Displaying publications 81 - 100 of 248 in total

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  1. 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; Diabetes Mellitus, Experimental/drug therapy*
  2. Azemi AK, Mokhtar SS, Sharif SET, Rasool AHG
    Pharm Biol, 2021 Dec;59(1):1432-1440.
    PMID: 34693870 DOI: 10.1080/13880209.2021.1990357
    CONTEXT: Atherosclerosis predisposes individuals to adverse cardiovascular events. Clinacanthus nutans L. (Acanthaceae) is a traditional remedy used for diabetes and inflammatory conditions.

    OBJECTIVES: To investigate the anti-atherosclerotic activity of a C. nutans leaf methanol extract (CNME) in a type 2 diabetic (T2D) rat model induced by a high-fat diet (HFD) and low-dose streptozotocin.

    MATERIALS AND METHODS: Sixty male Sprague-Dawley rats were divided into five groups: non-diabetic fed a standard diet (C), C + CNME (500 mg/kg, orally), diabetic fed an HFD (DM), DM + CNME (500 mg/kg), and DM + Metformin (DM + Met; 300 mg/kg). Treatment with oral CNME and metformin was administered for 4 weeks. Fasting blood glucose (FBG), serum lipid profile, atherogenic index (AI), aortic tissue superoxide dismutase levels (SOD), malondialdehyde (MDA), and tumour necrosis factor-alpha (TNF-α) were measured. The rats' aortas were stained for histological analysis and intima-media thickness (IMT), a marker of subclinical atherosclerosis.

    RESULTS: The CNME-treated diabetic rats had reduced serum total cholesterol (43.74%; p = 0.0031), triglycerides (80.91%; p = 0.0003), low-density lipoprotein cholesterol (56.64%; p = 0.0008), AI (51.32%; p 

    Matched MeSH terms: Diabetes Mellitus, Experimental/complications; Diabetes Mellitus, Experimental/drug therapy
  3. Abu Bakar Sajak A, Mediani A, Maulidiani, Mohd Dom NS, Machap C, Hamid M, et al.
    Phytomedicine, 2017 Dec 01;36:201-209.
    PMID: 29157816 DOI: 10.1016/j.phymed.2017.10.011
    BACKGROUND: Ipomoea aquatica (locally known as "kangkung") has previously been reported to have hypoglycemic activities on glucose level in diabetes patients. However, the effect of I. aquatica ethanolic extract on the metabolites in the body has remained unknown.

    PURPOSE: This study provides new insights on the changes of endogenous metabolites caused by I. aquatica ethanolic extract and improves the understanding on the therapeutic efficacy and mechanism of I. aquatica ethanolic extract.

    METHODS: By using a combination of 1H nuclear magnetic resonance (NMR) with multivariate analysis (MVDA), the changes of metabolites due to I. aquatica ethanolic extract administration in obese diabetic-induced Sprague Dawley rats (OB+STZ+IA) were identified.

    RESULTS: The results suggested 19 potential biomarkers with variable importance projections (VIP) above 0.5, which include creatine/creatinine, glucose, creatinine, citrate, carnitine, 2-oxoglutarate, succinate, hippurate, leucine, 1-methylnicotinamice (MNA), taurine, 3-hydroxybutyrate (3-HB), tryptophan, lysine, trigonelline, allantoin, formiate, acetoacetate (AcAc) and dimethylamine. From the changes in the metabolites, the affected pathways and aspects of metabolism were identified.

    CONCLUSION: I. aquatica ethanolic extract increases metabolite levels such as creatinine/creatine, carnitine, MNA, trigonelline, leucine, lysine, 3-HB and decreases metabolite levels, including glucose and tricarboxylic acid (TCA) intermediates. This implies capabilities of I. aquatica ethanolic extract promoting glycolysis, gut microbiota and nicotinate/nicotinamide metabolism, improving the glomerular filtration rate (GFR) and reducing the β-oxidation rate. However, the administration of I. aquatica ethanolic extract has several drawbacks, such as unimproved changes in amino acid metabolism, especially in reducing branched chain amino acid (BCAA) synthesis pathways and lipid metabolism.

    Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/metabolism*
  4. Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S
    Int J Biol Sci, 2011 Mar 14;7(2):244-52.
    PMID: 21448302 DOI: 10.7150/ijbs.7.244
    Diabetes mellitus is associated with deterioration of glycemic control and progressive metabolic derangements. This study investigated the effect of honey as an adjunct to glibenclamide or metformin on glycemic control in streptozotocin-induced diabetic rats. Diabetes was induced in rats by streptozotocin. The diabetic rats were randomized into six groups and administered distilled water, honey, glibenclamide, glibenclamide and honey, metformin or metformin and honey. The animals were treated orally once daily for four weeks. The diabetic control rats showed hypoinsulinemia (0.27 ± 0.01 ng/ml), hyperglycemia (22.4 ± 1.0 mmol/L) and increased fructosamine (360.0 ± 15.6 µmol/L). Honey significantly increased insulin (0.41 ± 0.06 ng/ml), decreased hyperglycemia (12.3 ± 3.1 mmol/L) and fructosamine (304.5 ± 10.1 µmol/L). Although glibenclamide or metformin alone significantly (p < 0.05) reduced hyperglycemia, glibenclamide or metformin combined with honey produced significantly much lower blood glucose (8.8 ± 2.9 or 9.9 ± 3.3 mmol/L, respectively) compared to glibenclamide or metformin alone (13.9 ± 3.4 or 13.2 ± 2.9 mmol/L, respectively). Similarly, glibenclamide or metformin combined with honey produced significantly (p < 0.05) lower fructosamine levels (301.3 ± 19.5 or 285.8 ± 22.6 µmol/L, respectively) whereas glibenclamide or metformin alone did not decrease fructosamine (330.0 ± 29.9 or 314.6 ± 17.9 µmol/L, respectively). Besides, these drugs or their combination with honey increased insulin levels. Glibenclamide or metformin combined with honey also significantly reduced the elevated levels of creatinine, bilirubin, triglycerides, and VLDL cholesterol. These results indicate that combination of glibenclamide or metformin with honey improves glycemic control, and provides additional metabolic benefits, not achieved with either glibenclamide or metformin alone.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/drug therapy*
  5. 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*; Diabetes Mellitus, Experimental/pathology
  6. Mohamed J, Shing SW, Idris MH, Budin SB, Zainalabidin S
    Clinics (Sao Paulo), 2013 Oct;68(10):1358-63.
    PMID: 24212844 DOI: 10.6061/clinics/2013(10)11
    OBJECTIVES: The aim of this study was to investigate the protective effects of aqueous extracts of roselle (Hibiscus sabdariffa L. UKMR-2) against red blood cell (RBC) membrane oxidative stress in rats with streptozotocin-induced diabetes.

    METHODS: Forty male Sprague-Dawley rats weighing 230-250 g were randomly divided into four groups (n = 10 rats each): control group (N), roselle-treated control group, diabetic group, and roselle-treated diabetic group. Roselle was administered by force-feeding with aqueous extracts of roselle (100 mg/kg body weight) for 28 days.

    RESULTS: The results demonstrated that the malondialdehyde levels of the red blood cell membranes in the diabetic group were significantly higher than the levels in the roselle-treated control and roselle-treated diabetic groups. The protein carbonyl level was significantly higher in the roselle-treated diabetic group than in the roselle-treated control group but lower than that in the diabetic group. A significant increase in the red blood cell membrane superoxide dismutase enzyme was found in roselle-treated diabetic rats compared with roselle-treated control rats and diabetic rats. The total protein level of the red blood cell membrane, osmotic fragility, and red blood cell morphology were maintained.

    CONCLUSION: The present study demonstrates that aqueous extracts of roselle possess a protective effect against red blood cell membrane oxidative stress in rats with streptozotocin-induced diabetes. These data suggest that roselle can be used as a natural antioxidative supplement in the prevention of oxidative damage in diabetic patients.

