The effect of a strongly basic alkaloidal fraction of Rhazya stricta, a traditional medicinal plant, on cytochrome P450-mediated metabolism of theophylline in mice.

The strongly basic alkaloidal fraction of the traditional medicinal plant Rhazya stricta (RS) was given orally to mice, in a single dose of 10 mg/kg (group 1) or, twice daily for 3 days at the same dose (group 2). A third group (control) received normal saline. Liver homogenates from all animals were used to assess the microsomal activity of cytochrome P450 and its isoforms as well as its catalytic activity (using theophylline as a substrate). RS alkaloidal fraction had no significant effect on the total amount of microsomal cytochrome P450, but it caused a significant increase in the cytochrome P450 isoforms CYPs 1A1 and 1A2. It also significantly increased the concentrations of some metabolites of theophylline. These results suggest that RS has the potential to interact with other drugs that are biotransformed by cytochrome P450, when given concomitantly with it.

Central nervous system activity of Leucas inflata Benth. in mice.

The analgesic activity of the methanol and acetone extracts of Leucas inflata L. (family Labiatae) was evaluated in mice using different experimental models. The effect of the two extracts on pentobarbitone-sleeping time, motor activity, sensorimotor coordination, carrageen induced inflammation, and brewer's yeast-induced pyrexia has also been investigated. The two crude extracts have been phytochemically analyzed and some constituents isolated and characterized. These included stigmasterols, a chromone and coumarins. Extracts of L. inflata L., given at single oral doses of 0.25, 0.5, 1.0 or 2.0 g/kg, significantly and dose-dependently, reduced formalin-induced pain, acetic acid induced abdominal constrictions and increased the reaction time in the hot-plate test. Both extracts caused significant and dose-related impairment in the sensorimotor control and ambulatory and total motor activity of treated mice. Both extracts exhibited anti-inflammatory action by reducing paw edema of treated mice. The extracts did not significantly affect the rectal temperature of normothermic mice. However, they were effective in preventing Brewers yeast induced pyrexia. It is concluded that the crude methanol and acetone extract of L. inflata has CNS depressant properties, manifested as antinociception and sedation. Both extracts have anti-inflammatory and antipyretic actions.

Some effects of Salvia aegyptiaca L. on the central nervous system in mice.

Salvia aegyptiaca L. is used for treating various unrelated conditions that include nervous disorders, dizziness, trembling, diarrhoea and piles. This work examines some effects of the crude acetone and methanol extracts of the plant given at single oral doses of 0.25, 0.5, 1 or 2 g/kg, on the central nervous system (CNS) in mice. The extracts were also tested for anti-inflammatory and antipyretic actions. Several models of nociception have been used to examine the analgesic effect of the extract. In treated mice, the extracts caused dose-related inhibition of acetic acid-induced abdominal constriction, and significantly reduced formalin-induced pain. Treatment with the extracts at doses of 0.5 and 1 g/kg significantly increased the reaction time in the hot-plate test. In treated mice both extracts caused significant and dose-related impairment of the sensorimotor control and motor activity. Treatment with both extracts did not significantly affect the rectal temperature of normothermic mice. The methanol extract (0.5 and 1.0 g/kg) did not affect the rectal temperature of hyperthermic mice, but the acetone extract was effective in significantly reducing the rectal temperature of hyperthermic mice, 0.5 and 1 h after administration of the extract at doses of 0.25-2 g/kg. It is concluded that the crude methanol and acetone extracts of S. aegyptiaca have CNS depressant properties, manifested as antinociception and sedation. Both extracts have some anti-inflammatory and antipyretic actions. On the whole, the acetone extract appeared to be slightly more effective than the methanol extract in this regard.

Effect of Rhazya stricta Decne on monoamine oxidase and cholinesterase activity and brain biogenic amine levels in rats.

The effect of treatment with the medicinal plant Rhayva stricta Decne, on monoamine oxidase (MAO) and cholinesterase activity, and on the concentration of brain biogenic amines was studied in rats. R. stricta extract, at doses of 0.2 and 0.5 g kg(-1), significantly (P < 0.05-0.01) increased the hepatic and cerebral activity of MAO by 36-127%. The higher doses used (2.0 and 8.0 g kg(-1)) produced smaller (10-26%) and statistically insignificant increases in MAO activity in liver and brain. Cholinesterase activity in blood, liver and brain was not significantly influenced by treatment with R. stricta. The concentrations of the measured biogenic amines (noradrenaline, adrenaline, 5-hydroxytryptamine and dopamine) were significantly lowered in rats treated with R. stricta. The observed increase in MAO activity may be responsible for the lowered biogenic amines levels and may, in part, be responsible for the pharmacological effects of R. stricta extract in rats.

