Displaying publications 101 - 120 of 248 in total

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  1. Effect of syringin (eleutheroside B) on the physiological and hematological parameters in STZ induced Type II diabetic Wistar rats
    Us MR, Zin T, C SS, Iqbal M
    Pak J Pharm Sci, 2020 Nov;33(6):2601-2606.
    PMID: 33867336
    To investigate the physiological indices such as body weight, food and fluid drinking concern to antidiabetic properties of syringin and its useful outcome on hematological parameters in streptozotocin stimulated diabetic rats. Six normal and 18 diabetic rats totally 24 rats have been used for the present investigation. Streptozotocin was injected in male Wistar rats to induce diabetes through intraperitoneal route. After the confirmation of diabetes, the test animals were treated with distilled water through oral route or syringin 5 mg/kg body weight/ rat /day for 10 days. The diabetic treated groups compared with the controls were evaluated based on their hematological parameters such as red blood cells, white blood cells and its functional indices. The blood glucose levels significantly decreased in syringin injected rats. The intake of water and feed in diabetic rats were significantly decreased, whereas after syringin administration the weight loss was minimized. Congruently, the level of red blood cells, white blood cells and their functional key characters were also considerably enhanced. It can be conjectured that syringin has antihyperglycemic properties. In addition, it can positively amend some hematological parameters.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  2. Palmatine Inhibits Up-Regulation of GRP78 and CALR Protein in an STZ-Induced Diabetic Rat Model
    Okechukwu PN, Ekeuku SO, Chan HK, Eluri K, Froemming GRA
    Curr Pharm Biotechnol, 2021;22(2):288-298.
    PMID: 32744968 DOI: 10.2174/1389201021666200730124208
    BACKGROUND: Diabetes Mellitus (DM) is characterized by hyperglycemia (high blood glucose levels) which is due to the destruction of insulin-producing β-cells in the islets of Langerhans in the pancreas. It is associated with oxidative and endoplasmic reticulum stress. The plant alkaloid Palmatine has been previously reported to possess antidiabetic and antioxidant properties as well as other protective properties against kidney and liver tissue damage.

    OBJECTIVE: Here, we investigated the ability of Palmatine to reduce the up-regulation of chaperone proteins Glucose Regulatory Protein 78 (GRP78), and Calreticulin (CALR) protein in a Streptozotocin (STZ)-induced diabetic rat model.

    METHODS: Streptozotocin (STZ) induced diabetes in Sprague Dawley rats treated with 2mg/kg of Palmatine for 12 weeks after the elevation of plasma glucose levels above 11mmol/L post-STZ administration. Proteins were extracted from the pancreas after treatment and Two-Dimensional gel electrophoresis (2-DE), PDQuest 2-D analysis software genomic solutions and mass spectrometer were used to analyze differentially expressed protein. Mass Spectrometry (MS/MS), Multidimensional Protein Identification Technology (MudPIT) was used for protein identification.

    RESULTS: There was an up-regulation of the expression of chaperone proteins CALR and GRP78 and down-regulation of the expression of antioxidant and protection proteins peroxidoxin 4 (Prdx4), protein disulfide isomerase (PDIA2/3), Glutathione-S-Transferase (GSTs), and Serum Albumin (ALB) in non-diabetic rats. Palmatine treatment down-regulated the expression of chaperone proteins CALR and GRP78 and up-regulated the expression of Prdx4, PDIA2/3, GST, and ALB.

    CONCLUSION: Palmatine may have activated antioxidant proteins, which protected the cells against reactive oxygen species and endoplasmic stress. The result is in consonance with our previous report on Palmatine.

    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/drug therapy*
  3. Immunolocalization of insulin-like growth factors and their receptors in the diabetic mouse oviduct and uterine tissues during the preimplantation period
    Zakaria R, Rajikin MH, Yaacob NS, Nor NM
    Acta Histochem, 2009;111(1):52-60.
