Clinical characteristics and genetic analysis of 6 cases of neonatal diabetes mellitus / 中国新生儿科杂志

Objective:To study the clinical features, genetic characteristics and prognosis of neonatal diabetes mellitus (NDM).Methods:From January 2015 to January 2022, neonates with NDM admitted to the Department of Neonatology of our hospital were retrospectively reviewed.Their clinical manifestations, biochemical data, genetic tests, treatments and outcomes were analyzed.Results:A total of 6 cases with NDM were included, with 3 males and 3 females. All 6 cases were full-term infants, 5 were low birth weight infants and 1 had family history of diabetes. High blood glucose were found on 1~11 d (average 4 d) after birth. 3 cases were diagnosed during blood glucose screening for low birth weight and 3 cases were diagnosed due to infection and/or diabetic ketoacidosis. Blood C-peptide levels were below normal range in all 6 cases. Blood insulin levels were decreased in 5 cases and remained at the lower limit of normal range in 1 case. All infants received genetic tests and 4 showed abnormal results, including 2 cases of ABCC8 gene mutation [c.2060C>T (p.T687M), not reported; c.674T>C (p.L225P), reported], 1 case of KCNJ11 gene mutation [c.602G>A (p.Arg201His), not reported] and 1 case of paternal uniparental disomy (UPD)6q24 (reported). All 6 cases were treated with insulin. Glibenclamide was experimented to replace insulin in 3 cases and 1 case was successful. During follow-up (at the age 4 months~5 years old), 4 cases were diagnosed with transient NDM, 1 case with permanent NDM and 1 case died at the age of 4 months without classification. 1 case showed psychomotor and language delay and the others had otherwise normal development.Conclusions:Most NDM infants are low birth weight infants with reduced blood insulin and C-peptide.Transient NDM are common. Proactive genetic testing may help treatment.

Pharmacognostic Evaluation and Anti-Diabetic Activity of Ethanol Extract of Triumfetta cordifolia A. Rich (Tiliaceae) Leaves

Aim: The study was aimed at evaluating some pharmacognostic parameters and investigates the anti-diabetic activity of ethanol extract of Triumfetta cordifolia leaf Methods: The pharmacognostic profiling of Triumfetta cordifolia leaves was carried out using some standard pharmacognostic tools for crude drug standardization such as qualitative and quantitative microscopy, analytical evaluation and phytochemical screening. The plant material was extracted using cold maceration method in ethanol and fractionation was carried out using n-hexane, ethylacetate and butanol. The acute toxicity study was done following standard method. Diabetes in albino wistar rats was intraperitoneally induced using 120 mg/kg body weight of alloxan monohydrate. The diabetic rats where treated with 200 and 400 mg/kg body weight of the crude extract and 400mg/kg of each of the fractions. Glibenclamide was used as the standard drug (5 mg/kg) and diabetic rats without treatment as negative control. The procedure was also similarly performed using the non-diabetic rats. The administration of all treatments was done orally, once daily for 21 days and blood sera of the blood samples from rats across the groups were collected at the end of the treatment period and the concentrations of Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and Alanine aminotransferase (ALT) were evaluated. Results: The results of the qualitative microscopic evaluation of Triumfetta cordifolia leaf revealed paracytic stomata, unicellular trichomes, wavy wall epidermal cells and prismatic calcium oxalate. Quantitative microscopic study gave 23.67 ± 0.58 stomata number, 0.023 ± 0.00058 stomata index, 18.33 ± 1.53 Palisade ratio and 10.67 ± 0.58 vein-islet number while the analytical standard revealed 9.3 total ash, 3.5 water soluble ash and 1.34 acid insoluble ash. The phytochemical analysis revealed the presence of alkaloids, glycosides, Tannins, flavonoids steroids and terpenoids in the Triumfetta cordifolia leaves ethanol extract (TCEE). A significant reduction (P?0.05) in fasted blood sugar level of diabetic rats was observed during treatment with Triumfetta cordifolia leaves extract and the blood sugar level lowering potential was comparable to the glibenclamide’s group. There was improvement of body weight in TCEE treated groups and ethylacetate fraction group. The Leaf extract of Triumfetta cordifolia showed a high significant (P?0.05) ameliorating potential on liver’s degenerating hepatocytes evidenced by the comparable reduction in AST, ALT and ALP levels with the glibenclamide’s and diabetic’s groups. Conclusion: The overall results showed that Triumfetta cordifolia leaf possesses blood sugar lowering and liver hepatocytes regenerating potentials while the pharmacognostic profiling of the plant can serve as a reference and guide for future researchers.

