Molecular details of castor oil’s laxative effect
May 21, 2012 § Leave a comment
Castor oil has been suggested over the ages to loosen up the body’s plumbing or induce labor in overdue pregnant women (the ancient Egyptians apparently slurped castor oil). Now researchers have figured out how a molecule from one of the world’s oldest drugs triggers a signal transduction pathway in smooth muscle cells.
Castor oil comes from the seed of the flowering plant Ricinus communis. When someone swallows a spoonful of castor oil, the lipases in his or her intestines releases a hydroxylated fatty acid called ricinoleic acid. What ricinoleic acid actually does in the body has been an unsolved mystery.
But in a paper just out in the Proceedings of the National Academy of Sciences, a team led by Stefan Offermanns at the Max-Planck-Institute for Heart and Lung Research says it has figured out ricinoleic acid’s mechanism of action. The molecule activates the EP3 prostanoid receptor in smooth muscle.
Given castor oil’s long history as a laxative and labor inducer, one may wonder why it took so long for scientists to figure out how it works. Offermanns explains that when research activities to elucidate the mechanism of action for castor oil were at their height from the 1960s to 1980s, “methods were not available to perform non-biased searches. Also, most people expected the intestinal epithelium to be the site of action, and not the smooth muscle layer.”
With modern molecular methods, Offermanns and colleagues were able to screen for biologically active lipids, including ricinoleic acid, for cellular effects that looked like they were mediated by G-protein coupled receptors, which are heavily involved in signal-transduction cascades. When they noticed an effect in response to ricinoleic acid, they performed a unbiased screen using small interfering RNA against all known receptors and identified the EP3 prostanoid receptors.
The investigators went on to show that mice missing the EP3 receptors didn’t respond to castor oil’s laxative or uterine contraction effects. Offermanns and colleagues concluded that ricinoleic acid gets smooth muscles in the intestine and uterus contracting when it binds to EP3 prostanoid receptors. Offermann says the finding isn’t too surprising because there are structural similarities between ricinoleic acid and prostaglandin E2, which normally binds these receptors.
The investigators said in their paper, “This discovery provides the long-sought mechanism of action of one of the oldest drugs, which is still used in conventional, alternative, and folk medicine.” Offermann adds that knowing how castor oil works may promote its use as it is a safe and effective laxative.