Displaying publications 1 - 20 of 59 in total

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  1. Metabolite Variation in Lean and Obese Streptozotocin (STZ)-Induced Diabetic Rats via (1)H NMR-Based Metabolomics Approach
    Abu Bakar Sajak A, Mediani A, Maulidiani, Ismail A, Abas F
    Appl Biochem Biotechnol, 2017 Jun;182(2):653-668.
    PMID: 27995574 DOI: 10.1007/s12010-016-2352-9
    Diabetes mellitus (DM) is considered as a complex metabolic disease because it affects the metabolism of glucose and other metabolites. Although many diabetes studies have been conducted in animal models throughout the years, the pathogenesis of this disease, especially between lean diabetes (ND + STZ) and obese diabetes (OB + STZ), is still not fully understood. In this study, the urine from ND + STZ, OB + STZ, lean/control (ND), and OB + STZ rats were collected and compared by using (1)H NMR metabolomics. The results from multivariate data analysis (MVDA) showed that the diabetic groups (ND + STZ and OB + STZ) have similarities and dissimilarities for a certain level of metabolites. Differences between ND + STZ and OB + STZ were particularly noticeable in the synthesis of ketone bodies, branched-chain amino acid (BCAA), and sensitivity towards the oral T2DM diabetes drug metformin. This finding suggests that the ND + STZ group was more similar to the T1DM model and OB + STZ to the T2DM model. In addition, we also managed to identify several pathways and metabolism aspects shared by obese (OB) and OB + STZ. The results from this study are useful in developing drug target-based research as they can increase understanding regarding the cause and effect of DM.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism*
  2. Effect of Ipomoea aquatica ethanolic extract in streptozotocin (STZ) induced diabetic rats via1H NMR-based metabolomics approach
    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/metabolism*
  3. Marantodes pumilum (Kacip fatimah) enhances in-vitro glucose uptake in 3T3-L1 adipocyte cells and reduces pancreatic complications in streptozotocin-nicotinamide induced male diabetic rats
    Adam SH, Giribabu N, Bakar NMA, Salleh N
    Biomed Pharmacother, 2017 Dec;96:716-726.
    PMID: 29040959 DOI: 10.1016/j.biopha.2017.10.042
    Marontades pumilum is claimed to have beneficial effects in the treatment of diabetes mellitus (DM), however the underlying mechanisms were not fully identified. In this study, we hypothesized that M. pumilum could help to enhance cellular glucose uptake and reduces pancreatic complications, which contributed towards its beneficial effects in DM.

    METHODS: Two parameters were measured (i) rate of glucose uptake by 3T3-L1 adipocyte cells in-vitro (ii) degree of pancreatic destruction in streptozotocin-nicotinamide induced male diabetic rats receiving M. pumilum aqueous extract (M.P) (250 and 500mg/kg/day) as reflected by levels of pancreatic oxidative stress, inflammation and apoptosis. In the meantime, phyto-chemical compounds in M.P were also identified by using LC-MS.

    RESULTS: M.P was found able to enhance glucose uptake by 3T3-L1 adipocyte cells in-vitro while its administration to the male diabetic rats causes decreased in the fasting blood glucose (FBG), glycated haemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL) levels but causes increased in insulin and high-density lipoprotein (HDL) levels, to near normal. Levels of oxidative stress in the pancreas as reflected by levels of lipid peroxidation product (LPO) decreased while levels of anti-oxidantive enzymes (SOD, CAT and GPx) in pancreas increased. Additionally, levels of inflammation as reflected by NF-κB p65, Ikkβ and TNF-α levels decreased while apoptosis levels as reflected by caspase-9 and Bax levels decreased. Anti-apoptosis marker, Bcl-2 levels in pancreas increased.

    CONCLUSIONS: The ability of M.P to enhance glucose uptake and reduces pancreatic complications could account for its beneficial effects in treating DM.

    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism
  4. 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/metabolism*
  5. Effects of magnesium taurate on the onset and progression of galactose-induced experimental cataract: in vivo and in vitro evaluation
    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/metabolism
  6. Modulation of vascular reactivity in normal, hypertensive and diabetic rat aortae by a non-antioxidant flavonoid
    Ajay M, Achike FI, Mustafa MR
    Pharmacol Res, 2007 May;55(5):385-91.
