Castor oil induces laxation and uterus contraction via ricinoleic acid activating prostaglandin EP ₃ receptors

Abstract

Castor oil is one of the oldest drugs. When given orally, it has a laxative effect and induces labor in pregnant females. The effects of castor oil are mediated by ricinoleic acid, a hydroxylated fatty acid released from castor oil by intestinal lipases. Despite the wide-spread use of castor oil in conventional and folk medicine, the molecular mechanism by which ricinoleic acid acts remains unknown. Here we show that the EP 3 prostanoid receptor is specifically activated by ricinoleic acid and that it mediates the pharmacological effects of castor oil. In mice lacking EP 3 receptors, the laxative effect and the uterus contraction induced via ricinoleic acid are absent. Although a conditional deletion of the EP 3 receptor gene in intestinal epithelial cells did not affect castor oil-induced diarrhea, mice lacking EP 3 receptors only in smooth-muscle cells were unresponsive to this drug. Thus, the castor oil metabolite ricinoleic acid activates intestinal and uterine smooth-muscle cells via EP 3 prostanoid receptors. These findings identify the cellular and molecular mechanism underlying the pharmacological effects of castor oil and indicate a role of the EP 3 receptor as a target to induce laxative effects.G-protein coupled receptor | peristalsis | Ricinus communis | PGE 2

Evaluation of Punica granatum Peels Extracts and its Phenolic, Alkaloid and Terpenoid Constituents Against Chemically Induced Diarrhoea in Rats

“…These results are in agreement with Ramakrishna et al (1994), Qnais et al (2007) and Sorin et al (2012) who confirmed delay castor oil-induced diarrhoea as a result to inhibition of prostaglandin biosynthesis.…”

Evaluation of the anti-diarrheal activity of the aqueous stem extract of Lantana camara Linn (Verbenaceae) in mice

“…Castor oil produces diarrhoea due to its active metabolite, a ricinoleic acid which is liberated by the action of lipases in the upper part of the small intestine [34]. It mediates its action by binding to EP3 prostanoid receptors on smooth muscle cells [35] and facilitates the accumulation of fluid in the intestine by inhibiting absorption and enhancing secretion of fluid and electrolytes [36]. Furthermore, this metabolite also alters the motility of GI smooth muscles [37].…”

Evaluation of the Antidiarrhoeal and Antidiabetic Activities of the Leaf Aqueous Extract of Syzygium cordatum Hoscht. ex C.Krauss (Mytraceae) in Rodents

“…Castor oil, an irritant laxative, is thought to produce diarrhoea by being hydrolysed in the upper small intestine to ricinoleic acid which exerts its effects by irritating the mucosa of the gastrointestinal tract, resulting in an increase in intestinal motility (Altman, 2001 ). Fwthermore, ricinoleic acid has been shown to diminish the permeability of sodiun and chloride ions and also stimulate the release of prostaglandin, known to cause diarrhoea (Tunaru et al, 2012;Zavala et al, 1998). In addition, the works of Capasso et al (1994) and Mascolo et al (1994), on the effect of NG-nitro-L-arginine methyl ester, an inhibitor of Nitric Oxide (NO) synthase, on the dissociation of castor oil-induced diarrhoea and mucosal injwy inrat, showed that nitric oxide may mediate castor oil-induced diarrhoea.…”