Sidaverin, a crystalline compound extracted from a polar fraction of Sida veronicaefolia (Lam), elicited oxytocin-like contractions in the non-gravid rat isolated uterus preparation with a concentration-response relationship. Equipotent concentrations of oxytocin and sidaverin, using matched responses, were approximately 0.16 U and 0.4 micrograms ml-1, respectively. Sidaverin-induced contractile response was atropine reversible. The concentration-response curves for sidaverin and oxytocin were parallel, and both responses were inhibited by the specific oxytocin antagonist, Atosiban, indicating possible involvement of oxytocin receptors in the action of sidaverin. There were potentiation of action of one drug to that of the other, irrespective of the order of administration and even after washing off the first before introducing the second drug. In the gravid uterus, sidaverin produced contractions in preparations from day 1 to day 6 or 7, caused relaxation in days 7-11, and elicited contractions in day 11 through term, the sensitivity of the preparations increasing exponentially toward term with strong sustained contractions. With the exception of days 7-11, when sidaverin antagonized oxytocin action, it potentiated action of oxytocin on the gravid uterus.
Measurement of rates of propulsion in the small intestine in control and experimental groups of male Sprague-Dawley rats (200-250 g) were carried out as a means of assessing antidiarrhoeal activity of aqueous extracts of the leaf of Psidium guajava (L.), using morphine as the standard drug of reference. Hyperpropulsion (diarrhoea) was induced by gavaging rats in a control group with Microlax, using phenol red mixed into it as a marker in the intestine, and the mean rate of the hyperpropulsion was determined. The normal rate of propulsion, defined as the percentage of the length of the ileum traversed by the front of the dye in 1 h after gavaging animals with a liquid paraffin-phenol red meal, was also determined in another control group. In experimental groups pretreated with enteral administration of either morphine or aqueous extracts, 1 h before the challenge with Microlax, the percentage inhibition to the hyperpropulsive rate (antidiarrhoeal activity) was calculated. Both morphine and the extracts produced a dose-response relationship in their antidiarrhoeal effects. A dose of 0.2 ml/kg fresh leaf extract produced 65% inhibition of propulsion. This dose is equiactive with 0.2 mg/kg of morphine sulphate. The antidiarrhoeal action of the extract may be due, in part, to the inhibition of the increased watery secretions that occur commonly in all acute diarrhoeal diseases and cholera.
The electrically stimulated guinea-pig ileum and spontaneously contracting guinea-pig ileum preparations were employed in studies on the effects of an alcoholic extract and two flavonoid compounds, quercetin and quercetin-3-arabinoside, extracted from the leaves of Psidium guajava. The extract showed a morphine-like inhibition of acetylcholine release in the coaxially stimulated ileum, together with an initial increase in muscular tone, followed by a gradual decrease. The morphine-like inhibition was found to be due to quercetin, starting at concentrations of 1.6 micrograms/ml. The glycoside did not show any such action at concentrations of up to 1.28 mg/ml. The extract inhibited spontaneous contractions in the unstimulated ileum with a concentration-response relationship.
Studies were carried out on the suppression of both exploratory and spontaneous locomotor activities in the mouse by a non-polar fraction from a methanol extract of the dried leaves of Psidium guajava. Shortly after intraperitoneal administration of this fraction, typical narcotic-like effects were observed, including catalepsy, analgesia, Straub tail, shallow respiratory movements and exophthalmos. The dose for 90% suppression of exploratory activity was between 3.3 and 6.6 mg/kg intraperitoneally and the onset of action was 6-8 min. The duration of activity was dose-dependent and, for a dose of 13.2 mg/kg given intraperitoneally, it was found to be more than 6 h. Qualitatively similar results on exploratory activity were obtained when the extract was administered orally. Doses of 3.3-6.6 mg/kg i.p. depressed spontaneous locomotor activity and tunnel running was curtailed. Higher doses abolished the spontaneous locomotor reflex action. A flavonoid compound or compounds appear to account for the activity seen.