[Show abstract][Hide abstract] ABSTRACT: Localized deposits of amyloid structures are observed in various pathological conditions. One example of when local amyloidosis occurs is following repeated insulin injections in diabetic patients. The present study aimed to simulate the same condition in mice. To obtain the amyloid structures, regular insulin was incubated at 57°C for 24 h. The subsequently formed amyloid fibrils were analyzed using the Congo red absorbance test, as well as transmission electron microscopy images, and then injected into mice once per day for 21 consecutive days. Firm waxy masses were developed following this period, which were excised, prepared as thin sections and stained with hematoxylin and eosin, Congo red and Sudan black. Histological examination revealed that these masses contained adipose cells and connective tissue, in which amyloid deposition was visible. Thus, localized amyloidosis was obtained by the subcutaneous injection of insulin fibrils. The present results may be of further use in the development of models of amyloid tumors.
Experimental and therapeutic medicine 08/2014; 8(2):405-408. · 0.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The deposition of amyloid peptides is associated with Alzheimer's disease (AD). These amyloid peptides are derived from the amyloid protein precursor (APP). Silymarin, a standardized extract of milk thistle, which is currently used in liver diseases, may be effective in the inhibition of amyloid formation. However, its effect has not been assessed on APP expression.
In this study, first, the effect of silymarin was examined on the passive avoidance learning in a rat model of AD. This model was induced by the intracerebroventricular injection of Abeta peptide (Abeta1-42) in Wistar rats. Rats were treated with 70 and 140 mg/kgof the extract, once a day, for 4 weeks. Memory function that was evaluated in a shuttle-cage test, showed improvement upon administration of this extract. Brain amyloid plaques had also decreased upon administration of the extract. Furthermore, APP gene expression was compared in treated and untreated groups. The result showed that silymarin was able to suppress APP expression.
Our results are in accordance with the in vitro tests concerning the positive antiamyloidogenic property of the main component of silymarin, namely silibinin. We suggest that the beneficial effect of sylimarin in the AD model is related to its capacity to disaggregate amyloid plaques and to suppress APP expression. Considering the limited side effects of silymarin, this compound could be of use in AD therapy.
DARU-JOURNAL OF FACULTY OF PHARMACY 01/2014; 22(1):24. · 0.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inhibitors of the mammalian alpha-amylases have been widely studied as medicines to be used in diabetes and obesity. However, there are few reports on activation of the enzyme, which could be detrimental in those conditions. Here, the effect of purine-derivated compounds has been studied on porcine pancreatic alpha-amylase. Methylxanthine-derivatives pentoxyfilline, theobromine and caffeine caused a 20â30% increase in enzyme activity in the presence of the natural substrate, starch. The activation effect was not dose-dependent, observed in the range of 10â200 Î¼M of the compounds, and hypothesized to be related with the hyperglycemia that is observed upon consuming caffeine.:
Obesity Research & Clinical Practice 12/2013; 7(6):e431-500. · 0.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Alzheimer's disease (AD) is an irreversible neurodegenarative condition in which abnormal accumulation of amyloid plaques is observed, and for which no effective treatment still exist. In recent years, many aromatic small molecules have been observed to have anti-amyloid effect, and may have the potential to attenuate AD symptoms. The indole core and the flavonoid precursor trans-chalcone have been studied here as representative of these group of molecules. Formation of amyloid plaques has been induced in a rat model of AD, after what the two compounds were given to experimental groups. Shuttle box experiment and histological examination of brain amyloid plaques was then performed in order to test the effect of 28 days treatment on rats memory and brain tissue integrity. In conclusion, it was found that both compounds were effective in ameliorating the rats condition, and could be considered as interesting potential drug candidates.
