The effect of nigellone and thymoquinone on inhibiting trachea contraction and mucociliary clearance.

NIGELLA SATIVA L. has many effects including those on the gastrointestinal tract and trachea and is, therefore, used in the Mediteranean area and in India/Pakistan. Our aim was to investigate the effect of two main constituents, nigellone and thymoquinone, on trachea (antispasmodic effect) and their influence on respiratory clearance. The effects on Ba (2+)-, carbachol- and leukotriene-induced trachea contractions and the transport of the fluorescence dye rhodamin B concerning ciliary action in the tracheal area were investigated using a microdialysis technique. Nigellone and high concentrations of thymoquinone had a concentration-dependent inhibitory effect on the trachea when being contracted by the depolarizing effect of Ba (2+). The trachea contractions induced by leukotriene-d (4) were inhibited by nigellone and by thymoquinone. The cholinergic system (stimulation by carbachol) was hardly involved. The rate of ciliary clearance (mucociliary transport) was slightly modified by a high thymoquinone concentration (153.0 vs. 505.0 sec/12 mm distance, respectively), and was highly increased by nigellone (217.5 vs. 505.0 sec/12 mm distance). In conclusion, this study provides evidence for an antispasmodic effect and an increase in mucociliary clearance for nigellone but not for thymoquinone. Altogether the data indicate that nigellone but not thymoquinone may be useful in treatment of different respiratory diseases.

The hypoglycemic effect of Nigella sativa oil is mediated by extrapancreatic actions.

A plant mixture containing extracts of Nigella sativa possesses blood glucose lowering effects, but the direct antidiabetic effect of Nigella sativa is not yet established. Therefore, the effect of Nigella sativa oil (NSO) on blood glucose concentrations was studied in streptozotocin diabetic rats. In addition, the effect of NSO, nigellone and thymoquinone were studied on insulin secretion of isolated rat pancreatic islets in the presence of 3, 5.6 or 11.1 mM glucose. NSO significantly lowered blood glucose concentrations in diabetic rats after 2, 4 and 6 weeks. The blood lowering effect of NSO was, however, not paralleled by a stimulation of insulin release in the presence of NSO, nigellone or thymoquinone. The data indicate that the hypoglycemic effect of NSO may be mediated by extrapancreatic actions rather than by stimulated insulin release.

Nigella sativa oil, nigellone and derived thymoquinone inhibit synthesis of 5-lipoxygenase products in polymorphonuclear leukocytes from rats.

In the present study, Nigella sativa oil (NSO), nigellone (polythymoquinone) and derived thymoquinone were studied to evaluate their effect on the formation of 5-lipoxygenase (5-LO) products from polymorphonuclear leukocytes (PMNL).NSO produced a concentration dependent inhibition of 5-LO products and 5-hydroxy-eicosa-tetra-enoic acid (5-HETE) production with half maximal effects (IC(50)) at 25+/-1 micro g/ml, respectively 24+/-1 micro g/ml. Nigellone caused a concentration-related inhibition of 5-HETE production (IC(50): 11.9+/-0.3 micro g/ml). Moreover thymoquinone, the active principle of NSO inhibited the production of 5-LO products (IC(50): 0.26+/-0.02 micro g/ml) and 5-HETE production (IC(50): 0.36+/-0.02 micro g/ml) in a similar way. The effects are probably due to an antioxidative action. The data may in part explain the effect of the oil, its derived thymoquinone and nigellone in ameliorating inflammatory diseases.

Nigella sativa L. oil protects against induced hepatotoxicity and improves serum lipid profile in rats.

The effects of 4 weeks oral intake of Nigella sativa L. (NS) oil on some liver function tests and D-galactosamine- or carbon tetrachloride-induced hepatotoxicity were investigated in male albino rats. In another series of experiments, the effect of the oil on serum lipid profile was examined in male spontaneously hypertensive rats of stroke prone strain and Wistar Kyoto rats. The study showed that daily administration of the oil per se (800 mg/kg orally for 4 weeks) did not adversely effect the serum transaminases (ALT and AST), alkaline phosphatase, serum bilirubin or prothrombin activity in normal albino rats. When the oil was given for 4 weeks prior to induction of hepatotoxicity by D-galactosamine or carbon tetrachloride, it was able to give complete protection against d-galactosamine and partial protection against carbon tetrachloride hepatotoxicity. NS oil showed a favourable effect on the serum lipid pattern where the administration of the oil (800 mg/kg orally for 4 weeks) caused a significant decrease in serum total cholesterol, low density lipoprotein, triglycerides and a significant elevation of serum high density lipoprotein level.

Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats.