    PMID: 18676006 DOI: 10.1016/j.acthis.2008.04.002
    The aim of the present study was to analyze the immunolocalization of insulin-like growth factor (IGF)-1 and IGF-2 and their receptors in the oviduct and uterus of control and diabetic mice. Sexually mature female ICR mice aged 6-8 weeks were rendered diabetic by streptozotocin (200 mg/kg, administered intraperitoneally). Oviductal and uterine tissues were obtained from the superovulated control and diabetic mice at 48, 72 and 96 h post-human chorionic gonadotropin (hCG) treatment. Localization of IGF-1, IGF-2, IGF-1R and IGF-2R was determined by immunohistochemistry and a semi-quantitative scoring of immunolabelling was performed using a standardized 5-point system. The immunohistochemical scorings for both IGF-1 and IGF-1R were significantly decreased in the oviducts of diabetic mice at 96 h post-hCG treatment. The scores for IGF-2 were significantly increased in the oviducts of diabetic mice at 48 and 72 h post-hCG treatment, and for IGF-2R at 72 h post-hCG treatment. However, there was no significant difference in the scores of IGFs and their receptors in the uterus of control and diabetic mice. In conclusion, the oviductal immunolabelling for IGFs and their receptors was significantly altered by maternal diabetes, which may be of importance in the pathogenesis of preimplantation diabetic embryopathy.
    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/metabolism; Diabetes Mellitus, Experimental/pathology
  4. Fulltext Assessment of DNA strand breakage in streptozotocin-induced diabetic rats
    Siti Balkis Budin, Norfadilah Rejab, Abdul Gapor Mohd Top, Wan Nazaimoon Wan Mohamud, Mokhtar Abu Bakar, Khairul Osman, et al.
    Jurnal Sains Kesihatan Malaysia, 2005;3(1):2-12.
    MyJurnal
    This study was conducted to evaluate the oxidative damage in diabetic mellitus induced rats. The evaluation of DNA damage was carried out by the Alkaline Comet Assay using peripheral lymphocyte cells taken from streptozotocin-induced diabetic rats (50 mg/kg) and control rats. The levels of malondealdehyde (MDA), 4-hydroxynonenal (4-HNE), fasting blood glucose (FBG) and HbA1c were also measured. All the induced diabetic rats were hyperglycemic until the end of the study with significantly higher levels of FBG and HbA1c as compared to the control rats. The results showed the percentage of tail DNA and tail moment values were also significantly higher in the diabetic induced rats. The same observations were made on the levels of plasma MDA and 4-HNE. In conclusion, this study indicated that hyperglycemic condition in diabetic induced rats could generate oxidative DNA damage.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  5. Fulltext In vivo antidiabetic and acute toxicity of spray-dried Vernonia amygdalina water extract
    Yeap, S.K., Beh, B.K., Liang, W.S., Ho, W.Y., Yousr, A.N., Alitheen, N.B.
    International Food Research Journal, 2013;20(2):613-616.
    MyJurnal
    The spray-dried Vernonia amygdalina water extract was evaluated for antidiabetic effect using normoglycaemic, glucose induced hyperglycaemic and streptozotocin induced diabetic mice. This effect was compared with an oral dose of Momordica charantia. Besides, acute toxicity of the extract was also evaluated at concentration 2000 and 5000 mg/kg body weight. The extract was able to reduce blood glucose level in glucose and streptozotocin induced hyperglycaemic mice without causing hypoglycemic effect on fasting normoglycaemic mice. Moreover, mice appeared to be normal and no mortality was observed in the acute toxicity study after treated with up to 5000mg/kg of extract. These results indicated that the spray-dried Vernonia amygdalina water extract was a potential antidiabetic agent which does not induce hypoglycemic and acute toxicity on normal subject.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  6. Fulltext Hypoglycaemic properties of Malaysian cocoa (Theobroma cacao) polyphenols-rich extract
    Ruzaidi, A., Abbe Maleyki, Amin, I., Nawalyah, A.G., Muhajir, H., Pauliena, M.B.S.M., et al.