Archives italiennes de biologie 09/2013; 151(3):106-13. · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Inhibitors of pancreatic alpha-amylase are potential drugs to treat diabetes and obesity. In order to find compounds that would be effective amylase inhibitors, in vitro and in vivo models are usually used. The accuracy of models is limited, but these tools are nonetheless valuable. In vitro models could be used in large screenings involving thousands of chemicals that are tested to find potential lead compounds. In vivo models are still used as preliminary mean of testing compounds behavior in the whole organism. In the case of alpha-amylase inhibitors, both rats and rabbits could be chosen as in vivo models. The question was which animal could present more accuracy with regard to its pancreatic alpha-amylase. RESULTS: As there is no crystal structure of these enzymes, a molecular modeling study was done in order to compare the rabbit and rat enzymes with the human one. The overall result is that rabbit enzyme could probably be a better choice in this regard, but in the case of large ligands, which could make putative interactions with the 4 subsite of pancreatic alpha-amylase, interpretation of results should be made cautiously. CONCLUSION: Molecular modeling tools could be used to choose the most suitable model enzyme that would help to identify new enzyme inhibitors. In the case of alpha-amylase, three-dimensional structures of animal enzymes show differences with the human one which should be taken into account when testing potential new drugs.
DARU-JOURNAL OF FACULTY OF PHARMACY 11/2012; 20(1):77. · 0.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serum small dense low-density lipoprotein (sd-LDL) concentrations were measured in patients with angiographically defined coronary artery disease (CAD) and compared to concentrations in healthy subjects. Five hundred and seventy patients with stable CAD were divided into CAD- and CAD+ based on angiography. Patients in whom stenosis was <50 % in diameter were classified as having a 'normal' angiogram (CAD-), otherwise the patients were allocated to the CAD+ group. The CAD+ group was further subcategorized into single-, double- and triple-vessel disease (VD). Serum sd-LDL concentrations were significantly lower in controls compared with CAD+ and CAD- patients (P < 0.001). Moreover, CAD+ patients had higher concentrations of sd-LDL than CAD- patients (P < 0.01). sd-LDL levels were not significantly associated with severity of CAD defined by the number of stenosed coronary arteries (P = 0.245). All participants were also categorized into subgroups with or without metabolic syndrome. Subjects with metabolic syndrome had higher levels of sd-LDL than subjects without metabolic syndrome (P < 0.01). Multiple linear regressions showed that in CAD patients, triacylglycerol, total-cholesterol, body mass index, and waist circumferences were the most important determinants of serum sd-LDL concentrations. We found that sd-LDL levels were significantly higher in patients presenting with symptoms of CAD. Moreover, patients with significant stenosis of their coronary arteries (>50 % stenosis) had higher levels of sd-LDL compared to patients without significant lesions.
[Show abstract][Hide abstract] ABSTRACT: Zinc has a role in the synthesis, storage, and secretion of insulin, and has been suggested to be beneficial when used in the diabetic state. Effect of zinc intake in pregnant rats has been studied here on diabetized offspring. Pregnant rats were divided in two groups; the control group received normal food and water, and the experimental group received zinc sulfate during pregnancy and 3 weeks after offspring birth. Male offspring from the control (C) and experimental (E) groups were divided each in three groups: C1, fed with normal food and water; C2, diabetized with alloxan; C3, received zinc sulfate; E1, fed with normal food and water; E2, diabetized with alloxan; and E3, receiving zinc sulfate. After 30 days, the histological changes of pancreatic tissues were investigated by light microscopy. Body weight, blood glucose, serum insulin levels, food intake, water intake, and urine quantity were also compared between the groups. Water intake and urine quantity were decreased significantly (p < 0.01and p < 0.001) in E2 (experimental diabetic group) in comparison with C2 (control diabetic group), but there was no significant difference in the body weight in C2 in comparison with E2, while blood glucose was decreased significantly (p < 0.001) and blood insulin level was increased significantly (p < 0.01) in E2 in comparison with C2. Microscopic evaluation of pancreas showed that E2 were protected against alloxan-induced beta-cell degeneration. In conclusion, this work showed that maternal zinc intake may influence subsequent deleterious effects of diabetes on alloxan-diabetized offspring.