Anti-hyperglycemic and anti-hypercholesterolemic activity of Schouwia schimperi in glucose loaded and streptozotocin induced diabetic rats

Background: Diabetes mellitus has assumed epidemic proportion, its incidence is continuously increasing although of that estimates are imprecise, only providing a rough picture, and probably underestimate the disease burden. There were about 150 million cases estimated in the year 2000 which rose to 422 million people worldwide in 2020 according to the World Health Organization statistics. Medicinal plants such as Schouwia schimperi are one of many traditional treatments used in folk medicine by the people of Eastern Sudan for diabetes mellitus but have not been studied or evaluated scientifically. Aims and Objectives: This study evaluates the hypoglycemic and hypolipidemic effect of S. schimperi ethanol extract and compares it with standard glibenclamide in glucose loaded rats and streptozotocin induced diabetic rats. Materials and Methods: Diabetes mellitus was experimentally induced in rats by subcutaneous injection of streptozotocin at a dose of 60 mg/kg. S. schimperi ethanol extract was given orally at doses of 200 and 400 mg/kg and compared with control (2 ml distilled water) and standard (Glibenclamide 10 mg/kg). The same doses were given to glucose loaded diabetic rats as a model for type 2 diabetes mellitus. Results: The 200 mg/kg dose significantly lowered the plasma glucose levels in glucose loaded rats by 31% 2 h after the glucose load (P < 0.05) and by 68% in comparison to the negative control, the 400 mg/kg dose reduced plasma glucose levels by 33% in comparison to negative control (P < 0.05). Reductions in plasma glucose levels were 33.12% and 12.34% after 4 h of the glucose load for the 200 mg/kg and the 400 mg/kg doses respectively. In streptozotocin diabetic rats no significant reductions in plasma glucose levels were seen. However, strong hypocholesterolemic effect was seen after 3 h for both of the 200 mg/kg and 400 mg/kg doses by 85.4% (P < 0.05) and 88.2% (P < 0.05), respectively, and by 89.97% (P < 0.001) and 90.6% (P < 0.001) respectively 6 h after oral administration. Conclusion: Our study concludes that S. schimperi extract has a favorable effect in reducing plasma glucose in glucose loaded rats and excellent hypolipidemic effects.

Ceiling effect of Postconditioning and Atrial Natriuretic Peptide in Cardioprotection against Ischemia Reperfusion Injury in Ovariectomized rat hearts

Abstract Ischemic postconditioning (IPTC) brings cardioprotection endogenously, Atrial natriuretic peptide (ANP) produces the same effect. It happens due to down expression of endothelial nitric oxide synthase (eNOS). Thus, experimental protocol associating IPTC has been formulated to find the role of ANP in the cardioprotection of heart in OVX rats. For this experiment, heart was isolated from OVX rat and held tightly on Langendorff's apparatus in a manner that ischemia of 30 min and reperfusion of 120 min were also given. Simultaneously, IPTC with four cycles of 5 min ischemia and 5 min reperfusion of each was applied. Parameters like size of myocardial infarct, levels of lactate dehydrogenase (LDH) and release of creatine kinase- MB (CK-MB) in coronary effluent were noted after each stage of experiment for ensuring the extent of myocardial injury. Some significant changes were also seen in the histopathology of cardiovascular tissues. The cardio-protection has been made by four cycles of IPTC. It was confirmed by decline in the size of myocardial infarct. It diminishes the release of LDH and CK-MB in heart of OVX rat. Thus, IPTC induces cardio-protection in the isolated heart from OVX rat. Perfusion of ANP associating with IPTC favors the cardioprotection which is further confirmed by rise in the NO release and heart rate. The level of myocardial damage changes using IPTC, IPTC+OVX, IPTC+OVX+ANP, IPTC+ OVX+ANP+L-NAME and other groups were observed significantly and were found to be less than those in I/R control group. Thus, it is recommended that ANP involving IPTC restores attenuated cardio-protection in OVX rat heart. Therefore, Post-conditioning is useful in various clinical aspects.