    International Food Research Journal, 2008;15(3):305-312.
    MyJurnal
    The objective of the study was to investigate the hypoglycaemic properties of Malaysian cocoa (Theobroma cacao) polyphenols extract in-vivo and insulin sensitivity in-vitro. Cocoa extract (CE) (containing 190 - 286 mg total polyphenol per gram extract) was prepared from fermented and roasted (140°C, 20 min) beans by extracting with 80% ethanol in the ratio of 1 to 10. For the in-vivo study, the CE was administered in three dosages (1%, 2%, and 3%) to groups of normal and diabetic rats for a period of 4 weeks by forcefeeding. Results showed that dosages of 1% and 3% CE significantly reduced (p < 0.05) plasma glucose levels in the diabetic rats. An in-vitro study (BRIN-BD11 cell lines) was used to evaluate the effect of CE on insulinsensitivity. The results demonstrated that CE at a concentration of 0.1 mg/ml significantly increased (p < 0.05) insulin level compared to the control. The results of this study showed that Malaysian cocoa polyphenol extract have the potential of being an insulin-mimetic agent. Further studies are on-going to elucidate the underlying mechanisms of polyphenols present in CE that contribute to the reduction of plasma glucose levels and insulin mimicking activity.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  7. New isatin derivative inhibits neurodegeneration by restoring insulin signaling in brain
    Aftab MF, Afridi SK, Mughal UR, Karim A, Haleem DJ, Kabir N, et al.
    J. Chem. Neuroanat., 2017 04;81:1-9.
    PMID: 28093241 DOI: 10.1016/j.jchemneu.2017.01.001
    Diabetes is associated with neurodegeneration. Glycation ensues in diabetes and glycated proteins cause insulin resistance in brain resulting in amyloid plaques and NFTs. Also glycation enhances gliosis by promoting neuroinflammation. Currently there is no therapy available to target neurodegenration in brain therefore, development of new therapy that offers neuroprotection is critical. The objective of this study was to evaluate mechanistic effect of isatin derivative URM-II-81, an anti-glycation agent for improvement of insulin action in brain and inhibition of neurodegenration. Methylglyoxal induced stress was inhibited by treatment with URM-II-81. Also, Ser473 and Ser9 phosphorylation of Akt and GSK-3β respectively were restored by URM-II-81. Effect of URM-II-81 on axonal integrity was studied by differentiating Neuro2A using retinoic acid. URM-II-81 restored axonal length in MGO treated cells. Its effects were also studied in high fat and low dose streptozotocin induced diabetic mice where it reduced RBG levels and inhibited glycative stress by reducing HbA1c. URM-II-81 treatment also showed inhibition of gliosis in hippocampus. Histological analysis showed reduced NFTs in CA3 hippocampal region and restoration of insulin signaling in hippocampii of diabetic mice. Our findings suggest that URM-II-81 can be developed as a new therapeutic agent for treatment of neurodegenration.
    Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy; Diabetes Mellitus, Experimental/metabolism*; Diabetes Mellitus, Experimental/pathology
  8. Quercetin and pioglitazone synergistically reverse endothelial dysfunction in isolated aorta from fructose-streptozotocin (F-STZ)-induced diabetic rats
    Kunasegaran T, Mustafa MR, Achike FI, Murugan DD
    Eur J Pharmacol, 2017 Mar 15;799:160-170.
