Synthesis and evaluation of 2-phenylamino-1, 4-naphthoquinones derivatives as potential hypoglycaemic agents / Síntese e avaliação de derivados de 2-fenilamino-1, 4-naftoquinonas como potenciais agentes hipoglicemiantes

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo "cloro" tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents

Abstract Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of chloro group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Resumo Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo cloro tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Systematic Review On Medicaments Used In Management Of Diabetes Mellitus

Diabetes has a global prevalence in developed countries and rapidly flexing its roots in middle-and low-income countries. According to the World Health Organization, it is a major cause of kidney collapse, heart problems, and lower limb amputation. Diabetes mellitus is a metabolic disorder showing an uncontrolled increase in blood glucose levels. To date, no permanent cure has been developed for the complete restoration of impaired glucose haemostasis. With the use of therapeutic agents and nontherapeutic agents, glucose levels can be kept in control for a very long time. The foremost goal of all current ongoing treatments is to control high blood glucose levels, reduction in elevated lipid levels, and delay in the progression of diabetes-related complications. Various therapeutics agents are developed in recent decades, which shown very promising results in the management of diabetes mellitus. These agents prescribed after reviewing the clinical symptoms and situation of an individual patient. This review compiles noteworthy information related to clinically approved medicaments for diabetes mellitus. Review emphasis on categorization, mechanism of action, noted adverse effects along with the physiological responses of used medicines to treat diabetes mellitus.

Triterpenoids from Gynostemma pentaphyllum and their inhibition activity to α-glycosidase and protein tyrosine phosphatase 1B / 中草药

Objective: To determine the total saponins from Gynostemma pentaphyllum, the dammarane-type triterpenoids of its hydrolysate, and its hypoglycemic activity. Methods: Compounds from the acid hydrolyzate extracts and total saponins were isolated by silica gel, recrystal and preparative liquid chromatography, and their structures were identified by the NMR spectral analysis. The sensitive screening modles of α-glucosidase and PTP1B inhibitors were established in vitro. The inhibitory kinetics of compounds were also investigated. Using the method of computer aided drug design of active site, PTP1B interact with the strongest active compound for docking simulation. Results: Seven compounds were isolated from the acid hydrolyzate of total saponins, which identified as gpsapogenin A (1), 20(S)-panaxadiol (2), gypensapogenin F (3), 20(R)-protopanaxadiol (4), (23S)-3β- hydroxydama-20,24-diene-21-carboxylic acid 21,23-lactone (5), gypsapogenin A (6), and (20S,24S)-3β,20,21β,23β,25- pentahydroxy-21,24-epoxydammarane (7). Five compounds were isolated from total saponins, including (20R,23R)- 3β,20-dihydroxydammar-24-en-21-oic acid 21,23-lactone 3-O-[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-6-O- acetyl-β-D-glucopyranoside (8), (20S,23S)-3β,20-dihydroxydammar-24-en-21-oic acid 21,23-lactone 3-O-[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-6-O-acetyl-β-D-glucopyranoside (9), (20R,23R)-19-oxo-3β,20-dihydroxydammar-24-en-21-oci acid 21,23-lactone3-O-[α-L-rhamnopyranosyl-(1→2)][β-D-xylopyranosyl(1→3)]-α-L-arabinopyranoside (10), (20S)-3β,20,21- trihydroxydammar-23,25-diene 3-O-{[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl(1→3)]-β-D-glucopyranosyl}-21-O-β- D-glucopyranoside (11), and (20S,23S)-3β,20-dihydroxydammar-24-en-21-oic acid and 21,23-lactone 3-O-[α-L-rhamnopyranosyl(1→2)][β-D-xylopyranosyl-(1→3)]-β-D-glucopyranoside (12). Conclusion: Beside compound 4, the other compounds showed inhibitory activity against α-glucosidase and PTP1B. For the α-glucosidase and PTP1B inhibitions assay, compound 9 indicated the strongest inhibitory effect with IC50 2.10 and 1.07 μmol/L, respectively.

