Fractionation of a Herbal Antidiarrheal Medicine Reveals Eugenol as an Inhibitor of Ca2+-Activated Cl− Channel TMEM16A

• Published in: PloS one Vol. 7; no. 5; p. e38030
• Main Authors: Yao, Zhen, Namkung, Wan, Ko, Eun A., Park, Jinhong, Tradtrantip, Lukmanee, Verkman, A. S.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 30.05.2012; Public Library of Science (PLoS)
• Subjects: Analgesics - chemistry; Analgesics - pharmacology; Anoctamin-1; Antidiarrheals - chemistry; Antidiarrheals - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biology; Calcium; Cell growth; Cell Line; Chloride Channels - antagonists & inhibitors; Chromatography; Conductance; Cystic fibrosis; Eugenol; Eugenol - analysis; Eugenol - pharmacology; Fractionation; Herbal medicine; High-performance liquid chromatography; Humans; Inhibition; Interstitial cells; Interstitial cells of Cajal; Intestine; Liquid chromatography; Medicine; Muscle contraction; Muscles; Neoplasm Proteins - antagonists & inhibitors; Oils & fats; Pain; Pharmaceutical sciences; Pharmacy; Physiology; Plant Extracts - chemistry; Plant Extracts - pharmacology; Resistance; Rodents; Signaling; Smooth muscle; Structure-Activity Relationship; Tumors; United States > US; San Francisco California; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0038030

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.