    PMID: 28213289 DOI: 10.1016/j.ejphar.2017.02.022
    Pioglitazone is an anti-diabetic drug with potential to cause adverse effects following prolonged use. This study, therefore, investigated the effects of combination treatment of a subliminal concentration of pioglitazone and quercetin, a potent antioxidant, on vascular reactivity of aorta isolated from fructose-streptozotocin (F-STZ)-induced diabetic rats. Relaxation to acetylcholine and sodium nitroprusside, and contraction to phenylephrine were tested in organ bath chambers following pre-incubation with vehicle (DMSO; 0.05%), quercetin (10-7 M), pioglitazone (10-7 M), or their combination (P+Q; 10-7 M each drug). Subliminal concentration of quercetin or pioglitazone did not alter the acetylcholine- induced relaxation nor the phenylephrine-induced contraction in both normal rat and diabetic F-STZ induced tissues. However, P+Q combination synergistically improved the impaired acetylcholine-induced relaxation and decreased the elevated phenylephrine-induced contraction in aortic rings from diabetic, but not in the normal rats. Neither mono nor combination treatment altered sodium nitroprusside-induced relaxation. The combination also synergistically decreased superoxide anion and increased nitric oxide production compared to the individual treatments in aorta from diabetic rats. Overall, these data demonstrated a synergistic effect, in which, a combination (P+Q; 10-7 M each drug) caused a significantly greater effect than 10-6 M of either agent in improving endothelial function of isolated diabetic aorta. In conclusion, a combination of subliminal concentrations of pioglitazone and quercetin is able to decrease oxidative stress and provide synergistic vascular protection in type 2 diabetes mellitus and thus the possibility of using quercetin as a supplement to pioglitazone in the treatment of diabetes with the goal of reducing pioglitazone toxicity.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  9. Biological activities of Anastatica hierochuntica L.: A systematic review
    Zin SRM, Kassim NM, Alshawsh MA, Hashim NE, Mohamed Z
    Biomed Pharmacother, 2017 Jul;91:611-620.
    PMID: 28486192 DOI: 10.1016/j.biopha.2017.05.011
    Anastatica hierochuntica L. (A. hierochuntica) is a desert plant consumed by people across the globe to treat various medical conditions. This review is aimed at providing a summary of the scientific findings on biological activities of A. hierochuntica and suggests areas in which further research is needed. This systematic review was synthesized from the literature obtained from the following databases; PubMed, Science Direct, Web of Science, Ovid Medline, Scopus, Google Scholar and WorldCat. Previous studies have indicated that the methanolic and aqueous extracts of this plant have antioxidant, antifungal and antimicrobial activities. It was shown to have the ability to activate phagocytes and to possess microbicidal activity, thereby causing increased resistance to infection. Both methanolic and aqueous extracts of this plant were also demonstrated to have a hypoglycaemic property, whilst the methanolic extract significantly exhibited hypolipidaemic effects in diabetic rats. Moreover, the methanolic extract of A. hierochuntica has been suggested to have hepatoprotective properties. This is supported by its ability to significantly decrease transaminase and alkaline phosphatase activities in alloxan-induced diabetic rats. Besides, this desert plant exhibited anti-inflammatory, anti-melanogenic and gastroprotective activities. Even though A. hierochuntica is widely used, studies on this plant are still scarce, thus its reputed biological activities and medical benefits require critical evaluation. Before A. hierochuntica can be used clinically, further studies need to be conducted to increase our understanding of the effects of this plant, its constituents, and possible mechanisms of action.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  10. Fulltext Induction of hepatic glutathione-S-transferase activity by Orthosiphon stamineus, Benth in STZ-induced diabetic rats
    Chin, J.H., Ismail, S., Hussin, A.H.
    Malaysian Journal of Pharmaceutical Science, 2008;6(1):59-68.