Phytochemical Composition and Biochemical Studies of the Aqueous Leaf Extracts of Brillantaisia guianensis P. beauv on Alloxan Treated Wistar Albino Rats

The present study was carried out on the phytochemical composition and biochemical studies oftheleafextract ofBrillantaisia guinensis peuvon alloxan treated Wistar albinorats.The experimental rats were administered with 80mg/kgbodyweight of alloxan,viathetailvein.After five days treatment with alloxan, thetreatment with the extractscommenced. Extracts wereadministeredorallyat100,200and 300mg/kg bw(both tonormal andtreated rats) for twenty-one days.Metformin,which served as a standard drug was administered at50mg/kg. Chromatographicanalysisof thephytochemical content of the leaf extract, revealed the presence of flavonoids (30.7mg/100g), saponins(50.6mg/100g), phytosterol (6.22mg/100g), tannins (7.50mg/100g) and glycosides(29.3mg/100g). Comparedtotest and normalcontrol,the extractsdose-dependentlyand significantlylowered(P<0.05) plasmaglucose and triglycerides, during the experimental period. Thisstudy revealedthe presence of pharma cologically bioactive compounds inthelea fextract and showed that the leaf extract had a dose-dependent hypoglycemic and hypotriglyceridemic effect on the Wistaralbino rats. The findings suggest a likely protective role of the extracts against hyperglycemia and hypertriglyceridemia thereby useful in the treatment and management of diabetes mellitus, obesity and other related cardiovascular diseases.

A study on management of type 2 diabetic patients with complications

Background: Diabetes is a major public health problem both in developing and non-developing countries across the world. It is a chronic disease, which in long term causes several complications resulting in poly pharmacy for its management. Hence, this study was determined to analyze the drug utilization pattern for the management of type 2 diabetes with complications.Methods: A prospective, observational and non-interventional study was carried out in 100 diabetic patients with one or other complications admitted in medicine wards at Dhiraj Hospital. Patients who signed informed consent form were only included in the study. All the data were recorded from patients’ case files and analyzed.Results: Result of total 100 patients, maximum number 52 (52%) were falling in group of 61-70 kg and only 2 (2%) in 81-90 kg. Out of 100 diabetic patients, 40 (40%) were managed with insulin in addition to oral antidiabetic agents, 37 (37%) were managed with only Oral Hypoglycemic Agents (OHA) and 23 (23%) were managed with only insulin. The most commonly prescribed oral antidiabetic group of drug was Biguanides in 60 (60%) and most prescribed insulin was short acting Insulin in 40 (40%) patients.Conclusions: The diabetic patients are more prone to cardiovascular and other complications leading to a co morbid condition. The poly pharmacy is likely to occur in diabetic patients suffering with secondary complications. Therefore, intense blood sugar control with proper education can prevent the co morbid state and finally helps in reducing the economic burden.

The Effect of Aqueous Extract of MomordicaCharantia on Blood Glucose Level in Alloxan Induced Diabetic Rats

Introduction: Diabetes mellitus is one of the five leadingcauses of death in the world.Objective: Our main goal is to estimate the effect of aqueousextract of Momordica charantia on blood glucose level inalloxan induced diabetic rats.Methodology: This experimental study was carried out atDepartment of pharmacology, Dhaka medical college, Dhakafrom July 2014 to June 2015 where the study was divided intotwo parts, Experiment-1 and Experiment-2. In Experiment-1include group A and group B. Experiment-2 include group C,group D and group E. Blood was collected from group A andgroup B on day 1 and day 15 and from group C,D and E onday 1,4 and 15 of experiment.Results: During the result in group-A (served as control andreceived normal rat diet for 14 days) the blood glucose levels(mean ± SD) were 4.90±0.50 mmol/L and 5.3±0.38mmol/L onday 1 and day 15 respectively. Percent inhibition was 4.8 andin group-B the blood glucose levels (mean ± SD) were5.00±0.36mmol/L and 5.05±0.32 mmol/L on day 1 and 15respectively. Also for in group C, the blood glucose levels(mean ± SD) were 5.31± 0.45 and 14.24±.51 on day 1 andday 15 respectively.Conclusion: From the analysis we can conclude that thataqueous extract of Momordica charantia has hypoglycaemiceffect, thus provide a rational for its use in development of newdrug require for treatment and prevention of complications ofdiabetes mellitus.