Antioxidant action of extract of the traditional medicinal plant Rhazya stricta Decne. in rats.

The effects of a leaf extract of the traditional medicinal plant Rhazya stricta (0.25, 1.0 and 4.0 g/kg/day for 3 days) on reduced glutathione (GSH), lipid peroxidation (LP) and ascorbic acid (AA) concentrations in the liver and kidneys were studied in rats 24 h after the last dose. The plant extract, at a dose of 0.25 g/kg, did not significantly affect the concentrations of GSH, LP or AA in the liver or kidneys. At a dose of 1.0 g/kg, the plant extract significantly increased the GSH concentration in the liver, but did not affect the GSH concentration in the kidneys, or LP or AA in the liver or kidneys. The plant extract (4.0 g/kg) significantly increased the GSH and decreased LP peroxidation, but did not affect the AA concentrations in the liver and kidneys. It may be concluded that the R. stricta extract, at some of the doses used, has antioxidant actions in the rat.

Phytochemistry, pharmacology and toxicity of Rhazya stricta decne: a review.

Phytochemical, pharmacological and toxicological properties of the medicinal plant Rhazya stricta Decne. are reviewed. Several types of alkaloids and a few flavonoids have been isolated and their structures and stereochemistry characterized. However, in most cases the biological activity of these compounds has not been studied. Most of the pharmacological activity of the plant resides in its alkaloidal fractions which cause depression of the central nervous system and hypotension. Extracts of R. stricta appear to have low toxicity, although its use in pregnant women may be inadvisable.

Mechanism of the hypotensive action of Rhazya stricta leaf extract in rats.

The hypotensive action of Rhazya stricta lyophilized leaf extract was found to be partly caused by the electrolyte content of the extract, and partly caused by a strongly basic alkaloidal fraction (AF). AF (0.05-1.6 mg animal(-1)) caused a dose-dependent reduction in mean arterial blood pressure (MAP) of urethane-anaesthetized rat preparations. In naiuml;ve pithed rats, AF administration (0.5-2.0 mg animal(-1)) significantly increased MAP. In pithed or spinalized rats made normotensive by noradrenaline infusion, AF (0.25 mg animal(-1)) did not cause any significant changes. Direct intracerebroventricular injection of AF (0.1-0.4 mg) markedly and significantly reduced MAP. It is suggested that the hypotensive action of AF to be mediated by a central mechanism.

The effect of Rhazya stricta Decne, a traditional medicinal plant, on spontaneous and drug-induced alterations in activity of rats.

The effect of acute and chronic treatment of rats with a lyophilized extract of the leaves of the medicinal plant Rhazya stricta on total and ambulatory activity was studied. Given acutely at single oral doses of 1, 2, 4, and 8 g/kg, the extract produced dose-dependent decreases in total activity and ambulatory activity. Diazepam (20 mg/kg, orally) produced a decrease in rat activity comparable to that produced by a dose of 1 g/kg of the extract. When given daily at an oral dose of 2 g/kg for 21 consecutive days, the extract produced, on the last day of treatment, significant decrease in activity amounting to about 30% of control activity levels. Subcutaneous (SC) treatment of rats with caffeine (7.5, 15, and 30 mg/kg), dose-dependently and significantly increased total activity and ambulatory activity. These effects were dose-dependently attenuated when the extract was given concomitantly with caffeine at oral doses of 1, 2, and 4 mg/kg. Treatment of rats with zoxazolamine alone (10, 20, or 40 mg/kg, SC) or R. Stricta (1 and 4 g/kg orally) alone significantly decreased total and ambulatory activities. Concomitant treatment with zoxazolamine and R. Stricta decreased the rats activity to a greater degree than with either treatment given alone.

Effect of extract of Rhazya stricta, a traditional medicinal plant, on rat brain tribulin.

Rhazya stricta leaves, which have both antidepressant and sedative properties in animal models, are widely used in folk medicine in the Arabian peninsula. In this study, the effects of oral administration of leaf extracts on rat brain tribulin levels [endogenous monoamine oxidase (MAO) A and B inhibitory activity], were determined. In an acute study, low doses brought about an increase in MAO A inhibitory activity, while intermediate doses caused a significant reduction. The highest doses had no significant effects on activity. There were no significant effects on MAO B inhibitory activity at any dose. Subchronic administration (21 days) caused a significant decrease in MAO A inhibitory activity, most prominent at low dosage, and an increase in MAO B inhibitory activity. Acute intramuscular administration also resulted in a similar pattern. Such paradoxical effects were at least partially explained when different extracts of the leaves were used; a weakly basic chloroform fraction caused an increase in MAO A inhibitory activity, whereas butanol extracts brought about a decrease. These fractions had no significant effects on MAO B inhibitory activity. The findings show that Rhazya stricta leaves contain at least two different components that affect MAO inhibitory activity in opposite directions. It may be that the antidepressant and sedative actions of the plant are explicable in terms of these different components.