    MyJurnal
    The aim of this study was to investigate the acute (one-day treatment) effect of a methanol extract of
    Orthosiphon stamineus, Benth on glutathione-S-transferase (GST) activity in streptozotocin (STZ)-induced diabetic young male and female Sprague Dawley (SD) rats. The methanol extract of O. stamineus was administered orally (5, 31.25, 125 and 500 mg/kg) to diabetic rats, and the effect on GST activity was measured by the method of Habig et al. (1974). No lethality and no significant changes in body weight and water intake were observed in the treated group as compared to the control group. A significant increase in the activity of GST was observed in the liver S-9 cytosolic fraction of diabetic male SD rats treated with 125 mg/kg (P < 0.01) and 500 mg/kg (P < 0.01) of the methanol extract O. stamineus. Administration of 500 mg/kg (P < 0.01) of the methanol extract of O. stamineus to diabetic female SD rats increased GST activity when compared to the control group. This study indicates that the methanol extract of O. stamineus could affect the activity of GST in rat liver and the effect seen was dose-dependent.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  11. Fulltext Antihyperglycemic and glucose tolerance activity of ficus deltoidea ethanolic extract in diabetic rats
    Zainah Adam, Muhajir Hamid, Amin Ismail, Shafii Khamis, Norazizah Marsidi
    Jurnal Sains Kesihatan Malaysia, 2010;8(1):25-30.
    MyJurnal
    Ficus deltoidea or Mas cotek is one of the common medicinal plants used in Malaysia has been claimed to have antidiabetic activity. However, scientific evidence to confirm its efficacy is still lacking. Thus, the present study was undertaken to evaluate the potential of ethanolic extract of Ficus deltoidea to reduce hyperglycaemia in streptozotocininduced diabetic rats at different prandial state. The results showed that, ethanolic extract of Ficus deltoidea significantly reduced fasting and postprandial hyperglycemia particularly after 4 and 6 hours of extract administration. Likewise, glucose tolerance activity was significantly improved in the presence of Ficus deltoidea ethanolic extract at a low dose, 100 mg/kg. It is suggested that ethanolic extract of Ficus deltoidea at particular doses, possess fasting and postprandial antihyperglycemic activity as well as glucose tolerance activity in streptozotocin-induced diabetic rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  12. Fulltext The effects of palm vitamin E supplementation on glycemic control and lipid profile in streptozotocin-induced diabetic rats
    Siti Balkis Budin, Abdul Gapor Mohd Top, Wan Nazaimoon Wan Mohamud, Mokhtar Abu Bakar, Khairul Osman, Yau, Monica Swee Eng, et al.
    Jurnal Sains Kesihatan Malaysia, 2005;3(1):1-12.
    MyJurnal
    In this study, the effects of palm vitamin E (PV) supplementation on glycemic control and lipid profile in diabetic-induce Sprague-Dawley rats have been evaluated. Diabetes in the rats was induced by a single intravenous streptozotocin (50 mg/kg body weight). The diabetic rats were divided into two groups; supplemented with 200 mg/kg body weight/day of PV and non-supplemented with PV (No PV group). Non-diabetic rats (NDM) formed the control group and only received saline injection. After eight weeks of daily supplementation, PV significantly lowered the fasting blood glucose (FBG) and glycosylated haemoglobin (HbA1c) levels (p
    Matched MeSH terms: Diabetes Mellitus, Experimental
  13. Fulltext Assessment on Functionality and Viability of β cells Following Repetitive Dosage Administration of Ethanolic Extracts of Andrographis paniculata on Streptozotocin-induced Diabetic Rats
    Abdul Razak, K., Mariam, A., Amirin, S., Mohd Zaini, A.
    International Medical Journal Malaysia, 2010;9(1):21-26.
    MyJurnal
    Introduction: The study was done at the aim to assess the functionality and viability of the β cells of the streptozotocin-induced diabetic rats model following repetitive dosage of administration of ethanolic extracts of Andrographis paniculata. Materials and Methods: The diabetic rats were treated with the extracts for fourteen days and at the dose given was 500 mg/kg twice daily. The assessments were made on fasting blood glucose, insulin, and immunohistochemical aspect of β cells before and after treatment. Results: The results showed that there was a signifi cant reduction on fasting blood glucose levels in metformin, 95% and 50% ethanolic plant extracts-treated groups but on insulin level only 95% and 50% ethanolic extracts-treated groups gave a signifi cant reduction(p
    Matched MeSH terms: Diabetes Mellitus, Experimental
  14. Fulltext Down-regulation of steroidogenesis-related genes and its accompanying fertility decline in streptozotocin-induced diabetic male rats: ameliorative effect of metformin
    Nna VU, Bakar ABA, Ahmad A, Mohamed M
    Andrology, 2019 01;7(1):110-123.
