Alloxan-induced Diabetic Animals Research Articles

Evaluation of metformin performance on alloxan-induced diabetic rabbits.

This study aimed to evaluate metformin as a widely used oral hypoglycemic agent and identify the effects on biochemical and antioxidant body systems of rabbits. Four groups of rabbits were randomly allocated as the control, the alloxan-induced diabetic, metformin-treated, and alloxan treated with metformin. The results revealed that alloxan leads to significant elevation in glucose (Glc) levels, malondialdehyde (MDA), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), triglycerides (TGs), and total cholesterol (TCH), and a significant decline in high-density lipoprotein (HDL) and glutathione (GSH) as compared with the control group. Metformin alone caused a significant decline in Glc and HDL with significant elevation in LDL and MDA without significant changes in TCH, TGs, VLDL, and GSH. When metformin was offered as a treatment for alloxan-induced diabetic animals, it caused a significant decline in Glc, TCH, TGs, LDL, and VLDL levels with significant elevation in GSH and without a significant change in HDL and MDA. Metformin causes a decline in glucose levels due to its ability to decrease the use of substances hepatic cells use to create glucose and its ability to induce the enzymes participating in glucose oxidation.

HYPOGLYCAEMIC EFFECTS OF JAVANESE GINSENG (Talinum paniculatum (Jacq.) Gaertn.) ROOT INFUSION ON ALLOXAN-INDUCED DIABETIC RATS

To examine whether Javanese ginseng root has an antihyperglycaemic effect, twenty-one male Rattus norvegicus rats were randomly divided into four groups: negative control (n= 3), positive control (n= 4), treatment (n= 7), and placebo (n= 7). Alloxan was injected intraperitoneally at a single dose of 80 mg/kg BW to rats to induce hyperglycaemia. Infusion of Javanese ginseng root or distilled water was given at a dose of 2% w/v solution with a volume of 1.8 mL/200 g BW per day for 14 days through an enteral feeding tube to either the treatment or placebo group, respectively. Blood glucose levels were measured using the colorimetric method. One-way analysis of variance (ANOVA) was used to examine differences in the mean of delta blood glucose (post intervention minus post alloxan blood glucose levels) among groups, followed by Tukey’s post hoc analysis. A P value 0.05 was considered statistically significant. There was a significant difference (P= 0.0001) in delta blood glucose among groups. Post hoc analysis revealed that delta blood glucose in the treatment group (-102.99±2.26 mg/dL) was significantly (P= 0.0001) greater than in the placebo (2.45±0.29 mg/dL), positive control (3.05±0.70 mg/dL) and negative control (1.60±0.17 mg/dL) grou p. In conclusion, Javanese ginseng root has potential as a hypoglycemic agent in alloxan-induced diabetic animal models

Hypoglycemic Activity of Aqueous Extract of Latex from Hancornia speciosa Gomes: A Study in Zebrafish and In Silico

Hancornia speciosa Gomes is a tree native to Brazil and has therapeutic potential for several diseases. Ethnopharmacological surveys have reported that the plant is used as a hypoglycemic agent and to lose weight. This study aimed to evaluate the effects of the aqueous extract from H. speciosa latex (LxHs) in a zebrafish model of diabetes. The extract was evaluated through high-performance thin-layer chromatography (HTPLC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FT-IR). We then tested treatments with LxHs (500, 1000, and 1500 mg/kg) by assessing blood glucose levels in alloxan-induced diabetic animals, and metformin was used as a control. The toxicity was evaluated through histopathology of the pancreas and biochemical assessment of serum levels of AST, ALT, creatinine, and urea. The extract was also assessed for acute toxicity through several parameters in embryos and adult animals. Finally, we performed in silico analysis through the SEA server and docking using the software GOLD. The phytochemical study showed the compounds cornoside, dihydrocornoide, and 1-O-methyl-myoinositol (bornesitol). The treatment with all doses of LxHs significantly decreased alloxan-induced hyperglycemia without any significant histological or biochemical abnormalities. No significant frequency of teratogenesis was observed in the embryos exposed to the extract, and no significant behavioral changes or deaths were observed in adult animals. In silico, the results showed a potential interaction between inositol and enzymes involved in carbohydrates’ metabolism. Overall, the results show a hypoglycemic activity of the extract in vivo, with no apparent toxicity. The computational studies suggest this could be at least partially due to the presence of bornesitol, since inositols can interact with carbohydrates’ enzymes.