Determination of structural properties in the adsorption of drugs on chitosan-hydrogels for type 2 diabetes by means of the PM6 method / Determinación de propiedades estructurales en la adsorción de fármacos en hidrogeles de quitosano para diabetes tipo 2 mediante el método PM6 / Determinação das propriedades estruturais en adsorção de drogas em hidrogelos de quitosan para diabetes do tipo 2 pelo método PM6

Abstract Computational chemistry performs the modeling and calculation of physicochemical properties that allow understanding of the different molecular interactions at the nanometric scale in medical applications such as the design of controlled release systems. The PM6 model was used to analyze metformin and glibenclamide. First, the energy properties as the Gibbs free energy and enthalpies were obtained. The results showed the affinity of both drugs with water (glibenclamide: -7.96 and metformin: -11.49) due to the formation of hydrogen bonds, which were verified by the electronegativities corresponding to the dipole moment and to the partition coefficient (Log P). Subsequently, the main properties for the design of a release system using the metformin/glibenclamide complex in the chitosan hydrogel were determined. In this process it was appreciated that the Gibbs free energy (-2157.60 kcal/ mol) determined the thermodynamic stability of the adsorption. In addition, the Log P (-25.82) indicated an instantaneous solubility through the formation of hydrogen bonds and were verified by the electronic distribution and the change in dipole moment.

Resumen La química computacional realiza el modelado y el cálculo de propiedades fisicoquímicas que permiten comprender las diferentes interacciones moleculares a escala nanométrica en aplicaciones médicas como el diseño de sistemas de liberación controlada, por ejemplo. El modelo PM6 se utilizó para analizar metformina y glibenclamida. Primero se obtuvieron las propiedades energéticas como la energía libre de Gibbs y las entalpias. Los resultados mostraron la afinidad de ambos fármacos con el agua (glibenclamide: -7,96 y metformina: -11,49) debido a la formación de enlaces de hidrógeno que fueron verificados por las electronegatividades correspondientes al momento dipolar y al coeficiente de partición (Log P). Posteriormente, se determinaron las principales propiedades para el diseño de un sistema de liberación que usa el complejo metformina/glibenclamida en el hidrogel de quitosano. En este proceso se apreció que la energía libre de Gibbs (-2157,60 kcal/mol) determinó la estabilidad termodinámica de la adsorción. Además, el Log P (-25,82) indicó una solubilidad instantánea a través de la formación de enlaces de hidrógeno y se verificó mediante la distribución electrónica y el cambio en el momento dipolar.

Resumo A química computacional realiza a modelagem e o cálculo das propriedades físico-químicas que permitem compreender as diferentes interações moleculares em escala nanométrica em aplicações médicas, como o projeto de sistemas de liberação controlada. O modelo PM6 é usado para analisar metformina e glibenclamida. Primeiro, obtenha as propriedades energéticas como a energia livre de Gibbs e as entalpias. Os resultados mostram a afinidade de ambos os componentes com água (glibenclamida: -7.96 e forma: -11.49) debitados na forma de ligações de hidrogénio, que verificam por eletronegatividades correspondentes no momento dipolar e coeficiente de participação (Log P). Posteriormente, selecione as principais propriedades para o projeto de um sistema de liberação que usa o método completo/glibenclamida no hidrogel de quitosano. Neste processo, aprecie a energia livre de Gibbs (-2157.60 kcal/mol) que determina a estabilidade termodinâmica da adsorção. Além disso, o Log P (-25.82) indica uma solução instantânea para a passagem de forma de hidrogénio e é verificada usando a distribuição eletrônica e o câmbio no momento dipolar.

Influence of silymarin and chromium picolinate on the pharmacotherapy of rats with induced diabetes / Influência da silimarina e picolinato de cromo na farmacoterapia de ratos com diabetes induzida

SUMMARY Food supplements are easily acquired and used in various countries. Silymarin has been indicated for diseases of the liver and Chromium picolinate has been indicated for body weight loss and for the improvement of glycemic index. The objective of the present study was to assess the effects of short-term treatment with a combination of silymarin (50 mg/kg) and chromium picolinate (5 µg/kg) on the standard glibenclamide treatment (10 mg/kg) of rats with induced diabetes. DM2 was induced with streptozotocin. Experimental groups of rats: healthy control group, glibenclamide diabetic group, silymarin diabetic group, and silymarin, chromium picolinate and glibenclamide group. After 10 days of oral treatment, we determined body weight, fasting glycemia, glycemia 1 h after gastric gavage with sucrose, and AST and ALT transaminases. Statistical analysis of the data indicated that there was no change in body weight or fasting glycemia, but that glycemia increased after gavage with sucrose in the group submitted to combined therapy. Thus, we concluded that the combination of silymarin and chromium picolinate reduced the efficacy of glibenclamide in the short term, although the two substances had a protective effect on the liver as observed by the reduction of blood transaminase levels.