    PMID: 17317209
    In this study, we report the effects of a non-antioxidant flavonoid flavone on vascular reactivity in Wistar-Kyoto (WKY) rat isolated aortae. Whether flavone directly modulates vascular reactivity in spontaneously hypertensive rat (SHR) and streptozotocin-induced diabetic-WKY rat isolated aortae was also determined. Thoracic aortic rings were mounted in organ chambers and exposed to various drug treatments in the presence of flavone (10 microM) or its vehicle (DMSO), which served as control. Pretreatment with flavone enhanced relaxant effects to endothelium-dependent vasodilator acetylcholine (ACh) and attenuated contractile effects to alpha(1)-receptor agonist phenylephrine (PE) in WKY aortae compared to those observed in control aortic rings. Flavone had no effect on relaxations to ACh in WKY aortae incubated with either L-NAME or methylene blue, but enhanced relaxations to ACh in WKY aortae incubated with indomethacin or partially depolarized with KCl. Relaxations to ACh are totally abolished in both control or flavone pretreated endothelium-denuded WKY aortae. Flavone attenuated the inhibition by beta-NADH of ACh-induced relaxation in WKY aortae, but it had no significant effect on the transient contractions induced by beta-NADH nor the pyrogallol-induced abolishment of ACh-induced relaxation in WKY aortae. Flavone enhanced endothelium-independent relaxation to sodium nitroprusside (SNP) in both endothelium-intact and -denuded WKY aortae. Flavone enhanced relaxation to ACh and SNP as well as attenuated contractile effects to PE in SHR and diabetic aortae, a finding similar to that observed in normal WKY aortae. From these results, we conclude that flavone modulates vascular reactivity in normal as well as hypertensive and diabetic aortae. These effects of flavone results probably through enhanced bioactivity of nitric oxide released from the endothelium.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism
  7. Fulltext In vitro and in vivo effects of standardized extract and fractions of Phaleria macrocarpa fruits pericarp on lead carbohydrate digesting enzymes
    Ali RB, Atangwho IJ, Kuar N, Ahmad M, Mahmud R, Asmawi MZ
    BMC Complement Altern Med, 2013;13:39.
    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/metabolism
  8. Fulltext Bioassay-guided antidiabetic study of Phaleria macrocarpa fruit extract
    Ali RB, Atangwho IJ, Kaur N, Abraika OS, Ahmad M, Mahmud R, et al.
    Molecules, 2012 Apr 30;17(5):4986-5002.
    PMID: 22547320 DOI: 10.3390/molecules17054986
    An earlier anti-hyperglycemic study with serial crude extracts of Phaleria macrocarpa (PM) fruit indicated methanol extract (ME) as the most effective. In the present investigation, the methanol extract was further fractionated to obtain chloroform (CF), ethyl acetate (EAF), n-butanol (NBF) and aqueous (AF) fractions, which were tested for antidiabetic activity. The NBF reduced blood glucose (p < 0.05) 15 min after administration, in an intraperitoneal glucose tolerance test (IPGTT) similar to metformin. Moreover, it lowered blood glucose in diabetic rats by 66.67% (p < 0.05), similar to metformin (51.11%), glibenclamide (66.67%) and insulin (71.43%) after a 12-day treatment, hence considered to be the most active fraction. Further fractionation of NBF yielded sub-fractions I (SFI) and II (SFII), and only SFI lowered blood glucose (p < 0.05), in IPGTT similar to glibenclamide. The ME, NBF, and SFI correspondingly lowered plasma insulin (p < 0.05) and dose-dependently inhibited glucose transport across isolated rat jejunum implying an extra-pancreatic mechanism. Phytochemical screening showed the presence of flavonoids, terpenes and tannins, in ME, NBF and SFI, and LC-MS analyses revealed 9.52%, 33.30% and 22.50% mangiferin respectively. PM fruit possesses anti-hyperglycemic effect, exerted probably through extra-pancreatic action. Magniferin, contained therein may be responsible for this reported activity.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism
  9. Fulltext Gold nanoparticles attenuate albuminuria by inhibiting podocyte injury in a rat model of diabetic nephropathy
    Alomari G, Al-Trad B, Hamdan S, Aljabali A, Al-Zoubi M, Bataineh N, et al.