Hypoglycemic effect of p-hydroxycinnamic diesters extracted from carnauba wax powder (Copernicia Prunifera) in alloxan-induced diabetic animals

Diabetes is a chronic non-transmissible disease and the number of cases is increasing every year. Plants appear as an alternative therapy since ancient civilizations. Among the species that have promising pharmacological activities are carnauba (Copernicia prunifera (Miller) H. E. Moore). Carnauba wax powder consists of a mixture of heterogenic compounds, among them, p-hydroxycinnamic diesters (HCA). Therefore, this study aimed to investigate the hypoglycemic effect of HCA in alloxan-induced diabetic animals. Therefore, this study was performed with 50 female Swiss mice, distributed in 5 groups (n = 10). The animals of the negative and positive control groups were treated with water: healthy and diabetic mice, respectively; animals of the HCA groups 25 and 50 were diabetic animals and they were treated with the HCA solution at doses of 25 and 50 mg / Kg, respectively; and with metformin, standard drug, at the dose of 200 mg / kg. After 28 days of HCA treatment, a significant hypoglycemic effect was observed in animals treated with HCA at the lowest dose tested (25 mg / kg). In the present study, HCA shown to be a promising compound with good scientific applicability due to the reduction of glycemia of diabetic animals induced by alloxan.

Methanol leaf extract of Momordica charantia protects alloxan-induced hepatopathy through modulation of caspase-9 and interleukin-1β signaling pathways in rats

Background and Aim:Momordica charantia is a highly valued plant, widely distributed in the tropical and subtropical regions. The plant is reported to have a wide range of medicinal uses. This study was designed to explore the ameliorative potential of M. charantia methanol leaf extract in alloxan-induced diabetic animal model with a particular focus on the liver.Materials and Methods:Hepatoprotective effect of methanol leaf extract of M. charantia was assessed in alloxan-induced toxicity in 50 rats divided into five groups (A-E) (n=10). Group A normal control, Group B was toxicant group, and Group C animals received glibenclamide treatment while Groups D and E received extracts at 200 and 400 mg/kg doses, respectively. The experiment lasted for 28 days. Histopathological changes, blood glucose level, and serum enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, oxidative status and caspase-9, and interleukin-1β (IL-1β) were evaluated.Results:Extract-treatment caused a decreased blood glucose level, markers of oxidative stress such as malondialdehyde and hydrogen peroxide (H2O2). Treatment of rats with leaf extract of M. charantia resulted in increased levels and activities of protein thiols, non-protein thiols, glutathione (GSH), glutathione peroxidase, glutathione S-transferase, and superoxide dismutase indicating its antioxidant potential. The liver section revealed mild distortion of the hepatic architecture compared to the toxicant group, while decreased expressions of caspase-9 and IL-1β in extract-treated groups was observed.Conclusion:The plant extract exhibited antioxidant, anti-apoptotic, and anti-inflammatory effects, thus showing its hepatoprotective property.

Chemical constituents of Cochlospermum regium (Schrank) Pilg. root and its antioxidant, antidiabetic, antiglycation, and anticholinesterase effects in Wistar rats

