The effects simultaneous inhibition of dipeptidyl peptidase-4 and P2X7 purinoceptors in an in vivo Parkinson’s disease model

Metabolic Brain Disease - Loss of dopaminergic neurons following Parkinson’s disease (PD) diminishes quality of life in patients. The present study was carried out to investigate the...     

Mechanisms underlying quercetin-induced vasorelaxation in aorta of subchronic diabetic rats: an in vitro study

In this study, the mechanisms involved in vasorelaxant effect of the flavonoid quercetin was investigated in isolated aortic rings from streptozotocin (STZ)-diabetic rats. After 4 weeks, addition of quercetin (0.1 microM-1 mM) caused a significant dose-dependent relaxation of noradrenaline (NA)- and KCl-preconstricted rings in both control and diabetic groups with a significant inter-group difference of P<0.01. Furthermore, both nitro-L-arginine-methyl ester (L-NAME, 100 microM) and indomethacin (10 microM) markedly attenuated the vasorelaxant responses following quercetin application. Meanwhile, endothelium removal significantly attenuated the quercetin-induced vasorelaxation. It is concluded that the quercetin can relax the preconstricted rings of aorta in subchronic STZ-diabetic rats through nitric oxide- and -prostaglandin-mediated pathways, which themselves could be considered as endothelium-dependent.     

Vascular mechanisms of cyanidin-3-glucoside response in streptozotocin-diabetic rats

Background and objective: Considering the high incidence of cardiovascular disorders in diabetes mellitus and some evidence on the antioxidant and antidiabetic potential of cyanidin-3-glucoside (C3G), this study was conducted to evaluate the possible beneficial effect of C3G administration on vascular reactivity of isolated thoracic aorta in diabetic rats and some of its underlying mechanisms. Materials and methods: Male diabetic rats received C3G (10 mg/kg; i.p.) on alternate days for 8 weeks one week after streptozotocin (STZ) diabetes induction. Results: It was found out that treatment of diabetic rats with C3G exerted a hypoglycaemic effect and attenuated the increased malondialdehyde (MDA) content and reduced the activity of superoxide dismutase (SOD) in aortic tissue. Maximum contractile response of endothelium-intact aortic rings to phenylephrine (PE) was significantly lower in C3G-treated diabetic rats relative to untreated diabetics and endothelium removal abolished this difference. Meanwhile, endothelium-dependent relaxation to acetylcholine (ACh) was significantly higher in C3G-treated diabetic rats as compared to diabetic group. Conclusion: Chronic treatment with C3G may prevent some diabetes-related changes in vascular reactivity observed in diabetic rats directly and/or indirectly due to its hypoglycaemic effect and attenuation of lipid peroxidation and through endothelial-derived factors.     

Chronic epigallocatechin-gallate improves aortic reactivity of diabetic rats: Underlying mechanisms

Diabetes mellitus is associated with major cardiovascular risk factors which are responsible for excess morbidity and mortality. Green tea catechins including epigallocatechin-3-gallate (EGCG) could exert beneficial health effects to ameliorate cardiovascular and metabolic diseases. Thus, the effect of chronic administration of EGCG was studied on aortic reactivity of streptozotocin (STZ)-diabetic rats. Male diabetic rats received EGCG 25 mg/kg/day for 8 weeks 1 week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were obtained from aortic rings. Maximum contractile response of endothelium-intact rings to KCL and PE was significantly lower in EGCG-treated diabetic rats relative to untreated diabetic ones. Endothelium removal abolished the significant difference between EGCG-treated and untreated diabetic groups regarding contractile response to KCl and PE. Meanwhile, endothelium-dependent relaxation to ACh was significantly higher in EGCG-treated diabetic rats as compared to diabetic ones. Pretreatment of rings with N(omega)-L-arginine methyl ester (L-NAME) and indomethacin (INDO) significantly attenuated the observed responses. Meanwhile, two-month diabetes resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity in aortic tissue and EGCG treatment attenuated the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with EGCG could prevent the abnormal functional changes in vascular reactivity in diabetic rats through nitric oxide- and prostaglandin-dependent pathways and via attenuation of aortic lipid peroxidation.     

Thymoquinone Attenuates Astrogliosis, Neurodegeneration, Mossy Fiber Sprouting, and Oxidative Stress in a Model of Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is a rather common and difficult-to-treat variant of epilepsy. Nearly one third of people with epilepsy do not respond effectively to currently available anticonvulsants. In this study, we evaluated the protective effect of thymoquinone (TQ), the main constituent of black seed with antioxidant and anti-inflammatory effects, in the intrahippocampal kainate model of TLE in rat. Following kainate injection, seizure activity was observed that was significantly diminished by TQ pretreatment at a dose of 10 mg/kg, p.o. Intrahippocampal kainate also increased malondialdehyde (MDA), nitrite, and nitrate levels and decreased activity of superoxide dismutase and TQ only significantly attenuated MDA. In addition, intrahippocampal kainate caused a significant reduction of neurons in CA1, CA3 and the hilar regions, and TQ significantly attenuated these changes. Timm histochemistry showed a marked mossy fiber sprouting (MFS) in the dentate gyrus of kainate-lesioned rats, and TQ significantly lowered MFS intensity. Meanwhile, a number of reactive astrocytes (astrogliosis) increased significantly in the kainate group, and TQ pretreatment significantly decreased it. These data suggest that TQ pretreatment could attenuate seizure activity and lipid peroxidation, lower hippocampal neuronal loss and MFS, and mitigate astrogliosis in kainate model of TLE.     

