Objective: The present study was carried out to determine the role of thymoquinone (TQ) in modulating the levels of neurotransmitter and reducing the oxidative stress in animal models of depression. Material and Methods: Mice were divided into 5 groups, each group had 6 animals. TQ (20”‰mg/kg) in corn oil and fluoxetine (10”‰mg/kg) in normal saline were administered intraperitoneally (i.p.) half an hour before performing behavioural tests. Modified forced swim test (MFST) and tail suspension test (TST) were used to assess the antidepressant effect in mice. Animals were sacrificed and their brains were removed for biochemical estimation after performing behavioural tests. Results: TQ treatment showed increased swimming, climbing and decreased immobility times in MFST and TST. Combination of TQ with fluoxetine in MFST and TST showed potentiating effect in the present study. A significant elevation of 5-hydroxytryptamine (5-HT) levels was observed following TQ administration in the behavioural models studied. MFST and TST reduced glutathione and elevated TBARS levels in mice. Pre-treatment of TQ restored glutathione and decreased TBARS levels. TQ combination with fluoxetine also showed reduction of TBARS and increased glutathione levels. Conclusion: TQ demonstrated antidepressant effects in MFST and TST respectively in the present study. It further demonstrated antioxidant effects by reducing thiobarbituric acid reactive substance (TBARS) and increasing reduced glutathione (GSH) levels. Although our results are preliminary, further investigations may be required however, based on afore mentioned results, it may be suggested that TQ could be a potential candidate for the management of depression.

BACKGROUND:

Neuroimmune factors have been proposed as contributors to the pathogenesis ofdepression. Beside other therapeutic effects including neuroprotective, antioxidant, anticonvulsant and analgesic effects, Nigella sativa and its main ingredient, thymoquinone (TQ), have been shown to have anti-inflammatory effects. In the present study, the effects of Nigella sativa hydro-alcoholic extract andthymoquinone was investigated on lipopolysaccharide- induced depression like behavior in rats.

MATERIALS AND METHODS:

50 male Wistar rats were divided into 5 groups: Group 1 (control group) received saline instead of NS extract, thymoquinone or lipopolysaccharide. The animals in group 2 (lipopolysaccharide (LPS)) were treated by saline instead of NS extract and were injected LPS (100μg/kg, ip) 2 hours before conducting each forced swimming test. Groups 3 (LPS + NS 200) and 4 (LPS + NS 400) were treated by 200 and 400 mg/kg of NS (ip), respectively, from the day before starting the experiments and before each forced swimming test. These animals were also injected LPS 2hours before conducting each swimming test. The animals in group 5 received TQ instead of NS extract. Forced swimming test was performed 3 times for all groups (in alternative days), and immobility time was recorded. Finally, the animals were placed in an open- field apparatus, and the crossing number on peripheral and central areas was observed.

RESULTS:

The immobility time in the LPS group was higher than that in the control group in all 3 times (P<0.001). The animals in LPS + NS 200, LPS + NS 400 and LPS + TQ had lower immobility times in comparison with LPS groups (P<0.01, and P<0.01). In the open- field test, the crossing number of peripheral in the LPS group was higher than that of the control one (P<0.01) while the animals of LPS + NS 200, LPS + NS 400 and LPS + TQ groups had lower crossing number of peripheral compared with the LPS group (P <0.05, and P<0.001). Furthermore, in the LPS group, the central crossing number was lower than that of the control group (P<0.01). In the animals treated by NS or TQ, the central crossing number was higher than that of the LPS group (P<0.05, and P<0.001).

CONCLUSIONS:

The results of the present study showed that hydro-alcoholic extract of Nigella sativa can prevent LPS-induced depression like behavior in rats. These results support the traditional belief on the beneficial effects of Nigella sativa in the nervous system. Moreover, further investigations are required in order to better understand this protective effect.

A healthy, balanced diet is essential for both physical and mental well-being. Such a diet must include an adequate intake of micronutrients, essential fatty acids, amino acids and antioxidants. The monoamine neurotransmitters, serotonin, dopamine and noradrenaline, are derived from dietary amino acids and are involved in the modulation of mood, anxiety, cognition, sleep regulation and appetite. The capacity of nutritional interventions to elevate brain monoamine concentrations and, as a consequence, with the potential for mood enhancement, has not been extensively evaluated. The present study investigated an extract from oregano leaves, with a specified range of active constituents, identified via an unbiased, high-throughput screening programme. The oregano extract was demonstrated to inhibit the reuptake and degradation of the monoamine neurotransmitters in a dose-dependent manner, and microdialysis experiments in rats revealed an elevation of extracellular serotonin levels in the brain. Furthermore, following administration of oregano extract, behavioural responses were observed in mice that parallel the beneficial effects exhibited by monoamine-enhancing compounds when used in human subjects. In conclusion, these data show that an extract prepared from leaves of oregano, a major constituent of the Mediterranean diet, is brain-active, with moderate triple reuptake inhibitory activity, and exhibits positive behavioural effects in animal models. We postulate that such an extract may be effective in enhancing mental well-being in humans.

This study aimed to assess the effects of thymoquinone (TQ) on pyrogallol-induced endothelial dysfunction in isolated rabbit aorta. The protective effects of TQ were examined by incubating aortic rings in TQ concomitant with pyrogallol. The results revealed that pyrogallol produced significant enhancement of phenylephrine-induced contraction and impairment of acetylcholine-induced relaxation. Pyrogallol caused a significant increase in lipid peroxidation and reduction in the level of superoxide dismutase and reduced glutathione in the aortic homogenates. In addition, pyrogallol produced a significant decrease in nitrite/nitrate concentrations (NOx), constitutive nitric oxide synthase (cNOS) activity and an increase in inducible nitric oxide synthase (iNOS) activity in the aortic homogenates. These changes were counteracted by TQ co-incubation as TQ attenuated pyrogallol-induced impairment in vascular reactivity in a dose-dependent manner. Furthermore, TQ showed potent antioxidant activity as well as causing a significant increase in NOx and cNOS activity, anddepression in iNOS activity. These results suggest that TQ can protect against pyrogallol-induced endothelial dysfunction which probably results from its potent antioxidant capacity that leads to an increase in NO production as well as its ability to enhance the generation and bioavailability of NO.