The main physiological consequence of diabetes mellitus is chronic hyperglycemia. This condition is related to the formation of free radicals including advanced glycation end products (AGES) and to an increase in inflammatory processes. Cochlospermum regium (Schrank) Pilg., part of the Bixaceae family, is a cerrado plant known for its anti-inflammatory effects. The objectives of this study were to analyze the constituent compounds of C. regium roots and to evaluate the antioxidant, antiglycation, antidiabetic, and anticholinergic effects of its hydromethanolic extract through in vitro and in vivo experimental models. The presence of phenols, flavonoids, condensed tannins, and flavonols was analyzed by liquid chromatography - photodiode array (LC/PDA) analysis. Whereas antioxidant activity was investigated via DPPH, ABTS, β-carotene/linoleic acid, and malondialdehyde colorimetric assays. Inhibition of AGEs was examined via a bovine serum albumin system whose glycosylating agent was glucose. Antidiabetic potential was examined in normoglycemic Wistar rats that received glucose overload, in alloxan-induced diabetic rats, and in rats that received a hyperglycemic diet. Disaccharidase inhibition was assessed using in vitro and in vivo methods, as was acetylcholinesterase (AChE) inhibition in brain structures. The hydromethanolic extract (CRHE) possessed a high concentration of phenolic compounds and showed antioxidant effects. The LC-DAD results revealed that CRHE contained a high concentration of phenolic acids and the majority was gallic acid. Treatment with CRHE caused significant inhibition of AGE formation. The oral glucose tolerance test (OGTT) in normoglycemic animals showed a reduction in blood glucose levels after treatment with 100 mg/kg CHRE, accompanied by an increase in hepatic glycogen content. There was also a significant reduction in the fasting glucose levels of alloxan-induced diabetic animals after 7 days of treatment with daily doses of 100 mg/kg. After 14 weeks of hyperglycemic diet, the last four or which were combined with 100 mg/kg CRHE treatment, there was a decrease in blood triglyceride levels. There was also a statistically significant decrease in the enzymatic activity of maltase, lactase and sucrase. The results demonstrate that oral administration of 30 and 100 mg/kg CRHE inhibited AChE activity in different brain structures. Thus, the extract of C. regium showed promising antioxidant, antiglycation, and antidiabetic effects that may be related to its high phenolic content.

EFFECTS OF CINNAMON EXTRACT IN DIABETIC RAT MODELS IN COMPARISON WITH ORAL HYPOGLYCEMIC DRUGS

Objective: To evaluate the anti diabetic effect of cinnamon extract in alloxaninduced diabetic animal model (albino rats) in comparison with oral hypoglycemic drugs. StudyDesign: An Experimental study. Place of Study: Al Tibri Medical College, Isra University, KarachiCampus. Duration of Study: December 2012 to December 2013. Materials and Methods: Total60 Albino rats of both genders were divided into 6 groups consisting of 10 rats in each group.Each group of animals was further divided into two sub groups containing 5 rats in each groupResults: The results obtained from the data indicated that there is significant reduction in bloodglucose level rats treated with low dose of cinnamon extract. The animals of low dose cinnamonextract (200mg/kg. bw) when compared with other groups; there is a reduction in the bloodglucose level in alloxan induced diabetic rats. Also tolbutamide and acarbose treated groupsshowed better antidiabetic effects as compared with cinnamon extract treated groups (pvalue<0.007 and p value<0.012 respectively), but cinnamon extract treated group showedsynergetic effects when it was given in combination with tolbutamide or acarbose havingsignificant p value<0.001 and p value<0.011 respectively. Conclusions: Tolbutamide andAcarbose showed better anti diabetic effect in comparison with cinnamon extract treated groupswhen used individually. This effect was enhanced when cinnamon was used in combination witheither tolbutamide or acarbose.

Taxifolin prevents postprandial hyperglycemia by regulating the activity of α-amylase: Evidence from an in vivo and in silico studies.

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.

Resveratrol regulates hyperglycemia-induced modulations in experimental diabetic animal model

Type 2 diabetes mellitus (T2DM) is a metabolic disorder that is associated with variable degrees of glucose intolerance, impaired insulin secretion, insulin resistance and increased hepatic glucose production. The aim of present study was to investigate the therapeutic potentials of resveratrol (RSV) alone and/or in combination with vitamin-E (Vit-E) against hyperglycemia-induced modulations using experimentally alloxan-induced diabetic animal model. Alloxan was used to induce diabetes mellitus in white albino rats and metformin (MF) was used as standard anti-diabetic drug to compare the therapeutic potentials of RSV (alone and/or with Vit-E) by estimating the effect of treatment on glycemia, insulin resistance, liver and kidney function biomarkers, anti-oxidant status, and serum levels of calcium and magnesium. The results of present study indicate the RSV (P < 0.001) alone and/or in combination with Vit-E (P < 0.001) exhibited a highly significant therapeutic potentials by ameliorating the glycemia-induced modulations. Moreover, we also found that RSV in combination with Vit-E also exhibited a better therapeutic effects when compared with that of MF (P < 0.001) and Vit-E (P < 0.05), respectively. Hence, we conclude that RSV alone and/or in combination with Vit-E exhibit its significant therapeutic potentials against hyperglycemia-induced modulations in experimental diabetic animal model and may be one of the most exciting prospect for future treatment of T2DM.