Modulation of Glycemic Responses by "Nutricare-DM"- A Functional Food Formulation for Type 2 Diabetic Subjects

Introduction: The incidence of diabetes has reached alarming levels worldwide, and there is a high risk of developing associated disorders in diabetic subjects. An effective approach to combat type 2 diabetes is through dietary management. Methods:A functional food was formulated, namely "Nutricare DM" (N-DM), its nutritionally important starch fractions were determined (in-vitro), and its glucose lowering effect was studied by supplementing 50 g carbohydrate portion of the test food for a period of 4 months in type 2 diabetic subjects. Subjects who met the inclusion criteria were recruited based on willingness to participate. Anthropometric measurements, blood glucose levels, lipid profile and hepatic enzyme levels were studied before and after the study period. Results: The addition of functional ingredients, namely oats, barley, and rice bran as fibre sources positively influenced the Starch Digestibility Index (SDI). The SDI of Nutricare DM chapathi (13±1.01) was significantly (p<0.05) lower than that of the control chapathi ((20±1.00). Supplementation of Nutricare DM for 3 months decreased glycated haemoglobin (HbA,C) from 7.1+1.38 to 6.1 ± 0.95, while a gradual and consistent decrease in fasting blood glucose from 129 mg/dl to 99 mg/dl was observed. A significant decrease in the liver enzymes alanine aminotransferase (ALT) (from 47.69+ 7.84 to 36.06+4.351U/I) and aspartate aminotransferase (AST)(from 61.07+16.46 to 34.20+8.95 IU/I) indicated a protective effect of the nutritional intervention against liver damage. Conclusion: Results suggest that long term supplementation would be beneficial in modulating the glycaemic responses and hence serve as an effective dietary management.

Modulation of Glycemic Responses by "Nutricare-DM"- A Functional Food Formulation for Type 2 Diabetic Subjects

The incidence of diabetes has reached alarming levels worldwide, and there is a high risk of developing associated disorders in diabetic subjects. An effective approach to combat type 2 diabetes is through dietary management. Methods:A functional food was formulated, namely "Nutricare DM" (N-DM), its nutritionally important starch fractions were determined (in-vitro), and its glucose lowering effect was studied by supplementing 50 g carbohydrate portion of the test food for a period of 4 months in type 2 diabetic subjects. Subjects who met the inclusion criteria were recruited based on willingness to participate. Anthropometric measurements, blood glucose levels, lipid profile and hepatic enzyme levels were studied before and after the study period. Results: The addition of functional ingredients, namely oats, barley, and rice bran as fibre sources positively influenced the Starch Digestibility Index (SDI). The SDI of Nutricare DM chapathi (13±1.01) was significantly (p<0.05) lower than that of the control chapathi ((20±1.00). Supplementation of Nutricare DM for 3 months decreased glycated haemoglobin (HbA,C) from 7.1+1.38 to 6.1 ± 0.95, while a gradual and consistent decrease in fasting blood glucose from 129 mg/dl to 99 mg/dl was observed. A significant decrease in the liver enzymes alanine aminotransferase (ALT) (from 47.69+ 7.84 to 36.06+4.351U/I) and aspartate aminotransferase (AST)(from 61.07+16.46 to 34.20+8.95 IU/I) indicated a protective effect of the nutritional intervention against liver damage. Conclusion: Results suggest that long term supplementation would be beneficial in modulating the glycaemic responses and hence serve as an effective dietary management.

SECTION A: Pathophysiology of Type 2 Diabetes Mellitus in Children. SECTION B: Clinical scenario of Type 2 Diabetes mellitus in children. SECTION C: Epidemiology and Prevention of Type 2 Diabetes mellitus in children.