    Drug Deliv Transl Res, 2020 Feb;10(1):216-226.
    PMID: 31637677 DOI: 10.1007/s13346-019-00675-6
    Several recent studies have reported that gold nanoparticles (AuNPs) attenuate hyperglycemia in diabetic animal models without any observed side effects. The present study was intended to provide insight into the effects of 50-nm AuNPs on diabetic kidney disease. Adult male rats were divided into three groups (n = 7/group): control (non-diabetic, ND), diabetic (D), and diabetic treated intraperitoneally with 50-nm AuNPs (AuNPs + D; 2.5 mg/kg/day) for 7 weeks. Diabetes was induced by a single-dose injection of 55 mg/kg streptozotocin. The result showed that AuNP treatment prevented diabetes-associated increases in the blood glucose level. Reduction in 24-h urinary albumin excretion rate, glomerular basement membrane thickness, foot process width, and renal oxidative stress markers was also demonstrated in the AuNP-treated group. In addition, the results showed downregulation effect of AuNPs in renal mRNA or protein expression of transforming growth factor β1 (TGF-β1), fibronectin, collagen IV, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor-A (VEGF-A). Moreover, the protein expression of nephrin and podocin, podocyte markers, in glomeruli was increased in the AuNPs + D group compared with the D group. These results provide evidence that 50-nm AuNPs can ameliorate renal damage in experimental models of diabetic nephropathy through improving the renal function and downregulating extracellular matrix protein accumulation, along with inhibiting renal oxidative stress and amelioration of podocyte injury.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism
  10. Fulltext Effect of Catha edulis (khat) on pancreatic functions in streptozotocin-induced diabetes in male Sprague-Dawley rats
    Alsalahi A, Alshawsh MA, Chik Z, Mohamed Z
    Exp Anim, 2018 Nov 01;67(4):517-526.
    PMID: 29973470 DOI: 10.1538/expanim.18-0057
    People consume Catha edulis (khat) for its euphoric effect, and type 1 diabetics have claimed that khat could reduce elevated levels of blood sugar. However, khat has been suggested to provoke diabetes mellitus through destruction of pancreatic β-cells. This study investigated the effect of an ethanolic khat extract on pancreatic functions in type 1 diabetes (T1DM)-induced male Sprague-Dawley rats and to assess its in vitro cytotoxicity in rat pancreatic β-cells (RIN-14B). T1DM was induced in a total of 20 rats with a single intraperitoneal injection of 75 mg/kg of streptozotocin. The rats were distributed into four groups (n=5): the diabetic control, 8 IU insulin-treated, 200 mg/kg khat-treated, and 400 mg/kg khat-treated groups. Another 5 rats were included as a nondiabetic control. Body weight, fasting blood sugar, and caloric intake were recorded weekly. Four weeks after treatment, the rats were sacrificed, and blood was collected for insulin, lipid profile, total protein, amylase, and lipase analysis, while pancreases were harvested for histopathology. In vitro, khat exerted moderate cytotoxicity against RIN-14B cells after 24 and 48 h but demonstrated greater inhibition against RIN-14B cells after 72 h. Neither 200 mg/kg nor 400 mg/kg of khat produced any significant reduction in blood sugar; however, 200 mg/kg khat extract provoked more destruction of pancreatic β-cells as compared with the diabetic control. Ultimately, neither 200 mg/kg nor 400 mg/kg of khat extract could produce a hypoglycemic effect in T1DM-induced rats. However, 200 mg/kg of khat caused greater destruction of pancreatic β-cells, implying that khat may cause a direct cytotoxic effect on pancreatic β-cells in vitro.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism*
  11. Alpha1A- and alpha1D-adrenoceptors are the major functional subtypes of renal alpha1-adrenoceptors in streptozotocin-induced diabetic and normal Sprague-Dawley rats
    Armenia, Sattar MA, Abdullah NA, Khan MA, Johns EJ
    Auton Autacoid Pharmacol, 2008 Jan;28(1):1-10.
