Effects of co-administration of methanol leaf extract of Catharanthus roseus on the hypoglycemic activity of metformin and glibenclamide in rats

Objective:To investigate the interacting effects of co-administration of methanol leaf extract of Catharanthus roseus（C.roseus） on the hypoglycemic activity of metformin as well as glibenclamide using experimental rats.Methods:Phytochemical analysis as well as acute toxicity and lethality(LD50) test were carried out on its methanol leaf extract.The alloxan model for experimental induction of diabetes in rats was employed.Six groups comprising five rats each were used.GroupsⅡ,ⅢandⅣreceived 250 mg/kg of extract,100 mg/kg of metformin and 1 mg/kg of glibenclamide respectively,while V and VI were administered metformin-extract and glibenclamide-extract combinations respectively at doses as above.Group I served as negative control and received only distilled water.All administration was done once daily for seven days. Fasting blood glucose was determined at 2,12,24,72 and 168 h using a glucometer.One-way ANOVA with post-hoc tests was used to assess for significant difference due to administration of drug alone and with co-administration of drug and extract.Results:The LD50 was 2 121.32 mg/kg. The phytochemical studies indicated the presence of saponins,tannins,alkaloids,phlotatannins, flavonoids,triterpenoids,reducing sugars,anthraquinones and glycosides.All medicaments significantly reduced blood glucose levels when compared with control alone（P【0.05） with the highest percentage reduction in blood glucose（64.86%） exhibited by metformin-extract combination.Conclusions:The leaf extract of C.roseus significandy increases the hypoglycemic effect of metformin.

Effects of long-term monotherapy with glimepiride vs glibenclamide on glycemic control and macrovascular events in Japanese Type 2 diabetic patients

We investigated whether long-term glimepiride (GP) monotherapy improves insulin resistance and exerts a beneficial effect on beta cell function, as compared with glibenclamide (GC). One hundred Japanese Type 2 diabetic patients were randomly assigned to the GP (n = 50) or the GC (n = 50) group. During a 5-year monitoring period, patients received the indicated SU monotherapy, while changes in SU doses were allowed as needed to maintain HbA1C below 7.0%. The GC group, in parallel with fasting insulin, showed a rapid homeostatic model assessment (HOMA)-R increase and maintained a high HOMA-R level. In contrast, HOMA-R in the GP group decreased continuously, from 2.9 at baseline to 1.8 at study completion. In the GC group, HOMA-b was markedly increased in the first 6 months, then gradually decreased through 18 months. While the HOMA-β elevation in the GP group was more moderate than that in the GC group, HOMA-β levels were maintained with a slight decrease. The cumulative macrovascular disease outcome was 1 for the GP and 7 for the GC group, showing a significant difference. These results suggest that glimepiride monotherapy markedly improved HOMA-R with moderate insulin stimulation, which may account for the difference in macrovascular disease development as compared with the group receiving glibenclamide.

Autophagy induced by glibenclamide serves as a defense against apoptosis in INS-1 rat insulinoma cells

Glibenclamide, a blocker of ATP-sensitive potassium channels, has been found to induce apoptosis in some cell types, including pancreatic beta-cells. Since autophagy plays doubleedged roles in pancreatic beta-cell survival, frequently through cross-talking with apoptosis, we investigated if glibenclamide induced autophagy in INS-1 rat insulinoma cells and the influence of autophagy on apoptosis. Mammalian target of rapamycin (mTOR) is a negative regulator of autophagy. As one of the substrates of mTOR, p70 S6 kinase (p70 S6K) is phosphorylated upon mTOR activation. Our results showed that glibenclamide induced an elevated protein level of the autophagy marker LC3-II, while decreasing phosphorylated p70 S6K, indicative of inhibition on mTOR signaling in INS-1 cells. Furthermore, inhibiting glibenclamide-induced autophagy via knocking down the autophagy essential gene Atg7 decreased cell viability and increased apoptosis in INS-1 cells. Our results indicate that glibenclamide induces autophagy in INS-1 cells, and that autophagy activation is exerting a protective activity against apoptosis.

