Displaying publications 1 - 20 of 49 in total

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  1. Dongare S, Gupta SK, Mathur R, Saxena R, Mathur S, Agarwal R, et al.
    Mol Vis, 2016;22:599-609.
    PMID: 27293376
    PURPOSE: Diabetic retinopathy is a common microvascular complication of long-standing diabetes. Several complex interconnecting biochemical pathways are activated in response to hyperglycemia. These pathways culminate into proinflammatory and angiogenic effects that bring about structural and functional damage to the retinal vasculature. Since Zingiber officinale (ginger) is known for its anti-inflammatory and antiangiogenic properties, we investigated the effects of its extract standardized to 5% 6-gingerol, the major active constituent of ginger, in attenuating retinal microvascular changes in rats with streptozotocin-induced diabetes.

    METHODS: Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels.

    RESULTS: Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract-treated group compared to the vehicle-treated group.

    CONCLUSIONS: The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation.

    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  2. Choo CY, Sulong NY, Man F, Wong TW
    J Ethnopharmacol, 2012 Aug 1;142(3):776-81.
    PMID: 22683902 DOI: 10.1016/j.jep.2012.05.062
    The leaves of Ficus deltoidea are used as a traditional medicine by diabetes patients in Malaysia.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  3. Lee WC, Mokhtar SS, Munisamy S, Yahaya S, Rasool AHG
    Cell Mol Biol (Noisy-le-grand), 2018 May 30;64(7):60-69.
    PMID: 29974854
    Diabetes mellitus is an epidemic that is gaining global concern. Chronic hyperglycemia in diabetes induces the excess production of free radicals. The deleterious effects of excess free radicals are encountered by endogenous antioxidant defense system. Imbalance between free radicals production and antioxidants defense mechanisms leads to a condition known as "oxidative stress". Diabetes mellitus is associated with augmented oxidative stress that induced micro- and macrovascular complications, which presents a significant risk for cardiovascular events. Low vitamin D levels in the body have also been reported to be associated with the pathogenesis of diabetes and enhanced oxidative stress. The article is to review available literature and summarize the relationship between oxidative stress and vitamin D levels in diabetes. We also review the effects of vitamin D analogs supplementation in improving oxidative stress in diabetics.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  4. Wan Nazaimoon WM, Khalid BA
    Malays J Pathol, 2002 Dec;24(2):77-82.
    PMID: 12887164
    This study determined the effects of palm vitamin E (TRF) diet on the levels of blood glucose, glycated hemoglobin (gHb), serum advanced glycosylation end-products (AGE) and malondialdehyde (MDA) of diabetic Sprague-Dawley rats. The rats received either control (normal rat chow), TRF diet (normal chow fortified with TRF at 1 g/kg) or Vitamin C diet (vitamin E-deficient but contained vitamin C at 45 g/kg). The animals were maintained on the respective diet for 4 weeks, made diabetic with streptozotocin (STZ), then followed-up for a further 8 weeks. At week-4, mean serum AGE levels of rats given TRF diet (0.7 +/- 0.3 units/ml) were significantly lower than those of control or Vitamin C diet rats (p pounds 0.03). The levels increased after STZ and became comparable to the other groups. At week 12, blood glucose (20.9 +/- 6.9 mM) and gHb (10.0 +/- 1.6%) of rats on TRF diet remained significantly low compared to that of control or Vitamin C diet rats (p pounds 0.03). MDA however, was not affected and remained comparable between groups throughout the study. This study showed that TRF may be a useful antioxidant; effectively prevented increase in AGE in normal rats, and caused decrease in blood glucose and gHb in diabetic rats. Further studies are needed to elucidate the mechanisms of action of TRF.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  5. Noor H, Hammonds P, Sutton R, Ashcroft SJ
    Diabetologia, 1989 Jun;32(6):354-9.
    PMID: 2668082
    In Malaysia, Tinospora crispa extract is taken orally by Type 2 (non-insulin-dependent) diabetic patients to treat hyperglycaemia. We have evaluated the claimed hypoglycaemic property by adding aqueous extract to the drinking water of normal and alloxan-diabetic rats. After one week, fasting blood glucose levels were significantly (p less than 0.01) lower and serum insulin levels were significantly (p less than 0.01) higher in treated diabetic animals (10.4 +/- 1.0 mmol/l and 12.8 +/- 1.1 muU/ml respectively) compared to untreated diabetic controls (17.4 +/- 1.7 mmol/l and 8.0 +/- 0.7 muU/ml respectively). The insulinotropic action of T. crispa was further investigated in vitro using isolated human or rat islets of Langerhans and HIT-T15 cells. In static incubations with rat islets and HIT-T15 B cells, the extract induced a dosage dependent stimulation and potentiation of basal and glucose-stimulated insulin secretion respectively. This insulinotropic effect was also evident in perifused human and rat islets and HIT-T5 B-cells. The observations that (i) in all three models insulin secretory rates rapidly returned to basal levels on removal of the extract and (ii) in rat islets, a second challenge with T. crispa induced an additional, stimulated response, are all consistent with physiological release of insulin by B cells. Moreover, the rate of HIT-T15 glucose utilisation was not affected by incubation with T. crispa, suggesting that the cells were viable throughout. These are the first studies to provide biochemical evidence which substantiates the traditional claims for an oral hypoglycaemic effect of Tinospora crispa, and which also show that the hypoglycaemic effect is associated with increased insulin secretion.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  6. Budin SB, Othman F, Louis SR, Bakar MA, Das S, Mohamed J
    Clinics (Sao Paulo), 2009;64(3):235-44.
    PMID: 19330251
    OBJECTIVE: This study examined the effects of palm oil tocotrienol-rich fractions on streptozotocin-induced diabetic rats.