RESUMO Suplementos alimentares são de fácil aquisição e uso em diversos países. A silimarina tem sido indicada para desordens hepáticas e o picolinato de cromo tem sido utilizado para perda de peso corporal e melhoria do índice glicêmico. O objetivo deste trabalho foi avaliar os efeitos do tratamento utilizando uma combinação de silimarina (50 mg/kg) e picolinato de cromo (5 µg/kg) sobre o tratamento com glibencla-mida (10 mg/kg) em ratos com diabetes induzida com estreptozotocina. Os grupos experimentais foram: grupo controle sadio, grupo diabético glibenclamida, grupo diabético silimarina e grupo diabético silimarina, picolinato de cromo e glibencla-mida. Após 10 dias de tratamento via oral, determinou-se o peso corpóreo, glicemia de jejum, glicemia após uma hora de gavagem gástrica com sacarose e transaminases hepáticas. A análise estatística dos dados indicou que não ocorreu alteração significativa no peso corpóreo e na glicemia de jejum, mas ocorreu aumento significativo dos níveis glicêmicos no grupo diabético silimarina, picolinato de cromo e glibenclamida após a gavagem com sacarose no grupo com a terapia combinada. Portanto, conclui-se que a combinação utilizada reduziu a eicácia da glibenclamida em curto prazo, embora ambas substancias tenham exibido efeito hepatoprotetor, observado pela redução dos níveis plasmáticos de transaminases.

Pharmacological Evaluation Of Antidiabetic And Diuretic Activity Of Hydro-Alcoholic Extract Of Anogeissus Latifolia Bark

The objective of the present investigation was to study the antidiabetic and diuretic potential of Anogeissus latifolia (A. latifolia) bark in experimental rats. The A. latifolia bark was extracted with hydro-alcoholic solvent by cold extraction method. Acute toxicity study was performed according to OECD 425 guidelines for hydro-alcoholic extracts of A. latifolia bark (ALBE). The dose of 150 mg/kg p.o. and 300 mg/kg, p.o. of ALBE was selected for further studies. Animals were prepared diabetic by administration of alloxan (120 mg/kg, i.p.). The albino rats were divided in to five groups for oral glucose tolerance test (OGTT) and alloxan induced anti diabetic model with six animals in each group. Diabetic animals were treated with hydro-alcoholic extract of A. latifolia bark for 20 days. The blood glucose level was estimated according to standard procedures. Diuretic activity hydro-alcoholic extracts of A. latifolia was evaluated by Lipshitz method. The result shows that hydro-alcoholic extract from bark of Anogeissus latifolia 300 mg/kg (ALBE-II) shown significant hypoglycemic activity as compared to glibenclamide and diabetic group. The ALBE does not exhibit significant diuretic activity which is considered as positive marker in diabetic phenomena. Hence in present study extract of A. latifolia posses antidiabetic activity. This study may be benchmark in future to use of this drug scientifically.

Comparative study of hypoglycemic activity of Morus alba with oral glibenclamide in streptozotocin induced diabetic rats

Background: Diabetes is a chronic metabolic disorder that continues to present a major worldwide health problem, characterized by absolute or relative deficiencies in insulin secretion and/or insulin action associated with chronic hyperglycaemia and disturbances of carbohydrate, lipid, and protein metabolism. It is fast growing disease, gains the status of a potential epidemic in India with prevalence of more than 62 million diabetic individuals currently diagnosed with the diabetes.Methods: The study was conducted at Department of Pharmacology, Kurnool Medical College, Kurnool for a period of 1 year from January 2017 to December 2018. Animals used were albino rats, of Wistar strain, weighing between 150-200gm of either sex. The animals were divided into six groups as: control group (I); pathogenic control group (II) injected intravenously (i.v.) with single dose of STZ (60mg/kg); Morus alba stem bark extract (group-III; 200mg/kg), and group-IV (400mg/kg); group-V animals treated with glibenclamide (5mg/kg, p.o.) following STZ treatment; group-VI, animals treated with bark extract per se (400 mg/kg).Results: The results of this study showed a significant decrease blood glucose level, glycosylated heamoglobin level, and reduction in glutathione and insulin level after STZ administration. These parameters were significantly (p<0.05) reversed by extracts dose dependently.Conclusions: Thus, authors conclude that M. alba stem bark extracts produced significant antidiabetic and antioxidant effect which might be due to the presence of bioactive components such as phenolic and flavonoid content in the extract. The study warrants the need for further evaluated in certain other models of diabetes.