SECTION A: Pathophysiology of Type 2 Diabetes mellitus in children Dr. Jyoti Kini While Type 2 diabetes mellitus (T2DM) continues to be a disease of the elderly and the middle aged, currently there has been an upsurge in the incidence of T2DM in the adolescents and the young. Family history, maternal gestational diabetes, low birth weight have contributory role to play in the pathophysiology of T2DM. The pathophysiology underlying the development of alterations in glucose metabolism ranging from abnormal fasting glucose (AFG) to impaired glucose intolerance (IGT) is multifactorial. The early onset of diabetes in childhood or adolescence heralds a long disease interval with resultant escalation of the probability of development of co-morbidities and the entire range of macro- and microvascular complications. SECTION B: Clinical scenario of Type 2 Diabetes mellitus in children Dr. Mallikarjungowda S Patil Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder, characterized by peripheral insulin resistance and failure of beta cells to keep up with increasing insulin demand. T2DM children are usually obese, may present with mild symptoms of polyuria and polydypsia. A systemic approach for treatment of T2DM should be implemented according to the natural course of the disease, including adding insulin when oral hypoglycemic agents failure occurs. Life style modification is an essential part of management. When lifestyle interventions fail to normalize blood glucose, oral hypoglycemic agents are introduced for management of persistent hyperglycemia. SECTION C: Epidemiology and Prevention of Type 2 Diabetes mellitus in children Dr. Savindika Nawarathna , Dr. Animesh Jain Type 2 diabetes mellitus was considered rare amongst children, but recently the incidence has increased worldwide with almost half of the newly diagnosed cases being children and adolescents. Type 2 diabetes mellitus (T2DM) is primarily characterized by insulin resistance detected at the level of skeletal muscle, liver, and adipose tissues with a failure of β-cell compensation and a relative insulin deficiency. A variety of risk factors like race, obesity, insulin resistance, family history, psychococial factors, birth weight, exposure to maternal DM and breastfeeding can influence the development of T2DM. Type 2 DM screening in the paediatric population should be clinically focused and take into account not only those risk factors identified in the American Diabetes Association guidelines, but also the clinical context, pubertal status, and the results of simple screening measures such as fasting glucose and triglycerides. More outcome-based research is required before general screening, to identify children and adolescents with pre-diabetes or insulin resistance can be recommended. The pathophysiology underlying the development of alterations in glucose metabolism ranging from abnormal fasting glucose (AFG) to impaired glucose intolerance (IGT) is multifactorial. The early onset of diabetes in childhood or adolescence heralds a long disease interval with resultant escalation of the probability of development of co-morbidities and the entire range of macro- and microvascular complications.

Efficacy and safety of Tinospora cordifolia (Tc) as an add-on therapy in patients with type-2 diabetes.

Background: Type 2 diabetes has become a global epidemic. Tinospora cordifolia is being used in the treatment of type 2 diabetes since ancient times. It is a common misconception that Ayurvedic medicines are always safe. In fact, they also pose serious health risks either in the form of adverse reactions or in the form of drug interactions. Hence this study was undertaken to study the efficacy and safety of Tc on human subjects. Methods: We recruited 40 type 2 diabetic patients who were on oral hypoglycaemic agents. These patients were then randomly divided into two groups, A and B. Patients in group A continued with their anti-diabetic medications while in group B Tc was given at a dose of 500 mg three times daily along with their conventional medications. The fasting and post prandial blood glucose levels, renal function tests and liver function tests were recorded at baseline, 3 months and 6 months. Results: During the course of study we observed a decrease in the fasting and post prandial blood glucose levels of the patients. No significant change was observed in the renal function tests and liver function tests and no other event of any adverse drug reactions were recorded. Conclusion: Tinospora cordifolia (Tc) is effective as an add-on therapy in patients with type-2 diabetes. There is no negative impact of Tc on the renal as well as liver function tests.

Effect of oral hypoglycaemic agents on bone metabolism in patients with type 2 diabetes mellitus & occurrence of osteoporosis.