Journal of physiology and biochemistry 06/2012; · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we used sugars as stabilizing additives to improve the thermostability and to inhibit aggregation of firefly luciferase. The combination of sucrose and trehalose has a strong stabilizing effect on firefly luciferase activity and prevents its thermoinactivation. These additives can also increase optimum temperature. It has been shown that the presence of both sucrose and trehalose can inhibit thermal aggregation of firefly luciferase and decrease bioluminescence decay rate. In order to understand the molecular mechanism of thermostabilization, we investigated the effects of sucrose and trehalose combination on the secondary structure of luciferase by Fourier transform infrared spectroscopy. Minor changes in content of secondary structure of firefly luciferase are observed upon treatment with additives.
Applied biochemistry and biotechnology 05/2011; 165(2):572-82. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Trans-chalcone (1,3-diphenyl-2-propen-1-one), a biphenolic core structure of flavonoids precursor was tested for inhibitory activity toward alpha-amylase. Porcine pancreatic alpha-amylase was observed to be effectively inhibited by this compound, which showed competitive behavior with a K(i) of 48 μM. Soluble starch (the natural substrate of the enzyme) was used in this study in order to obtain more realistic results. The possible binding mode of the compound was assessed in silico, and the two residues Trp59, and Tyr62 were proposed as main interacting residues with trans-chalcone. In conclusion, this compound could be used to design effective inhibitors of alpha-amylase.
[Show abstract][Hide abstract] ABSTRACT: trans-Chalcone is the core structure of naringenin chalcone, located halfway in the biosynthesis pathway of flavonoids. Flavonoids have been reported as mammalian alpha-amylase inhibitors, a property which could be useful in the management of postprandial hyperglycemia in diabetes and related disorders. As a mammalian alpha-amylase inhibitor in vitro, the putative beneficial effect of trans-chalcone on diabetes was tested in a streptozotocin-induced rat model of diabetes type 1, and the results analyzed with commonly used statistical methods. Significant reduction of blood glucose levels and beneficial effect on dyslipidemia were observed in diabetic rats, as well as reduction of disturbing consequences of diabetes such as high urine volume and water intake. trans-chalcone was observed to have a weight loss-inductive effect, alongside with a reduction in food intake, which is suggestive of a therapeutic potential of this compound in overweight and obese patients.
[Show abstract][Hide abstract] ABSTRACT: Silybin, an extract from seeds of milk thistle (Silybum marianum), is known to have hepato-protective, anticarcinogenic, and estrogenic effects. Given that estrogen effects on memory have been reported, silybin may cause structural changes in the hippocampal CA1 and dentate gyrus (DG) neurons and as a result it may enhance learning and memory. Wistar rats were provided with silybin (from day 7 of gestational age up to 4 weeks after birth) with 2 dosages of 18 mg/kg in the experimental group 1 (Exp1) and 9 mg/kg in the experimental group 2 (Exp2). Offspring memory retention was compared by duration of step-through latency in passive avoidance apparatus. Furthermore, histological changes were investigated in experimental groups and control group (CG). Both the experimental groups showed significantly longer step-through latency than CG (p < 0.001 for Exp1 and p < 0.01 for Exp2). The average number of pyramidal cells in hippocampal CA1 and granular cells in hippocampal DG was remarkably higher in Exp1 and Exp2 compared with CG. The difference was significant between Exp1 and Exp2 for pyramidal cells (p < 0.05) but not for granular cells. Silybin administration during pregnancy resulted in histological changes in hippocampus and better memory function. These data may lay the ground work using silybin in memory impairment diseases.