    METHODS: Animals were divided into three groups: (i) normal non-diabetic (NDM), (ii) diabetic treated (tocotrienol-rich fractions - TRF) and (iii) diabetic untreated (non-TRF). The treatment group received oral administration of tocotrienol-rich fractions (200 mg/kg body weight) daily for eight weeks. The normal non-diabetic and the diabetic untreated groups were fed standard rat feed. Blood glucose and lipid profiles, oxidative stress markers and morphological changes of the thoracic aorta were evaluated.

    RESULTS: Tocotrienol-rich fractions treatment reduced serum glucose and glycated hemoglobin concentrations. The tocotrienol-rich fractions group also showed significantly lower levels of plasma total cholesterol, low-density lipoprotein cholesterol, and triglyceride, as compared to the untreated group. The tocotrienol-rich fractions group had higher levels of high-density lipoprotein cholesterol, as compared to the untreated group. Superoxide dismutase activity and levels of vitamin C in plasma were increased in tocotrienol-rich fractions-treated rats. The levels of plasma and aorta malondealdehyde + 4-hydroxynonenal (MDA + 4-HNE) and oxidative DNA damage were significant following tocotrienol-rich fractions treatment. Electron microscopic examination showed that the normal morphology of the thoracic aorta was disrupted in STZ-diabetic rats. Tocotrienol-rich fractions supplementation resulted in a protective effect on the vessel wall.

    CONCLUSION: These results show that tocotrienol-rich fractions lowers the blood glucose level and improves dyslipidemia. Levels of oxidative stress markers were also reduced by administration of tocotrienol-rich fractions. Vessel wall integrity was maintained due to the positive effects mediated by tocotrienol-rich fractions.

    Matched MeSH terms: Diabetes Mellitus, Experimental/blood*
  7. Ruzaidi A, Amin I, Nawalyah AG, Hamid M, Faizul HA
    J Ethnopharmacol, 2005 Apr 8;98(1-2):55-60.
    PMID: 15763363
    The present study aims to investigate the effect of cocoa extract on serum glucose levels and lipid profiles in streptozotocin-diabetic rats. Cocoa extract (contained 285.6 mg total polyphenol per gram extract) was prepared from fermented and roasted (140 degrees C, 20 min) beans by extracting using 80% ethanol in the ratio of 1-10. The extract of three dosages (1, 2, and 3%) was fed to normal and diabetic rats for a period of 4 weeks. In hyperglycaemic group, cocoa extract (1 and 3%) diets were found to significantly lower (p<0.05) the serum glucose levels compared to the control. Furthermore, supplementation of 1 and 3% cocoa extract had significantly reduced (p<0.05) the level of total cholesterol in diabetic rats. In addition, 1, 2, and 3% cocoa extract diets had significantly lowered (p<0.05) the total triglycerides. Interestingly, this study found that serum HDL-cholesterol had increased significantly (p<0.05) in diabetic rats fed with 2% cocoa extract, while the LDL-cholesterol had decreased significantly (p<0.05) in the 1% treated group. These results indicate that cocoa extract may possess potential hypoglycaemic and hypocholestrolemic effects on serum glucose levels and lipid profiles, respectively. The results also found that the effect of cocoa extract was dose-dependent.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  8. Farsi E, Ahmad M, Hor SY, Ahamed MB, Yam MF, Asmawi MZ, et al.
    BMC Complement Altern Med, 2014 07 04;14:220.
    PMID: 24993916 DOI: 10.1186/1472-6882-14-220
    BACKGROUND: Recently, there has been increasing interest in Ficus deltoidea Jack. (Moraceae) due to its chemical composition and the potential health benefits. The present study was undertaken to investigate the effect of extracts of F. deltoidea leaves on diabetes.