Effect of naringenin on intracerebroventricular streptozotocin-induced cognitive deficits in rat: a behavioral analysis

Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive impairment in rats. The beneficial effect of naringenin (NAR) was investigated on ICV STZ-induced learning, memory, and cognitive impairment in male rats. For this purpose, rats were injected with ICV STZ bilaterally, on days 1 and 3 (3 mg/kg). The STZ-injected rats received NAR (50 mg/kg/day p.o.) starting 1 day pre-surgery for 3 weeks. The learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, radial eight-arm maze (RAM) task was used. It was found out that NAR-treated STZ-injected rats show higher correct choices and lower errors in RAM than vehicle-treated STZ-injected rats. In addition, NAR administration significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test. Therefore, these results demonstrate the effectiveness of NAR in preventing the cognitive deficits caused by ICV STZ in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.     

Berberine chloride improved synaptic plasticity in STZ induced diabetic rats

Previous studies indicated that diabetes affects synaptic transmission in the hippocampus, leading to impairments of synaptic plasticity and defects in learning and memory. Although berberine treatment ameliorates memory impairment and improves synaptic plasticity in streptozotocin (STZ) induced diabetic rats, it is not clear if the effects are pre- or post-synaptic or both. The aim of this study was to evaluate the effects of berberine chloride on short-term plasticity in inhibitory interneurons in the dentate gyrus of STZ-induced diabetic rats. Experimental groups included: The control, control berberine treated (100 mg/kg), diabetic and diabetic berberine treated (50,100 mg/kg/day for 12 weeks) groups. The paired pulse paradigm was used to stimulate the perforant pathway and field excitatory post-synaptic potentials (fEPSP) were recorded in dentate gyrus (DG). In comparison with control, paired pulse facilitation in the diabetic group was significantly increased (P?<?0.01) and this effect prevented by chronic berberine treatment (50,100 mg/kg). However, there were no differences between responses of the control berberine 100 mg/kg treated and diabetes berberine treated (50 and 100 mg/kg) groups as compared to the control group. The present results suggest that the pre-synaptic component of synaptic plasticity in the dentate gyrus is affected under diabetic conditions and that berberine prevents this effect.     

Chronic treatment of silymarin improves hyperalgesia and motor nerve conduction velocity in diabetic neuropathic rat

The effect of chronic silymarin (SM) treatment on hyperalgesia, sciatic motor nerve conduction velocity (MNCV) and oxidative stress in streptozotocin (STZ)‐diabetic neuropathic rat was evaluated. Rats were divided into control, diabetic, SM‐treated control and diabetic, and sodium salisylate (SS)‐treated control and diabetic. SM was administered daily at a dose of 100 mg/kg for two months. Finally, hyperalgesia and sciatic MNCV and oxidative stress markers were assessed. Diabetic rats showed a significant deficit in MNCV and markedly exhibited chemical and thermal hyperalgesia, indicating development of diabetic neuropathy. Antioxidant enzyme superoxide dismutase (SOD) level significantly reduced and malondialdehyde (MDA) level significantly increased in diabetic rats compared to control rats; SM treatment significantly ameliorated the alteration in MNCV, hyperalgesia, MDA level and antioxidant enzyme SOD in diabetic rats. These results clearly suggest the potential effect of SM in prevention and treatment of diabetic neuropathy. Copyright © 2009 John Wiley & Sons, Ltd.     

Chronic Administration of Daidzein,a Soybean Isoflavone,Improves Endothelial Dysfunction and Attenuates Oxidative Stress in Streptozotocin‐induced Diabetic Rats

The effect of chronic daidzein, a soybean isoflavone, on aortic reactivity of streptozotocin‐diabetic rats was studied. Male diabetic rats received daidzein for 7 weeks a week after diabetes induction. Contractile responses to KCl and phenylephrine (PE) and relaxation response to acetylcholine (ACh) were obtained from aortic rings. Maximum contractile response of endothelium‐intact rings to PE was significantly lower in daidzein‐treated diabetic rats relative to untreated diabetic rats, and endothelium removal abolished this difference. Endothelium‐dependent relaxation to ACh was significantly higher in daidzein‐treated diabetic rats as compared with diabetic rats and pretreatment of rings with nitric oxide synthase inhibitor N(G)‐nitro‐l‐arginine methyl ester and/or indomethacin attenuated it. Two‐month diabetes also resulted in an elevation of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activity, and daidzein treatment significantly reversed the increased MDA content and reduced activity of SOD. Therefore, chronic treatment of diabetic rats with daidzein could prevent some abnormal changes in vascular reactivity in diabetic rats through nitric oxide and prostaglandin‐related pathways, and via attenuation of oxidative stress in aortic tissue and endothelium integrity seems essential for this effect. Copyright © 2012 John Wiley & Sons, Ltd.     

Hypoglycemic and hypolipidemic effect and antioxidant activity of chronic epigallocatechin-gallate in streptozotocin-diabetic rats

Background and objective: Green tea catechins including epigallocatechin-3-gallate (EGCG) could exert beneficial health effects to ameliorate metabolic diseases. The effect of chronic administration of EGCG was evaluated on serum glucose and lipid profile and hepatic lipid peroxidation in streptozotocin (STZ)-diabetic rats. Materials and methods: Rats received EGCG 25 mg/kg/day for 8 weeks 1 week after diabetes induction. Serum glucose, triglyceride, total cholesterol, HDL- and LDL-cholesterol levels and MDA level and SOD activity in hepatic tissue were spectrophotometrically measured. Results: Treatment of diabetic rats with EGCG produced a hypoglycemic effect and there were appropriate changes regarding serum lipids in treated diabetic group. Meanwhile, EGCG treatment attenuated the increased MDA content and reduced activity of SOD in liver. Conclusion: Chronic treatment of diabetic rats with EGCG could prevent abnormal changes in blood glucose and lipid profile and attenuat hepatic lipid peroxidation.