Effect of 'Double C' therapy combined with glibenclamide in the treatment of GDM patients and its influence on serum omentin-1 and VF levels

Objective: To analyze the effect of 'double C' therapy combined with glibenclamide in the treatment of GDM and its influence on serum omentin-1 and VF levels. Methods: 100 patients with GDM admitted to our hospital from January 2016 to May 2018 were randomly divided into observation group and control group. The control group was treated with routine treatment, while the observation group was treated with 'double C' therapy combined with glibenclamide. Blood sugar level, cesarean section rate, premature delivery rate, pregnancy-induced hypertension rate, fetal distress and incidence of macrosomia were investigated. The levels of omentin-1 and VF in serum were measured. Results: The levels of HbA1c, FPG, 1 h PBG and 2 h PBG in blood of the two groups before delivery were significantly lower than those of the control group (P<0.05), and the levels of HbA1c, FPG, 1 h PBG and 2 h PBG in the observation group were significantly lower than those in the control group (P<0.05);the levels of omentin-1 and VF in the two groups before delivery were significantly higher (P<0.05), and the levels of omentin-1 in the observation group were significantly higher than those in the control group (P<0.05). After treatment, the rate of cesarean section, premature delivery, pregnancy-induced hypertension, fetal distress and macrosomia in the observation group were higher than those in the control group, and the difference was statistically significant (P<0.05). Conclusions: The combination of double C therapy and glibenclamide can improve the curative effect of GDM and the levels of omentin-1 and VF in blood.

Optimization of Isolation and Identification Conditions of Glibenclamide Annotation

A method for dispersive liquid-liquid microextraction of glibenclamide on model mixtures with urine has been developed. The extraction conditions have been optimized and the influence of extractants and dispersing agent for allocation of toxicant from biosubstrate has been experimentally established. The method of TLC （thin layer chromatography） screening in order to remove endogenous and exogenous substances has been developed. The method of IR-spectroscopy for confirmatory analysis has been used. The combination of the two methods of analysis allows identifying glibenclamide quickly and reliably isolated from bioliquid and reducing the risk of false-positive results.

Effects of low dose Glibenclamide on secondary damage after acute spinal cord injury in rats

Objective To investigate the effects of Glibenclamide on reduction of secondary damage after acute spinal cord injury in rats.Methods Ninety rats were randomly divided into control group(laminectomy alone),spinal cord injury group(injury group),and treatment group(treated

Glibenclamide pretreatment attenuates early hematoma expansion of warfarin-associated intracerebral hemorrhage in rats by alleviating perihematomal blood-brain barrier dysfunction

Background Hematoma expansion is a determinant of poor outcome of intracerebral hemorrhage but occurs frequently,especially in warfarin-associated intracerebral hemorrhage(W-ICH).In the present study,we employ the warfarin-associated intracerebral hemorrhage(W-ICH)rat model,to explore the efficacy and potential mechanism of glibenclamide pretreatment on hematoma expansion after intracerebral hemorrhage,hoping to provide proof of concept that glibenclamide in stroke primary and secondary prevention is also potentially beneficial for intracerebral hemorrhage patients at early stage.Methods In the present study,we tested whether glibenclamide,a common hypoglycemic drug,could attenuate hematoma expansion in a rat model of W-ICH.Hematoma expansion was evaluated using magnetic resonance imaging;brain injury was evaluated by brain edema and neuronal death;and functional outcome was evaluated by neurological scores.Then blood-brain barrier integrity was assessed using Evans blue extravasation and tight junction-related protein.Results The data indicated that glibenclamide pretreatment significantly attenuated hematoma expansion at 24 h after W-ICH,thus mitigating brain edema and neuronal death and promoting neurological function recovery,which may benefit from alleviating blood-brain barrier disruption by suppressing matrix metallopeptidase-9.Conclusions The results indicate that glibenclamide pretreatment in stroke primary and secondary prevention might be a promising therapy for hematoma expansion at the early stage of W-ICH.