    METHODS: The petroleum ether, chloroform and methanol extracts of F. deltoidea were prepared and subjected to standardization using preliminary phytochemical and HPLC analysis. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. w.) as per OECD guidelines. Diabetes mellitus was induced with streptozotocin and rats found diabetic were orally administered with the extract (250, 500 and 1000 mg/kg) for 14 days. Levels of blood glucose and insulin were measured in control as well as diabetic rats on 0, 7 and 14th day. In addition, glucose metabolism regulating gene expression was assessed using RT-PCR.

    RESULTS: HPLC analysis revealed that the methanol extract is enriched with C-glycosylflavones particularly, vitexin and isovitexin. In oral glucose tolerance test, oral administration of the methanol extract increased the glucose tolerance. The methanol extract showed significant (P blood glucose level in streptozotocin-induced diabetic rats. The streptozotocin-related weight loss in rats was noticeably reversed by the extract treatment. Finally, RT-PCR analysis revealed a novel mechanisms for the anti-diabetic action of methanol extract of F. deltoidea. The extract exerted its effect via an increase of insulin secretion which impeded the hepatic glucose production, via down-regulation of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase genes expression on one hand, and up-regulation of hepatic GK and PPARγ genes expression on the other hand. The extract caused an increased expression of GLUT-4 gene expression in skeletal muscles which leads to normalize the hyperglycemia. The extract also nullified the toxic effects of streptozitocin by blocking its entry into the islet β-cells through reducing the expression of GLUT-2 gene.

    CONCLUSION: It can be concluded that, F. deltoidea could potentially inhibits the streptozitocin-induced hyperglycemia in rats. Further the herb can be utilized as useful remedy for alleviation of diabetes complications.

    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  9. Husen R, Pihie AH, Nallappan M
    J Ethnopharmacol, 2004 Dec;95(2-3):205-8.
    PMID: 15507337 DOI: 10.1016/j.jep.2004.07.004
    Screening of aqueous extract of Phyllantus niruri (PL), Zingiber zerumbet (ZG), Eurycoma longifolia (TA-a and TA-b) and Andrographis paniculata (AP) to determine their blood glucose lowering effect were conducted in normoglycaemic and Streptozotocin-induced hyperglycaemic rats. Significant reduction in blood glucose level at 52.90% was shown when hyperglycaemic rats were treated with 50 mg/kg body weight (BW) aqueous extract of AP. This effect is enhanced when freeze-dried material was used, where 6.25 mg/kg BW gave 61.81% reduction in blood glucose level. In the administration of TA-a and TA-b, positive results in hyperglyacaemic rats were only obtained when 150 mg/kg BW of the aqueous extract was used. No significant reduction in blood glucose level were shown in hyperglycaemic rats treated with PL and ZG at all concentrations used (50, 100 and 150 mg/kg BW). In normoglycaemic rats, no significant reduction was noted when all the same extracts were used.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  10. Motshakeri M, Ebrahimi M, Goh YM, Matanjun P, Mohamed S
    J Sci Food Agric, 2013 May;93(7):1772-8.
    PMID: 23208488 DOI: 10.1002/jsfa.5971
    BACKGROUND: Sargassum polycystum, a brown seaweed, contains various nutrients and bioactive compounds that have antioxidant and healing properties. The research hypothesises that antioxidants and pigments in dietary S. polycystum extracts can improve insulin sensitivity, blood sugar levels and blood lipid levels in a rat model of type 2 diabetes. The diabetes was induced by a high-sugar, high-fat diet for 16 weeks to enhance insulin resistance, followed by a low-dose intraperitoneal injection of streptozotocin (35 mg kg(-1) body weight). The doses of S. polycystum tested on diabetic rats were 150 and 300 mg kg(-1) body weight for the ethanolic extract or 150 and 300 mg kg(-1) for the water extract. Normal rats, untreated diabetic and metformin-treated diabetic rats (n = 6) were used as control.