Hypoglycemic Effect of the Methylene Chloride-methanolic Extract of the Fresh and Dried Fruits of Gongronema latifolium in Normoglycemic and Alloxan-induced Diabetic Rats

Objective: The study investigated the hypoglycemic effect of the methylene chloride/methanol (1:1) extracts (methylene methanolic extracts) of fresh and dried fruits of Gongronema latifolium in both normoglycemic and alloxan-induced diabetic animals. Activities of these extracts were also tested in combination with reference antidiabetic drug – Glibenclamide. Methods: Qualitative screening for secondary metabolites and acute toxicities of the extracts were carried out using standard methods and modified Lorke’s method respectively. Diabetes was induced intraperitoneally using alloxan monohydrate (120 mg/kg) and blood samples drawn by tail milking at 0 hr, 30 minutes, 1hr, 2hrs, and 4 hours respectively for the determination of blood glucose. The extracts were tested at 50 and 100 mg/kg while the combination study was tested at 50 mg/kg of the extracts + 5 mg/kg gibenclamide in both alloxan-induced diabetic and normoglycemic rats. Results: Phytochemical analysis revealed presence of varying amount of secondary metabolites like alkaloids, glycosides, tannins, steroids, terpenoids, saponins and resins. The acute toxicity tests indicated no obvious sign of toxicity or mortality. The fresh and dried fruit extracts produced significant (p< 0.05) dose-dependent hypoglycemic activities in both normoglycemic and alloxan-induced hyperglycemic rats. Co-administration of the fresh fruit extract at 50 mg/kg and glibenclamide at 5 mg/kg showed a significantly (p < 0.05) increased activity over glibenclamide alone throughout the duration of the experiment. Conclusion: This study establishes the antidabetic activities of the fresh and dried fruits of G. latifolium and proves the treatment benefit in combining the methylene methanolic extract of this fruit with a standard oral hypoglycemic agent.

Anti-diabetic Effect of the Methanolic Leaf Extract of Axonopus compressus (P. Beauv) in Alloxan Induced Diabetic Rats

Aims: This study is a preliminary step in investigating the anti-diabetic effect of the methanolic extract of the leaf of Axonopus compressus (P. Beauv) in alloxan-induced diabetic rats. Study Design/Methodology: Intraperitoneal (i.p.) injection of alloxan monohydrate at the dose of 180 mg/kg b.w was carried out to induce diabetes in the rat models. Different doses (250, 500 and 1000 mg/kg b.w.) of the extract was administered per oral through gastric gavage to the alloxan induced diabetic rats, and 2 mg/kg b.w. of glibenclamide was used as the standard drug, and only tween 20 solution (10 ml/kg) given to the negative control group. AccuCheck Active® (an autoanalyzer) glucose kit was used to assay the effects of the P. Beauv extract and the standard drug on the fasting blood glucose level at 0, 1, 3 and 6 hr(s) using the blood collected through the snip made in the tail of the rats. Results: The different doses of 250, 500 and 1000 mg/kg b.w. produced a significant (p < 0.05) reduction in the blood glucose level of the alloxan-induced diabetic animal models in the degree of Original Research Article Chimere et al.; IJBCRR, 12(1): 1-5, 2016; Article no.IJBCRR.25425 2 31.5%, 19.8% and 24.5% respectively, compared to the negative control group and this was time dependent (at the end of the 6 hour, although a decrease in the blood glucose was also noticed at the 1 and 3 hours). 2 mg/kg glibenclamide decreased the blood glucose levels by 69.9% while the blood glucose level of the negative control group increased by 15.2% at the 6 hour. Conclusion: It is obvious from the above findings that Axonopus compressus deserves further investigations into the active ingredients and structural allucidation to validate the anti-diabetic property it possess.