Administration of Fenugreek Seed Extract Produces Better Effects in Glibenclamide-Induced Inhibition in Hepatic Lipid Peroxidation: An in vitro Study

Objective: To evaluate the comparative effects of fenugreek(Trigonel a 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(Fe So4),hydrogen peroxide(H2 O2) and carbon tetrachloride(CCl4) and the effects of test seed extract and/or GLB were evaluated.Results: While Fe So4,H2 O2 and CCl4 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,chemical y 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'-azino-bis,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 mel itus and other diseases that are LPO mediated.

Changes in the pharmacokinetics of glibenclamide in rats with streptozotocin-induced diabetes mellitus

The aim of this study was to investigate the pharmacokinetics of glibenclamide(Gli)administrated orally and intravenously to normal and diabetic rats.The AUC(0–720 min)of orally administered Gli in diabetic rats(321.24 mg min/L)was greater than that(57.752 mg min/L)in normal rats.CL(0.019 L/min/kg)was significantly slower than that(0.092 L/min/kg)of normal rats.The AUC(0–480min)of intravenous Gli in diabetic rats(1528.280 mg min/L)also was significantly greater than that(509.523 mg min/L)in normal rats,and CL was decreased approximately 3-fold.No significant difference in intestinal absorption of Gli was observed between normal and diabetic rats as determined by in situ single-pass intestinal perfusion.The clearance of Diclofenac(a substrate of CYP2C9)was determined to evaluate changes in hepatic drug-metabolizing enzyme activity in rats.The CL in diabetic rats was significantly lower(42.43%decrease)than that in normal rats.Hepatic protein expression of CYP2C9 was measured using Western blot analysis;compared with normal rats,the hepatic protein expression of CYP2A9 was decreased in diabetic rats.Therefore,the slower clearance of Gli in diabetic rats can be attributed primarily to the lower expression of hepatic CYP2C9.

Hypoglycemic efficacy of Ocimum gratissimum and Vernonia amygdalina compared with insulin and glibenclamide in type Ⅰ and type Ⅱ diabetic rat models

Objective: To compare the efficacy of Ocimum gratissimum (O. gratissimum) and Vernonia amygdalina (V. amygdalina) with those of insulin and glibenclamide.Methods: Type Ⅰ and Ⅱ diabetes mellitus (DM) were induced by a single intraperitoneal injection of 65 mg/kg of streptozotocin and intraperitoneal administration of nicotinamide (100 mg/kg) along with streptozotocin, respectively. The state of diabetes was confirmed weekly by testing blood glucose level using a glucometer.Results: The weekly blood glucose levels were higher in type I DM than in type Ⅱ DM. Type Ⅰ DM plus O. gratissimum showed a weekly progressive significant reduction in blood glucose compared to type Ⅰ DM control. Type Ⅰ DM control showed a duration dependent significant higher blood glucose concentration compared to normal control. Type I DM plus V. amygdalina also showed a time dependent significant lower glucose level compared to normal control and type Ⅰ DM control. Combination treatment of type Ⅰ DM (O. gratissimum plus V. amygdalina) showed a significantly elevated glucose concentration compared to normal control which was similar to type I DM control. Insulin treatment in type I DM showed a weekly progressive significant reduction of glucose concentration compared to normal control and type I DM control. Type Ⅱ DM control showed a fairly constant blood glucose concentration throughout the duration of treatment that was significantly higher than that of the normal control. Type Ⅱ DM plus O. gratissimum showed a fairly steady significant reduction of glucose concentration compared to type Ⅱ DM control and normal control. Type Ⅱ DM plus V. amygdalina also showed a fairly constant significant reduction of glucose concentration compared to type Ⅱ DM control and normal control. Type II DM (O. gratissimum plus V. amygdalina) showed a slightly progressive significant reduction of glucose concentration compared to normal control and type Ⅱ DM control. Type Ⅱ DM with glibenclamide showed almost steady significant reduction in glucose concentration compared to normal control and type Ⅱ DM control. Conclusions: From the result, it is evident that O. gratissimum and V. amygdalina administration produces more potent hypoglycemic activity than insulin and glibenclamide in type I and Ⅱ DM models, respectively.