    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/metabolism*
  7. Borkataki S, Katoch R, Goswami P, Bhat A, Chakraborty D
    Trop Biomed, 2021 Mar 01;38(1):86-93.
    PMID: 33797529 DOI: 10.47665/tb.38.1.015
    The study was aimed to evaluate the effectiveness of maggot therapy in healing of cutaneous infected wound in streptozotocin (STZ) induced diabetic Wistar rat. For live maggots, the sterilized eggs of Lucilia sericata were obtained from colonies established in laboratory. Diabetes model was established in 48 male Wister rat by intra-peritoneal injection of STZ at the dose of 60 mg/kg body-weight. Cutaneous wounds exposed with mixed colonies of bacteria like Staphylococcus aureus, E. coli and Pseudomonas aeruginosa were prepared in all rat. The animals equally divided in 4 groups with 12 rats each being presented as treatment group of control, antibiotic, maggot and maggot with antibiotic in combination. All treatments were done once and hold for 24 hours. Wound kinetics and bacterial bio burden were measured at weekly interval to till complete healing. Significant reduction in wound area with maximum contraction was found (>95%) in maggot treated group when compared to antibiotic treated (79%) and control (72%). In maggot as well as maggot and antibiotic in combination group showed early elimination of bacterial bio-burden 7.88±0.03log CFU/ml to 1.12±0.65log CFU/ml and 7.86±0.04) log CFU/ml to 1.54±0.52log CFU/ml respectively in three weeks of time. Early healing indication was also experienced on histomorphological examination of wounded tissue of maggot treated groups by early and better epithelialization, collagenation and neovascularization with complete healing of wound in three weeks in comparison to antibiotic and control respectively. However, the present study did not show any difference in healing of wound with use of maggot alone or in antibiotic combination. Live maggot of Lucilia sericata effectively lower bacterial bioburden and and accelerate healing of infected cutaneous wound in diabetic conditions.
    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/complications*
  8. Atangwho IJ, Yin KB, Umar MI, Ahmad M, Asmawi MZ
    PMID: 25358757 DOI: 10.1186/1472-6882-14-426
    This study evaluated the impact of Vernonia amygdalina (VA) on the transcription of key enzymes involved in cellular modulation of glucose in streptozotocin-induced diabetic rats in a bid to understand the possible anti-diabetic mechanism of VA.
    Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy; Diabetes Mellitus, Experimental/enzymology*; Diabetes Mellitus, Experimental/metabolism
  9. Al-Obaidi MM, Al-Bayaty FH, Al Batran R, Hussaini J, Khor GH
    ScientificWorldJournal, 2014;2014:908098.
    PMID: 25485304 DOI: 10.1155/2014/908098
    To estimate the impact of ellagic acid (EA) towards healing tooth socket in diabetic animals, after tooth extraction.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/pathology
  10. Balakumar P, Varatharajan R, Nyo YH, Renushia R, Raaginey D, Oh AN, et al.
    Pharmacol Res, 2014 Dec;90:36-47.
    PMID: 25263930 DOI: 10.1016/j.phrs.2014.08.008
    Low-doses of fenofibrate and dipyridamole have pleiotropic renoprotective actions in diabetic rats. This study investigated their combined effect relative to their individual treatments and lisinopril in rats with diabetic nephropathy. Streptozotocin (55mg/kg, i.p., once)-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Diabetic rats after 10 weeks developed nephropathy with discernible renal structural and functional changes as assessed in terms of increase in kidney weight to body weight ratio (KW/BW), and elevations of serum creatinine, urea and uric acid, which accompanied with elevated serum triglycerides and decreased high-density lipoproteins. Hematoxylin-eosin, periodic acid Schiff and Masson trichrome staining confirmed renal pathological changes in diabetic rats that included glomerular capsular wall distortion, mesangial cell expansion, glomerular microvascular condensation, tubular damage and degeneration and fibrosis. Low-dose fenofibrate (30mg/kg, p.o., 4 weeks) and low-dose dipyridamole (20mg/kg, p.o., 4 weeks) treatment either alone or in combination considerably reduced renal structural and functional abnormalities in diabetic rats, but without affecting the elevated glucose level. Fenofibrate, but not dipyridamole, significantly prevented the lipid alteration and importantly the uric acid elevation in diabetic rats. Lisinopril (5mg/kg, p.o., 4 weeks, reference compound), prevented the hyperglycemia, lipid alteration and development of diabetic nephropathy. Lipid alteration and uric acid elevation, besides hyperglycemia, could play key roles in the development of nephropathy. Low-doses of fenofibrate and dipyridamole treatment either alone or in combination markedly prevented the diabetes-induced nephropathy. Their combination was as effective as to their individual treatment, but not superior in preventing the development of diabetic nephropathy.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/pathology