    RESULTS: Both doses of the alcohol extract of S. polycystum and the 300 mg kg(-1) water extract, significantly reduced blood glucose and glycosylated haemoglobin (HbA1C ) levels. Serum total cholesterol, triglyceride levels and plasma atherogenic index were significantly decreased after 22 days treatment in all seaweed groups. Unlike metformin, S. polycystum did not significantly change plasma insulin in the rats, but increased the response to insulin.

    CONCLUSION: The consumption of either ethanolic or water extracts of S. polycystum dose dependently reduced dyslipidaemia in type 2 diabetic rats. S. polycystum is a potential insulin sensitiser, for a comestible complementary therapy in the management of type 2 diabetes which can help reduce atherogenic risk.

    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  11. Dehghan F, Hajiaghaalipour F, Yusof A, Muniandy S, Hosseini SA, Heydari S, et al.
    Sci Rep, 2016 Apr 28;6:25139.
    PMID: 27122001 DOI: 10.1038/srep25139
    Saffron is consumed as food and medicine to treat several illnesses. This study elucidates the saffron effectiveness on diabetic parameters in-vitro and combined with resistance exercise in-vivo. The antioxidant properties of saffron was examined. Insulin secretion and glucose uptake were examined by cultured RIN-5F and L6 myotubes cells. The expressions of GLUT2, GLUT4, and AMPKα were determined by Western blot. Diabetic and non-diabetic male rats were divided into: control, training, extract treatment, training + extract treatment and metformin. The exercise and 40 mg/kg/day saffron treatments were carried out for six weeks. The antioxidant capacity of saffron was higher compare to positive control (P  0.05). Serum glucose, cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein, insulin resistance, and glycated hemoglobin levels decreased in treated rats compared to untreated (p  0.05). The findings suggest that saffron consuming alongside exercise could improve diabetic parameters through redox-mediated mechanisms and GLUT4/AMPK pathway to entrap glucose uptake.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  12. Salman IM, Ameer OZ, Sattar MA, Abdullah NA, Yam MF, Abdullah GZ, et al.
    Neurourol Urodyn, 2011 Mar;30(3):438-46.
    PMID: 21284025 DOI: 10.1002/nau.21007
    We assessed the role of renal sympathetic nervous system in the deterioration of renal hemodynamic and excretory functions in rats with streptozotocin (STZ)-induced diabetic kidney disease (DKD).
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  13. Abdul Nasir NA, Agarwal R, Sheikh Abdul Kadir SH, Vasudevan S, Tripathy M, Iezhitsa I, et al.
    PLoS One, 2017;12(3):e0174542.
    PMID: 28350848 DOI: 10.1371/journal.pone.0174542
    Cataract, a leading cause of blindness, is of special concern in diabetics as it occurs at earlier onset. Polyol accumulation and increased oxidative-nitrosative stress in cataractogenesis are associated with NFκB activation, iNOS expression, ATP depletion, loss of ATPase functions, calpain activation and proteolysis of soluble to insoluble proteins. Tocotrienol was previously shown to reduce lens oxidative stress and inhibit cataractogenesis in galactose-fed rats. In current study, we investigated anticataract effects of topical tocotrienol and possible mechanisms involved in streptozotocin-induced diabetic rats. Diabetes was induced in Sprague Dawley rats by intraperitoneal injection of streptozotocin. Diabetic rats were treated with vehicle (DV) or tocotrienol (DT). A third group consists of normal, non-diabetic rats were treated with vehicle (NV). All treatments were given topically, bilaterally, twice daily for 8 weeks with weekly slit lamp monitoring. Subsequently, rats were euthanized and lenses were subjected to estimation of polyol accumulation, oxidative-nitrosative stress, NFκB activation, iNOS expression, ATP levels, ATPase activities, calpain activity and total protein levels. Cataract progression was delayed from the fifth week onwards in DT with lower mean of cataract stages compared to DV group (p<0.01) despite persistent hyperglycemia. Reduced cataractogenesis in DT group was accompanied with lower aldose reductase activity and sorbitol level compared to DV group (p<0.01). DT group also showed reduced NFκB activation, lower iNOS expression and reduced oxidative-nitrosative stress compared to DV group. Lenticular ATP and ATPase and calpain 2 activities in DT group were restored to normal. Consequently, soluble to insoluble protein ratio in DT group was higher compared to DV (p<0.05). In conclusion, preventive effect of topical tocotrienol on development of cataract in STZ-induced diabetic rats could be attributed to reduced lens aldose reductase activity, polyol levels and oxidative-nitrosative stress. These effects of tocotrienol invlove reduced NFκB activation, lower iNOS expression, restoration of ATP level, ATPase activities, calpain activity and lens protein levels.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  14. Roslan J, Giribabu N, Karim K, Salleh N
    Biomed Pharmacother, 2017 Feb;86:570-582.
    PMID: 28027533 DOI: 10.1016/j.biopha.2016.12.044
    Quercetin is known to possess beneficial effects in ameliorating diabetic complications, however the mechanisms underlying cardioprotective effect of this compound in diabetes is not fully revealed. In this study, quercetin effect on oxidative stress, inflammation and apoptosis in the heart in diabetes were investigated. Normal and streptozotocin-nicotinamide induced adult male diabetic rats received quercetin (10, 25 and 50mg/kg/bw) orally for 28days were anesthetized and hemodynamic parameters i.e. systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were measured. Blood was collected for analyses of fasting glucose (FBG), insulin and cardiac injury marker levels (troponin-C, CK-MB and LDH). Following sacrificed, heart was harvested and histopathological changes were observed. Heart was subjected for analyses of oxidative stress marker i.e. lipid peroxidation and activity and expression levels of anti-oxidative enzymes i.e. SOD, CAT and GPx. Levels of inflammation in the heart were determined by measuring nuclear factor (p65-NF-κB), tumor necrosis factor (TNF-α), interleukins (IL)-1β and IL-6 levels by using enzyme-linked immunoassay (ELISA). Distribution and expression levels of TNF-α and Ikk-β (inflammatory markers), caspase-3, caspase-9, Blc-2 and Bax (apoptosis markers) in the heart were identified by immunohistochemistry and Western blotting respectively.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  15. Adam SH, Giribabu N, Kassim N, Kumar KE, Brahmayya M, Arya A, et al.
    Biomed Pharmacother, 2016 Jul;81:439-452.
    PMID: 27261624 DOI: 10.1016/j.biopha.2016.04.032
    INTRODUCTION: Protective effects of Vitis Vinifera seed aqueous extract (VVSAE) against pancreatic dysfunctions and elevation of oxidative stress, inflammation and apoptosis in the pancreas in diabetes were investigated. Histopathological changes in the pancreas were examined under light microscope.

