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Background: Diabetes can impair cognitive performance and lead to dementia. Patients with type 1 diabetes mellitus (T1DM) are reported with different levels of cognitive dysfunctions in various cognitive domains ranging from general intellectual testing to specific deficits with visuospatial abilities, motor speed, writing, attention, reading, and psychomotor efficiency. The present study aimed to investigate the effect of Citrullus colocynthis on cognitive functions. Methods: A total of 42 male Wistar rats (3-4 months old and weighing 200-250 g) were tested in the current study. Rats were randomly allocated into 3 groups of control, Diabetes, and Diabetes + Drug. The diabetic rats received Citrullus colocynthis extraction orally. The behavioral tests included the open field, elevated plus maze (EPM), novel object recognition (NOR), passive avoidance tests, and Morris Water Maze (MWM) tests. Data were analyzed using student and paired t-tests via SPSS software version 16. Results: Our results showed the protective effects of Citrullus colocynthis administration against cognitive impairments. This is followed by STZ-induced diabetes in the MWM, novel object recognition, and passive avoidance tasks. Also, it was found that Citrullus colocynthis improved anxiety in diabetic rats. Conclusion According to the findings of this study, the administration of 200 mg/kg C. colocynthis once per day for 40 days can lead to ameliorated cognitive impairments and antidiabetic effects such as increasing body weight and decreasing FBS. [ABSTRACT FROM AUTHOR]

Evidence has shown that inflammation and oxidative stress are implicated in the development of a great number of human diseases. Trehalose possesses various biological effects including antioxidant and anti-inflammatory activities. However, there is little data on the effects of trehalose on human cells including peripheral blood mononuclear cells (PBMCs). Here, we aimed to investigate whether trehalose could attenuate oxidative stress and inflammation induced by lipopolysaccharides (LPS) in PBMCs. The enzyme-linked immunosorbent assay (ELISA) and RT-PCR were used to assess the levels of inflammatory cytokines. To investigate the phosphorylation of c-Jun N-terminal kinase (JNK) and NF-κB, western blot analysis was utilized. Oxidant-antioxidant markers were assessed using ELISA and colorimetric procedures. The results revealed that trehalose significantly mitigated the effect of LPS on the phosphorylation of JNK and NF-κB-P65 (p <.00). This mitigation was associated with significantly reduced levels of inflammatory cytokines IL-6, TNF-α, and IL-1β and increased levels of anti-inflammatory cytokine IL-10 (P <.05). The antioxidant N-acetyl cysteine (NAC) also showed similar effects on JNK and NF-κB-P65 phosphorylation and inflammatory cytokines (p <.00). Furthermore, trehalose alleviated oxidative stress in LPS-stimulated PBMCs as it reversed the altered levels of malondialdehyde and total thiols (p ≤.05) and restored the activity of antioxidant enzymes glutathione peroxidase and manganese superoxide dismutase (p <.001). The results of this study indicated that trehalose prevented inflammation and oxidative stress in the LPS-stimulated PBMCs, providing evidence for the benefits of trehalose as a potential therapeutic agent in inflammatory conditions. LPS: Lipopolysaccharide; NAC: N-Acetyl cysteine; ROS: Reactive oxygen species; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-alpha; SOD: Superoxide dismutase; GPx: Glutathione peroxidase; MDA: Malondialdehyde; MAPK: Mitogen-activated protein kinases; JNK: c-Jun N-terminal kinase; NF-κB: Nuclear factor kappa-light-chain-enhancer of activated B cells. [ABSTRACT FROM AUTHOR]