The effect of Rhazya stricta Decne, a traditional medicinal plant, on the forced swimming test in rats.

Immobility induced by forced swimming is well known as an animal model of depression. Using this paradigm, we have, in the present work, tested the possibility that the medicinal plant Rhazya stricta, which has previously been found to affect the monoamine oxidase inhibitory activity in rat brain, may have an antidepressant-like action. Rats were pretreated with various doses (0.025-6.4 g/kg) of the lyophilized extract of the plant leaves, or with desipramine (10, 20, and 40 mg/kg) and were subjected to the forced swimming test. The results indicated that the plant extract produced a biphasic (bell-shaped) effect on the immobility time. The lower doses (0.1, 0.2, and 0.4 g/kg) elicited a highly significant and inversely dose-dependent decrease in immobility time, and the higher doses (0.8, 1.6, and 6.4 g/kg) showed a dose-dependent decrease in immobility time. Under the same experimental conditions desipramine (20 and 40 mg/kg) produced dose-dependent significant decreases in immobility time. Following administration of R. stricta (6.4 g/kg) the immobility time recovered progressively with time, and 4 h after its administration the immobility time was about 70% of the control level (statistically insignificant). It is concluded that R. stricta extract [or component(s) thereof] may possess an antidepressant-like effect.

Some effects of Cassia italica on the central nervous system in mice.

This work examines some effects of the crude ethanolic extract of the medicinal plant Cassia italica, given at single oral doses of 0.25, 0.5 or 1 g kg-1, on the central nervous system in mice. Several models of nociception have been used to examine the analgesic effect of the extract. HPLC fingerprinting of the extract was performed to ensure uniformity of the extract material used. In treated mice, the extract caused dose-related inhibition of acetic acid-induced abdominal constriction, and in the formalin test of antinociception the extract reduced formalin-induced pain in the second (late) but not in the first (early) phase of the pain. Treatment with the extract at doses of 0.5 and 1 g kg-1 significantly increased the reaction time in the hot-plate and warm-water tail-flick tests. Naloxone was ineffective in antagonizing the analgesic effect of C. italica on tail-flick and abdominal constriction tests, possibly indicating that the effect occurs via non-opiate pathways. The C. italica extract caused slight dose-related impairment of motor control which was significant only at a dose of 1 g kg-1. Treatment at the three doses used did not affect the rectal temperature of normothermic mice, but was effective in significantly reducing the rectal temperature of hyperthermic rats, 0.5 and 1 h (but not 6 h) after administration of the extract at doses of 0.5 and 1 g kg-1. The extract also produced progressive diminution in the ambulatory and total activity of treated mice for up to 2 h after administration. It is concluded that the crude ethanolic extract of C. italica has CNS depressant properties, manifested as antinociception and sedation.

Effect of previous chloroquine intake on in vivo P. falciparum drug sensitivity.

Investigation of the in vivo response of P. falciparum malaria parasites to chloroquine was conducted during 1993/94 in Al-Ain District of Abu Dhabi Emirate, UAE. Sixty seven expatriates who developed falciparum malaria on their return from Pakistan, Oman and Sudan were recruited for the WHO in vivo tests. Of the 67 patients, eight were classified as having RII and RIII responses, while 59 remained aparasitaemic at the end of the seven-day WHO standard test. On continuation into the 28-day WHO extended test, a further 34 patients exhibited RI resistance. Resistance of parasites to chloroquine was confirmed by measurement of plasma chloroquine using High-Performance Liquid Chromatography. In all 67 patients, the level of chloroquine was well above the minimum therapeutic level. The outcome of the in vivo test in patients treated for the first time was significantly different from that in patients who were previously on chloroquine. Among patients treated for the first time, 36 out of 41 (88%) had a resistant response, whereas, among those previously on chloroquine only six out of 26 (23%) had a resistant response. The difference is probably due to the higher initial plasma level of chloroquine among patients who were previously on the drug. Curing more patients with higher plasma chloroquine implies that chloroquine shall continue to be useful, particularly if resistance is at the RI level. Appropriate higher therapeutic levels of chloroquine should be defined for such patients.

Neuromuscular and microvascular changes associated with chronic administration of an extract of Teucrium stocksianum in mice.

