Abdulrahman M. Ageel

Evaluation of some Pharmacological, Microbiological and Physical Properties of Zizyphus spina-christi

AbstractZizyphus spina-christi is a commonly available plant used by Saudi folk medicine practitioners for various purposes. The experimental testing of these claimed properties in animals, using the ethanolic extract of the leaves, showed that it has a considerable anti-inflammatory and moderate antipyretic activities. It also inhibited the growth of Bacillus subtilis. However, no analgesic or diuretic activity could be demonstrated. The aqueous extract of the leaves exhibited surface activity with critical micelle concentration found at 0.25% w/v concentration.

Evaluation of the antiinflammatory activity of sodium valproate in rats and mice

1. Treatment of rats with sodium valproate (100, 200 and 400 mg/kg i.p.) reduced the paw oedema induced by carrageenan by 36, 15 and 48%, respectively, within 3 h . 2. The effect produced by the higher dose (400 mg/kg) was equivalent to that produced by indomethacin (100 mg/kg). At 100 and 400 mg/kg, sodium valproate decreased the granuloma formation by a significant level. Similar doses of sodium valproate did not affect the rectal temperature in yeast-fevered mice, except with a dose of 200 mg/kg, which showed a significant decrease at 180 and 240 min posttreatment. 3. In comparison, sodium salicylate reduced the hyperthermia very significantly throughout the study period. 4. In normothermic mice, the rectal temperature changed only with a 400 mg/kg dose, but did not respond to lower SV doses. 5. The results indicate that sodium valproate, useful clinically as an epileptic drug, may have a potential therapeutic use as a mild antiinflammatory agent.

Pharmacological actions of the leaves of Solenostemma argel (Hayne): Spasmolytic and uterine relaxant activities

AbstractThe effects of the chloroform-methanol (CM) (1:IV/V) and the chloroform (C) extracts of Solenostemma argel leaves were examined on the spontaneously contracting rabbit jejunum and rat uterus. CM (400 μg/ml) produced a biphasic effect on the rabbit jejunum: an initial reversible inhibition followed by delayed and sustained inhibition. The inhibitions were not antagonized by haloperidol, propranolol or guanethidine. MC also suppressed the activity of the uterus and the effect was not antagonized by cimetidine, haloperidol, or propranolol. Furthermore, MC exhibited a local anaesthetic activity when tested on the foot withdrawal reflex of the frog. The C extract stimulated the uterus. This effect was antagonized by atropine or cyproheptadine. It was concluded that the inhibitory activity may be due to presence of local anaesthetic components whereas the stimulant effect may be due to activation of muscarinic and/or serotonergic uterine receptors.

Effect of praziquantel and oxamniquine on prostacyclin synthesis by the rat arterial and myometrial tissues

1. The influence of the two antischistosomal drugs (+/-) praziquantel and (+/-) oxamniquine on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium in vitro was investigated using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with praziquantel (64-512 microM) or oxamniquine (36-288 microM) for 30 min at 37 degrees C significantly inhibited basal PGI2 synthesis in a concentration-dependent manner (P less than 0.005, n = 5-6). 3. Both drugs failed to inhibit PGI2 synthesis in presence of exogenous arachidonic acid (AA) (16.6 microM). 4. Furthermore, they did not antagonize AA (4 nmol kg-1)-induced hypotension in urethane-anaesthetized rats. Thus, the drugs seemed to act via inhibition of phospholipase A2 enzyme (PLA2). 5. The highly lipophilic drugs may interact with membrane phospholipids resulting in prevention of interaction between the substrates and the enzymes active site.