    PMID: 30515996 DOI: 10.1111/andr.12567
    BACKGROUND: Metformin has long been used for glycemic control in diabetic state. Recently, other benefits of metformin beyond blood glucose regulation have emerged.

    OBJECTIVES: To investigate the effect of metformin on the expression of testicular steroidogenesis-related genes, spermatogenesis, and fertility of male diabetic rats.

    MATERIALS AND METHODS: Eighteen adult male Sprague Dawley rats were divided into three groups, namely normal control (NC), diabetic control (DC), and metformin-treated (300 mg/kg body weight/day) diabetic rats (D+Met). Diabetes was induced using a single intraperitoneal injection of streptozotocin (60 mg/kg b.w.), followed by oral treatment with metformin for four weeks.

    RESULTS: Diabetes decreased serum and intratesticular testosterone levels and increased serum but not intratesticular levels of luteinizing hormone. Sperm count, motility, viability, and normal morphology were decreased, while sperm nuclear DNA fragmentation was increased in DC group, relative to NC group. Testicular mRNA levels of androgen receptor, luteinizing hormone receptor, cytochrome P450 enzyme (CYP11A1), steroidogenic acute regulatory (StAR) protein, 3β-hydroxysteroid dehydrogenase (HSD), and 17β-HSD, as well as the level of StAR protein and activities of CYP11A1, 3β-HSD, and 17β-HSD, were decreased in DC group. Similarly, decreased activities of epididymal antioxidant enzymes and increased lipid peroxidation were observed in DC group. Consequently, decreased litter size, fetal weight, mating and fertility indices, and increased pre- and post-implantation losses were recorded in DC group. Following intervention with metformin, we observed increases in serum and intratesticular testosterone levels, Leydig cell count, improved sperm parameters, and decreased sperm nuclear DNA fragmentation. Furthermore, mRNA levels and activities of steroidogenesis-related enzymes were increased, with improved fertility outcome.

    DISCUSSION AND CONCLUSION: Diabetes mellitus is associated with dysregulation of steroidogenesis, abnormal spermatogenesis, and fertility decline. Controlling hyperglycemia is therefore crucial in preserving male reproductive function. Metformin not only regulates blood glucose level, but also preserves male fertility in diabetic state.

    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/genetics*; Diabetes Mellitus, Experimental/pathology*
  15. Fulltext Structural changes in the urinary bladder of streptozotocin-induced diabetic rats and the possible protective role of insulin
    Elnagar, Amir M. Bassam, Suhaidah Ibrahim, Abouelnaga, Mostafa A.M., Soliman, Amro Mohamed
    International Medical Journal Malaysia, 2018;17(3):39-48.
    MyJurnal
    Introduction: Diabetes mellitus possesses severe adverse effects on the urinary bladder. Urinary bladder dysfunction is a common health problem affecting diabetic patients causing recurrent infections and urinary incontinence. Objective: To evaluate the histopathological changes in the tissue of urinary bladder in Streptozotocin (STZ) diabetic rats and the protective role of insulin. Methods: Thirty rats were classified into three groups: a control group which received no treatment (Group A), STZ diabetic group (Group B) and Insulin diabetic group (Group C). Animals were sacrificed after six weeks and urinary bladders were harvested and processed for light and electron microscopy. Results: Several histopathological changes were observed in the urinary bladder of the diabetic group including an increase in the thickness of the urothelium, epithelial cells with dark nuclei and large lenticular vesicles, and wide intercellular spaces with numerous collagen fibers. Treatment with insulin reduced the pathological changes induced by STZ. Conclusion: Diabetes mellitus caused significant pathological changes in the urinary bladder of experimental rats. For instance, treating diabetic animals with insulin prevented the development of damaging effects of diabetes on the urinary bladder.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  16. Evaluation and docking of indole sulfonamide as a potent inhibitor of α-glucosidase enzyme in streptozotocin -induced diabetic albino wistar rats
    Taha M, Imran S, Salahuddin M, Iqbal N, Rahim F, Uddin N, et al.