UV Spectroscopic Method for Optimization and Determination of Glibenclamide in Bulk,Pharmaceutical Dosage Form and its Application for In Vitro Interaction Studies

A simple,easy and cost-efficient UV spectroscopic method was developed and validated for glibenclamide,the second generation of sulfonylureas,using 0.1 N NaOH as a solvent.The proposed method is linear(R^(2)>0.999)with the range 5-25μg mL^(−1),accurate(99.60%),precise(inter and intraday variation 0.241 and 0.019%,respectively)and robust(<1%).The quantification and detection limit were 1.46 and 0.48μg mL^(−1),respectively.The validated method was applied for in vitro interaction studies of glibenclamide(GLB)with commonly prescribed quinolones(ciprofloxacin,levofloxacin,moxifloxacin,and gemifloxacin)and nonsteroidal anti-inflammatory drugs(NSAIDs)(diclofenac sodium,ibuprofen,mefenamic acid,and aspirin)using UV spectrophotometer.The in vitro interaction studies were carried out in different artificially prepared physiological buffers at 37°C for 2 h.Results showed raised level of glibenclamide when interacted with gemifloxacin(pH 7.4),levofloxacin(pH 9),ciprofloxacin(pH 4.5)and with moxifloxacin(pH 4.5,7.4 and 9).Interaction with NSAIDs results in increased%availability of glibenclamide in the presence of diclofenac sodium,ibuprofen,and mefenamic acid at pH 4.5.The anticipated method can be successfully applied for the routine analysis and also for the interaction of glibenclamide with other drugs.

In vitro α-amylase inhibitory activity and in vivo hypoglycemic effect of methanol extract of Citrus macroptera Montr.fruit

Objective:To investigate the therapeutic effects of methanol extract of Citrus macroptera Montr,fruit inα-amylase inhibitory activity(in vitro)and hypoglycemic activity in normal and glucose induced hyperglycemic rats(in vivo).Methods:Fruits of Citrus macroptera without rind was extracted with pure methanol following cold extraction and tested for presence of phytochemical constituents,α-amylase inhibitory activity,and hypoglycemic effect in normal rats and glucose induced hyperglycemic rats.Results:Presence of saponin,steroid and terpenoid were identified in the extract.The results showed that fruit extract had moderateα-amylase inhibitory activity[IC_(50)value=(3.638±0.190)mg/mL]as compared to acarbose.Moreover at 500 mg/kg and 1000 mg/kg doses fruit extract significantly(P<0.05 and P<0.01 respectively)reduced fasting blood glucose level in normal rats as compared to glibenclamide(5 mg/kg).In oral glucose tolerance test,500 mg/kg dose significantly reduced blood glucose level(P<0.05)at 2 h but 1000 mg/kg dose significantly reduced blood glucose level at 2 h and 3 h(P<0.05 and P<0.01 respectively)whereas glibenclamide(5 mg/kg)significantly reduced glucose level at every hour after administration.Overall time effect is also considered extremely significant with F value=23.83 and P value=0.0001 in oral glucose tolerance test.Conclusion:These findings suggest that the plant may be a potential source for the development of new oral hypoglycemic agent.

And-hyperglycemic activity of leaves extract of Hyptis suavcolens L.Poit in streptozotocin induced diabetic rats

Objective:To evaluate the antihyperglycemic activity of leaves of Hyptis suaveolens using streptozotocin model.Mothods:Hyptis suaveolens extract(HSE) 250 and 500 mg/kg body weight was administered orally to streptozotocin induced diabetes,once daily for 21 days.Results:A significant reduction in blood glucose was observed in diabetic animals treated with HSE at different doses when compared with diabetic rats.Levels of triglyceride,total cholesterol,low density lipoprolein.very low density lipoprotein were decreased while administering HSE at different doses,compared with their control values in diabetic animals.Conclusions:Our results show that HSE possesses significant antihyperglycemic activity which might be attributed to stimulating effects on glucose utilization and antioxidant enzyme.