Bioassay Guided Isolation and Evaluation of the Antidiabetic Principles of Combretum dolichopetalum Root

Aims: The present study was aimed at investigating the antidiabetic potentials of Combretum dolichopetalum root in alloxan-induced animals with the hope of isolating its antidiabetic principles. Study Design: Sixty four Wistar albino rats of either sexes were randomly segregated into 16 groups (n=4). Also, thirty two albino mice were segregated into 8 groups. These received various doses of the plant sample, vehicle or glibenclamide for the antidiabetic study. Place and Duration of Study: This study was done in the laboratory of the Department of Pharmaceutical and Medicinal Chemistry, University of Nigeria, Nsukka between March and October, 2013. Methodology: The root of C. dolichopetalum was extracted with methanol (ME) and fractionated successively with various solvents (n-hexane, chloroform, ethylacetate, methanol and water) to afford the respective fractions: HF, CF, EF, MF and AF. CF was further fractionated to afford six sub-fractions: C1-C6. Acute toxicity study was done using ME. Antidiabetic activity of various doses (p.o.) of ME (100, 200, 400 and 600 mg/kg body weight), its fractions (200 and 400 mg/kg) and sub-fractions (200 mg/kg), glibenclamide (0.2 mg/kg) and vehicle (control) were investigated in alloxan-induced (i.p.) diabetic animals for 9 h. Phytochemical analysis was also carried on ME and fractions. Results: The extract was considered safe with LD50 greater than 5000 mg/kg. ME (400 mg/kg), CF (400 mg/kg) and C3 (200 mg/kg) produced maximum reduction (36.78%, 72.43% and 83.17% respectively) in fasting blood glucose of animals after 9 h which were significantly (P &lt; .01, P &lt; .001) different from the control and better than glibenclamide (48.18%). Phytochemical analysis showed alkaloids, flavonoids, terpens and steroids as the likely antidiabetic agent(s). Conclusion: The root of C. dolichopetalum possesses potent antidiabetic activity which increases as the extract is purified. The antidiabetic effect of the plant may likely be due to the presence of alkaloids, flavonoids, terpens or steroids.

Development and Biological Evaluation of Gymnema Sylvestre Extract-Loaded Nonionic Surfactant-Based Niosomes

To develop and characterize Gymnema sylvestre extract-loaded niosomes using nonionic surfactants, and to evaluate their antihyperglycemic efficacy in comparison with the parent extract. Nonionic surfactant-based G. sylvestre extract-loaded niosomes were prepared using the thin-film hydration method. The optimized formulation was screened for entrapment efficiency of the constituents, as well as other parameters such as release kinetics, vesicle size, zeta-potential and stability studies. The parent extract and optimized niosomal formulation were evaluated for their antihyperglycemic potential in an alloxan-induced diabetic animal model. Niosomes prepared using Span™ 40 (SD Fine Chemicals Ltd, Mumbai, India) provided sterically stable vesicles 229.5 nm in size with zeta-potential and entrapment efficiency of 150.86 mV and 85.3 ± 4.5%, respectively. The surface morphology of vesicles was confirmed to be spherical by scanning electron microscopy studies. An in vitro release study demonstrated 77.4% of phytoconstituents release within 24 h. The niosome formulation demonstrated significant blood glucose level reduction in an oral glucose tolerance test, and increased antihyperglycemic activity compared with the parent extract in an alloxan-induced diabetic model. This study reveals the merits of G. sylvestre extract-loaded niosomes, and justifies the potential of niosomes for improving the efficacy of G. sylvestre extract as antidiabetic. Original submitted 30 March 2012; Revised submitted 29 August 2012; Published online 24 December 2012.