  11. Yankuzo H, Ahmed QU, Santosa RI, Akter SF, Talib NA
    J Ethnopharmacol, 2011 Apr 26;135(1):88-94.
    PMID: 21354289 DOI: 10.1016/j.jep.2011.02.020
    Murraya koenigii (Linn.) Spreng (curry leaf) is widely used as a nephroprotective agent in kidney's infirmities among diabetics by the traditional practitioners in Malaysia. However, the latter role of curry leaf has been grossly under reported and is yet to receive proper scientific evaluation.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/complications*; Diabetes Mellitus, Experimental/pathology
  12. Abdollahi M, Zuki AB, Goh YM, Rezaeizadeh A, Noordin MM
    Histol Histopathol, 2011 01;26(1):13-21.
    PMID: 21117023 DOI: 10.14670/HH-26.13
    The aim of this research was to determine the effects of Momordica charantia (MC) fruit aqueous extract on pancreatic histopathological changes in neonatal STZ-induced type-II diabetic rats. Diabetes mellitus was induced in one day Sprague-Dawley neonatal rats using a single intrapretoneal injection of streptozotocin (STZ) (85 mg/kg body weight) and monitored for 12 weeks thereafter. The diabetic rats were separated into three groups, as follows: the diabetic control group (i.e. nSTZ), the diabetic group (i.e. nSTZ/M) - which was orally given 20 mg/kg of MC fruit extract, and the diabetic group (i.e. nSTZ/G) - that was treated with glibenclamide, 0.1 mg/kg for a period of four weeks. At the end of treatment, the animals were sacrificed and blood samples were collected from the saphenous vein to measure the blood glucose and serum insulin level. The pancreatic specimens were removed and processed for light microscopy, electron microscopy examination and immunohistochemical study. The results of this study showed that MC fruit aqueous extract reduced the blood glucose level as well as glibenclamide and increased the serum insulin level in the treated diabetic rats (P<0.05). The fruit extract of MC alleviated pancreatic damage and increased the number of β-cells in the diabetic treated rats (P<0.05). Our results suggest that oral feeding of MC fruit extract may have a significant role in the renewal of pancreatic β-cells in the nSTZ rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/pathology*
  13. Balkis Budin S, Othman F, Louis SR, Abu Bakar M, Radzi M, Osman K, et al.
    Rom J Morphol Embryol, 2009;50(1):23-30.
    PMID: 19221642
    PREMISES AND OBJECTIVES: Antioxidant plays an important role in preventing the progression of diabetes mellitus (DM) complications. The aim of the present study was to investigate the effect of alpha lipoic acid (ALA) supplementation on plasma lipid, oxidative stress and vascular changes in diabetic rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/pathology; Diabetes Mellitus, Experimental/physiopathology*
  14. Ali RB, Atangwho IJ, Kuar N, Ahmad M, Mahmud R, Asmawi MZ
    PMID: 23425283 DOI: 10.1186/1472-6882-13-39
    One vital therapeutic approach for the treatment of type 2 diabetes mellitus is the use of agents that can decrease postprandial hyperglycaemia by inhibiting carbohydrate digesting enzymes. The present study investigated the effects of bioassay-guided extract and fractions of the dried fruit pericarp of Phaleria macrocarpa, a traditional anti-diabetic plant, on α-glucosidase and α-amylase, in a bid to understand their anti-diabetic mechanism, as well as their possible attenuation action on postprandial glucose increase.
    Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/enzymology; Diabetes Mellitus, Experimental/metabolism
  15. Agarwal R, Iezhitsa I, Awaludin NA, Ahmad Fisol NF, Bakar NS, Agarwal P, et al.
    Exp Eye Res, 2013 May;110:35-43.
    PMID: 23428743 DOI: 10.1016/j.exer.2013.02.011