Histological changes and antidiabetic activities of Icacina trichantha tuber extract in beta-cells of alloxan induced diabetic rats

Objective:To investigate the antidiabetic,hypolipidaemic activities and histopathological changes ofIcacina trichantha(I.trichantha)tuber extract in alloxan induced diabetic rats.Methods:In the present study,80%methanol extract of I.trichanthatuber was tested on alloxan induced diabetic rats.They were randomly grouped into control(distilled water and glibenclamide)and experimental(200,400 and 600 mg/kg body weight).Diabetes was induced by a single intraperitoneal injection of 160 mg/kg body weight of alloxan.Blood glucose levels weremeasured using blood glucose test strips with AccuCheck Advantage II glucometer at 1,3,6,and 24 h on the first day and 1 h after treatment on Day 7,14 and 21.Blood samples were collected and centrifuged to separate serum for estimation of lipid profile and other biochemical parameters.Histopathological changes in diabetic rats pancreas were also studied after extract treatment.Results:Daily oral administration ofI.trichanthatuber extract(200,400,and 600 mg/kg bodyweight)and glibenclamide(2 mg/kg)showed beneficial effects on blood glucose level(P<0.01)as well as improving liver,kidney functions and hyperlipidaemia due to diabetes.The extract had a favourable effect on the histopathological changes of the pancreas in alloxan induced diabetes.Conclusions:I.trichanthatuber extracts posses antidiabetic activities as well as improve liver and renal profile and total lipids levels.I.trichanthatuber extracts also have favourable effects to inhibit the histopathological changes of the pancreas in alloxan induced diabetes.

Comparative study between the effect of <i>Momordica charantia</i>(wild and hybrid variety) on hypoglycemic and hypolipidemic activity of alloxan induced type 2 diabetic long-evans rats

This study was undertaken to evaluate the hypoglycemic and hypolipidemic effect of Momordica charantia (wild and hybrid variety) powder on alloxan induced type 2 diabetic male Long-Evans rats. Oral feeding of the M. charantia powder slightly decreased serum total cholesterol, triglyceride levels and LDL-cholesterol compared with wild, hybrid and standard drug. M. charantia wild variety showed more significant (p M. charantia did not show any significant effect on HDL-cholesterol and liver glycogen. Thus, results of the study prove that the wild variety of M. charantia fruit have potent antidiabetic and antilipidemic property.

Antidiabetic Drugs in Combination with Hydroxychloroquine Improve Glycemic Control in Alloxan Induced Diabetic Rats

Worldwide prevalence of diabetes mellitus has become an issue of great concern in current decades. This life threatening disease is associated with worsening of glycemic control and progressive metabolic dysfunctions. Objective: Current study aimed to investigate the effect of hydroxychloroquine (HCQ) as an adjunct to glibenclamide or metformin on glycemic control in alloxan induced diabetic rats. Methods: HCQ was combined separately with two conventional anti-diabetic drugs;glibenclamide and metformin. At first, alloxan (120 mg/kg) induced diabetic rats were treated with single dose of metformin (850 mg/70 kg BW), glibenclamide (10 mg/70 kg BW) and HCQ (300 mg/70 kg BW) intraperitoneally once daily for two weeks. Then non fixed dose combinations of glibenclamide (5 mg/70 kg BW) with HCQ (150 mg/70 kg BW) and metformin (425 mg/70 kg BW) with HCQ (150 mg/70 kg BW) were injected along with those of the three drugs alone once daily for four weeks. Results: In alloxan induced diabetic rats, glibenclamide, metformin and their combination therapies reduced blood glucose level significantly but combination therapies are the most effective. Glibenclamide or metformin in combination with HCQ also significantly (P < 0.05) reduced the elevated levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol (LDL-C) level and increased high density lipoprotein cholesterol (HDL-C) level. Moreover, HCQ potentiates the liver glycogen synthesis of metformin or glibenclamide. Conclusion: Outcomes of this investigation indicate that combination of glibenclamide or metformin with HCQ improves glycemic control and provides additional metabolic benefits, not achieved with either glibenclamide or metformin alone.