MODULATING EFFECT OF CAMEL’S MILK ON ALLOXAN-INDUCED EXPERIMENTAL DIABETES IN LABORATORY ANIMAL MODEL

The present study was conducted to evaluate the hypoglycemic effect of camel's milk in alloxan-induced diabetic animal model compared to control and cow's milk receiving groups. This study was carried out on thirty five female white albino rats and divided into 2 main groups: optimizing and experimental group. Optimizing group (n = 20) was used to determine the optimal dose of alloxan to induce diabetes in a pattern of dose response relationship. This group was divided into four subgroups, sG1 to sG4, (n = 5 each). sG1, sG2, sG3, and sG4 were injected intra- peritoneally with alloxan monohydrate at a dose 100, 140, 180 and 200 mg/kg B.W., respectively. Experimental group (n =15) was divided into three subgroups (n = 5 each) as following: diabetic rats receiving no treatment and acts as a positive control (sG1), diabetic rats receiving camel's milk (sG2) and diabetic rats receiving cow's milk (sG3). Their blood glucose levels (BGLs) were estimated at weekly interval for 5 consecutive weeks. A baseline BGL was determined before conducting the experiment and it was 79.85 ± 4.2 mg/dl. The results showed that 140 mg/kg B.W. of alloxan was the optimal dose to induce stable diabetes in the optimizing group. In the experimental group, the initial mean BGLs for sG1, sG2, and sG3 were 399.5 ± 18.3, 429.4 ± 66.4 and 404.6 ± 53.6 mg/dl, respectively and after 5 th week there were 488.2 ± 20.8, 308.28 ± 52.2, 519.8 ± 131.5 mg/dl respectively. Most diabetic animals that received cow's milk exhibits severe signs of diabetes at 4 th week of experiment and died by 5 th week while animals that received camel's milk showed marked improvement and one of them exhibited normal BGL by the end of experiment. Our findings suggested that administration of camel's milk was effective in improvement of the alloxan-induced diabetic rats and recommended as nutraceuticals supplement in diabetic patient.

Supplementation with apple enriched with L‐arginine may improve metabolic control and survival rate in alloxan‐induced diabetic rats

Supplementation with L-arginine or fresh food with high content of this amino acid is associated with favorable effects in the metabolic control of diabetes. We aimed to determine whether supplementation with apples enriched with L-arginine offer additional benefits compared to L-arginine by itself in a preclinical study of diabetes. This study combines food-engineer technologies with in vivo and in vitro analysis. In vitro experiments show that cells derived from non-diabetic animals and exposed to high glucose (25 mM, 12 H) and cells isolated from alloxan-induced diabetic animals exhibited a reduction (∼50%) in the L-arginine uptake. This effect was reverted by L-arginine pretreatment (12 H) in both the normal and diabetes-derived cells. In preclinical studies, normoglycemic (n = 25) and diabetic groups (n = 50) were divided into subgroups that received either L-arginine (375 mg/kg per 10 days) or apple enriched with L-arginine or vehicle (control). In a preliminary analysis, supplementation with L-arginine by itself (50%) or apple enriched with L-arginine (100%) improve survival rate in the diabetic group compared to control (0%) at the end of the follow up (17 days). This phenomenon was associated with a partial but sustained high plasma level of L-arginine, as well as plasma concentration of nitrites and insulin in the L-arginine or apple + L-arginine groups after supplementation. Apple + L-arginine supplementation in diabetic animals induced the highest and longest effects in the level of these three markers among the studied groups. Therefore, apple enriched by L-arginine offers more benefits than L-arginine by itself in this preclinical study.

Hypoglycaemic activity of &lt;i&gt;Commelina africana&lt;/i&gt; and &lt;i&gt;Ageratum conyzoides&lt;/i&gt; in relation to their mineral composition

Many plants with antidiabetic properties probably act in part through their content of fibre, vitamins, bioactive or mineral content This study investigated the mineral, proximate, phytochemical compositions and hypoglycaemic effect of Commelina africana and Ageratum conyzoides extracts in diabetic rats, and the likely relationship between this property and the mineral, proximate and phytochemical compositions of the plants. The plants were subjected to mineral, proximate composition and phytochemical analysis. Attempt was made to see (if any) the relationship between the hypoglycaemic effect and the mineral, proximate compositions and phytochemistry of the plants. Alloxan-induced diabetic animals were administered 500 mg/kg body weight aqueous extracts of the plants and glibenclamide as the reference hypoglycaemic agent. Aqueous extract of Ageratum conyzoides reduced fasting blood glucose of experimental animals by 39.1% while Commelina africana reduced the same by 78.0%. Alkaloids, cardenolides, saponins, and tannins were detected in both plants. Anthraquinones was absent in C. africana but a trace of it was detected in A. conyzoides. The hypoglycaemic effect of Commelina africana was comparable with the reference hypoglycaemic agent. Ageratum conyzoides showed comparably weaker hypoglycaemic effect than exhibited by reference hypoglycaemic agent. Comparatively, Commelina africana had higher mineral concentrations (except Na) than Ageratum conyzoides. Plants' extracts minerals (magnesium, potassium and iron) and bioactive components (alkaloids and cardenolides) seemingly enhanced their hypoglycaemic effect. Furthermore, these minerals, alkaloids and cardenolides could be helpful in ameliorating complications of diabetes like hypertension and cardiovascular disease.

