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 muM-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 muM) and indomethacin (10 muM) 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. (C) 2004 Elsevier Inc. All rights reserved

Endothelium-dependent attenuating effect of Trigonella foenum-graecum on the contractile vascular reactivity of diabetic rats

The present study was undertaken to determine whether two-month treatment of streptozotocin (STZ)-diabetic rats with aqueous leaf extract of Trigonella foenum-graecum (TFG; 200 mg/kg; i.p.) could improve thoracic aortic responsiveness and to evaluate its endothelium dependency. For this purpose, vascular responses to KCl and noradrenaline (NA) were measured. Diabetic state significantly increased contractile responses to KCl and NA in aortic rings in both endothelium-intact and -denuded rings. Extract-treated diabetic rats showed a significant lower maximal contractile response to KCl only in endothelium-intact rings as compared to diabetic rings. It is concluded that intraperitoneal administration of aqueous leaf extract of TFG for two months could improve some functional indices of the vascular system in diabetic state and the integrity of the endothelium is essential for its beneficial effects

Protective Effects of Water Extract of Morus Nigra L. on 6-Hydroxydopamine Induced Parkinson’s Disease in Male Rats

Background: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is unknown, but major biochemical processes such as oxidative stress is largely described. Angiotensin II activates NADPH depending oxidases and produce superoxides formation. Morus nigra L. extract is an Angiotensin Converting Enzyme (ACE) inhibitor and tested for anti-Parkinsonism effects by biochemical and behavioral evaluations.Materials and Methods: In total 48 Male Wistar rats weighting 200-250 g were divided into 4 groups: (1) Sham (normal saline was injected in the left SNC), (2) Neurotoxin (injection of 6-hydroxydopamine into left SNC), (3) Morus nigra L. aqueous extract and (4) captopril. Morus nigra (10 mg/kg) and captopril (5 mg/kg) were daily-injected i.p. from 6 days before neurotoxin injection, until one day after 6-hydroxydopamine injection. Muscle stiffness and apomorphine test were assessed in 6 rats of any groups after two weeks. Protein oxidation, lipid peroxidation and ACE activity were assessed in brains of 6 rats of each group after 24 hours.Results: Rotation test with apomorphine, Rigidity with Murprogo’s test, and lipid peroxidation in sham, captopril and Morus nigra groups were significantly lower than neurotoxin group. Protein oxidation in Morus nigra group was significantly lower than neurotoxin group. Brain ACE activity in neurotoxin, captopril and Morus nigra groups were inhibited.Conclusion: Morus nigra L. extract had protective effects on neuronal oxidation and death and improved signs of PD possibly by ACE inhibition

Genistein inhibits aggregation of exogenous amyloid-beta1-40 and alleviates astrogliosis in the hippocampus of rats. Brain Res

Abstract We addressed the question of whether injection of Aβ in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Aβ 1-40 . Genistein is a plant-derived compound with a structure similar to that of the female sex hormone oestrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an amyloid beta (Aβ) 1-40 rat model of Alzheimer&apos;s disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Aβ 1-40 positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P &lt; 0.0001), CA1 (P = 0.03), and CA3 (P = 0.002); an increased number of iNOS-expressing cells (P = 0.01) and gliosis. Genistein given to rats by gavage one hour before Key words: amyloid-beta, Alzheimer&apos;s disease, genistein, neuronal degeneration 1 1 Abbreviations: AD, Alzheimer&apos;s disease; iNOS, inducible nitric oxide synthase; nNOS, neuronal nitric oxide synthase; CA1, cornu ammonis 1; CA2, cornu ammonis 2; CA3, cornu ammonis 3; Aβ, amyloid beta; DGlb, lateral blade of dentate gyrus; DGmb, medial blade of dentate gyrus; GFAP, glial fibrillary acidic protein; CC, corpus callosum; MAP, mitogenactivated protein; NFĸB, nuclear factor kappa B; MnSOD, manganese superoxide dismutase; APP, amyloid precursor protein; CrEL, Cremophor E

Original Article Antioxidant and Antiepileptic Activity of 1-[1-(3-Methoxyphenyl) (Tetralyl)] Piperidine as a New Derivative of Phencyclidine on Pentylentetrazole-Induced Kindling Mice

