Inhibitory effects of thymoquinone, the major component of Nigella sativa l. seeds, on spontaneous and evoked contractions of guinea pig isolated ileum

It has been recently shown that essential oil of Nigella sativa seeds and its major constituent, thymoquinone [TQ], possess relaxant activity on isolated trachea and ileum. Several mechanisms have been suggested to explain the smooth muscle relaxant effects of the essential oil of Nigella sativa seeds. But, only in one study, it has been shown that TQ exerts its relaxant activity probably through the inhibition of histaminergic and serotonergic receptors. Objective: This study was carried out in order to further evaluating the mechanism [s] of muscle relaxant activity of TQ. Tension recording technique using an isometric transducer connected to a physiograph in an organ bath set up was used. The spontaneous contractions of isolated ileum and contractile responses evoked by acetylcholine [Ach], histamine [His], potassium chloride [KC1], and repetitive electrical field stimulation [EFS], were recorded. ACh [10 pM], His [100 HM], KC1 [10 mM], and EFS [20 Hz, 0.2 ms, 130 V], were applied before and after adding TQ [10, 20, 40, 80,100 micro M]. Moreover, in order to evaluate the role of Ca[2+]-channels in TQ-induced relaxation of ileum, the amplitude of contractions evoked by EFS were recorded in the presence and absence of TQ [80 micro M], in Ca[2+]-free Krebs solution, as well as following adding of cumulative concentrations of CaCl[2] [0.1, 0.2, 0.4,1,2 mM]. The results showed that TQ at the minimum concentration of 20

decreased the amplitude of spontaneous contractility [p<0.01] and His- and EFS- evoked contractions [p<0.05]. Also, the amplitude of ACh- and KC1 - evoked contractions were decreased by TQ at the minimum concentration of 40 micro M [p<0.01 and p<0.001, respectively]. The maximum inhibitory effects of TQ against ileum contractility were achieved by the concentration of 100 micro M. Furthermore, the cumulative concentrations of CaCl[2] in the presence of TQ [80 micro M], failed to increase the amplitude of contractions induced by EFS, which were suppressed in Ca[2+]-free medium. These findings indicated that TQ possesses inhibitory effects on contractility of guinea pig isolated ileum, and that effects may be responsible for the smooth muscle relaxant activity of Nigella sativa seeds. The mechanism by which TQ relaxes ileum contractility was exerted, at least in part, through an antagonistic activity on calcium channels in guinea pig ileum smooth muscle cells

effects of carbenoxolone, a gap junction channel blocker, on spatial learning inMorris water maze task in rats

High frequency oscillations [ripples] are proposed to involve in memory consolidation. Ripple oscillations persist in the absence of chemical synaptic transmission and inhibitors of gap junctions were shown to block high frequency oscillations in hippocampal slices. In this study, we investigated the effects of carbenoxolone, as a gap junction blocker, on spatial learning in the rat. Cognitive performance was assessed using Morris water maze [MWM]. Adult male rats were bilaterally cannulated into the CA1 region of their hippocampus. Carbenoxolone [1.23, 2.46, 4.92 microg/side], scopolamine [microg/side] and saline were injected through the cannulas before training for 4 consecutive trials and one probe trial that was conducted 24 h after the training trials with the platform removed. The results showed that carbenoxolone could significantly reduced percent of time spent, distance traveled and quadrant entry in Q2 compared to control group and failed to use a selective search strategy during probe trial in which the platform was removed.The results of the present study suggest that carbenoxolone as a gap junction channels blocker can decelerate learning performances of rats in a spatial memory task such as the MWM that requires the integrity of hippocampus

Study on the anticonvusant activity of thymoquinone, the major constituent of Nigella Sativa L.seeds, through intracerebroventricular injection

Thymoquinone, the major constituent of Nigella sativa seeds, is a biologically active compound, which possesses several pharmacological effects. The aim of the present study was to evaluate the anticonvulsant effect of thymoquinone through intracerebroventricular [i.c.v.] injection. The anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, were investigated using pentylenetetrazole [PTZ]-induced seizure model. In PTZ-induced epileptic seizures, the i.c.v. injection of thymoquinone [200 and 400 mol] prolonged the onset and reduced the duration of tonic-clonic seizures. The protective effect of thymoquinone against lethality was 45% and 50% in the mentioned doses, respectively. In this study, flumazenil [1 nmol, i.c.v.] reversed the anticonvulsant activity of thymoquinone. Also, pretreatment with naloxone [10 mol, i.c.v.] antagonized the prolongation of tonic-clonic seizure latency, as well as reduction in seizure duration both induced by thymoquinone [200 mol, i.c.v.]. These results indicate that thymoquinone may possess anticonvulsant activity probably through an opioid receptor-mediated increase in GABAergic tone

[ effect of carbenoxolone on lipid peroxidation level during global ischemic-reperfusion in hippocampal rat slices]

Present studies have shown that gap junction channels could be a novel target to reduce brain damage during cerebral ischemia. Carbenoxolone, a gap junction channel blocker decreased the spread of cell death in in vitro brain ischemic model and inhibition of lipid peroxidation has been of much interest to ameliorate excitotoxic neuronal damage. Thus the aim of the present study was to determine the effect of carbenoxolone on lipid peroxidation in experimental global ischemicreperfusion in the rat hippocampus. The brain damages were determined using the measurement malondialdehyde [MDA]. Cerebral ischemia was induced by four-vessel-occlusion [4VO]. Carbenoxolone [50-200mg/kg], phenytoin [50 mg/kg] and normal saline [10 ml/kg] were administered intraperitoneally immediately after reperfusion. The malondialdehyde [MDA] was measured using the thiobarbituric acid [TBA] test. The MDA level was higher in the saline group during ischemic reperfusion than the sham group. The MDA levels recovered significantly upon phenytoin and carbenoxolone [100-200 mg.kg] therapy in the ischemicreperfusion. These results suggest that carbenoxolone may protect the brain against lipid peroxidation in cerebral ischemia

[ effect of thymoquinone on global ischemia-reperfusion in rats]

Thymoquinone is the major active constituent of the volatile oil of Nigella sativa seeds. It has been previously reported that thymoquinone prevents oxidative injury in various hepatotoxicity models and may prevent membrane lipid peroxidation. In order to clarify the effect of thymoquinone on lipid peroxidation in CNS, we induced cerebral ischemic/reperfusion injury in rats using four-vessel occlusion [4-VO] method and consequently determined malondialdehyde [MDA] levels in hippocampus based on its reaction with thiobarbituric acid [TBA]. Thymoquinone [2.5-10 mg/kg], phenytoin [50 mg/kg] and control [10 ml/kg] were administered immediately after reperfusion. The MDA level was higher in control group [normal saline] following ischemic-reperfusion than thymoquinone treated groups. The MDA levels recovered significantly upon phenytoin and thymoquinone [5, 10 mg/kg] therapy following ischemic/reperfusion. These results suggest that thymoquinone may exhibit neuroprotective effect through an inhibitory activity against lipid peroxidation during cerebral ischemia in rats