Malvidin is an anthocyanin which is involved in inhibiting inflammatory‐related mediators in inflammatory diseases; however, its mechanism of action in THP‐1 cells is not yet known. THP‐1 is a human monocytic cell line that is derived from patients with acute monocytic leukemia. The present study aimed to investigate the effect of malvidin on inflammatory responses and oxidative stress in lipopolysaccharide (LPS)‐induced THP‐1 cells. THP‐1 cells were stimulated with LPS (50 ng/ml) to induce inflammation in the presence or absence of malvidin. The anti/proinflammatory cytokines were evaluated by real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Total protein levels/phosphorylation of c‐Jun N‐terminal kinase (JNK), P65‐NF‐κB, and IKKα/IKKβ were evaluated by western blot analysis. Malondialdehyde (MDA) and nitric oxide (NO) metabolite levels, ferric reducing antioxidant power (FRAP), total thiol (T‐SH) content, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activity were measured to evaluate the antioxidant activity of malvidin in THP‐1 cells. Treatment of LPS‐stimulated THP‐1 cells with malvidin (100 and 200 μM) led to the significant inhibition of interleukin‐6 (IL‐6), tumor necrosis factor‐α, and IL‐1β messenger RNA (mRNA) expression and protein levels as well as a significant increase in the IL‐10 mRNA expression and protein secretion. Moreover, 200 μM malvidin treatment reduced the phosphorylation of JNK, IKKα/IKKβ, and P65‐NF‐κB. These findings showed that malvidin not only decreased the MDA and NO metabolite levels but also increased the FRAP and T‐SH content as well as SOD and GPx activities. The findings of the present study demonstrated the potential role of malvidin in blocking inflammation and oxidative stress induced by LPS in THP‐1 cell line, suggesting that malvidin is likely to be a therapeutic agent for inflammatory diseases. [ABSTRACT FROM AUTHOR]

To develop a convenient animal model of T2D by pretreatment with low-dose 10% w/v fructose (FRC) solution followed by the injection of low doses of streptozotocin (STZ) in Wistar rats. For this 8-week experimental study; rats were first fed a standard chow ad-libitum diet and either tap water (n=40) or 10% w/v FRC solution (n=40) for 4 weeks. Next, rats in each category were randomly allocated to 4 subgroups (n=10 each) of low-dose STZ (25,35, and 45 mg/kg). The final mean fasting blood sugar (FBG) of FRC+STZ45 (197±55.87 mg/dl) were significantly higher than that of the STZ45 (P=0.015) and FRC (P=0.019) groups. FRC+STZ45 showed the highest insulin resistance demonstrated by insulin tolerance test [area under the curve (AUC) of insulin tolerance test; P<0.05]. AUC was not significantly different between the STZ45 and non-STZ groups and between FRC and non-FRC fed groups. Furthermore, FBG levels did not differ between FRC and non-FRC groups. Body weight measurement showed that the FRC+STZ45 group had the lowest body weight compared to all other groups. Our data provide the evidence that FRC and STZ45 synergistically could induce hyperglycemia and insulin resistance in Wistar rats. Here we presented a feasible model for initial forms of T2D by employing pretreatment with low-dose FRC solution and treatment with low-dose STZ. [ABSTRACT FROM AUTHOR]

Palmitate induces insulin resistance and apoptosis in insulin target tissues. Rosiglitazone (RSG), a peroxisome proliferator-activated receptor γ (PPAR γ) agonist, can activate both pro-apoptotic and anti-apoptotic pathways in different cells; however, its effect on palmitate-induced apoptosis in skeletal muscle cells remains to be elucidated. After differentiation of C2C12 cells, myotubes were treated with palmitate, RSG and GW9662 (PPAR γ antagonist). MTT and terminal deoxynucleotide transferase dUTP nick end labelling (TUNEL) assays and caspase-3 activity were used to investigate the apoptosis. To study the underlying mechanism, glucose uptake, gene expression and protein levels were evaluated. A total of 0.75 mM palmitate reduced cell viability by 43% and increased TUNEL-positive cells and caspase-3 activity by 15-fold and 6.6-fold, respectively. RSG (10 μM) could markedly decrease the level of TUNEL-positive cells and caspase-3 activity in palmitate-treated cells. The protective effect of RSG on apoptosis was abrogated by GW9662. To investigate the molecular mechanism of this effect, gene expression and protein level of protein tyrosine phosphatase 1B (PTP1B) were evaluated. Palmitate and RSG individually increased the expression and protein level of PTP1B, whereas combined treatment (palmitate and RSG) were able to further increase the expression of PTP1B in C2C12 cells. We also evaluated the effect of RSG on palmitate-induced insulin resistance in muscle cells. RSG could significantly improve glucose uptake by 0.4-fold in myotubes treated with palmitate. Moreover, RSG could restore the phosphorylation of Akt in palmitate-treated cells. These data suggest that RSG protects skeletal muscle cells against palmitate-induced apoptosis and this effect appears to be mediated via the PPAR γ-dependent and PTP1B-independent mechanisms. Copyright © 2014 John Wiley & Sons, Ltd. SIGNIFICANCE OF THE STUDY Saturated free fatty acids (FFAs), such as palmitate, have been shown to induce cellular apoptosis. Strategies for preventing the cytotoxic effect of palmitate are useful in reduction of diabetes complications. In this study, we introduced RSG as an agent that protects skeletal muscle cells against palmitate-induced apoptosis and insulin resistance. It appears that RSG protects skeletal muscle cells against palmitate-induced apoptosis via the PPARγ-dependent and PTP1B-independent mechanisms. Given the role of FFAs in skeletal muscle apoptosis, these findings support the idea that RSG can ameliorate diabetes complications such as skeletal muscle loss. [ABSTRACT FROM AUTHOR]

