effect of chronic administration of safranal on systolic blood pressure in rats

Safranal, the main component of Crocus sativus essential oil, exhibits different pharmacological activities. In this study, the effects of safranal, on blood pressure of normotensive and desoxycorticosterone acetate [DOCA]-salt induced hypertensive rats in chronic administration were investigated. Three doses of safranal [1, 2 and 4 mg/Kg/day] and spironolactone [50 mg/Kg/day] were administrated to the different groups of normotensive and hypertensive rats [at the end of 4 weeks treatment by DOCA-salt] for Five weeks. Then the effects of safranal on mean systolic blood pressure [MSBP] and heart rate [HR] were evaluated using tail cuff method. The duration of effect of safranal on SBP, was also evaluated. Our results indicated that chronic administration of safranal could reduce the MSBP in DOCA salt treated rats in a dose dependent manner. Safranal did not decrease the MSBP in normotensive rats. The data also showed that antihypertensive effects of safranal did not persist. In summary, our results showed that safranal exhibits antihypertensive and normalizing effect on BP in chronic administration

Effects of aqueous saffron extract [Crocus sativus L.] on the acquisition and reinstatement of morphine-induced conditioned place preference in mice

In the present study, the effects of aqueous saffron extract [Crocus sativus L.] on the acquisition and reinstatement of morphine-induced conditioned place preference [CPP] in mice were investigated. Subcutaneous administration of morphine [40 mg/kg for four days] produced place preference. Intraperitoneal administration of aqueous extract [40 and 80 mg/kg for four days] 30 min before the morphine administration decreased the acquisition of morphine CPP. In other groups of animal, following extinction of a place preference induced by morphine [40 mg/kg], single administration of morphine [10 mg/kg] reinstated the place reference. The aqueous extract [80 mg/kg] 30 min before this priming dose of morphine blocked morphine-induced reinstatement of place preference. These results show that aqueous saffron extract can reduce the acquisition and reinstatement of morphine-induced conditioned place preference

Evaluation of nitric oxide or opioid receptors involvement in antinociceptive properties of silymarin

It has been shown that Silybum marianum or its extracts have hepatoprotective, antioxidant, anticancer, anti-inflammatory and anti-diabetic effects. Nitric oxide [NO] plays an important role in neurotransmission, neuroprotection, neurotoxicity and pathological pain, as a neurotransmitter or neuromodulator in the central nervous system. Therefore, this experiment was performed in order to assess the analgesic effects of single and multiple-dosed ip administration of silymarin and the probable role of nitric oxide or opioid receptors using tail flick assay. Based on our results, only silymarin 100 mg/kg showed analgesic properties. Since naloxone did not change silymarin's analgesic effects, it is concluded that opioid receptors are not involved. Although in the presence of L-arginine, analgesic effect of silymarin remained intact, but it is not possible to strongly determine the involvement of nitric oxide pathway here. Based on our results, the difference between anti nociceptive properties of single and multiple-dosed treatment of silymarin 100 mg/kg is not significant. It is concluded that silymarin exert its analgesic effects via other mechanisms. Inhibiting 5-lipooxygenase and neutrophil chemotaxis to inflammation location could be the probable ways of silymarin's action

Effects of erythropoietin on electrocardiogram changes in carbon monoxide poisoning: an experimental study in rats

The aim of this study was to define the electrocardiogram [ECG] changes following the moderate to severe CO intoxication in rats, and also evaluating the effect of erythropoietin [EPO] on observed cardiac disturbances. The growing literature on erythropoietin effect on cardiac ischemia led us to question its effect on cardiotoxicity due to the carbon monoxide poisoning. Wistar rats were exposed to three different concentrations of CO [250 PPM, 1000 PPM or 3000 PPM]. EPO was administrated [5000 IU/Kg, intraperitoneal injection] at the end of CO exposure and then the animals were re-oxygenated with ambient air. Subsequently ECG recording, heart rate and carboxyhemoglobin values were evaluated. ECG changes following the CO intoxication included ST segment elevation and depression, T wave inversion and first-degree AV block. Ischemic ECG changes reduced significantly in EPO-treated animals. In the present study, for the first time, EPO was investigated for the management of cardiac complications due to the CO poisoning. Our results showed that EPO could inhibit ischemic changes of ECG after the CO poisoning

Synthesis and vasorelaxant effect of 9-aryl-1,8-acridinediones aspotassium channel openers in isolated rat aorta

ATP-sensitive potassium [K[ATP]] channel openers have a relaxation effect due to the lower cellular membrane potential and inhibit calcium influx. There has been considerable interest in exploring K[ATP] channel openers in the treatment of various diseases such as cardiovascular, cerebrovascular, and urinary system disease and premature labor. The purpose of this study was to synthesize 3,3,6,6-tetramethy l-9-aryl-octahydro-1,8-acridindiones and investigate their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rings of rat aortic smooth muscle. In this study, four new derivatives of 3,3,6,6-tetramethy l-9-aryl-octahydro-1,8-acridindione [2a-d] were synthesized by the reaction of 5, 5-dimethyl-1,3-cyclohexanedione with an aromatic aldehyde, 2-alkylthio-1-[4-fluorobenzyl]-5-formylimidazole or 3-substituted benzaldehyde, in the presence of ammonia in methanol. Their effects on vascular potassium channels and mechanism of induced relaxations on phenylephrine-induced contractile responses in isolated rat aorta were investigated. Minoxidil was used as a standard potassium channel opener and Glibenclamide was used as a standard potassium channel blocker. The effects of compounds on KCl-induced contractile response which is an indicator of ca-channel blocking activity was also investigated and compared to that of nifedipine as a standard calcium channel blocker. Compounds 3a-d and Minoxidil relaxed the contractions exerted by using phenylephrine with the potency order as follows: Minoxidil > 3c > 3d > 3a > 3b. This effect was sensitive to the potassium channel blocker Glibenclamide. It can be concluded that these compounds act via ATP-sensitive potassium [K[ATP]] channels. Selectivity index [SI] for these compounds and Minoxidil also shows that these compounds are selective to ATP-sensitive potassium [K[ATP]] channels and the selectivity of compounds 3a-d is less than Minoxidil.

