hemoglobin levels. Maximally effective dose of SFDP P.o. and P.c. was 500 mg/kg. The highest reduction in the serum glucose level was observed 120 minutes after administration of mushrooms. A single dose of P.o. and P.c. significantly (P < 0.05) reduced the serum glucose levels of male diabetic rats. The hypoglycemic activity in female rats was highest in proestrous stage. The hypoglycemic effect of P.o. and P.c. is comparable with metformin and glibenclamide. Daily single administrations of P.o. and P.c. to diabetic rats exert apparent control on the homeostasis of blood glucose. SFDP P.o. and P.c. possessed marked and significant oral hypoglycemic activity. This study suggests the consumption of P.o. and P.c. mushrooms might bring health benefits to mankind as it shows hypoglycemic activity in rats.

Hypoglycaemic effects of Mammea africana (Guttiferae) in diabetic rats

Aim of the study The stem bark of Mammea africana Sabine (Guttiferae) is used in African rain forest to treat various diseases, including diabetes mellitus. We investigated whether Mammea africana extract induced hypoglycaemic activity in rats. Materials and methods We tested the effects of acute (5 h) and sub-acute (21 days) oral administrations of the CH 2Cl 2–MeOH stem bark extract of Mammea africana (19–300 mg/kg body weight) on blood glucose levels of normal and streptozotocin (STZ)-induced type 1 diabetic rats. The effects were compared with those of glibenclamide. Results Acute administration reduced blood glucose in the diabetic rats only (33.87%, P < 0.01). Sub-acute treatment for 21 days also reduced blood glucose level in diabetic rats (73.29%, P < 0.01). A reduction or stabilization in total serum protein, triglyceride, cholesterol and alanine amino transferase levels was also observed. No effect was observed on body weight loss but food and water intakes were significantly reduced ( P < 0.01) in diabetic rats. The maximal anti-diabetic effect was obtained with the dose of 75 mg/kg and was more important than that of glibenclamide. Conclusion It can be concluded that extracts of Mammea africana exhibited a significant anti-hyperglycaemic activity and improved the metabolic alterations in STZ-diabetic rats. These results provide a rationale for the use of Mammea africana to treat diabetes mellitus and hypercholesterolemia.

Hypoglycemic activity of aqueous seed extract of Hunteria umbellata in normal and streptozotocin-induced diabetic rats

The present study evaluated the aqueous seed extract of Hunteria umbellata K. Schum (Apocynaceae) for hypoglycemic activity in rats. Diabetes was induced by a single dose of streptozotocin (50 mg/kg i.p.). Daily doses of 400, 800, and 1000 mg/kg of extract were orally administered to fasted normal and diabetic rats. Blood glucose levels were monitored after 0, 2, 4, 8, 12 h and on day 14 post treatment. Liver glycogen levels were also estimated on day 14. In normal rats, only 400 mg/kg of the extract produced a significant reduction in blood glucose at the 4 h (P < 0.05) which was 22.15 ± 4.88%. In diabetic rats, the extract, 400, 800 mg/kg, caused significant reduction (P < 0.01), 51.87% ± 5.79% and 43.47% ± 8.06% respectively, with maximum effect at 8 h. This reduction in blood glucose was greater than that of glibenclamide (31.03% ± 8.86%). Diabetic rats administered with 400 mg/kg extract produced a significant reduction (P < 0.01) on day 14 (43.60% ± 8.10%). Liver glycogen levels were significantly increased (P < 0.05) in diabetic rats administered with doses of 400 and 800 mg/kg extracts and these were comparable to glibenclamide. Acute toxicity data showed no mortality in mice up to 17.5 g/kg. We conclude that the extract possesses marked hypoglycemic effects in diabetic rats possibly through increased glycogenesis, thus justifying its use in herbal medicine for the treatment of diabetes.

Effect Of Aqueous Extracts Of Leaves Of Globimetula Cupulata (Dc) Van Tieghem In Normoglycemic Rats

Globimetula cupulata leaves were evaluated for their hypoglycemic activity in rats. The animals were divided into 4 groups (n=6). Water extract of G. cupulata leaves was administered in graded doses of 0, 300, 600 and 900 mg kg body weight (wt) of experimental animals for 14days. Blood samples were collected by cardiac puncture. The levels of blood glucose were significantly reduced (p < 0.05) by 35.79 – 43.48% on consumption of the extracts, with greater effect exhibited by the 900mg/kg body wt extract. Histological studies showed increases in the number and density of the pancreatic islet cells. The result suggested restorative (protective) effect of the extract on pancreatic islet cells. Administration of aqueous extract of Globimetula cupulata leaves may contribute significantly to the reduction of blood glucose levels by a pancreatotrophic action and possible potentiation of insulin secretion, which may be useful in the treatment of diabetes.