Physicochemical Equivalence and Validation of an HPLC Analytical Method for the Quantification of Glibenclamide and Its Sulfonamide Impurity in Prescribed Glibenclamide Tablets in Nigeria

Objective: To investigate the physicochemical equivalence of four brands of commercially available glibenclamidetablets in Nigeria and to develop a validation method using HPLC for the quantitative determination of glibenclamide and its sulfonamide impurity present in thesetablets.Methods: Uniformity of weight, friability tests, hardness/crushing strength, dissolution,anddisintegration tests were carried out on tablets/drug samples of each brand. Theirfunctional groups were determined and compared with pure glibenclamide sample (reference standard) using Fourier Original Research Article Transform Infrared Spectroscopy (FTIR) between a range of 4000cm-1to 400cm-1. High-Performance Liquid Chromatography (HPLC) was used to determine the percentage of glibenclamide and its sulfonamide impurity present in each tablet brand. Results: From the physicochemical evaluation of the four brands ofglibenclamide tablets tested, the brands passed all the British Pharmacopeia specifications,but they all failed the hardness/crushing strength tests and one of the brands failed the assay test requirement for drug content. The developed HPLC method had apercentage recovery between the acceptable limit of 95-105% with percentage relative standard deviation (%RSD) of < 3% while the precision of the method was 0.102%and 0.383% for glibenclamide and its sulfonamide impurity, respectively. The Limit of Detection (LOD)and Limit of Quantification (LOQ)of the developed analytical method for the four brands were 0.075μg/ml and 0.227μg/ml for glibenclamide while that of sulfonamide impurity were0.114μg/ml and 0.345μg/ml,respectively.In addition, the percentage impurity of sulfonamide in all the brands was less than the acceptable limit of 1%.Conclusion: Theresultsfrom thephysicochemical evaluation of the glibenclamide brands justified the need forconstant monitoring of marketed drug products. The results obtained from theHPLC quantification methoddeveloped for this study show that our data is reproducible based on the linearity, precision, and accuracyof data generated forglibenclamide and its sulfonamide impurity inthe four brands of glibenclamide tablets prescribed to DM patients in Nigeria, which were judged to besatisfactoryat the time of this study

Modulatory effect of baicalein on gene expression and activity of antioxidant enzymes in streptozotocin-nicotinamide induced diabetic rats

Oxidative stress plays the central role in the pathogenesis and progression of diabetic complications. The present study aims to investigate the beneficial effect of oral administration of flavone baicalein in streptozotocin-nicotinamide (STZ-NA) induced diabetic rats by measuring oxidative stress markers, antioxidant enzyme activities and expression analysis of antioxidant genes. Experimental diabetes was induced by a single intraperitoneal (i.p.) injection of STZ (55 mg /kg b.wt), 15 min after the i.p. administration of NA. At the end of the experimental period, thiobarbituric acid reactive substances (TBARS), activities of antioxidant enzymes and expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and glutathione peroxidase (GPx) were measured in diabetic rats along with serum biochemical parameters namely total cholesterol (TC), total triglyceride (TG), aspartate transaminase (AST) alanine transaminase (ALT) and glycosylated hemoglobin (HbA1c). Oral administration of baicalein (40 mg/kg b.wt/day) demonstrated a significant ameliorative effect on all studied biochemical and oxidative stress parameters. Biochemical findings were corroborated by qPCR expression analysis which showed significant upregulation of antioxidant genes in diabetic rats. These results suggest that baicalein supplementation may reduce diabetes and its complications by suppressing oxidative stress and enhancing gene expression and antioxidant enzyme activities in diabetic rats.

Mechanism of Chinese Medicine Ingredients Combined with Glibenclamide from Xiaoke Pill for the Treatment of Diabetes Mellitus Based on Biomolecules Network / 中国药学杂志

OBJECTIVE: To explore the synergistic molecular network mechanism of Chinese medicine ingredients and glibenclamide from Xiaoke pill for the treatment of diabetes mellitus. METHODS: After obtained diabetic-related genes of Xiaoke pill, STRING software was used to construct biomolecular network, DAVID software was used to identify KEGG pathways, Cytoscape software was used to construct the network for Xiaoke pill ingredients-key target-disease related pathway. RESULTS: The results showed that Xiaoke pill targeted 123 diabetic-related genes. Glibenclamide mainly affected pathways involved in type 2 diabetes, whereas Chinese medicine ingredients from Xiaoke pill was associated with inflammatory-related pathways such as TNF, Jak-STAT, NF-kB and cytokine pathway, islet β cell-related pathways such as PI3K/Akt, mTOR and MAPK pathway, AGE-RAGE and metabolic pathways. By combining Chinese medicine ingredients and glibenclamide, Xiaoke pill widely targeted diabetic-related pathways. CONCLUSION: It indicates that Xiaoke pill, a combination of traditional Chinese and Western medicine, can prevente diabetes and diabetic syndrome possibly by improving insulin resistance and protecting β cells and inhibiting inflammatory response.