Background & objectives: Type 2 diabetes mellitus (T2DM) is considered to be a protective factor against development of osteoporosis. But oral hypoglycaemic agents (OHA) are likely to increase the risk of osteoporosis. This study was carried out to evaluate the effect of various OHA on bone mineral density (BMD) in patients with T2DM. Methods: Forty one patients (study group) with T2DM (mean age 51.9±5.5 yr; 31 females) receiving treatment with oral hypoglycaemic agents (OHA) [thiazolidinediones alone (n=14) or in combination with other OHA (n=27)] for a period of at least three consecutive years and 41 age- and gender-matched healthy controls (mean age 51.4±5.1 yr) were included in the study. A detailed clinical history was taken and all were subjected to physical examination and recording of anthropometric data. BMD was assessed for both patients and controls. Results: The mean body mass index (kg/m2) (26.5±4.90 vs 27.3 ±5.33) and median [inter-quartile range (IQR)] duration of menopause (yr) among women [6(2-12) vs 6(1-13)] were comparable between both groups. The bone mineral density (BMD; g/cm2) at the level of neck of femur (NOF) (0.761±0.112 vs 0.762±0.110), lumbar spine antero-posterior view (LSAP) (0.849±0.127 vs 0.854±0.135); median Z-score NOF {0.100[(-0.850)-(0.550)] vs -0.200[(-0.800)-(0.600)]}, LSAP {-1.200[(-1.700)-(-0.200)] vs -1.300 [(-1.85)-(-0.400)]} were also similar in study and control groups. Presence of normal BMD (9/41 vs 8/41), osteopenia (16/41 vs 18/41) and osteoporosis (16/41 vs 15/41) were comparable between the study and control groups. No significant difference was observed in the BMD, T-scores and Z-scores at NOF and LSAP among T2DM patients treated with thiazolidinediones; those treated with other OHA and controls. Interpretation & conclusions: The present findings show that the use of OHA for a period of three years or more does not significantly affect the BMD in patients with T2DM.

Antihyperglycemic Activity of Oil Palm Elaeis guineensis Fruit Extract on Streptozotocin-induced Diabetic Rats / Jurnal Sains Kesihatan Malaysia

Hypoglycaemic and antihyperglycemic activity of oil palm Elaeis guineensis fruit extract on normal and Streptozotocin-induced diabetic rats was studied. The oil palm fruit extract (OPF) were administered orally at different concentrations (100, 200 and 500 mg kg-1 b.w.) in fasting and post-prandial rats. Hypoglycaemia was not observed in the group of normal rats treated with OPF. In fasting rats, OPF (500 mg kg-1 b.w.) has caused the blood glucose level (BGL) to reduce significantly. For post-prandial diabetic rats, the antihyperglycemic activity was observed after OPF treatment at concentrations 200 and 500 mg kg-1. Chronic OPF treatments (for 28 days) had increased the diabetic rat’s body weight and reduced BGL as well as improved plasma insulin secretion. The result of this study suggests E. guineensis palm fruit extract show evidence of antihyperglycemic properties from the reduction of the BGL in diabetic rats.

Hypoglycemic and Hypolipidemic Activities of Methanolic Extract of Sphenocentrum jollyanum on Streptozotocin-induced Diabetic Wistar Rats.

Aims: This study is to provide scientific basis for the folkloric use of Sphenocentrum jollyannum roots in the management and/control of Diabetes mellitus. The effects of the extract on blood glucose level and serum lipid profile in Streptozotocin-induced diabetic rats was investigated. The efficacy was also compared with that of glibenclamide, a known antidiabetic drug. Study Design: Experimental Study. Place and Duration of Study: Department of Anatomy and Cell Biology, Obafemi Awolowo University, Ile-Ife, Nigeria and Department of Chemical Pathology, Ekiti State University Teaching Hospital, Ado Ekiti, Nigeria, between November, 2010 and April, 2012. Methodology: Twenty four adult Wistar rats were randomly divided into four groups (A, B C and D) of six rats each and used for this research. Diabetes mellitus was induced in groups B, C and D by a single intraperitoneal injection of streptozotocin (80mg/kg body weight) dissolved in 0.1 M citrate buffer. Group A, the control rats were intraperitoneally injected with an equivalent volume of citrate buffer. Group B diabetic rats were untreated while groups C and D received Methanolic extract of Sphenocentrum jollyanum (MESJ) (200mg/kg) and glibenclamide (0.5mg/kg) once daily for two weeks respectively. Results: The result showed a significant (P < 0.05) fall in blood glucose and serum lipid levels with MESJ and glibenclamide administration. A significant (P < 0.05) decrease in the raise of lipids in serum and improvement in the lipid levels to an almost normal condition was also observed. Conclusion: Sphenocentrum jollyanum roots possess hypoglycemic and hypolipidemic effects on diabetic rats lending credence to its use in the traditional management and/or control of Diabetes mellitus.