This work examines the effect on the weights of vital body organs, on blood biochemical variables, on neuromuscular coordination and on cerebral microcirculation of aqueous extracts of Teucrium stocksianum, given to mice in drinking water at concentrations of 2 and 4% for 56 days. The treatment caused progressive impairment of neuromuscular coordination, as evidenced by the time spent on the rota-rod. After photochemical challenge, the time for first observable platelet aggregation in arterioles was shorter than for the control group by 22 and 45% in the 2 and 4% T. stocksianum-treated groups, respectively. Platelet aggregation on the venular side was not affected by the treatment nor were microvascular diameters. Treatment with the plant extract produced no statistically significant effect on the plasma biochemical variables that are considered indices of liver and kidney function. Histologically, brains obtained from mice treated with T. stocksianum showed loss of cerebellar Purkinje cells. Although it is likely that the accelerated platelet aggregation might have contributed to an ischaemic effect which could, at least in part, have caused the cytotoxicological changes, this does not exclude the possibility of a direct cytotoxicological effect of the plant extract. Further pharmacological and toxicological investigations on Teucrium species seem warranted.

Some pharmacologic and toxicologic studies on Rhazya stricta decne in rats, mice and rabbits.

1. This work examines some in vivo and in vitro pharmacologic and toxicologic effects of extracts of Rhazya stricta, a medicinal plant in the United Arab Emirates. 2. R. stricta extracts at doses of 0.1-10 mg reduced the mean arterial blood pressure (MBP) of anesthetized rats in a dose-dependent manner. The depressor effect was partially sensitive to atropine (5 microM). Although the MBP was reduced by 50% by both doses of extracts, the normal electrocardiogram pattern and the heart rate remained unaltered. 3. Acute treatment of rats with the lyophilized extract at doses of 4 g/kg produced a significant rise in insulin concentration. In streptozotocin-diabetic rats loaded orally with glucose (1 g/kg), R. stricta at doses of 8 g/kg produced significant decreases in plasma glucose concentration at 0.5 and 1 h after treatment. 4. Chronic treatment of rats and mice for 28 days with the lyophilized extract of R. stricta did not affect the plasma glucose or insulin concentration or any of the hematological or biochemical indices measured. 5. The extracts of R. stricta (0.5-4 g/kg) dose-dependently decreased the gastrointestinal transit time in mice by 4-50%. 6. The butanolic extract of R. stricta (1 and 2 g/kg) significantly reduced the carrageenan-induced increase in raw paw edema 3 and 4 h after the extract administration. 7. The rectal temperatures of normothermic and pyrexic rats were reduced significantly 0.5 and 1 h after administration of butanolic R. stricta at doses of 1 and 2 g/kg. 8. The butanolic extract of R. stricta at doses of 1 and 2 g/kg significantly increased the reaction time on the hot plate 30 and 60 min after administration to rats. 9. At concentration < 0.05 mg/ml (bath concentration), lyophilized water and butanol extracts of R. stricta potentiated the twitch responses induced by indirect electrical stimulation in the rat phrenic nerve diaphragm preparation. The responses were inhibited by concentrations > 0.05 mg/ml. Neostigmine (2 x 10(-4)M) did not alter these effects of the extracts. 10. R. stricta extracts dose-dependently decreased the force of contraction and heart rate of the isolated rabbit heart. Atropine (1 x 10(-5)M) had no effect on the inhibitory activity of these extracts. The lyophilized water extract (> 10 mg) and butanol extract (> 5 mg) produced irreversible inhibition and disturbances in the force of contraction and heart rate.

Toxicological effects of Teucrium stocksianum after acute and chronic administration in rats.

Because of the widespread use of T. stocksianum (Boiss) in herbal medicine and reports of the toxicity of Teucrium chamaedrys to man, the effects of acute (2 and 4 g kg-1 single dose) and chronic (4% in lieu of drinking water for 48 days) administration of an aqueous extract of T. stocksianum has been studied in rats. After acute administration no change was found in reduced liver glutathione content, plasma total protein concentration or the enzyme activities of aminotransferase or gamma glutamyl transferase. After chronic administration, no change was noticed in the plasma concentrations of total protein, total bilirubin, creatinine, urea, glucose, triglycerides, calcium or phosphorus or the enzyme activities of aminotransferase, alanine aminotransferase, creatinine kinase, gamma glutamyl transferase or lactate dehydrogenase. There was no change in food or water intake or output of urine or faeces; the body weight of the treated animals was, however, slightly reduced. No change was observed in the weight of vital body tissues. Histological examination revealed occasional hepatic 'apoptosis' and cerebral neuronal loss in the cortex and hippocampus in treated animals; focal loss of Purkinje cells in the cerebellum was particularly noticed. The results did not indicate a major hepatotoxic effect of acute or chronic administration of T. stocksianum, unlike other Teucrium spp. We report a neurotoxic effect, however, which warrants monitoring of neurological function in people taking this plant.