    METHODS: Blood and pancreas were collected from adult male diabetic rats receiving 28days treatment with VVSAE orally. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin and lipid profile levels and activity levels of anti-oxidative enzymes (superoxide dismutase-SOD, catalase-CAT and glutathione peroxidase-GPx) in the pancreas were determined by biochemical assays. Histopathological changes in the pancreas were examined under light microscopy and levels of insulin, glucose transporter (GLUT)-2, tumor necrosis factor (TNF)-α, Ikkβ and caspase-3 mRNA and protein were analyzed by real-time PCR (qPCR) and immunohistochemistry respectively. Radical scavenging activity of VVSAE was evaluated by in-vitro anti-oxidant assay while gas chromatography-mass spectrometry (GC-MS) was used to identify the major compounds in the extract.

    RESULTS: GC-MS analyses indicated the presence of compounds that might exert anti-oxidative, anti-inflammatory and anti-apoptosis effects. Near normal FBG, HbAIc, lipid profile and serum insulin levels with lesser signs of pancreatic destruction were observed following administration of VVSAE to diabetic rats. Higher insulin, GLUT-2, SOD, CAT and GPx levels but lower TNF-α, Ikkβ and caspase-3 levels were also observed in the pancreas of VVSAE-treated diabetic rats (p<0.05 compared to non-treated diabetic rats). The extract possesses high in-vitro radical scavenging activities.

    CONCLUSION: In conclusions, administration of VVSAE to diabetic rats could help to protect the pancreas against oxidative stress, inflammation and apoptosis-induced damage while preserving pancreatic function near normal in diabetes.