ABSTRAC

Molecular characterization of familial hypercholesterolemia in Iranian patients

Abstract Familial hypercholesterolemia (FH) is an autosomal dominant disorder of lipoprotein metabolism caused mainly by mutations in the low-density lipoprotein receptor (LDLR) and apolipoprotein B 100 (APOB) genes. Until now, the molecular basis of FH has been demonstrated in detail in many populations, but there is still very limited Molecular data concerning FH in Iran. The aim of this study was to characterize the LDLR and APOB gene mutations in an Iranian population. A total of 30 non-related Iranian possible FH subjects were studied. Diagnosis of FH was based on the Dutch Lipid Clinic Network diagnostic criteria. All samples were initially tested for three common APOB gene mutations including R3500Q, R3500 W and R3531C using PCR-RFLP assay. Subsequently, promoter and coding region of the LDLR gene was screened by PCRSSCP analysis and positive results were confirmed by DNA sequencing. Four previously reported polymorphisms 1413G [A, 1725C [T, 1773T [C and 2140 ? 5G[A were found in *17% (5/30) of population studied. Moreover, no variation was found in APOB gene. Our data indicated that LDLR and APOB gene mutations have not contribution to possible FH in Iranian population studied here. However, we examined three common APOB mutations and LDLR in only 30 patients, and to determine the role of these genes in developing FH in Iran, more FH samples and populations needed to be investigated for the mutations of the related gene

The vasorelaxant effect of simvastatin in isolated aorta from diabetic rats

BACKGROUND: The increasing incidence of diabetes mellitus (DM) is of great clinical significance. In this study, we aimed to investigate whether exposure of endothelium-intact aortic rings to simvastatin could have a vasorelaxant effect in diabetic rats. METHODS: For induction of diabetes, streptozotocin (STZ) (60&thinsp;mg/kg, i.p., single dose) was used. After 1 month, the cumulative reaction of isolated endothelium-intact aortic rings was determined to KCl and phenylephrine (PE) in the absence and presence of nitric oxide (NO) synthase inhibitor, i.e., nitro-L-arginine-methyl ester (L-NAME), and prostaglandin synthesis inhibitor, i.e., indomethacin. Meanwhile, the role of extracellular calcium was assessed in this respect. RESULTS: At the end of the study, the addition of simvastatin (at a concentration &ge; 10&minus;5 M) caused a significant concentration-dependent relaxation response of PE-precontracted aortic rings for both control and diabetic groups (at a significant difference of P &lt; 0.050), and this difference did not exist for KCl-precontracted aortic rings. Furthermore, both L-NAME (100 &micro;M) and indomethacin (10 &micro;M) significantly diminished the vasorelaxant response following simvastatin addition. Meanwhile, there was no statistically significant difference between control and diabetic groups in the absence of extracellular calcium. CONCLUSION: The results of this study suggest that simvastatin is able to relax PE-precontracted aortic rings isolated from STZ-diabetic rats via modulation of NO- and prostaglandin-dependent signaling and its effect is not via modulation of calcium mobilization from intracellular stores

The effect of chronic silymarin on serum level of some enzyme markers and tissue level of malondialdehyde in diabetic rats

Background and Aim: Diabetes mellitus causes enhanced oxidative stress due to increased production of oxygen free radicals and decreased activity of antioxidant defense system. Flavonolignan Silymarin has an antidiabetic effect. This study was conducted to evaluate the effect of its chronic administration on serum levels of aspartate and alanine aminotranferase and the heart and liver level of malondialdehyde. Materials and Methods: In this experimental study, 40 male Wistar rats were divided into 5 equal groups, i.e. control, Silymarin -treated control (100 mg/kg), diabetic, and two Silymarin- treated diabetic groups (50 and 100 mg/kg). Silymarin was daily administered (i.p.) to each of the group members ten days after streptozotocin injection for 4 weeks. Serum levels of aspartate and alanine aminotranferase were measured both before and at the end of the study. In addition, level of malondialdehyde (MDA) was measured in the liver and the heart tissues on the basis of the reaction of thiobarbituric acid. Results: Serum glucose level in high dose Silymarin-treated diabetic group was significantly lower as compared to diabetics in the sixth week (P=0.007).Moreover, diabetic rats showed a significant increase in their aspartate serum level (P=0.028) and alanine aminotranferase (P=0.008) and Silymarin treatment only significantly reduced serum level of alanine aminotranferase (P=0.034). In addition, diabetes was followed by increased level of MDA in the liver (P=0.008) and the heart (P=0.009) tissues and high-dose Silymarin treatment significantly reduced MDA level only in the liver tissues (P=0.026). Conclusion: Long-term treatment with silymarin at a dose of 100 mg/kg can attenuate serum level of alanine aminotranferase and hepatic MDA level and does not have any significant effects on serum level of aspartate aminotranferase and cardiac tissue level of MDA in the administered dose