Cardiac safety evaluation of berberine combining with berberine-derived medicine / 药学学报

Drug-induced cardiotoxicity is a serious concern in recent years, and acquired long QT syndrome (LQTS) is an important manifestation of cardiotoxicity. hERG gene encodes the α subunit of the rapidly activated delayed rectifier potassium channel (Ikr), which plays an important role in action potential phase 3 repolarization. Drug inhibition of Ikr/hERG channel leads to prolonged QT interval, accompanied by Tdp malignant arrhythmia, which can cause sudden death. We studied the effect of berberines on the hERG K+ channels after combination with rosuvastatin and glibenclamide, and evaluated the cardiac safety of these drugs in combination. Whole cell patch clamp technique was used to detect the effect of the combinations of these drugs on hERG current on HEK293 cells stably expressing hERG gene. The results showed that the inhibitory effects of berberine or dihydroberberberine combined with rosuvastatin on hERG current were higher than single drug (P<0.05), but the combination had no effect on the kinetics of hERG channel. Berberine or dihydroberberberine combined with glibenclamide had higher inhibitory effects on hERG current than the application of single drug (P<0.05) while the time constant of hERG channel inactivation was shortened after the combination (P<0.05). In addition, the combination of berberine and glibenclamide inhibited hERG channel activation (P<0.05). In conclusion, our results demonstrated that the combination of berberine with rosuvastatin or glibenclamide significantly inhibited hERG current and the inhibition effects were higher than the application alone. Therefore, when the two drugs that have inhibitory effects on the hERG channel are combined, the risk of inducing prolonged QT interval is significantly increased, and therefore reducing cardiac safety.

Antihyperglycemic effects of aqueous leaf extract of Senna Fistulain streptozotocin-induced diabetic rats

@#This study investigated antihyperglycemic effects of chronic administration of aqueous leaf extract of Senna fistula in Streptozotocin-induced diabetic rat. Thirty rats were randomly assigned into six groups (A-F). Animals in group A werethe control non-diabetic,in groupB were diabetic and received distilled water, in group C werediabetic,treated with 2.5 mg/kg body weight of Glibenclamide, while animals in groups D, E and F were diabetic treated with 28.57, 57.14 and 114.28 mg/kg body weightrespectively of aqueous leaf extract of Senna fistula for 28 days. At the end of 28 days blood samples were collectedfor the assay ofInsulin, Superoxide Dismutase, Catalase,andGlutathione Peroxidasein serumand liver Glycogen.The result showed that the blood glucose levels of diabetic rats were significantly reduced in the extract and Glibenclamide treated animals when compared with diabetic rats that received distilled water. Similarly, there was a significant increase in serum Insulin level, Superoxide dismutase, Catalase and Glutathione peroxidaseactivitiesand liver glycogenin the extract and Glibenclamide treated diabetic groups when compared with diabetic untreated group. The results indicated that oral administrationof aqueous extract of Senna fistula has antihyperglycemic effect by stimulating Insulin secretion and activating antioxidant enzymes.

Administration of Fenugreek Seed Extract Produces Better Effects in Glibenclamide-Induced Inhibition in Hepatic Lipid Peroxidation: An in vitro Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the comparative effects of fenugreek (Trigonella foenum graecum) seed extract (FSE) alone and in combination with an antidiabetic conventional medicine, glibenclamide (GLB), on the inhibition of in vitro lipid peroxidation (LPO) in liver, the major target organ of a drug.@*METHODS@#LPO was induced by ferrous sulphate (FeSo), hydrogen peroxide (HO) and carbon tetrachloride (CCl) and the effects of test seed extract and/or GLB were evaluated.@*RESULTS@#While FeSo, HO and CCl markedly enhanced the hepatic LPO, simultaneous administration of FSE reduced it in a concentration dependent manner. However, when both FSE and GLB were added to the incubation mixture, chemically induced hepatic LPO was further inhibited. The test extract also exhibited high antioxidative activity in 1,1-diphenyl-2-picrylhydrazyl radical and in 2,2'-azinobis, 3-ethylbenzothiazoline-6-sulphonic acid radical scavenging assays.@*CONCLUSION@#FSE therapy in moderate concentration along with a hypoglycemic drug may prove to be advantageous in ameliorating diabetes mellitus and other diseases that are LPO mediated.