Palladium-α-lipoic acid complex attenuates alloxan-induced hyperglycemia and enhances the declined blood antioxidant status in diabetic rats

Palladium α-lipoic acid (Pd-LA) complex has unique electronic and redox properties that appear to be the key to its physiological effectiveness. A proprietary liquid blend containing Pd-LA as the major component was demonstrated to be effective in improving the activities of mitochondrial enzymes in aged rats. The Pd-LA complex was evaluated for its hypoglycemic effect against the alloxan-induced diabetic model, as well as in the oral glucose tolerance test in rats. The in vitro free radical scavenging activity of Pd-LA was also determined. Administration of Pd-LA (0.5 mL/kg; equivalent to 3.8 mg complexed α-lipoic acid/kg, p.o.) daily for 5 days to alloxan-induced diabetic animals significantly reduced the blood glucose level (P < 0.05). The blood antioxidant status in the diabetic animals was significantly improved by the treatment of Pd-LA (P < 0.05). Similarly, Pd-LA showed significant in vitro antioxidant activity in a concentration-dependent manner. Results of the study conclude that the Pd-LA complex is effective in lowering the blood glucose level and enhancing the declined antioxidant status in diabetic animals. Significant finding(s) of the study include: (i) Pd-LA significantly increased the tolerance of glucose and was also effective in ameliorating hyperglycemia induced by alloxan; (ii) Pd-LA significantly enhanced the activities of blood superoxide dismutase, catalase, glutathione peroxidase and level of glutathione in diabetic animals; and (iii) Pd-LA showed significant in vitro antioxidant activity. This study adds: The therapeutic efficiency of Pd-LA is demonstrated against declined antioxidant status as well as hyperglycemia associated with diabetes.

Anomalies in alloxan-induced diabetic model: It is better to standardize it first.

Sir, Antidiabetic effect of more than 500 plants has been proved in alloxan-induced diabetic animal models but further medical research does not support their effectiveness. We also have been not able to get a single effective antidiabetic molecule from them. It is also understood that alloxan-induced diabetic model does not exactly simulate the human type 2 diabetes mellitus. Some herbomineral products, which have antidiabetic effect in animal models, were not effective in humans as an antidiabetic. Shilajeet and Gymmema sylvestre have antidiabetic effects in alloxan-induced animal model but these herbs have no antidiabetic effects when studied in man. There are inconsistencies in doses of drugs, routes of administration, duration and severity of diabetes and methodology in alloxan-induced diabetic models, which make its accuracy controversial. The pharmacokinetic and pharmacodynamic profile of alloxan is ignored by researchers working on these aspects. We wish to make the following observations in this regard. Alloxan is very rapidly destroyed in the body. Its half-life is less than 1 minute. Hence, its action is most unpredictable unless it is administered by rapid intravenous injection. Slow rate of intravenous injection reduces the efficacy of the agent.[1] But in alloxan-induced models, researchers usually use intraperitoneal or other routes, which makes it less capable to induce diabetes of such duration as required for study. During intraperitoneal, intramuscular and subcutaneous routes of administration, onset of alloxan action would be delayed. Will it not be sufficient to destroy alloxan in body? Will delayed onset of action not make it less efficient in producing diabetes in animals? Very young animals have a high resistance to the diabetogenic effect of alloxan.[2] Damage to the renal tubules by alloxan also alters blood glucose level which may also influence the results of study. The susceptibility to both toxic and diabetogenic doses varies widely not only in different species but also among animals of the same species.[1] Rats were more sensitive to a constant dose of alloxan after a fore period on a high fat diet and less sensitive after a high carbohydrate and protein diet.[3] The spontaneous recovery is particularly evident in rats and mice, in which the majority of animals become normoglycemic. The recovery from the diabetes is believed to be the consequence of either a multiplication of β cells from the duct epithelium or the exocrine portion of the pancreas.[4] This is the reason why mild diabetes produced by alloxan recovers spontaneously in rats. Lower doses of alloxan (90-140 mg/kg, i.p.) can result in auto-reversion to normal state. It has been found that in many research studies, the dose of alloxan used to induce diabetes was suboptimal. In these studies, it was found that alloxan induces very mild diabetes. However, in these animals, revert back to the blood glucose values reverted back to normal in a week. β cells of islet of Langerhans in rats show regenerative capacity.[5] Thus, the illusion of antidiabetic effect of experimental product is produced. Production of diabetes also depends upon the speed of the intravenous injections at a given dose level, the slower injection rates causing less effect.[6] Human islet tissue is exceedingly resistant to the degenerative effects of alloxan. Alloxan diabetes differs strikingly from other types of experimental diabetes in the course and nature of the lesions which are developed. As yet, there is no evidence that alloxan-induced diabetes mellitus is related to human diabetes mellitus.[7] Hence, there are many inconsistencies and anomalies in alloxan-induced diabetic models. By analyzing the above observations and studies mentioned by many authors, it indicates that alloxan-induced diabetic model is a doubtful model for antidiabetic studies. Hence, further studies are needed to evaluate ideal antidiabetic model. Only then, we can develop new effective antidiabetic molecules.

