UTERINE AND GASTROINTESTINAL TRACT RESPONSES TO METHANOLIC EXTRACT OF CROTON PENDULIFLORUS IN LABORATORY MAMMALS

Abstract

Croton penduliflorus of the family Euphorbiaceae is an important medicinal plant in Southern Nigeria. It has been used extensively as a remedy for several stomach complaints. The plant is also known traditionally to be used as abortifacient agent. The present study was undertaken to evaluate some of these claims. The experiments which were both in-vitro and in-vivo were carried out on mice, rats and guinea pigs. The in-vivo studies included the effects of methanolic extract of Croton penduliflorus (MECP) on acute toxicity test in mice. basal and stimulated gastric acid secretion (GAS) in rats, and gastrointestinal motility in mice. The other investigation into the effect of MECP on guinea pig ileum (GPI) and uterine contractions in rats were in-vitro. The plant's seeds were ground using laboratory pestle and mortar. Two extracts of petroleum ether and methanol were prepared from the ground sample using soxhlet apparatus. Column and thin layer chromatographic separation of the extract gave eight precipitates. Toxicity of the extract in mice was tested using conventional method. The effects of MECP, column fractions and histamine on gastric acid secretion were investigated in rats. In another experiment in rats, the possibility of drug mechanism of action between MECP and histamine on GAS was assessed. Four groups of mice were used to study in-vivo intestinal transit of charcoal using MECP, normal saline, carbachol and atropine. These drugs were given intraperitoneally prior to oral administration of charcoal in tragacanth meal. The toxicity test gave an intraperitoneal LD50 of 891 mg/kg body weight of mice. On the gastric acid secretion, the extract stimulated group of rats secreted significantly more acid than their mean basal acid secretory values at doses of 10⁴ and 10³g/ml (P<0.05). However, there was no significant change in GAS with a dose of 10⁻⁵ g/ml extract compared with the mean basal acid secretion (P>0.05). There was also a significant reduction in histamine-induced GAS when extract was injected before histamine (P<0.05). The study on intestinal transit of charcoal in mice showed significant reduction in the intestinal transit of charcoal in extract treated mice (P<0.05) giving a peristaltic index of 1.31 ± 0.88 compared with control that gave 51.90±10.32. In the in-vitro studies, responses of guinea pig ileum (GPI) and isolated rat uterus strip (IRUS) preparations to extract were dose- dependent. The contractile responses of deal smooth muscle strips to extract were inhibited in a dose-related fashion by promethazine (a H₁-receptor antagonist) but not by atropine (a muscarinic receptor blacker). There was also contractile response of GPI strip to fraction; Cf₆ with melting point 2100ᵒC. In the IRUS study, the extract-induced increase in frequency of uterine contractions were not affected by oxytocin but were significantly reduced by indomethacin (an inhibitor of prostaglandin synthesis). However, none of the different Fractions of the extract showed contractile effect on the IRUS preparation. The results showed that the extract possesses contractile effect on both the GPI and IRUS preparations. The effect on rat uterus appears to be independent of oxytocin mediation, while that on ileal smooth muscle seems to be involved with H₁-receptor interaction. The gastric acid secretory effect is manifested at high doses which are relatively below the doses required for their contractile activity. The study in mice showed that the extract appears capable of reducing gastric emptying and thus preventing rapid evacuation of the stomach.