Kamal E.H. El Tahir

The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action.

1. The effects of the volatile oil (V.O.) of the black seed (Nigella sativa) on the arterial blood pressure and heart of urethane-anaesthetized rats were investigated and the effects were compared with those of its constituent thymoquinone (T.Q.). 2. Intravenous administration of V.O. in the dose range (4-32 microliters kg.-1) or T.Q. (0.2-1.6 mg kg-1) to rats decreased the arterial blood pressure and the heart rate in a dose-dependent manner. 3. The effects of V.O. were significantly antagonized by treatment of the animals with cyproheptadine, hexamethonium atropine and by spinal pithing. 4. Treatment of the animals with reserpine (5 mg kg- 1 day-1 for 2 days) significantly antagonized the cardiovascular depressant effects induced by 4 and 8 microliters of V.O. kg-1 but not those induced by the larger doses. 5. T.Q.-induced cardiovascular depressant effects were significantly antagonized by atropine and cyproheptadine but not by reserpine. 6. The results suggested that V.O.-induced cardiovascular depressant effects were mediated mainly centrally via indirect and direct mechanisms that involved both 5-hydroxytryptaminergic and muscarinic mechanisms. The direct mechanisms may be due to the presence of T.Q. in the V.O. The V.O. seemed to possess the potential of being a potent centrally acting antihypertensive agent.

The respiratory effects of the volatile oil of the black seed (Nigella sativa) in guinea-pigs: Elucidation of the mechanism(s) of action

1. The effect of the volatile oil (VO) of the black seed (Nigella sativa) on the respiratory system of the urethane-anaesthetized guinea-pig was investigated and compared with those of its constituent thymoquinone (TQ). 2. Intravenous administration of VO in the dose range (4-32 microliters kg-1) induced dose-dependent increases in the respiratory rate and the intratracheal pressure. 3. The effects of VO were significantly antagonized by treatment of the animals with mepyramine, atropine and reserpine. They were not antagonized by indomethacin, diethyl carbamazine or hydrocortisone. 4. Intravenous administration of TQ in the dose range (1.6-6.4 mg kg-1) induced significant increases in the intratracheal pressure without any effect in the respiratory rate. 5. The results suggested that VO-induced respiratory effects were mediated via release of histamine with direct involvement of histaminergic mechanisms and indirect activation of muscarinic cholinergic mechanisms. 6. Removal of TQ from VO may provide a potential centrally acting respiratory stimulant.

Pharmacological Actions of Magnoflorine and Aristolochic Acid-1 Isolated from the Seeds of Aristolochia bracteata

AbstractMagnoflorine and aristolochic acid-1 were isolated from Aristolochia bracteata and their pharmacologic actions studied. Magnoflorine decreased arterial blood pressure in rabbits and induced hypothermia in mice. Both compounds induced contractions in the isolated pregnant rat uterus and stimulated the isolated guinea pig ileum. Experiments with standard agents in these models suggest action on muscarinic and serotonergic systems, cither directly or indirectly.Ripe fruits of Aristolochia bracteata were collected in the Khartoum area (Sudan). The fruits were

Synthesis and Pharmacological Activity of N- Alkyl-1,2-Diphenylethanolamines

A series of N-alkyl-l,2-diphenylethanolamines were synthesized and their pharmacological activities evaluated on various mammalian organs and sytems. All compounds produced a generalized inhibitory effect on smooth and cardiac muscles and an increase in coronary flow as well as a brief reduction in rabbit blood pressure. The latter effect was not prevented by pretreatment of the animals with atropine, propranolol, or metoprolol. The compounds were devoid of local anesthetic activity and their inhibitions of the contraction of the isolated rabbit intestine and perfused heart were reversed by exogenous calcium ions. It is proposed that the compounds produce their effects through calcium-channel blockade. The inhibitory effects of some of these compounds were comparable to those of a known calcium-channel blocker.

The antiarrhythmic activity of N-alkyl-1,2-diphenylethanolamines.

The activity of N-alkyl-1,2-diphenylethanolamines against CaCl2-induced cardiac arrhythmia was evaluated in the rat. The potencies of the compounds were compared with that of the established calcium ion-channel blocker, verapamil. The N-methyl, N-ethyl, and N-isobutyl derivatives as well as verapamil at doses of 2–8 µmol kg−1 protected the animals against the induced arrhythmia. The potency order was verapamil > N methyl > N-ethyl > N-isobutyl derivatives. The N-isopropyl and N-butyl derivatives were inactive. The antiarrhythmic activity of the compounds was not due to local anesthetic activity but may be caused by calcium-channel inhibition.

Influence of niridazole and chloroquine on arterial and myometrial prostacyclin synthesis

1 The effects of niridazole and chloroquine on rat arterial and myometrial prostacyclin (PGI2) synthesis in vitro were investigated by use of a rat platelet antiaggregatory bioassay. Niridazole (233 μm) and chloroquine (97 μm) inhibited PGI2 synthesis in both tissues. 2 Niridazole‐induced inhibition in the myometrium was not reversed by exogenous arachidonic acid (33 μm) indicating a direct effect of the compound on PGI2 synthesizing enzymes. 3 Chloroquine‐induced inhibition in the myometrium was significantly reversed by exogenous arachidonic acid (33 μm) indicating a direct effect of the compound on arachidonic acid releasing enzymes (e.g. phospholipases A2 and C). 4 Niridazole and chloroquine also inhibited prostaglandin E2 synthesis in the myometrium. 5 Chloroquine‐and niridazole‐induced inhibition of prostaglandin synthesis may contribute towards a better understanding of some of their actions in vivo.

