Fractionation of a herbal antidiarrheal medicine reveals eugenol as an inhibitor of Ca2+-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.
Department of Medicine and Physiology, University of California San Francisco, San Francisco, California, United States of America.
Zhen
Z
Yao
Wan
W
Namkung
Eun A
EA
Ko
Jinhong
J
Park
Lukmanee
L
Tradtrantip
A S
AS
Verkman
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000075369:Anoctamin-1; D000930:Antidiarrheals / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D005054:Eugenol / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C476213:ANO1 protein, human; D000700:Analgesics; D000075369:Anoctamin-1; D000930:Antidiarrheals; D000970:Antineoplastic Agents; D018118:Chloride Channels; D009363:Neoplasm Proteins; D010936:Plant Extracts; D005054:Eugenol