Hypoglycaemic and Antidiabetic Effect of Setaria megaphylla on Normal and Alloxan Induced Diabetic Rats

Objective: To investigate the hypoglycaemic and anti-diabetic activities of ethanolic extraxts of leaves of Setaria megaphylla . Materials and Methods: The hypoglycaemic activity of the ethanolic leaves extract was evaluated in normal as well in as alloxan (150mg/kg 1.p) induced hyperglycaemic rats. Preliminary phytochemical screening and acute toxicity studies of the leaves were carried out. The potency of the ethanolic extract (100, 200 and 300mg/kg b.w. p.o) was evaluated after a single dose (acute study) and after prolonged treatment (chronic study) in normal and alloxan induced diabetic albino rats. The activity of the extract was compared with that of reference drug, chlorpropamide (100mg/kg bw.p.o). The blood glucose level was measured by using a glucometer. Results and Discussion: The extract produced a significant (P Setaria megaphylla exhibited a significant hypoglycaemic activity in rats and this confirms it's use in ethnomedical diabetic management.

Studies on hypoglycaemic activity of Solanum xanthocarpum Schrad. & Wendl. fruit extract in rats

Aqueous extract of the fruits of Solanum xanthocarpum Schrad. & Wendl. (Solanaceae) was investigated for hypoglycaemic activity in rats and mice. Screening for the hypoglycaemic activity was assessed on normoglycaemic, alloxan treated hyperglycaemic and glucose loaded rats along with in vitro study on glucose utilization by isolated rat hemidiaphragm. The various haematological and biochemical parameters were also studied. The extract was found to possess significant hypoglycaemic activity when compared with the reference standard glibenclamide. The in vitro study on glucose utilization by isolated rat hemidiaphragm suggests that the aqueous extract may have direct insulin like activity which enhances the peripheral utilization of glucose and have extra pancreatic effect. The toxicity studies report safety usage of the plant extract.

Study of the hypoglycaemic activity of Lepidium sativum L. aqueous extract in normal and diabetic rats

The hypoglycaemic effect of an aqueous extract of Lepidium sativum L. (LS) seeds was investigated in normal and streptozotocin (STZ)-induced diabetic rats. After a acute (single dose) or chronic (15 daily repeated administration) oral treatments, the aqueous LS extract (20 mg/kg) produced a significant decrease on blood glucose levels in STZ diabetic rats ( p < 0.001); the blood glucose levels were normalised 2 weeks after daily repeated oral administration of aqueous LS extract (20 mg/kg) ( p < 0.001). Significant reduction on blood glucose levels were noticed in normal rats after both acute ( p < 0.01) and chronic treatment ( p < 0.001). In addition, no changes were observed in basal plasma insulin concentrations after treatment either in normal or STZ diabetic rats indicating that the underlying mechanism of this pharmacological activity seems to be independent of insulin secretion. We conclude that the aqueous extract of LS exhibits a potent hypoglycaemic activity in rats without affecting basal plasma insulin concentrations.

Evaluation of Azadirachta indica leaf extract for hypoglycaemic activity in rats

AbstractWater soluble fractions separated from the crude leaf extract of Azadirachta indica A. Juss. lowered hyperglycaemia in streptozotocin diabetes. Systematic fractionation of the concentrates led to the isolation of flavonol glycosides, quercetin‐3‐O‐β‐D‐glucoside, myricetin‐3‐O‐rutinoside, quercetin‐3‐O‐rutinoside, kaempferol‐3‐O‐rutinoside, kaempferol‐3‐O‐β‐D‐glucoside and quercetin‐3‐O‐α‐L‐rhamnoside.

ChemInform Abstract: SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF 1‐(ARYLSULFONYL)‐3,5‐DIALKYL‐S‐TRIAZINE‐2,4,6‐(1H,3H,5H)‐TRIONES

AbstractDie Behandlung der Sulfonamide (I) mit einem Überschuß der Isocyanate (II) in Gegenwart von Triäthylamin führt zu den Triazintrionen (III).

Synthesis and Pharmacological Activity of 1-(arylsulfonyl)-3,5-dialkyl-s-triazine-2,4,6-(1H, 3H,5H)-triones

A series of five 1-(arylsulfonyl)-3,5-dialkyl-s-triazine-2,4,6-(1H,3H,5H)-triones was synthesized by the base-catalyzed reaction of arylsulfonamides with alkyl isocyanates. The compounds were tested for apomorphine antagonism in mice, diuretic activity in fasted rats, antiviral activity in mice, antiviral activity in infected cell cultures, CNS stimulant activity in mice, and hypoglycemic activity in rats. The only biological activity exhibited by these compounds was a slight tendency to lower blood sugar levels in glucose-primed, fasted rats. This activity may be attributable to their structural similarity to the sulfonylurea hypoglycemics.