Influence of bromocriptine on free amino acids in the kidneys and heart of the rat.

The effects of bromocriptine, sulpiride or their combination on free amino acids in the kidneys and the heart after acute and chronic treatment of rats were investigated, using an automatic LKB Amino Acid Analyzer. Bromocriptine at a single dose of 4 or 10 mg/kg (i.p.) did not affect the level of any amino acid; however, at a dose of 20 mg/kg it significantly elevated the content of taurine in the kidney from 7.00 +/- 0.30 to 9.70 +/- 0.1 and in the heart from 22.9 +/- 1.7 to 30 +/- 1.2 mumol/g wet tissue (P less than 0.05, N = 7). It also increased glutamic acid in the heart from 3 +/- 0.1 to 4.5 +/- 0.25 mumol/g wet tissue (P less than 0.05, N = 7). Chronic oral treatment of rats with bromocriptine (20 mg.kg-1.day-1) for 5 weeks significantly elevated the level of taurine in the kidney from 7.2 +/- 0.3 (control) to 11.1 +/- 0.90 and in the heart from 23.1 +/- 1.7 to 38.8 +/- 1.8 mumol/l g wet tissue. It also increased cardiac glutamic acid content from 3 +/- 0.1 to 4.8 +/- 0.24 mumol/g wet tissue (P less than 0.01, N = 7). Concurrent administration of sulpiride (20 mg/kg) significantly suppressed bromocriptine-induced increases in taurine and glutamic acid in both organs, suggesting an activation of D2 receptors by bromocriptine. Due to the similarities between bromocriptine and the affected amino acids in renal and cardiac actions, it is suggested that mobilization of taurine and glutamic acid may at least in part contribute towards bromocriptine-induced renal and cardiac actions.

Chemical and Biological Study of Flueggea virosa Native to Saudi Arabia

Flueggea virosa (Roxb. ex Willd.) Royle (Phyllanthaceae), also known as Chinese waterberry, is a shrub up to 4 m high growing wild in tropical Africa, Middle East, tropical Asia, Japan, Australia, and Polynesia and can also be grown domestically. It has many recorded uses in Chinese herbal medicine. The plant has been used for the treatment of fever, malaria, sexual dysfunction, pain, diabetes, epilepsy, snakebite, venereal disease, rheumatism, arrhythmia, rash, diarrhea, pneumonia, cough, hepatitis, and HIV-related illness, and as a contraceptive [1, 2]. The methanol and water extracts of the plant have been reported to possess a number of biological activities such as antiplasmodial, trypanocidal, and antiarrhythmic [3, 4]. Previous phytochemical studies of F. virosa showed the presence of triterpenoids [2], tannins, flavonoids, saponins [5, 7], resins, glycosides, glycerin carbohydrates, anthraquines, steroids [5], alkaloids [6, 8], cardiac glycosides [5, 6], and anthraquinones [6]. In our phytochemical investigation of this plant [9], a total of 14 compounds were isolated from the ethanolic extract of the aerial parts of F. virosa, collected from the Southern part of Saudi Arabia, in June 2000. The plant (air-dried crushed aerial parts, 1 kg) was macerated with 95% EtOH at room temperature overnight (1 L each 3). The dried crude EtOH extract (40 g) was dissolved in 0.1 N HCl (1 L; pH 1) and partitioned with n-hexane and n-BuOH (500 mL 3) successively. The n-BuOH fraction was subjected to flash column chromatography (CC) over silica gel to afford bergenin [white crystals, mp 236–238 C (1, 10 g)], menisdaurin [brown solid, mp 172–173 C (2, 1 g)] and amiroside [brown solid, mp 176–178 C (3, 25 mg)] [9, 10]. The defatted aqueous acidic fraction was basified with NH4OH (pH 11) and partitioned with EtOAc. The EtOAc fraction (3 g) was subjected to flash chromatography on silica gel with further purification using reverse phase CC over C-18 silica gel (MeCN–H2O, 9:1) to afford ent-phyllanthidine [yellow white crystals, mp 158–160 C (4, 30 mg)] [11], securinine [white powder, mp 140–142 C (5, 8 mg)], securinol [white powder, mp 136–137 C (6, 6 mg)], viroallosecurinine [dark yellow solid, mp 130–132 C (7, 40 mg)] [12], flavonoid rutin [yellow solid, mp 194–195 C (8, 40 mg)] [13], gallocatechin (9) and epi-gallocatechin [white solid, mp 188–190 C] (10, mixture, 12 mg) [14], 2,2 ,5,5 -tetrahydroxybiphenyl [white solid, mp 144–145 C (11, 12 mg)], ethylmanopyranoside [white solid, mp 154–156 C (12, 132 mg)], ethyl glucopyranoside [white powder, mp 163–164 C (13, 9 mg)] [9], and the triterpene precursor squalene [oil (14, 20 mg)] [15]. The identity of all the isolated compounds was confirmed by direct comparison with authentic samples, as well as their physical and spectral data (UV, IR, NMR and MS) with those published in the literature. This is the first report of the cyanogenetic glucosides menisdaurin (2) and amiroside (3) isolated from the genus Flueggea, as well as from the plant family Phyllanthaceae. They were previously reported from Ilex aquifolium and Guazuma ulmifolia [16].