Journal of Asian natural products research 06/2009; 11(6):514-22. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AimsA number of chemical compounds such as sodium tungstate and vanadyl sulfate have been assessed for their anti-diabetic effects in several animal models of diabetes. This study investigates the proper time for initiation of sodium tungstate treatment in diabetic Wistar rats and its histopathological effects on pancreas.Materials and methodsAnimals were divided into five groups (n = 10). Control (C), sodium tungstate-treated control (TC), streptozotocin-induced diabetic (D), streptozotocin-induced diabetic rats were treated by sodium tungstate form 1 week before streptozotocin (STZ) injection (TD1), and diabetic rats treated with sodium tungstate 1 week after STZ administration (TD2). The histopathologic changes in pancreas were investigated by light microscopy. Body weight, blood glucose, insulin levels, food intake and fluid intake were compared between groups. Serum insulin levels were determined by ultra-sensitive rat insulin kit, using double-antibody ELISA.ResultsGroup D and TD2 showed significant weight loss, polydipsia, polyuria and polyphagia compared to groups C and TC (p < 0.01). TD1 group protects diabetic-induced rats from elevation of glucose compared to groups D and TD2 (p < 0.01). Group TD1 showed significant decrease in fasting glucose levels and oral glucose tolerance test in comparison to groups D and TD2 (p < 0.01). Microscopic evaluation of pancreas showed that in TD1 group, tungstate protects STZ-induced beta-cells degenerations.Conclusion
Pre-treatment with sodium tungstate leads to amelioration of diabetic complications and short-term pre-treatment with tungstate can converts the diabetic state by sustaining a few, although it is critical, amount of beta-cells that adequately maintain normoglycemia.
Diabetes and Metabolic Syndrome Clinical Research and Reviews 01/2008; 2(4):259-265.
[Show abstract][Hide abstract] ABSTRACT: Background: Imatinib mesylate, a small-molecular analog of adenosine triphosphate (ATP) that potently inhibits tyrosine kinase activities of Bcr–Abl, PDGFR-β, PDGFR-α, c-Fms, Arg and c-kit, is one of the novel molecularly targeted drugs being introduced into cancer therapy. We tested the effect of imatinib on the ovarian histological structure and the concentration of estrogen and progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) in the serum of female Wistar rats. Materials and Methods: Two groups of rats (180 ± 15 grams) were gavaged with doses of 50 and 100 mg/kg body weight imatinib dissolved in distilled water for 14 days. The control group received sterile water. On day 7, after termination of the treatment, blood serum concentration was measured with the radioimmunoassay (RIA) method. Also, sections (5 μm thick) of ovaries stained with hematoxylin and eosin (H&E) were investigated histologically. Results: Progesterone concentration in the experimental groups was increased (p<0.001), estrogen and FSH concentrations were decreased (p<0.01), and the LH concentration decreased but was not statistically different in comparison with the control group. The weight of ovaries and number of atretic follicles in the experimental groups was increased compared with the control group (p<0.05). The diameter of corpus lutea were increased but the number of corpus lutea decreased in both experimental groups (p<0.01). Conclusion: These findings suggest that administration of imatinib may have profound effects on female fertility.
Royan Institue International Journal of Fertility and Sterility. 04/2002; 3:11-16.
[Show abstract][Hide abstract] ABSTRACT: Background: As potential anti-diabetic and anti-obesity agents, glycosidase inhibitors are the subject of numerous studies. Among these enzymes, alpha-amylases are of particular interest, and most of their reported inhibitors have so far been natural compounds. Citral is an isoprenoid compound of various essential oils, and based on its alpha-amylase inhibitory effect, was further studied here in an in vivo model of type 1 diabetes. Methods: In vitro effect of the compound was assessed on mammalian alpha-amylase activity with the use of the Bernfeld method. In vivo effect of the compound was studied on streptozotocin-induced diabetic rats (wistar). Non-diabetic and diabetic rats received citral at 2, 8, 16 or 32 mg/kg body weight; the compound was dissolved in grape seed oil. The control groups received grape seed oil alone. Treatment was done for 24 days, after what the animals were sacrificed under light ether anesthesia. Measured parameters included: food and water ingestion and urine volume (daily), blood glucose levels (every two days), cholesterol, triacylglycerol, concentrations, and alpha-amylase levels after 24 days . Results: Citral was found to be a moderate inhibitor of mammalian alpha-amylase, with an IC50 of 120 μM, and caused also a decrease of alpha-amylase levels in vivo. Moderate lowering of postprandial glucose, alongside with normalization of blood lipid profile was observed in diabetic rats upon treatment with the compound. Citral was also found to be able to promote weight loss and to decrease food intake. Conclusion: Citral could be proposed as a possible antihyperlipidemic agent in diabetes and potential therapeutic in obesity, although further studies are needed to establish its complete profile as potential medication .