Regulation of protein kinases and coregulatory interplay of S‐100β and serotonin transporter on serotonin levels in diabetic rat brain

Protein kinases are critical component in the regulation of signal transduction pathways, including neurotransmitters. Our previous studies have shown that serotonin (5-HT) altered under diabetic condition was accompanied by alterations of protein kinase C-alpha (PKC-alpha) and CaMKII, and those alterations were reversed after insulin administration. The current study showed that alloxan-induced diabetic animals revealed hyperglycemia and was associated with an increase in the content of 5-HT, PKC-alpha expression and PKC activity (P < 0.05) simultaneously in striatum (ST), midbrain (MB), pons medulla (PM), cerebellum (CB), and cerebral cortex (CCX) from 7 days to 60 days. Although the 5-HT levels in hippocampus (HC) and hypothalamus (HT) were not altered, the PKC-alpha expression and PKC activity showed increases (P < 0.05) in level in HC. Insulin administration reversed all these changes to a normal level. In contrast, the in vitro study has shown that the 5-HT levels correlated with PKC-alpha expressions as well as PKC activity (P < 0.05) only in ST, MB, and CB either after induction with phorbol 12-myristate 13-acetate (PMA) or blocking with chelerythrine, whereas PM and CCX remained elevated (P < 0.05), implying a regulatory role for PKC-alpha only in ST, MB, and CB. However, our consecutive studies have shown that the 5-HT level in PM was regulated by p38-mitogen-activated protein kinase (p38-MAPK) both in vivo and in vitro, whereas the 5-HT level in CCX was coregulated by S-100beta by protein-protein interaction with serotonin transporter (SERT) via 8-bromoadenosine 3',5'-cyclic monophosphate sodium salt (8-Br-cAMP)-induced cAMP/PKAII pathway(s).

Long term evaluation of functional and morphological bladder alterations on alloxan-induced diabetes and aging: experimental study in rats

to evaluate structural and functional effects of Alloxan- induced diabetes and aging on bladder of rats. evaluations were performed in three groups: A--8 weeks of age, B--44 weeks of age, C--44 weeks of age with alloxan-induced diabetes. Muscle layer thickness, extracellular matrix fibrosis and collagen were quantified on digital images of bladder samples. Cystometric evaluations before surgical vesical denervation (SVD), included maximum cystometric capacity (MCC), maximum bladder pressure (MBP), bladder contraction frequency (VCF), duration of bladder contraction (DC), threshold pressure (TP) and bladder compliance (BC). After SVD, maximum cystometric capacity (MCC), BC and maximum urethral closing pressure (MUCP) were also measured. Reduced extracellular matrix fibrosis concentration and contraction strength were found in the bladders of group C. Before SVD, bladder compliance was not different between groups. Alterations were observed in MCC after SVD. We did not notice smooth muscle hypertrophy in Alloxan-induced diabetic rats after 44 weeks. There was alteration in the total and relative amount of fibrosis and collagen. The cystometric studies support the idea that this morphological alterations are important to determine the different bladder functional patterns found in the aging and the Alloxan-induced diabetic animals.