    PMID: 18257746 DOI: 10.1111/j.1474-8673.2007.00412.x
    1 The present study investigated the effect of streptozotocin-induced diabetes on alpha(1)-adrenoceptor subtypes in rat renal resistance vessels. 2 Studies on renal haemodynamics were carried out 7 days after the last streptozotocin. Changes in renal blood flow were recorded in response to electrical stimulation of the renal nerve (RNS) and a range of adrenergic agonists; noradrenaline (NA), phenylephrine (PE) and methoxamine (MTX), either in the absence or the presence of nitrendipine (Nit), 5-methylurapidil (MEU), chlorethylclonidine (CEC) or BMY 7378. 3 In non-diabetic animals, Nit, MEU and BMY 7378 significantly attenuated renal vasoconstriction induced by adrenergic agonists, while CEC showed a significant accentuation in RNS-induced responses without having a significant effect on responses to adrenergic agonists. In diabetic rats, renal vasoconstriction was also significantly reduced in Nit-, MEU- and BMY 7378-treated groups and CEC potentiated RNS-induced contractions caused a change similar to that observed in non-diabetic rats. BMY 7378 significantly (P < 0.05) attenuated the PE- and MTX-induced vasoconstrictions but did not cause any significant (P > 0.05) alteration in the RNS- and NA-induced responses. 4 The results showed functional co-existence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SD rats irrespective of the presence of diabetes. A possible minor contribution of prejunctional alpha-adrenoceptor subtype has also been suggested in either experimental group, particularly possible functional involvement of alpha(1B)-adrenoceptor subtypes in non-diabetic SD rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism*
  12. Fulltext Functional subtypes of renal alpha1-adrenoceptor in diabetic and non-diabetic 2K1C Goldblatt renovascular hypertension
    Armenia A, Sattar MA, Abdullah NA, Khan MA, Johns EJ
    Acta Pharmacol Sin, 2008 May;29(5):564-72.
    PMID: 18430364 DOI: 10.1111/j.1745-7254.2008.00788.x
    This study investigates the subtypes of the alpha1-adrenoceptor mediating the adrenergically-induced renal vasoconstrictor responses in streptozotocin-induced diabetic and non-diabetic 2-kidney one clip (2K1C) Goldblatt hypertensive rats.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism*
  13. Anti-diabetic effects of Centratherum anthelminticum seeds methanolic fraction on pancreatic cells, β-TC6 and its alleviating role in type 2 diabetic rats
    Arya A, Looi CY, Cheah SC, Mustafa MR, Mohd MA
    J Ethnopharmacol, 2012 Oct 31;144(1):22-32.
    PMID: 22954496 DOI: 10.1016/j.jep.2012.08.014
    Seeds of Centratherum anthelminticum (Asteraceae) have been popularly used in Ayurvedic medicine to treat diabetes and skin disorders. Folk medicine from Rayalaseema (Andhra Pradesh, India) reported wide spread usage in diabetes.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism
  14. Fulltext Vernonia amygdalina simultaneously suppresses gluconeogenesis and potentiates glucose oxidation via the pentose phosphate pathway in streptozotocin-induced diabetic rats
    Atangwho IJ, Yin KB, Umar MI, Ahmad M, Asmawi MZ
    BMC Complement Altern Med, 2014;14:426.
    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/metabolism
  15. The wound healing properties of Channa striatus-cetrimide cream-wound contraction and glycosaminoglycan measurement
    Baie SH, Sheikh KA
    J Ethnopharmacol, 2000 Nov;73(1-2):15-30.