Hypoglycemic and Hypolipidemic Activities of Methanolic Extract of Sphenocentrum jollyanum on Streptozotocin-induced Diabetic Wistar Rats.

Aims: This study is to provide scientific basis for the folkloric use of Sphenocentrum jollyannum roots in the management and/control of Diabetes mellitus. The effects of the extract on blood glucose level and serum lipid profile in Streptozotocin-induced diabetic rats was investigated. The efficacy was also compared with that of glibenclamide, a known antidiabetic drug. Study Design: Experimental Study. Place and Duration of Study: Department of Anatomy and Cell Biology, Obafemi Awolowo University, Ile-Ife, Nigeria and Department of Chemical Pathology, Ekiti State University Teaching Hospital, Ado Ekiti, Nigeria, between November, 2010 and April, 2012. Methodology: Twenty four adult Wistar rats were randomly divided into four groups (A, B C and D) of six rats each and used for this research. Diabetes mellitus was induced in groups B, C and D by a single intraperitoneal injection of streptozotocin (80mg/kg body weight) dissolved in 0.1 M citrate buffer. Group A, the control rats were intraperitoneally injected with an equivalent volume of citrate buffer. Group B diabetic rats were untreated while groups C and D received Methanolic extract of Sphenocentrum jollyanum (MESJ) (200mg/kg) and glibenclamide (0.5mg/kg) once daily for two weeks respectively. Results: The result showed a significant (P < 0.05) fall in blood glucose and serum lipid levels with MESJ and glibenclamide administration. A significant (P < 0.05) decrease in the raise of lipids in serum and improvement in the lipid levels to an almost normal condition was also observed. Conclusion: Sphenocentrum jollyanum roots possess hypoglycemic and hypolipidemic effects on diabetic rats lending credence to its use in the traditional management and/or control of Diabetes mellitus.

Evaluation of the hypoglycaemic activity of Petiveria alliacea (Guinea Hen Weed) extracts in normoglycaemic and diabetic rat models / Evaluación de la actividad hipoglicémica de los extractos de Petiveria alliacea (Yerba de Guinea o Anamú) en modelos de ratas diabéticas y normoglicémicase

OBJECTIVE: Petiveria alliacea (p alliacea) has ethno-traditional use as a hypoglycaemic agent in Jamaica and is yet to be scientifically validated as such. Therefore, extracts of aerial parts of the plant were evaluated for hypoglycaemic activity in normoglycaemic and diabetic rats. METHODS: Aqueous and hexane extracts prepared from leaves of p alliacea were tested for hypoglycaemic activity. An acute administration of the extracts (200 and 400 mg/kg body weight) was evaluated in normoglycaemic rats. Additionally, the hypoglycaemic effect ofsub-chronic administration was assessed in streptozotocin-induced diabetic rats. Blood glucose was recorded using a glucometer and test strips. Data were analysed using Student's t-test (p < 0.05). RESULTS: The aqueous and hexane extracts demonstrated no significant reduction of fasting blood glucose (FBG) and no significant improvement of glucose tolerance in normal rats. The aqueous extract (400 mg/kg body weight) increased FBG from 4.75 ± 0.28 mmol/L to 5.88 ± 0.46 when compared to control (p < 0.001). In diabetic rats, the hexane extract (400 mg/kg body weight) caused reduction of FBG after two weeks of treatment (p < 0.010), but this was not sustained. The aqueous extract showed no reduction of FBG in diabetic rats. CONCLUSION: The aqueous extract of p alliacea demonstrated a hyperglycaemic effect in normoglycaemic rats and showed no hypoglycaemic activity in diabetic rats. The hexane extract caused no hypoglycaemic action in normal rats and failed to sustain an initial hypoglycaemic action in diabetic rats. This study presents evidence that does not support significant hypoglycaemic activity of p alliacea; this could hold significant implications for its use in ethno-traditional medicine.