    Bioorg Chem, 2021 05;110:104808.
    PMID: 33756236 DOI: 10.1016/j.bioorg.2021.104808
    We have synthesized new hybrid class of indole bearing sulfonamide scaffolds (1-17) as α-glucosidase inhibitors. All scaffolds were found to be active except scaffold 17 and exhibited IC50 values ranging from 1.60 to 51.20 µM in comparison with standard acarbose (IC50 = 42.45 µM). Among the synthesized hybrid class scaffolds 16 was the most potent analogue with IC50 value 1.60 μM, showing many folds better potency as compared to standard acarbose. Whereas, synthesized scaffolds 1-15 showed good α-glucosidase inhibitory potential. Based on α-glucosidase inhibitory effect, Scaffold 16 was chosen due to highest activity in vitro for further evaluation of antidiabetic activity in Streptozotocin induced diabetic rats. The Scaffold 16 exhibited significant antidiabetic activity. All analogues were characterized through 1H, 13CNMR and HR MS. Structure-activity relationship of synthesized analogues was established and confirmed through molecular docking study.
    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/metabolism
  17. Quercetin, a flavonoid antioxidant, modulates endothelium-derived nitric oxide bioavailability in diabetic rat aortas
    Machha A, Achike FI, Mustafa AM, Mustafa MR
    Nitric Oxide, 2007 Jun;16(4):442-7.
    PMID: 17513143 DOI: 10.1016/j.niox.2007.04.001
    The present work examined the effect of chronic oral administration of quercetin, a flavonoid antioxidant, on blood glucose, vascular function and oxidative stress in STZ-induced diabetic rats. Male Wistar-Kyoto (WKY) rats were randomized into euglycemic, untreated diabetic, vehicle (1% w/v methylcellulose)-treated diabetic, which served as control, or quercetin (10mgkg(-1) body weight)-treated diabetic groups and treated orally for 6 weeks. Quercetin treatment reduced blood glucose level in diabetic rats. Impaired relaxations to endothelium-dependent vasodilator acetylcholine (ACh) and enhanced vasoconstriction responses to alpha(1)-adrenoceptor agonist phenylephrine (PE) in diabetic rat aortic rings were restored to euglycemic levels by quercetin treatment. Pretreatment with N(omega)-nitro-l-arginine methyl ester (l-NAME, 10microM) or methylene blue (10microM) completely blocked but indomethacin (10microM) did not affect relaxations to ACh in aortic rings from vehicle- or quercetin-treated diabetic rats. PE-induced vasoconstriction with an essentially similar magnitude in vehicle- or quercetin-treated diabetic rat aortic rings pretreated with l-NAME (10microM) plus indomethacin (10microM). Quercetin treatment reduced plasma malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HNE) content as well as increased superoxide dismutase activity and total antioxidant capacity in diabetic rats. From the present study, it can be concluded that quercetin administration to diabetic rats restores vascular function, probably through enhancement in the bioavailability of endothelium-derived nitric oxide coupled to reduced blood glucose level and oxidative stress.
    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/enzymology
  18. The effects of high-fat diet and metformin on urinary metabolites in diabetes and prediabetes rat models
    Lee YF, Sim XY, Teh YH, Ismail MN, Greimel P, Murugaiyah V, et al.
    Biotechnol Appl Biochem, 2021 Oct;68(5):1014-1026.