Synthesis and effects of 4,5-diaryl-2-[2-alkylthio-5-imidazolyl] imidazoles as selective cyclooxygenase inhibitors

In recent years highly selective COX-2inhibitors were withdrawn from the market because of an increased risk of cardiovascular complications. In this study we were looking for potent compounds with moderate selectivity for COX-2. So, four analogues of 4, 5-diaryl-2-[2-alkylthio-5-imidazolyl] imidazole derivatives were synthesized and their anti-inflammatory and anti-nociceptive activities were evaluated on male BALB/c mice [25-30 g]. Molecular modeling and in vitro COX-1 and COX-2 isozyme inhibition studies were also performed. 2-[2-Alkylthio-5-imidazolyl]-4,5-diphenylimidazole compounds were obtained by the reaction of benzyl with 2-alkylthio-1-benzylimidazole-5-carbaldehyde, in the presence of ammonium acetate. Spectroscopic data and elemental analysis of compounds were obtained and their structures elucidated. Anti-nociception effects were examined using writhing test in mice. The effect of the analogues [7.5, 30, 52.5 and 75 mg/kg] against acute inflammation were studied using xylene-induced ear edema test in mice. Celecoxib [75 mg/kg] was used as positive control. All four analogues exhibited anti-nociceptive activity against acetic acid induced writhing, but did not show significant analgesic effect [P< 0.05] compared with celecoxib. It was shown that analogues injected 30 min before xylene application reduced the weight of edematic ears. All analogues were found to have less selectivity for COX-2 in comparison to celecoxib. Injected doses of synthesized analogues possesses favorite anti-nociceptive effect and also has anti-inflammatory effects, but comparing with celecoxib this effect is not significantly different. On the other hand selectivity index for analogues is less than celecoxib and so we expect less cardiovascular side effects for these compounds

Synthesis and effects of novel dihydropyridines as dual calcium channel blocker and angiotensin antagonist on isolated rat aorta

Four novel losartan analogues 5a-d were synthesized by connecting a dihydropyridine nucleus to imidazole ring. The effects of 5a and 5b on angiotensin receptors [AT1] and L-type calcium channels were investigated on isolated rat aorta. Aortic rings were pre-contracted with 1 microM Angiotensin II or 80 mM KC1 and relaxant effects of losartan, nifedipine, 5a and 5b were evaluated by cumulative addition of these drugs to the bath solution. The results showed that compounds 5a and 5b have both L-type calcium channel and AT1 receptor blocking activity. Their effects on AT1 receptors are 1000 and 100, 000 times more than losartan respectively. The activity of compound 5b on L-type calcium channel is significantly less than nifedipine but compound 5a has comparable effect with nifedipine. Finally we concluded that these two new Compounds can be potential candidates to be used as effective antihypertensive agents

Synthesis and calcium channel antagonist activity of 4-[[halobenzyl] imidazolyl] dihydropyridines

Seven analogues of nifedipine [in which the ortho nitrophenyl group at position 4] were replaced by 2-alkylthio-1-[halobenzyl-5-imidazolyl substituent] were synthesized and evaluated as calcium antagonists using the high K[+] contraction of rat ileal longitudinal smooth muscle. These analogues of nifedipine decreased the various contractile responses of the longitudinal smooth muscle of the isolated rat ileum in a dose-dependent manner. However, their potencies for inhibition of contraction varied significantly from each other. All tested compounds [except compound 5f], were stronger than nifedipine with IC50 1.16 x 10[-13]M. Compound 5a with IC[50] 6.73 x 10[-15]M was the most active compound tested

Review of the pharmacological and toxicological effects of Salvia leriifolia

Salvia leriifolia Benth. [vernacular names such as Nuruozak and Jobleh] is a perennial herbaceous plant that grows exclusively in south and tropical regions of Khorasan and Semnan provinces, I. R. Iran. Unlike other species of Salvia genus, the chemical constituents of S. leriifolia are not well recognized. The stem oil of the plant consisted mainly both monoterpenes and sesquiterpenes, while in leaf and flower oils monoterpenes predominated over sesquiterpenes. In recent years, the different properties of this plant such as the attenuation of morphine dependence, hypoglycemic, antinociceptive and anti-inflammatory, antioxidant, antiischemia, anticonvulsant, antiulcer effects, antibacterial activities and antimutagenic effects were evaluated. These effects introduce this plant for more toxicological and clinical trials evaluations as a herbal medicine