Introduction: Quercetin (3,3',4',5,7-pentahydroxyflavone) is a dietary flavonoid with good antioxidant and anti-inflammatory properties., Aims: The present study aims to determine these effects in peripheral blood mononuclear cells (PBMCs) evoked by lipopolysaccharides (LPS)., Methods: The mRNA expression and protein secretion of inflammatory mediators were evaluated by enzyme- linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR), respectively. Western blotting was utilized for assessing p65-NF-κB phosphorylation. Ransod kits evaluated the glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in the cell lysates. Ultimately, the molecular docking approach was performed to investigate the biological activity of Quercetin against NF-κB pathway proteins and antioxidant enzymes., Results: The findings revealed that quercetin significantly attenuated the expression and secretion of inflammatory mediators and p65-NF-κB phosphorylation in LPS-induced PBMCs. Additionally, quercetin dose-dependently improved the activities of SOD and GPx enzymes and decreased LPS-mediated oxidative stress in PBMCs. Moreover, quercetin has a considerable binding affinity to IκKb, the core element of the NF-κB pathway and the antioxidant enzyme SOD., Conclusion: The data show that quercetin plays a vital role in ameliorating inflammation and oxidative stress caused by LPS in PBMCs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aging is associated with an increase in oxidative stress, which damages organs such as the kidney. Trehalose has abundant beneficial activities including antioxidative effects. This study aimed to investigate the effects of trehalose on several antioxidant parameters of the aged kidney. Wistar rats were divided into three groups: young (4 months), aged (24 months), and aged-trehalose. The third group was treated with 2% trehalose for one month. The expression of target genes and enzyme activities in the kidney of the animals were evaluated by quantitative polymerase chain reaction (qPCR) and enzyme colorimetric procedures, respectively. Protein levels of NFE2L2 showed a 50% reduction in aged rats compared to young rats (P<0.001), which was restored by trehalose intervention. In addition, the activity and mRNA levels of catalase (CAT) increased in aged rats while treatment with trehalose reversed this trend. On the other hand, superoxide dismutase (SOD) activity was reduced in the kidneys of aged rats but was not affected by trehalose intervention .It is concluded that trehalose supplementation alleviates the antioxidant system impairments in the kidneys of aged rats. However, further investigations are needed to thoroughly describe the antioxidative impacts of trehalose on the kidneys during aging., Competing Interests: The authors declare no potential conflict of interest.

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling which is overexpressed in the liver of diabetic animals. The aims of this study were to generate liver-specific PTP1B knockout mice using a PTP1B‑short hairpin RNA (shRNA) plasmid and to investigate the effect of PTP1B inhibition on plasma glucose levels in streptozotocin-induced diabetic mice. We first validated the hydrodynamic tail vein injection in mice using a vector carrying the luciferase gene. Expression of the PTP1B gene was quantified by real-time PCR. The level of phosphorylated Akt was examined by western blot analysis. The injection of the plasmid containing firefly luciferase revealed that the highest transfer of the vector into the liver was obtained 24 h after the injection of 20 µg plasmid. The injection of PTP1B-shRNA, but not the scrambled shRNA plasmid, resulted in a reduction in PTP1B expression levels by up to 84% in the liver of the diabetic mice. Plasma glucose levels following the injection of PTP1B-shRNA remained significantly lower in the diabetic mice for 5 days. In addition, mice receiving PTP1B-shRNA in the basal and insulin-stimulated states had higher levels of Akt phosphorylation in the liver cells compared with mice that were injected with the scrambled sequence (35 and 60%, respectively; p<0.01). Furthermore, PTP1B overexpression was observed in the muscle, liver, adipose, heart and kidney tissues of the diabetic mice. The data from this study demonstrate that PTP1B inhibition may be a promising approach for lowering plasma glucose levels in diabetic patients. However, further studies using non-viral carriers are required to deliver the plasmid safely into the liver.