Influence of diethylcarbamazine and mefloquine on PGI2 synthesis by the rat thoracic aorta and myometrial tissues

1. The influence of the antifilarial drug diethylcarbamazine citrate (D) and DL-erythro mefloquine hydrochloride (Mf) on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium was investigated in vitro using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with D (25.5-204 microM) or Mf (24-192 microM) for 30 min at 37 degrees C significantly inhibited PGI2 synthesis in a concentration-dependent manner. 3. D exhibited its inhibitory effect even in presence of exogenous arachidonic acid (AA) (16.6 microM) whereas Mf lost its inhibitory effect in presence of AA. 4. Pretreatment of urethane-anaesthetized rats with D (32 mumol kg-1) but not Mf (7.5 mumol kg-1) for 30 min significantly antagonized AA (4 nmol kg-1)-induced hypotension. 5. Furthermore, D (0.25-0.5 microM) antagonized AA-induced aggregation in rabbit platelet-rich plasma without affecting that of ADP. 6. D seemed to interfere with the action of the PG endoperoxide synthase (PG cyclooxygenase) whereas Mf seemed to interfere with the action of phospholipase A2 (PLA2) enzyme. 7. D may have exerted its effect via release of toxic O2 radicals whereas Mf effect may have been due to an interaction with PLA2 substrate phospholipids. 8. The demonstrated inherent property of these two drugs to inhibit the synthesis of the potent vasodilator, platelet antiaggregatory, anticonvulsant and antiinflammatory mediator PGI2 may partly contribute towards better understanding of the biochemical mechanisms that underly some of the previously known but poorly understood actions of these drugs.

The Hypoglycaemic Effect of Saudin

AbstractSaudin (80 mg/kg p.o.) caused marked hypoglycaemic effects in fasted mice. At a dose of 40 mg/kg i.p., saudin exerted hypoglycaemic effect in non-alloxanized rather than in alloxanized fasted mice. In rats, saudin (40 mg/kg i.p.) was found to produce a hypoglycaemic effect in fed but not fasted non-alloxanized animals. The blood glucose level of alloxanized rats remained unchanged. The hypoglycaemic effect of saudin was associated with a significant decrease in the plasma insulin activity in rats. Saudin was also found to inhibit insulin release by isolated perfused islets of Langerhans. Saudins hypoglycaemic effect may involve mechanisms not related to insulin secretion.

Effect of taurine on arterial, uterine and cardiac PGI2 and TXA2 synthesis in the rat

The influence of taurine (in drinking water for 6 weeks) on PGI2 and TXA2 synthesis by some female rat organs was investigated using radioimmunoassay and platelet antiaggregatory bioassay. Taurine 100 and 200 mg/kg/day increased aortic PGI2 release from 0.59 +/- 0.04 (control) to 0.85 +/- 0.05 and 1.01 +/- 0.06 ng/mg, respectively and that by the myometrium from 0.24 +/- 0.02 (control) to 0.38 +/- 0.01 and 0.50 +/- 0.04 ng/mg wet tissue, respectively (P less than 0.05, n = 6). It did not affect PGI2 and TXA2 production in the heart or TXA2 in the aorta. Taurine 200 mg/kg depressed uterine TXA2 synthesis from 148.6 +/- 9.8 (control) to 85.4 +/- 6.8 pg/mg (P less than 0.05, n = 6). Furthermore taurine 0.4 and 0.8 mM in vitro stimulated PGI2 release by the myometrial and aortic tissues from pregnant rats. The stimulant effect of taurine on PGI2 may be related to its antioxidant effect whereas its inhibitory effect on uterine TXA2 may result from direction of synthesis towards PGI2. It is concluded that endogenous taurine may participate in regulation of PGs synthesis and that prostanoids may contribute to its known actions. On broad basis, taurine-induced release of PGI2 may prove of potential value in those ailments characterised by deficiency in PGI2 release.

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 tea and coffee beverages on prostacyclin synthesis by the rat aorta

Influences of 2.5 and 5% (w/v) aqueous tea and coffee beverages administered ad lib. to rats for two weeks on PGI2 synthesis by the rat thoracic aorta in vitro were investigated using a rat platelet antiaggregatory bioassay and HPLC methods. The 2.5% beverages did not affect PGI2 synthesis; however, the 5% beverages significantly decreased PGI2 synthesis. The observed decreases were significantly abolished in presence of exogenous arachidonic acid suggesting a beverage-induced inhibition of precursor release. The ability of the beverages to inhibit PGI2 synthesis may partly contribute towards better understanding of the biochemical mechanisms underlying some of the beverages-induced 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.