    Cataract, a leading cause of blindness, is characterized by lenticular opacities resulting from denaturation of lens proteins due to activation of calcium-dependent enzyme, calpain. Magnesium (Mg(2+)) plays an important role not only in maintaining a low lenticular calcium (Ca(2+)) and sodium concentration but also in preserving the lens redox status. Taurine has also been shown to reduce lenticular oxidative stress. Present study evaluated the anticataract effects of magnesium taurate in vivo and in vitro. Among the five groups of 9 Sprague Dawley rats each, two groups received 30% galactose diet with topical (GDMT) or oral treatment (GDMO) with magnesium taurate. Two groups received 30% galactose diet with topical (GDT) or oral vehicle (GDO). Remaining 1 group received normal diet (ND). Weekly slit lamp examination was done during 21 days experimental period and then all rats were sacrificed; Ca/Mg ratio and antioxidant parameters including reduced glutathione (GSH), catalase and superoxide dismutase (SOD) activities were measured in the isolated lenses using ELISA. In the in vitro study, 2 groups of 10 normal rat lenses were incubated in Dulbecco's Modified Eagle's Medium (DMEM) with galactose while 1 similar group was incubated in DMEM without galactose. In one of the groups, galactose containing medium was supplemented with magnesium taurate. After 48 h of incubation, lenses were photographed and Ca(2+)/Mg(2+) ratio and antioxidant parameters were measured as for in vivo study. The in vivo study, at the end of experimental period, demonstrated delay in the development of cataract with a mean opacity index of 0.53 ± 0.04 and 0.51 ± 0.03 in GDMO (p < 0.05 versus GDO) and GDMT (p < 0.01 versus GDT) respectively. Histopathological grading showed a lower mean value in treated groups, however, the differences from corresponding controls were not significant. Lenticular Ca(2+)/Mg(2+) ratio with a mean value of 1.20 ± 0.26 and 1.05 ± 0.26 in GDMO and GDMT was significantly lower than corresponding controls (p < 0.05) and in GDMT no significant difference was observed from ND. Lenticular GSH and catalase activities were significantly lower and SOD activity was significantly higher in all galactose fed groups. However, in GDMT, GSH and catalase were significantly higher than corresponding control with mean values of 0.96 ± 0.30 μmol/gm lens weight and 56.98 ± 9.86 μmol/g lens protein respectively (p < 0.05 for GSH and p < 0.01 for catalase). SOD activity with mean values of 13.05 ± 6.35 and 13.27 ± 7.61 units/mg lens protein in GDMO and GDMT respectively was significantly lower compared to corresponding controls (p < 0.05) signifying lesser upregulation of SOD due to lesser oxidative stress in treated groups. In the in vitro study, lenses incubated in magnesium taurate containing medium showed less opacity and a lower mean Ca(2+)/Mg(2+) ratio of 1.64 ± 0.03, which was not significantly different from lenses incubated in DMEM without galactose. Lens GSH and catalase activities were restored to normal in lenses incubated in magnesium taurate containing medium. Both in vivo and in vitro studies demonstrated that treatment with magnesium taurate delays the onset and progression of cataract in galactose fed rats by restoring the lens Ca(2+)/Mg(2+) ratio and lens redox status.
    Matched MeSH terms: Diabetes Mellitus, Experimental/diagnosis; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/metabolism
  16. Vattam KK, Raghavendran H, Murali MR, Savatey H, Kamarul T
    Hum Exp Toxicol, 2016 Aug;35(8):893-901.
    PMID: 26429928 DOI: 10.1177/0960327115608246
    In the present study, thirty six male Sprague Dawley rats were randomly divided into six groups and were injected with varying doses of alloxan (Ax) and nicotinamide (NA). The serum levels of glucose, insulin, and adiponectin were measured weekly up to 4 weeks.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood*; Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/pathology*
  17. Kunasegaran T, Mustafa MR, Murugan DD, Achike FI
    Biochimie, 2016 Jun;125:131-9.
    PMID: 27012965 DOI: 10.1016/j.biochi.2016.03.008