Identified Analytical Profile for Microelements, Trace Metals, Amino Acids and Screening of Anti-Diabetic Activity from Flower and Leaf Extracts of Moringa oleifera in Streptozotocin (STZ)-Induced Diabetic Rats

Background: Moringa oleifera plant is popularly known for its rich phytoconstituents and nutritional value and important medicinal values in both traditional and modern systems of medicine. We explored the present study for measurements of microelements, amino acid, phenolic content in hydro-al-coholic flower and leaf extracts of Moringa oleifera along with anti-diabetic activity in Streptozotocin (STZ)-induced diabetic male Wistar rats. Methodology: The micronutrients were determined by using atomic absorption spectrophotometer at 285 nm and 422 nm for Calcium (Ca), phosphorus (P), Iron (Fe), and Zinc (Zn), etc. The trace elements were also measured by spectrophotometer. The essential amino acid was determined by using Amino acid analyser. The total phenolic content in hydro-alcoholic extracts (flower and leaf) M. oleifera measured the absorbance at 760 nm by UV spectrophotometer. The screening of anti-diabetic activity HAFE and HALE of Moringa oleifera at two different dose of 100 and 200 mg/kg b.w. for 21 days were performed by determining the changes in biochemical parameters. Result and Discussion: The results revels that the presence of micronutrients, trace elements and amino acids in both flower and leaf of M. oleifera. The hydrolaocholic extracts of HAFE and HALE at 200 mg/kg b.w. showed significant antidiabetic activity compared with standard Glibenclamide. Whereas dose at 100 mg/kg b.w. showed moderate activity. Conclusion: In conclusion, the M. oleifera exhibits more effectiveness against STZ-induced diabetes. The HAFE and HALF extracts exhibited significant anti-diabetic property and active components may be isolated and clinical studies is required for further evaluation. Because of the rich source of phytoconstients, nutritional elements will be helpful in processed food products as dietary supplements especially for malnutrition in children in the current era.

Antidiabetic Potential of Carthamus oxycantha M.Bieb. Seeds in Alloxan Induced Diabetic Rats

Ethnopharmacological Relevance: Diabetes Mellitus is one of the most common disorders of metabolic abnormalities. It is characterized by hyperglycemia followed by abnormalities in insulin release, insulin work, or both. This persistent hyperglycemia is concerned with long-term complications, dysfunction and collapse of various organs, notoriously the kidneys, heart, nerves, blood vessels and eyes. The seeds of the Carthamus oxycantha have been used by the practitioners as a traditional remedy for diabetes mellitus in the rural areas of district Jhang as well as other areas of Pakistan. Aim of the Study: The purpose of the present study was to reveal the antidiabetic capability of seeds of Carthamus oxycantha in short-term and long-term studies. Materials and Methods: Aqueous ethanolic extract of seeds was prepared by a rotary evaporator. The antidiabetic activity of the seeds was assessed by using normoglycemic and glucose loaded rats. However, two kinds of studies i.e. short-term as well as long-term treatment were carried out in alloxan induced diabetic rats for the finalized both doses i.e. 50 mg/kg and 100 mg/kg. Blood samples were tested by an electrochemical technique using a glucometer. Results: The promising results were achieved for the antidiabetic potential of the ethanolic extract of seeds of Carthamus oxycantha at both of the doses i.e. 50 mg/kg and 100 mg/kg. The antihyperglycemic potential was also evaluated in normoglycemic and glucose loaded animals. Treatment with 100 mg/kg AEECO presented significant reduction (p < 0.05) as well as highly significant reduction (p < 0.01) in short term and long term study. Statistical data showed that AEECO presented comparable effects to that of the standard drug Glibenclamide at 0.5 mg/kg. Phytochemical studies of AEECO also disclosed the presence of flavonoids, resins, glycosides, steroids and alkaloids. In conclusion, the antidiabetic properties of AEECO may be attributed either due to the release of insulin or possibly due to the peripheral uptake of glucose. It may also be due to protection of beta cells from toxic effects of alloxan or the presence of flavonoids may exhibit various biological activities as they have been stated for their antidiabetic potential. However, further studies are required to explore the active moieties responsible for antidiabetic potential.