    PMID: 11025135
    Haruan has been proved to influence the different phases of wound healing process. The current research focuses on the effects of haruan on the different constituents of extracellular matrix of healing wounds in normal and diabetic rats. Anaesthetized normal and streptozotocin induced diabetic rats were provided with excision wounds at the back and then animals were divided into four groups as: group 1, wounds treated with cetrimide+haruan cream; group 2, wounds treated with haruan cream; group 3, wounds treated with cetrimide (commercial) cream; and group 4, wounds untreated and served as control. Animals were sacrificed after 3, 6, 9 and 12 days. These wounds were used to determine the hexosamine, protein, uronic acid and glycosaminoglycan contents and the wound contraction. The results suggested a marked increase (P<0.05) in the uronic acid, hexosamine and dermatan sulfate contents on day 3 of group 1 when compared with groups 2-4. Wound contraction of group 1 was also markedly enhanced of group 1 (P<0.01) when compared with groups 2- 4. On the basis of these results, we conclude that haruan enhances the synthesis of different glycosaminoglycans in healing wounds, which are the first component of extracellular matrix to be synthesized during the wound healing process. The enhanced levels of glycosaminoglycans may help in the formation of a resistant scar and enhanced wound contraction represents the positive influence of haruan on the fibroplastic phase of wound healing.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism*
  16. Carboxymethyl fenugreek galactomannan-gellan gum-calcium silicate composite beads for glimepiride delivery
    Bera H, Mothe S, Maiti S, Vanga S
    Int J Biol Macromol, 2018 Feb;107(Pt A):604-614.
    PMID: 28916379 DOI: 10.1016/j.ijbiomac.2017.09.027
    Novel carboxymethyl fenugreek galactomannan (CFG)-gellan gum (GG)-calcium silicate (CS) composite beads were developed for controlled glimepiride (GLI) delivery. CFG having degree of carboxymethylation of 0.71 was synthesized and characterized by FTIR, DSC and XRD analyses. Subsequently, GLI-loaded hybrids were accomplished by ionotropic gelation technique employing Ca+2/Zn+2/Al+3 ions as cross-linkers. All the formulations demonstrated excellent drug encapsulation efficiency (DEE, 48-97%) and sustained drug release behaviour (Q8h, 62-94%). These quality attributes were remarkably influenced by polymer-blend (GG:CFG) ratios, cross-linker types and CS inclusion. The drug release profile of the optimized formulation (F-6) was best fitted in zero-order model with anomalous diffusion driven mechanism. It also conferred excellent ex vivo mucoadhesive property and considerable hypoglycemic effect in streptozotocin-induced diabetic rats. Furthermore, the beads were characterized for drug-excipients compatibility, drug crystallinity, thermal behaviour and surface morphology. Thus, the developed hybrid matrices are appropriate for controlled delivery of GLI for Type 2 diabetes management.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism
  17. Antidiabetic and antidyslipidemic potential of Echinops echinatus in rat models of type I and type II diabetes
    Chaudhry SRY, Akram A, Aslam N, Wajid M, Iqbal Z, Nazir I, et al.
    Pak J Pharm Sci, 2019 Mar;32(2):505-514.
    PMID: 31081759
    Echinops echinatus is traditionally an important plant that finds its extensive use as a diuretic, anti-inflammatory, anti-pyretic, nerve tonic, abortifacient, aphrodisiac, antiasthmatic, and antidiabetic agent. The current study investigates protection against the hyperglycemia and dyslipidemia in alloxan-induced (type I diabetes) and fructose-fed insulin resistance (type II diabetes) models of diabetes treated with aqueous methanolic root extract of E. echinatus (Ee.Cr). Albino rats were treated orally with Ee.Cr at doses 100, 300 and 500mg/kg. The fasting blood glucose was measured by glucometer, while standard kits were used to determine the levels of serum total cholesterol, triglycerides and HDL. The administration of Ee.Cr significantly (P<0.001) reduced the FBG concentration in a dose-dependent pattern in alloxan-induced and fructose-fed diabetic rats. The Ee.Cr also corrected the dyslipidemia associated with fructose and alloxan-induced diabetes by significantly (P<0.001) decreasing the concentration of serum total cholesterol, triglycerides, and LDL and by increasing HDL concentration. Ee.Cr also significantly (P<0.001) improved the glucose tolerance in fructose-fed rats. We conclude that Ee.Cr has antidiabetic and antidyslipidemic effects in both insulin-dependent alloxan-induced diabetes and fructose-induced insulin resistance diabetes rat models.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism
  18. Moringa oleifera standardised aqueous leaf extract-loaded hydrocolloid film dressing: in vivo dermal safety and wound healing evaluation in STZ/HFD diabetic rat model
    Chin CY, Ng PY, Ng SF
    Drug Deliv Transl Res, 2019 04;9(2):453-468.