    This study investigated the effects of combined minimal concentrations of quercetin and pioglitazone on angiotensin II-induced contraction of the aorta from fructose-streptozotocin (F-STZ)-induced type 2 diabetic rats and the possible role of superoxide anions (O2(-)) and nitric oxide (NO) in their potential therapeutic interaction. Contractile responses to Ang II of aortic rings from Sprague-Dawley (SD) and F-STZ rats were tested following pre-incubation of the tissues in the vehicle (DMSO; 0.05%), quercetin (Q, 0.1 μM), pioglitazone (P, 0.1 μM) or their combination (P + Q; 0.1 μM each). The amount of superoxide anion was evaluated by lucigenin-enhanced chemiluminescence and dihydroethidium fluorescence, and NO by assay of total nitrate/nitrite, and 4-Amino-5-Methylamino-2',7'-Difluorofluorescein (DAF-FM) diacetate. The synergistic reduction of Ang II-induced contraction of diabetic but not normal aorta with minimally effective concentrations of P + Q occurs through inhibiting O2(-) and increasing NO bioavailability. This finding opens the possibility of maximal vascular protective/antidiabetic effects with low dose pioglitazone combined with quercetin, thus minimizing the risk of adverse effects.
    Matched MeSH terms: Diabetes Mellitus, Experimental
  18. 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; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/metabolism
  19. Mansur SA, Mieczkowska A, Bouvard B, Flatt PR, Chappard D, Irwin N, et al.
    J Cell Physiol, 2015 Dec;230(12):3009-18.
    PMID: 26016732 DOI: 10.1002/jcp.25033
    Type 1 diabetes mellitus is associated with a high risk for bone fractures. Although bone mass is reduced, bone quality is also dramatically altered in this disorder. However, recent evidences suggest a beneficial effect of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) pathways on bone quality. The aims of the present study were to conduct a comprehensive investigation of bone strength at the organ and tissue level; and to ascertain whether enzyme resistant GIP or GLP-1 mimetic could be beneficial in preventing bone fragility in type 1 diabetes mellitus. Streptozotocin-treated mice were used as a model of type 1 diabetes mellitus. Control and streptozotocin-diabetic animals were treated for 21 days with an enzymatic-resistant GIP peptide ([D-Ala(2) ]GIP) or with liraglutide (each at 25 nmol/kg bw, ip). Bone quality was assessed at the organ and tissue level by microCT, qXRI, 3-point bending, qBEI, nanoindentation, and Fourier-transform infrared microspectroscopy. [D-Ala2]GIP and liraglutide treatment did prevent loss of whole bone strength and cortical microstructure in the STZ-injected mice. However, tissue material properties were significantly improved in STZ-injected animals following treatment with [D-Ala2]GIP or liraglutide. Treatment of STZ-diabetic mice with [D-Ala(2) ]GIP or liraglutide was capable of significantly preventing deterioration of the quality of the bone matrix. Further studies are required to further elucidate the molecular mechanisms involved and to validate whether these findings can be translated to human patients.
    Matched MeSH terms: Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/metabolism; Diabetes Mellitus, Experimental/physiopathology
  20. Konidala SK, Kotra V, Danduga RCSR, Kola PK
    Bioorg Chem, 2020 11;104:104207.
    PMID: 32947135 DOI: 10.1016/j.bioorg.2020.104207
    Four series of thirteen new coumarin-chalcone hybrids (DPCU 1-13, DPCT 1-13, DCCU 1-13 and DCCT 1-13) were designed and synthesized using Biginelli synthesis, Pechmann condensation, Acetylation, and Claisen-Schmidt reactions. Synthesized compounds were tested for insulin receptor in silico docking studies (PDB ID: 1IR3); DCCU 13 and DCCT 13 derivatives received the lowest docking score; Streptozocin (STZ) and Nicotinamide (NA) induced type II diabetes was tested for their anti-diabetic activity in rats. In vivo tests suggested that fasting blood glucose levels of animals treated with DCCU 13 (30 mg/kg body weight) and DCCT 13 (30 mg/kg body weight) were significantly and moderately suppressed, respectively, relative to fasting blood glucose levels of diabetic control animals. Similarly, therapy with DCCU 13 and DCCT 13 attenuated oxidative stress parameters such as lipid peroxidation (MDA), superoxide dismutase (SOD) and increased the glutathione (GSH) in the liver and pancreas in a dose-dependent manner. In comparison, therapy with DCCU 13 (30 mg/kg body weight) mitigated alterations in the histological architecture of the liver and pancreatic tissue. These results indicated that the hybrids DUUC 13 and DCCT 13 at 30 mg/kg had an anti-hyperglycemic and antioxidant impact on STZ + NA mediated type II diabetes in rats. Further detailed work could be required to determine the precise mode of action of the anti-diabetic behavior of hybrids.
    Matched MeSH terms: Diabetes Mellitus, Experimental/chemically induced; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/pathology
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