Investigatory Study of Long Term Doses of <i>Costus afer</i>, Snail Slime, and Their Combination with a Standard Pharmaceutical Drug on Blood Glucose Level of Alloxan Induced Swiss Albino Rat

The Plant, Costus afer Ker Gawl. belongs to the family of Costaceae and has various uses where they exist. Their use in folk medicine and phytomedicine is in the treatment and management of variety of human ailment, like diabetes mellitus, abdominal problems etc. The search for new antidiabetic therapies has become increasingly urgent due to the development of adverse effects and resistance by the chemically synthesized drugs on one hand and effectiveness with low cost of the plant materials on the other hand. The investigations carried out is to determine the long term effects of Costus afer leaf methanol extract, snail slime and the combined Costus afer and snail slime extracts on blood glucose levels of alloxan induced diabetic Swiss albino rats treated orally for 21 days on graded dose of (100 mg/kg and 300 mg/kg). From the determination, the snail slime showed positive effect on blood glucose lowering level but less effective when compared with similar dose of the Costus afer leaf methanol extract. The investigation indicated that there was 103 mg/dL and 87 mg/dL blood glucose reduction for the low dose of Costus afer and Snail slime respectively while the standard hypoglycemic drug (Glibenclamide, 5 mg/kg) used for comparison yielded a blood glucose level reduction of 103 mg/dL. Similarly, the high dose used in the study gave a blood glucose reduction of 99 mg/dL and 95 mg/dL for Costus afer leaf methanol extract and Snail slime respectively. The results obtained when alloxan induced rats was treated with C. afer leaf methanol extract, Snail slime extract, and combined C. afer and snail slime extracts was analysed using Statistix 8.0 American version. The result showed a dose dependent fashion and the difference obtained from the compared results was statistically significant at p 1]. Still to that, medicinal and pharmacological activities of medicinal plants are often attributed to the presence of the so called secondary plant metabolites. Hence this regenerative capacity of snail slime and the fact that diabetes is characterized by damage of the pancreatic beta cells, may give credit to the hypoglycaemic effect observed in Costus afer methanol leaf extract and snail slime for possible drug formulation for anti-diabetic remedy. Our findings may approve snail slime which is insoluble in both acid and alkaline medium, to act as a carrier of chemical and biological nanoparticles for medical and pharmaceutical use.

Mathematical modeling of the biphasic dopaminergic response to glucose

In this work, we specify potential elements of the brain to sense and regulate the energy metabolism of the organism. Our numerical investigations base on neurochemical experiments demonstrating a biphasic association between brain glucose level and neuronal activity. The dynamics of high and low affine KATP channels are most likely to play a decisive role in neuronal activity. We develop a coupled Hodgkin-Huxley model describing the interactive behavior of inhibitory GABAergic and excitatory dopaminergic neurons projecting into the caudate nucleus. The novelty in our approach is that we include the synaptic coupling of GABAergic and dopaminergic neurons as well as the interaction of high and low affine KATP channels. Both are crucial mechanisms described by kinetic models. Simulations demonstrate that our new model is coherent with neurochemical in vitro experiments. Even experimental interventions with glibenclamide and glucosamine are reproduced by our new model. Our results show that the considered dynamics of high and low affine KATP channels may be a driving force in energy sensing and global regulation of the energy metabolism, which supports central aspects of the new Selfish Brain Theory. Moreover, our simulations suggest that firing frequencies and patterns of GABAergic and dopaminergic neurons are correlated to their neurochemical outflow.