Fractionation of a Herbal Antidiarrheal Medicine Reveals Eugenol as an Inhibitor of Ca.sup.2+-Activated Cl.sup.- Channel TMEM16A

The Ca.sup.2+ -activated Cl.sup.- 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.sup.- conductance. C18-reversed-phase HPLC fractionation of the herbal fo...

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Bibliographic Details
Published in:PloS one 2012-05, Vol.7 (5), p.e38030
Main Authors: Yao, Zhen, Namkung, Wan, Ko, Eun A, Park, Jinhong, Tradtrantip, Lukmanee, Verkman, A. S
Format: Article
Language:English
Subjects:
Gastrointestinal agents
High performance liquid chromatography
Phenols (Class of compounds)
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Summary:The Ca.sup.2+ -activated Cl.sup.- 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.sup.- 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.sup.- conductance with single-site IC.sub.50 ~150 [micro]M. Eugenol inhibition of TMEM16A in interstitial cells of Cajal produced strong inhibition of intestinal contraction in mouse ileal segments. TMEM16A Cl.sup.- channel inhibition adds to the list of eugenol molecular targets and may account for some of its biological activities.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0038030