    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  16. Abas R, Othman F, Thent ZC
    Oxid Med Cell Longev, 2014;2014:429060.
    PMID: 25371774 DOI: 10.1155/2014/429060
    In diabetes mellitus, cardiac fibrosis is characterized by increase in the deposition of collagen fibers. The present study aimed to observe the effect of Momordica charantia (MC) fruit extract on hyperglycaemia-induced cardiac fibrosis. Diabetes was induced in the male Sprague-Dawley rats with a single intravenous injection of streptozotocin (STZ). Following 4 weeks of STZ induction, the rats were subdivided (n = 6) into control group (Ctrl), control group treated with MC (Ctrl-MC), diabetic untreated group (DM-Ctrl), diabetic group treated with MC (DM-MC), and diabetic group treated with 150 mg/kg of metformin (DM-Met). Administration of MC fruit extract (1.5 g/kg body weight) in diabetic rats for 28 days showed significant increase in the body weight and decrease in the fasting blood glucose level. Significant increase in cardiac tissues superoxide dismutase (SOD), glutathione contents (GSH), and catalase (CAT) was observed following MC treatment. Hydroxyproline content was significantly reduced and associated morphological damages reverted to normal. The decreased expression of type III and type IV collagens was observed under immunohistochemical staining. It is concluded that MC fruit extract possesses antihyperglycemic, antioxidative, and cardioprotective properties which may be beneficial in the treatment of diabetic cardiac fibrosis.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  17. Sheshala R, Peh KK, Darwis Y
    Drug Dev Ind Pharm, 2009 Nov;35(11):1364-74.
    PMID: 19832637 DOI: 10.3109/03639040902939213
    AIM: The aim of this study was to prepare insulin-loaded poly(lactic acid)-polyethylene glycol microspheres that could control insulin release at least for 1 week and evaluate their in vivo performance in a streptozotocin-induced diabetic rat model.
    METHODS: The microspheres were prepared using a water-in-oil-in-water double emulsion solvent evaporation technique. Different formulation variables influencing the yield, particle size, entrapment efficiency, and in vitro release profiles were investigated. The pharmacokinetic study of optimized formulation was performed with single dose in comparison with multiple dose of Humulin 30/70 as a reference product in streptozotocin-induced diabetic rats.
    RESULTS: The optimized formulation of insulin microspheres was nonporous, smooth-surfaced, and spherical in structure under scanning electron microscope with a mean particle size of 3.07 microm and entrapment efficiency of 42.74% of the theoretical amount incorporated. The in vitro insulin release profiles was characterized by a bimodal behavior with an initial burst release because of the insulin adsorbed on the microsphere surface, followed by slower and continuous release corresponding to the insulin entrapped in polymer matrix.
    CONCLUSIONS: The optimized formulation and reference were comparable in the extent of absorption. Consequently, these microspheres can be proposed as new controlled parenteral delivery system.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
  18. 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
  19. Benchoula K, Khatib A, Quzwain FMC, Che Mohamad CA, Wan Sulaiman WMA, Abdul Wahab R, et al.
    Molecules, 2019 Apr 17;24(8).
    PMID: 30999617 DOI: 10.3390/molecules24081506
    A standard protocol to develop type 1 diabetes in zebrafish is still uncertain due to unpredictable factors. In this study, an optimized protocol was developed and used to evaluate the anti-diabetic activity of Psychotria malayana leaf. The aims of this study were to develop a type 1 diabetic adult zebrafish model and to evaluate the anti-diabetic activity of the plant extract on the developed model. The ability of streptozotocin and alloxan at a different dose to elevate the blood glucose levels in zebrafish was evaluated. While the anti-diabetic activity of P. malayana aqueous extract was evaluated through analysis of blood glucose and LC-MS analysis fingerprinting. The results indicated that a single intraperitoneal injection of 300 mg/kg alloxan was the optimal dose to elevate the fasting blood glucose in zebrafish. Furthermore, the plant extract at 1, 2, and 3 g/kg significantly reduced blood glucose levels in the diabetic zebrafish. In addition, LC-MS-based fingerprinting indicated that 3 g/kg plant extract more effective than other doses. Phytosterols, sugar alcohols, sugar acid, free fatty acids, cyclitols, phenolics, and alkaloid were detected in the extract using GC-MS. In conclusion, P. malayana leaf aqueous extract showed anti-diabetic activity on the developed type 1 diabetic zebrafish model.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood*
  20. George S, Ajikumaran Nair S, Johnson AJ, Venkataraman R, Baby S
    J Ethnopharmacol, 2015 Jun 20;168:158-63.
    PMID: 25858510 DOI: 10.1016/j.jep.2015.03.060
    Melicope lunu-ankenda leaves are used to treat diabetes in folklore medicinal practices in India and Malaysia. Here we report the isolation of an O-prenylated flavonoid (3,5,4'-trihydroxy-8,3'-dimethoxy-7-(3-methylbut-2-enoxy)flavone; OPF) from the leaves of M. lunu-ankenda and its antidiabetes activity against type-2 diabetes mellitus (T2DM).
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood
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