The present work was done to investigate the possible effects of Nigella sativa oil (NSO) on gastric secretion and ethanol-induced ulcer in rats. Thirty two adult male rats were used in this study (four groups) and several parameters were determined to assess any degree of protection. It was found that the administration of NSO in rats produced a significant increase in mucin content and glutathione level and a significant decrease in mucosal histamine content. Ethanol administration produced a 100% ulcer induction with an ulcer score of 12.62+/-1.35 (mean+/-S.E., n=8). It caused a significant reduction in free acidity and glutathione level while it produced a significant increase in mucosal histamine content. When animals were pretreated with NSO before induction of ulcer, there was a significant increase in glutathione level, mucin content and free acidity and a significant decrease in gastric mucosal histamine content with a protection ratio of 53.56% as compared to the ethanol group. It can be concluded that NSO imparted a protective action against ethanol induced ulcer in rats.

Different effects of the antidepressant drugs imipramine, maprotiline and bupropion on insulin secretion from mouse pancreatic islets.

In some previous studies, acute administration of some antidepressants has been reported to cause significant changes in the levels of blood glucose and insulin in the rabbit. In the present study the effects of several antidepressants representing classical groups of antidepressants, namely imipramine (CAS 50-49-7, I), maprotiline (CAS 10347-81-6, M) and bupropion (CAS 34911-55-2, (B) on insulin secretion from the isolated islets of Langerhans in mice was studied. Maprotiline and bupropion stimulated insulin release, while imipramine was without any effect in presence of 8.3 mmol/l glucose. On the other hand, in presence of 16.7 mmol/l imipramine and maprotiline suppressed the stimulated insulin secretion. Bupropion inversely significantly stimulated the insulin secretion in presence of 16.7 mmol/l glucose. It is concluded that the changes of blood glucose and plasma insulin observed in vivo may at least in part be due to respective changes of insulin secretion. The treatment of diabetic patients receiving antidepressant drugs with hypoglycaemic agents should be taken in consideration.

Single lung transplantation for alveolar micro-lithiasis: the first clinical report.

Pulmonary alveolar microlithiasis (P.A.M.) is a rare pulmonary disorder that pursues usually an asymptomatic course and can culminate in severe respiratory failure. We report a 48 year old Saudi female patient with P.A.M. who deteriorated rather steadily after the initial 18 years of asymptomatic course until a frank type I respiratory failure is established. Single lung transplantation (S.L.T.) was performed successfully and the patient returned to full daily activity and has now survived 12 months post S.L.T. The immunosuppression consisted of Cyclosporine-A 10 mg/kg/day, azathioprine (immuran) 2 mg/kg/day and prednisolone 10 mg daily. The bronchial anastomosis was done by telescoping the recipient and donor main bronchus without omental wrap. A significant bronchial stricture of the anastomotic site occurred 4 months post S.L.T. which was dilated endoscopically with good clinical and bronchoscopic result. No episodes of rejection or infection were encountered so far.

Interference with the autonomic nervous system by the converting enzyme inhibitor ramipril in conscious spontaneously hypertensive rats.

The interaction of the converting enzyme inhibitor (CEI) ramipril with sympathetic neurotransmission and the baroreceptor reflex (BRR) was investigated in conscious stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto (WKY) controls. Intravenous (i.v.) injection of ramipril (100 micrograms) attenuated the pressor responses to i.v. noradrenaline (NA) in SHRSP and WKY rats. Ganglionic blockade was performed with pentolinium (10 mg/kg i.v.), and blood pressure (BP) was subsequently supported with i.v. NA (1 microgram/min), angiotensin II (ANG II, 500 ng/min), or NA plus a subpressor dose (0.1 ng/min) of ANG II. Intravenous injection of ramiprilat (100 micrograms) significantly decreased NA-supported BP in SHRSP and WKY rats for more than 30 min, but did not lower BP in rats supported with ANG II or with NA plus a subpressor dose of ANG II. In SHRSP and WKY rats pretreated intracerebroventricularly (i.c.v.) with ramiprilat (0.5 microgram/min for 30 min), the slope of the BRR curve between increases in systolic BP and prolongation in pulse interval following bolus i.v. injections of methoxamine (10-100 micrograms/kg) was steeper than in vehicle-pretreated controls. In contrast, i.v. pretreatment with the same dose of the CEI did not increase BRR sensitivity. Our data in conscious animals demonstrate that CEI can interfere acutely with the autonomic nervous system through postsynaptic inhibition of neurotransmission and sensitization of the baroreceptor reflex. The relevance of this mechanisms for the chronic antihypertensive actions of CEI remains to be established.