    PMID: 29560587 DOI: 10.1007/s13346-018-0510-z
    Previously, Moringa oleifera leaf (MOL) standardised aqueous extract-loaded films were successfully developed and they showed potential wound healing activity in vitro. The objective of this study was to evaluate in vivo dermal safety as well as wound healing efficacy of these MOL film dressings (containing 0.1, 0.5 and 1% MOL) on diabetic rat model. The acute dermal toxicity was carried out on healthy rats, and signs of toxicity over 14 days were observed. For wound healing studies, excision and abrasion wounds were created out on the STZ/HFD-induced diabetic rat model and the wound healing was studied over 21 days. The wound healing evaluation determined by histology staining, hydroxyproline assay and ELISA assays on wound healing related-growth factors, cytokines and chemokines. MOL film formulations exhibited no signs of dermal toxicities. In excision wound model, 0.5% film significantly enhanced the wound closure by 77.67 ± 7.28% at day 7 compared to control group. While in abrasion wounds, 0.5% MOL films accelerated wound closure significantly at 81 ± 4.5% as compared to the control. The histology findings and hydroxyproline assay revealed that high collagen deposition and complete re-epithelialisation were observed for the wounds treated with 0.5 and 1% MOL films. All MOL film dressings had successfully tested non-toxic via in vivo safety dermal toxicity. It was concluded that the 0.5% MOL extract-loaded film had proven to be the most promising approach to accelerate diabetic wound healing process in both full-thickness excision and partial thickness abrasion wounds on the HFD/STZ-induced diabetic type II model.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism
  19. Fulltext Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo
    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/metabolism
  20. Effect of des-aspartate-angiotensin I on the actions of angiotensin II in the isolated renal and mesenteric vasculature of hypertensive and STZ-induced diabetic rats
    Dharmani M, Mustafa MR, Achike FI, Sim MK
    Regul. Pept., 2005 Jul 15;129(1-3):213-9.
    PMID: 15927718
    The present study investigated the action of des-aspartate-angiotensin I (DAA-I) on the pressor action of angiotensin II in the renal and mesenteric vasculature of WKY, SHR and streptozotocin (STZ)-induced diabetic rats. Angiotensin II-induced a dose-dependent pressor response in the renal vasculature. Compared to the WKY, the pressor response was enhanced in the SHR and reduced in the STZ-induced diabetic rat. DAA-I attenuated the angiotensin II pressor action in renal vasculature of WKY and SHR. The attenuation was observed for DAA-I concentration as low as 10(-18) M and was more prominent in SHR. However, the ability of DAA-I to reduce angiotensin II response was lost in the STZ-induced diabetic kidney. Instead, enhancement of angiotensin II pressor response was seen at the lower doses of the octapeptide. The effect of DAA-I was not inhibited by PD123319, an AT2 receptor antagonist, and indomethacin, a cyclo-oxygenase inhibitor in both WKY and SHR, indicating that its action was not mediated by angiotensin AT2 receptor and prostaglandins. The pressor responses to angiotensin II in mesenteric vascular bed were also dose-dependent but smaller in magnitude compared to the renal vasculature. The responses were significantly smaller in SHR but no significant difference was observed between STZ-induced diabetic and WKY rat. Similarly, PD123319 and indomethacin had no effect on the action of DAA-I. The findings reiterate a regulatory role for DAA-I in vascular bed of the kidney and mesentery. By being active at circulating level, DAA-I subserves a physiological role. This function appears to be present in animals with diseased state of hypertension and diabetes. It is likely that DAA-I functions are modified to accommodate the ongoing vascular remodeling.
    Matched MeSH terms: Diabetes Mellitus, Experimental/metabolism*
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