    PMID: 32931602 DOI: 10.1002/bab.2021
    High-fat diet (HFD) interferes with the dietary plan of patients with type 2 diabetes mellitus (T2DM). However, many diabetes patients consume food with higher fat content for a better taste bud experience. In this study, we examined the effect of HFD on rats at the early onset of diabetes and prediabetes by supplementing their feed with palm olein oil to provide a fat content representing 39% of total calorie intake. Urinary profile generated from liquid chromatography-mass spectrometry analysis was used to construct the orthogonal partial least squares discriminant analysis (OPLS-DA) score plots. The data provide insights into the physiological state of an organism. Healthy rats fed with normal chow (NC) and HFD cannot be distinguished by their urinary metabolite profiles, whereas diabetic and prediabetic rats showed a clear separation in OPLS-DA profile between the two diets, indicating a change in their physiological state. Metformin treatment altered the metabolomics profiles of diabetic rats and lowered their blood sugar levels. For prediabetic rats, metformin treatment on both NC- and HFD-fed rats not only reduced their blood sugar levels to normal but also altered the urinary metabolite profile to be more like healthy rats. The use of metformin is therefore beneficial at the prediabetes stage.
    Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy; Diabetes Mellitus, Experimental/metabolism*; Diabetes Mellitus, Experimental/urine
  19. Fulltext Calcitriol Supplementation Ameliorates Microvascular Endothelial Dysfunction in Vitamin D-Deficient Diabetic Rats by Upregulating the Vascular eNOS Protein Expression and Reducing Oxidative Stress
    Wee CL, Mokhtar SS, Singh KKB, Yahaya S, Leung SWS, Rasool AHG
    Oxid Med Cell Longev, 2021;2021:3109294.
    PMID: 33623633 DOI: 10.1155/2021/3109294
    Diabetes mellitus contributes to macro- and microvascular complications, leading to adverse cardiovascular events. This study examined the effects of vitamin D deficiency on the vascular function and tissue oxidative status in the microcirculation of diabetic rats and to determine whether these effects can be reversed with calcitriol (active vitamin D metabolite) supplementation. Streptozotocin-induced diabetic rats were fed for 10 weeks with control diet (DC) or vitamin D-deficient diet without (DD) or with oral calcitriol supplementation (0.15 μg/kg) in the last four weeks (DDS) (10 rats each group). A nondiabetic rat group that received control diet was also included (NR). After 10 weeks, rats were sacrificed; mesenteric arterial rings with and without endothelium were studied using wire myograph. Western blotting of the mesenteric arterial tissue was performed to determine the protein expression of endothelial nitric oxide synthase (eNOS) enzyme. Antioxidant enzyme superoxide dismutase (SOD) activity and oxidative stress marker malondialdehyde (MDA) levels in the mesenteric arterial tissue were also measured. The DC group had significantly lower acetylcholine-induced relaxation and augmented endothelium-dependent contraction, with reduced eNOS expression, compared to NR rats. In mesenteric arteries of DD, acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent relaxations were lower than those in DC. Calcitriol supplementation in DDS restored endothelium-dependent relaxation. Mesenteric artery endothelium-dependent contraction of DD was greater than DC; it was not affected by calcitriol supplementation. The eNOS protein expression and SOD activity were significantly lower while MDA levels were greater in DD compared to DC; these effects were not observed in DDS that received calcitriol supplementation. In conclusion, vitamin D deficiency causes eNOS downregulation and oxidative stress, thereby impairing the vascular function and posing an additional risk for microvascular complications in diabetes. Calcitriol supplementation to diabetics with vitamin D deficiency could potentially be useful in the management of or as an adjunct to diabetes-related cardiovascular complications.
    Matched MeSH terms: Diabetes Mellitus, Experimental/complications; Diabetes Mellitus, Experimental/enzymology*; Diabetes Mellitus, Experimental/pathology
  20. Metformin attenuated histopathological ocular deteriorations in a streptozotocin-induced hyperglycemic rat model
    Nahar N, Mohamed S, Mustapha NM, Lau S, Ishak NIM, Umran NS
    Naunyn Schmiedebergs Arch Pharmacol, 2021 Mar;394(3):457-467.
    PMID: 33047165 DOI: 10.1007/s00210-020-01989-w
    Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/pathology
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