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  1. Aziz MSA, Giribabu N, Rao PV, Salleh N
    Biomed Pharmacother, 2017 May;89:135-145.
    PMID: 28222394 DOI: 10.1016/j.biopha.2017.02.026
    Stingless bee honey (SLBH) has been claimed to possess multiple health benefits. Its anti-diabetic properties are however unknown. In this study, ability of SLBH from Geniotrigona thoracica stingless bee species in ameliorating pancreatic damage and in maintaining metabolic profiles were investigated in diabetic condition.

    METHODS: SLBH at 1 and 2g/kg/b.w. was given orally to streptozotocin (STZ)-nicotinamide-induced male diabetic rats for 28days. Metabolic parameters (fasting blood glucose-FBG and lipid profiles-LP and serum insulin) were measured by biochemical assays. Distribution and expression level of insulin, oxidative stress marker i.e. catalase, inflammatory markers i.e. IKK-β, TNF-α, IL-1β and apoptosis marker i.e. caspase-9 in the pancreatic islets were identified and quantified respectively by immunohistochemistry. Levels of NF-κβ in pancreas were determined by enzyme-linked immunoassay (ELISA).

    RESULTS: SLBH administration to diabetic male rats prevented increase in FBG, total cholesterols (TC), triglyceride (TG) and low density lipoprotein (LDL) levels. However, high density lipoprotein (HDL) and serum insulin levels in diabetic rats receiving SLBH increased. Additionally, histopathological changes and expression level of oxidative stress, inflammation and apoptosis markers in pancreatic islets of diabetic rats decreased with increased expression level of insulin in the islets. LC-MS analysis revealed the presence of several compounds in SLBH that might be responsible for these effects.

    CONCLUSIONS: SLBH has great potential to be used as agent to protect the pancreas against damage and dysfunction where these could account for its anti-diabetic properties.

    Matched MeSH terms: Diabetes Mellitus, Experimental/prevention & control*
  2. Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S
    Ann Endocrinol (Paris), 2010 Sep;71(4):291-6.
    PMID: 20398890 DOI: 10.1016/j.ando.2010.03.003
    Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas.
    Matched MeSH terms: Diabetes Mellitus, Experimental/prevention & control*
  3. Erejuwa OO, Sulaiman SA, Wahab MS, Salam SK, Salleh MS, Gurtu S
    Int J Mol Sci, 2010 May 05;11(5):2056-66.
    PMID: 20559501 DOI: 10.3390/ijms11052056
    Hyperglycemia exerts toxic effects on the pancreatic beta-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage.
    Matched MeSH terms: Diabetes Mellitus, Experimental/prevention & control*
  4. Dharmani M, Kamarulzaman K, Giribabu N, Choy KW, Zuhaida MZ, Aladdin NA, et al.
    Phytomedicine, 2019 Dec;65:153101.
    PMID: 31648126 DOI: 10.1016/j.phymed.2019.153101
    BACKGROUND: Oestrogen deficiency leads to metabolic disturbances such as insulin resistance and impairment of adipose tissue or lipid metabolism. Marantodes pumilum (Blume) Kuntze (Primulaceae) is believed to have phytoestrogenic properties and is claimed to have beneficial effects in the treatment of diabetes mellitus (DM), but the mechanism behind its phytoestrogenic effects on estrogen-deficient diabetic condition have not been fully examined.

    PURPOSE: The present study investigated the effects of oral treatment with M. pumilum var. alata (MPA) extracts on the estrogen receptor, metabolic characteristics and insulin signaling pathway in pancreas and liver of ovariectomised nicotidamide streptozotocin-induced diabetes in female rats.

    MATERIALS AND METHODS: Ovariectomised diabetic (OVXS) Sprague-Dawley rats were orally administered with either aqueous leaf extract and ethanol (50%) stem-root extract of MPA (50 or 100 mg/kg) respectively for 28 days. Metabolic parameters were evaluated by measuring fasting blood glucose, serum insulin, oral glucose and insulin tolerance test. Distribution and expression level of insulin, oxidative stress and inflammatory marker in the pancreatic islets and liver were evaluated by immunohistochemistry and western blot, respectively.

    RESULTS: Oral treatment with aqueous leaf and ethanol (50%) stem-root extracts of MPA (100 mg/kg) significantly reversed the elevated fasting blood glucose, impaired glucose and insulin tolerance. The protein expression of insulin, glucose transporter (GLUT-2 and GLUT-4) increased in the pancreatic islets and liver. Furthermore, marked improvement in the tissue morphology following treatment with MPA was observed. Similarly, the western blots analysis denotes improved insulin signaling in the liver and decreased reactive oxygen species producing enzymes, inflammatory and pro-apoptotic molecules with MPA treatment.

    CONCLUSIONS: Taken together, this work demonstrate that 100 mg/kg of aqueous leaf extract and ethanol (50%) stem-root extract of MPA improves β-cell function and insulin signaling in postmenopausal diabetes through attenuation of oxidative stress and partially mediated by oestrogen receptor stimulation.

    Matched MeSH terms: Diabetes Mellitus, Experimental/prevention & control*
  5. Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S
    Int J Mol Sci, 2011;12(3):1888-907.
    PMID: 21673929 DOI: 10.3390/ijms12031888
    Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress.
    Matched MeSH terms: Diabetes Mellitus, Experimental/prevention & control
  6. John CM, Ramasamy R, Al Naqeeb G, Al-Nuaimi AH, Adam A
    Curr Med Chem, 2012;19(30):5181-6.
    PMID: 23237188
    Gestational diabetes (GD) is a common complication during pregnancy. Metabolic changes in GD affect fetal development and fetal glucose homeostasis. The present study utilized a rat model of GD to evaluate the effects of nicotinamide on diabetic parameters; antioxidant gene expression viz, superoxide dismutase (SOD) and catalase (CAT); reactive oxygen species (ROS) production by neutrophils and enhancement of lymphocyte mediated immune response. Nicotinamide (50, 100 and 200 mg/kg) was orally supplemented to gestational diabetic rats from days 6 through 20 of gestation. After GD induction, the control group had elevated glucose and reduced insulin while nicotinamide (100 & 200 mg/kg) supplementation reversed these changes. The same doses of nicotinamide upregulated mRNA expressions of SOD and CAT genes in liver but reduced the oxidative burst activity of neutrophils in response to phorbol myristate acetate (PMA), N-formyl-methionyl-leucyl-phenylalanine (FMLP) or E. coli activation. Nicotinamide (100 & 200 mg/kg) supplementation also increased expression of activated T helper (CD4+CD25+) cells and induced proliferation of splenocytes. These findings provide evidence for utilizing nicotinamide as supplement or adjunct to support existing therapeutic agents for gestational diabetes and in pregnant individuals with weakened immune systems.
    Matched MeSH terms: Diabetes Mellitus, Experimental/prevention & control*
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