OBJETIVO: Petiveria alliacea (p alliacea) tiene uso etnotradicional como agente hipoglicémico en Jamaica, y todavía requiere ser validado científicamente. Por lo tanto, extractos de las partes aéreas de la planta fueron evaluados en relación con su actividad hipoglicémica en ratas normoglicémicas y diabéticas. MÉTODOS: Extractos acuosos y extractos de hexanos preparados a partir de hojas de p alliacea fueron sometidos a prueba a fin de detectar su actividad hipoglicémica. Se evaluó el efecto de una administración aguda de los extractos (200 y 400 mg/kg de peso corporal) en ratas normoglicémicas. Además, se evaluó el efecto hipoglicémico de la administración subcrónica en ratas con diabetes inducida por estreptozotocina. La glucosa en sangre fue registrada usando un glucómetro y tiras reactivas. Los datos se analizaron mediante la prueba t de Student (p < 0.05). RESULTADOS: Los extractos acuosos y los extractos de hexano no mostraron reducción significativa alguna de la glucemia en ayunas (GA), ni tampoco ninguna mejora significativa de la tolerancia a la glucosa en ratas normales. El extracto acuoso (400 mg/kg de peso corporal) aumentó la GA de 4,75 ± 0,28 mmol/L a 5,88 ± 0,46 en comparación con el control (p < 0.001). En las ratas diabéticas, el extracto de hexano (400 mg/kg de peso corporal), trajo por consecuencia la reducción de GA tras dos semanas de tratamiento (p < 0.010), pero este efecto no se mantiene. El extracto acuoso no mostró ninguna reducción de GA en las ratas diabéticas. CONCLUSIÓN: El extracto acuoso de p alliacea mostró un efecto hiperglicémico en las ratas normoglicémicas, y no mostró ninguna actividad hipoglicémica en las ratas diabéticas. El extracto de hexano no produjo ninguna acción hipoglicémica en ratas normales, y no mantuvo la acción hipoglicémica inicial en las ratas diabéticas. Este estudio presenta evidencias que no respaldan una actividad hipoglicémica significativa de p alliacea, lo cual podría tener importantes implicaciones para su uso en la medicina etnotradicional.

Antidiabetic Effect of Pleurotus ostreatus (Jacq.ex Fr) kumm.Mushroom on Alloxan-induced Diabetic Rats.

Antidiabetic effects of ethanolic extract of Pleurotus ostreatus (mushroom) on alloxan-induced diabetic rats was studied. The median lethal dose (LD50) of the extract was determined to be 3,472.14 mgkg-1 and a single dose of 380.0, 760.0 and 1140.0 body weight of the extract were intraperitoneally administered as the treatment dose and the blood glucose levels (BGL) examined for 7 hours and 15 hours (prolonged) at 2 and 4 hours intervals respectively. The extract exhibited significant (p<0.05 and p<0.01) reduction in the blood glucose levels of the albino rats. The extract compared favourably with the standard reference drug (metformin) which all gave their maximum BGL reduction at 5 hours duration. The confirmation of antidiabetic potentials of the Pleurotus ostreatus tuber has been justified in this study as claimed by traditional medicine practitionersin Akwa Ibom State.

Evaluation of hypoglycaemic and hypolipidemic activities of Globularin isolated from Globularia alypum L. in normal and streptozotocin-induced diabetic rats.