Evaluation of the relaxant activity of some United Arab Emirates plants on intestinal smooth muscle.

Although medicinal plants are used as antispasmodic agents in folk medicine there have been no scientific studies of the phytochemical composition and usefulness of these plants for such treatment. Extracts of 23 plants used in the traditional medicine of the United Arab Emirates were tested for their effects on intestinal smooth muscle activity. Most of the plants tested caused stimulation followed by inhibition of the motility of the rabbit jejunum and guinea-pig ileum. The inhibitory effect of plants that had EC50 values < 1 mg was confirmed in-vivo using the gastrointestinal transit time test. These plants were phytochemically screened for their secondary constituents. The effect of Rhazya stricta was investigated, particularly in relation to acetylcholine effect. The results indicated the potential of some of the plants, especially Rhazya stricta, as a source of antispasmodic agents.

Anti-inflammatory, antipyretic, and analgesic effects of Lawsonia inermis L. (henna) in rats.

Crude ethanolic extract of Lawsonia inermis L. (0.25-2.0 g/kg) produced significant and dose-dependent anti-inflammatory, analgesic, and antipyretic effects in rats. The extract also produced significant increases in pentobarbitone-induced sleeping time. Using a liquid-liquid extraction procedure, the extract was fractionated into chloroform, butanol, and water fractions, and these were tested for the above activities. The butanol and chloroform fractions showed more potent anti-inflammatory, analgesic, and antipyretic effects than the crude extracts, while the aqueous extract showed significantly less effect. As compared with the other extracts, the butanolic extract (500 mg/kg) was the most effective in the analgesic test. From the chloroform extract, a pure compound was isolated and identified, using chromatographic and spectroscopic techniques, as 2-hydroxy-1,4-naphthaquinone (lawsone). The isolated compound was found to possess significant anti-inflammatory, analgesic, and antipyretic activity. It potentiated significantly the pentobarbitone-induced sleeping time. The anti-inflammatory effect of lawsone (500 mg/kg) was not significantly different from that of the reference drug phenylbutazone (100 mg/kg).

Central nervous system activity of Rhazya stricta (Decne) in mice.

1. The effects of orally administered aqueous lyophilized extract of the leaves of Rhazya stricta (2, 4 & 8 g/kg) on aspects of nervous system function were investigated in mice. 2. In three antinociceptive tests (hot plate, abdominal constriction, and warm water tail flick tests), the extract exhibited dose-dependent and significant antinociceptive activity. Naloxone was ineffective in antagonizing the analgesic effect of Rhazya stricta on tail-flick and abdominal constriction tests, possibly indicating that this effect occurs via non-opiate pathways. 3.Pretreatment of mice with the xenobiotic metabolizing enzymes inhibitor cimetidine (50 mg/kg) did not significantly alter the antinociceptive action of the extract, indicating that the effect is probably due to the parent compound(s) present in the extract and not to metabolites thereof. 4. Rhazya stricta produce dose-dependent sedation, decreased motor activity, and impaired motor control. Time spent on a rotarod treadmill was significantly decreased after treatment with the extract. 5. Rhazya stricta extract (8 g/kg) produced a degree of sedation comparable to that produced by diazepam (5-10 mg/kg), and also significantly increased the reaction time of the tail-flick test, an action which was not produced by diazepam. 6. Administration of R. stricta extract potentiated pentobarbitone sleeping time in a dose dependent manner. The extract did not significantly antagonize picrotoxin induced convulsions. The extract (4 and 8 g/kg) significantly decreased the rectal temperature of normothermic and hyperthermic mice. 7. Pretreatment with R. stricta extract (8 g/kg) completely prevented the occurrence of aggressive behaviour in male mice. 8. It is concluded that the crude extract of R. stricta has central nervous system depressant properties.

Phytochemical and antimicrobial screening of some plants used in saudi folk medicine.

Thirty-two plants species belonging to 22 families commonly used in Saudi folk medicine were subjected to phytochemical and antimicrobial screening. The results showed that sterols/triterpenes, flavonoids and tannins were the most common constituents. Volatile oils, volatile bases, coumarins, anthraquinones and cardiac glycosides were also detected. A variable range of antimicrobial activity was observed by the extracts and MIC's were determined wherever activity was noticed.