Effect of nicorandil, on blood glucose level in alloxan induced diabetic rats and its pharmacodynamic interaction with glibenclamide

Background: Diabetes increases the risk of macrovascular complications and is often associated with angina in patient. Currently nicorandil, a potassium channel opener is being frequently used for the prevention and long-term treatment of angina pectoris. Glibenclamide exerts its antidiabetic action by closing the ATP sensitive potassium channels. Simultaneous use of nicorandil may antagonizes this action and may worsens the existing diabetes. To evaluate the pharmacodynamic interaction present study has been taken to study the effect of Nicorandil, a potassium channel opener on blood glucose level of alloxan induced diabetic rats and its pharmacodynamics interaction with Glibenclamide.Methods: Albino rats, weighing 150-200gm of male sex were used for the study. Diabetes was induced by injecting alloxan monohydrate 2% solution intra peritoneally in a dose of 150mg/kg body weight. Animal with Fasting Blood Sugar level between 250-300g/dl was selected for study and they were divided into 4 groups of 5 animals each. Group I- serving as control received 0.5ml normal saline orally for 28 days. Group II was given glibenclamide (0.5mg/kg body wt) for 28 days. Group III was treated orally with nicorandil (0.3mg/kg body wt) for 28 days. Group IV was given glibenclamide (0.5mg/kg) and nicorandil (0.3mg/kg) for 28 days. Fasting Blood Sugar level was recorded in all rats on 1st,3rd,7th,14th,21st and 28th day of the treatments.Results: results showed that glibenclamide significantly reduce blood sugar level (p <0.05) Wherase nicorandil showed rise in blood glucose level (p <0.05) While the combination (glibenclamide + nicorandil) showed rise in blood glucose (p <0.05) overall.Conclusions: Nicorandil worsen the existing diabetes and to be avoided or replaced with alternative drug in case of diabetes being treated with sulfonyl urease group of drugs.

Effect of tamsulosin on blood glucose levels in euglycemic and alloxan induced diabetic rats and its interaction with glibenclamide

Background: To evaluate the effect of tamsulosin on blood glucose levels in euglycaemic rats and to investigate the effect of glibenclamide, tamsulosin and their combination on alloxan induced diabetic rats.Methods: Albino male wistar rats were randomly assigned into 6 groups (2 euglycaemic and 4 alloxan induced diabetic rats groups). In Euglycaemic rats either normal saline (0.5ml P.O) or tamsulosin (0.072mg/kg P.O) were given and blood glucose levels was estimated at 0 hr, 30min, 1hr, 2hr, 4hr on day 1 and at 0hr and 1hr on day 3 and day 7. Four groups of diabetic rats were given normal saline (0.5ml P.O), glibenclamide (5mg/kg P.O), tamsulosin (0.072mg/kg P.O), combination of glibenclamide and tamsulosin respectively and blood glucose levels were estimated on day 1, 3 and 7. Repeated measures ANOVA or paired 憈 憈est were used for within group comparison and one way ANOVA or unpaired 憈� test were used for between group comparison.Results: In euglycaemic rats tamsulosin caused significant rise in blood glucose levels at 1 hr on all days and in diabetic rats tamsulosin itself did not cause any significant alteration in blood glucose levels. However, its combination with glibenclamide delayed the onset of hypoglycemic effect of glibenclamide & also reduced its hypoglycemic effect.Conclusions: Tamsulosin significantly increase blood glucose level in euglycaemic rats and it interact with Glibenclamide to reduce its hypoglycemic activity in diabetic rats.