The present study investigates the effect of intraperitoneal administration of Globularin on blood glucose levels in normal and streptozotocin diabetic rats. Globularin was an iridoid glucoside which was isolated from the leaves of Globularia alypum (3.4 %). This compound was identified by means of physical constants and spectral data UV, IR, MS, 1H-NMR, 13C-NMR, DEPT, COSY, HMBC. The acute toxicity test demonstrated that Globularin is not lethal up to dose of 1000 mg/kg body weight after intraperitoneal injection. In normal and streptozotocin diabetic rats, single intraperitoneal administration of Globularin at a dose 100 mg/kg body weight produced significant decrease of blood glucose levels. However, in prolonged treatment study, the repeated intraperitoneal administration of Globularin (2 x 100 mg/kg body weight) decreased significantly the blood glucose levels when compared to the diabetic control rats. In addition, daily injection of Globularin (2 x 100 mg/kg body weight) reduced significantly serum levels of total cholesterol (varied from 0.53 to 0.41 g/L) and triglycerides (varied from 1.71 to 0.79 g/L) in the diabetic rats.

Anti-diabetic Activity of Aqueous Extracts of Vitex doniana Leaves and Cinchona calisaya Bark in Alloxan–Induced Diabetic Rats.

Vitex doniana Sweet and Cinchona calisaya WEED are tropical medicinal plants endued with important pharmacological properties. The effects of aqueous extracts of V. doniana leaves and C. calisaya bark on alloxan-induced diabetes mellitus in Wistar albino rats were evaluated. Diabetes mellitus was induced by a single intraperitoneal ( i.p) injection of 150 mg/kg body wt of alloxan monohydrate. The aqueous extracts of V. doniana leaves and C. calisaya bark were administered intraperitoneally to four diabetic groups at same doses of 50 and 100 mg/kg body wt. The actions of the extracts were compared with that of the standard oral hypoglycaemic agent, glibenclamide. Both extracts caused significant (p < 0.001) decreases in blood sugar levels of the rats at both doses tested. At 50 mg/kg body wt. V. doniana leaf extract produced 82.9% reduction in blood sugar level (i.e from 492.8 to 84.5 mg/dl) after four days whereas, C. calisaya caused 64.4% decrease. Unlike C. calisaya bark, V. doniana at both doses tested, was more potent than the reference drug, glibenclamide (0.3 mg/ kg body wt.). The antidiabetic activity of V. doniana did not vary with the dose, whereas the observed effect of C. calisaya decreased with increase in dose. C. calisaya exhibited higher antidiabetic activity at a lower dose of 50 mg/kg body wt. Both medicinal plants therefore possess valuable antidiabetic property. Their effects on the antioxidant status were also investigated. V. doniana and C. calisaya extracts caused increases in the activity of SOD and lipid peroxidation when compared with control, but the increases were lower than that produced by alloxan, indicating attenuation of free radical generation. Quantitative phytochemical analyses of both extracts showed the presence of saponins(0.92%), flavonoids(7.05%), alkaloids(1.8%), and cardiac glycosides(2.8%) in V. doniana, whereas saponins(2.0%), flavonoids(5.0%), alkaloids(6.0%), and cardiac glycosides(3.54%) were detected in C. calisaya.

Pharmacological and Pharmaceutical Profile of Gliclazide: A Review.

Gliclazide is a second generation sulphonylurea oral hypoglycaemic agent used in the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It improves defective insulin secretion and may reverse insulin resistance observed in patients with NIDDM. These actions are reflected in a reduction in blood glucose levels which is maintained during both short and long term administration, and is comparable with that achieved by other sulphonylurea agents. Gradually accumulating evidence suggests that gliclazide may be useful in patients with diabetic retinopathy, due to its haemobiological actions, and that addition of gliclazide to insulin therapy enables insulin dosage to be reduced. Thus, gliclazide is an effective agent for the treatment of the metabolic defects associated with NIDDM and may have the added advantage of potentially slowing the progression of diabetic retinopathy. These actions, together with its good general tolerability and low incidence of hypoglycaemia have allowed gliclazide to be well placed within the array of oral hypoglycaemic agents available for the control of NIDDM.