Fractionation of a Herbal Antidiarrheal Medicine Reveals Eugenol as an Inhibitor of Ca(2+)-Activated Cl(−) Channel TMEM16A

The Ca(2+)-activated Cl(−) channel TMEM16A is involved in epithelial fluid secretion, smooth muscle contraction and neurosensory signaling. We identified a Thai herbal antidiarrheal formulation that inhibited TMEM16A Cl(−) conductance. C18-reversed-phase HPLC fractionation of the herbal formulation revealed >98% of TMEM16A inhibition activity in one out of approximately 20 distinct peaks. The purified, active compound was identified as eugenol (4-allyl-2-methoxyphenol), the major component of clove oil. Eugenol fully inhibited TMEM16A Cl(−) conductance with single-site IC(50)∼150 µM. Eugenol inhibition of TMEM16A in interstitial cells of Cajal produced strong inhibition of intestinal contraction in mouse ileal segments. TMEM16A Cl(−) channel inhibition adds to the list of eugenol molecular targets and may account for some of its biological activities.