Evaluation of antidiabetic activity of Tinospora cardifolia in alloxan induced diabetes in albino wistar rats

Background: The objective was to evaluate the antidiabetic activity of Tinospora cardifolia in alloxan induced diabetes in albino rats in comparison with a currently used oral hypoglycaemic glibenclamide.Methods: there were 24 rats with FBS in the range 80-115 mg/dl were selected for the study. Four groups each containing six rats, were induced diabetes with alloxan (150mg/kg). The diabetic control group (0.5ml normal saline), Standard control group (5mg/kg glibenclimide), Test group I (200mg/kg T. cardifolia) and test II group 400mg/kg T. cardifolia). FBS was recorded on 1, 3, 7, 14, 21 and 28th day using glucometer. Data was analysed by using one way ANOVA and posthoc Tukey’s test SPSS 21Version.Results: Extract of Tinospora cardifolia showed dependent hypoglycaemic action in both low dose (200mg/kg) and high dose group (400mg/kg). Hypoglycaemic action with high dose of Tinospora cardifolia is comparable to that of standard drug glibenclamide.Conclusions: This study demonstrates the hypoglycaemic action of T. cardifolia in diabetic rats. T. cardifolia can be a therapeutic potential to treat type 2 diabetes mellitus.

Evaluation of the oral hypoglycemic activity of methanolic extract of Garcinia indica seeds in streptozotocin induced diabetic Albino rats

Background: Diabetes mellitus is a multifactorial metabolic disorder with several microvascular and macrovascular complications. Several plants have been used as dietary adjuvants to conventional drug therapy. Garcinia indica exhibits significant hypolipidemic and hypoglycemic activity. This study was conducted to evaluate the hypoglycemic effects of methanolic extract of seeds of Garcinia indica on blood glucose levels in Streptozotocin induced diabetic albino rats.Methods: Five groups of wistar albino rats (n=6) weighing 150-200g of either sex aged 3-4 months were obtained for the study. After overnight fasting, streptozotocin (50mg/kg) was administered intraperitoneally to induce diabetes. Five groups are: Group-1: Non diabetic control group, Group-2: diabetic control, Group-3: diabetic standard, Group-4: test group, Group-5: half of test + half of standard. Fasting blood sugar was estimated on 1, 3, 7, 14 and 28th day by capillary blood glucose method. The data obtained were subjected to statistical analysis.Results: In this study, following Streptozotocin administration the blood glucose levels increased in all groups on day 0. In group 2, blood glucose level gradually increased to 445.6±1.75mg/dl over a period of 4 weeks. Following glibenclamide administration in Group 3 - there was a gradual reduction in blood glucose levels: 269.8mg/dl - day 7 to 101.8mg/dl - week 4. Group 4 - persistent and significant (p<0.05) fall in blood glucose levels reaching upto 107mg/dl at the end of 4 weeks. Group 5 - 330mg/dl on day 1 which significantly (p<0.05) reduced to 101mg/dl on day 28. There was improvement in weight in group 4 and group 5 diabetic rats.Conclusions: The extract alone and in combination with glibenclamide showed significant hypoglycemic activity in comparison to diabetic control group.

Evaluation of antidiabetic potential of hydroalcoholic extract of Annona squamosa (HAEAS) leaf in alloxan monohydrate induced diabetic Albino rats

Background: Diabetes is almost growing health concern worldwide and now emerging as an epidemic world over. Recently, full attention is being paid to the study of natural products as potential antidiabetics. Objective of the study was to evaluate the antidiabetic effect of hydroalcoholic leaf extract of Annona squamosa (HAEAS) plant in alloxan monohydrate induced diabetic albino rats.Methods: Almost a 30 Albino rats with 150- 200 grams weight were weighed and grouped into 5 equal groups taking 6 rats in every group. Group A served as normal control, Group B as diabetic control, received alloxan monnohydrate. Group C and D was received alloxan + HAEAS suspension at 350 and 700 mg/kg doses orally respectively, Group E was given alloxan + standard drug (Glibenclamide 5mg/kg) suspension for 28 successive days and the effect of HAEAS on blood sugar(BS) levels was measured at regular intervals. At the end portion of this investigational research study samples of blood were collected from all rats on 0day (initial), after 72 hrs and after 28th day (29thday) of given test drug HAEAS treatment for biochemical estimation of BS and the BS values were observed.Results: The present research study revealed that HAEAS leaves has antidiabetic effect against alloxan monohydrate induced diabetic rats on i.p. alloxan injection at 150mg/kg.b.w. and confirms that on i.p. alloxan injection causes a significant rise off BS in untreated albino rats when compared to control group. Diabetic rats treatment with HAEAS leaves for 28 days caused dose a dependent fall in BS values. Glibenclamide treated diabetic rats also showed a significant (P <0.00) fall in BS content after 28 days of treatment.Conclusions: This research study confirms that HAEAS leaves has shown significant antidiabetic effect at 350 and 700 mg/kg. b.w. doses in alloxan monohydrate induced diabetic rats.