fractionation of a herbal antidiarrheal medicine reveals eugenol as an inhibitor of ca2+-activated cl？ channel tmem16a分馏的草药止泻的药显示丁香酚的抑制剂ca2 +激活cl tmem16a频道.pdfVIP

Fractionation of a Herbal Antidiarrheal Medicine Reveals Eugenol as an Inhibitor of Ca2+-Activated Cl2 Channel TMEM16A 1 1,2 1 2 1 1 Zhen Yao , Wan Namkung , Eun A. Ko , Jinhong Park , Lukmanee Tradtrantip , A. S. Verkman * 1 Departments of Medicine and Physiology, University of California San Francisco, San Francisco, California, United States of America, 2 Yonsei University, College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Incheon, Korea Abstract The Ca2+-activated Cl2 channel TMEM16A is involved in epithelial fluid secretion, smooth muscle contraction and neurosensory signaling. We identified a Thai herbal antidiarrheal formulation that inhibited TMEM16A Cl2 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 Cl2 conductance with single-site IC50,150 mM. Eugenol inhibition of TMEM16A in interstitial cells of Cajal produced strong inhibition of intestinal contraction in mouse ileal segments. TMEM16A Cl2 channel inhibition adds to the list of eugenol molecular targets and may account for some of its biological activities. Citation: Yao Z, Namkung W, Ko EA, Park J, Tradtrantip L, et al. (2012) Fractionation of a Herbal Antidiarrheal Medicine Reveals Eugenol as an Inhibitor of Ca2+- Activated Cl2 Channel TMEM16A. PLoS ONE 7(5): e38030. doi:10.1371/journal.pone.0038030 Editor: Steven Barnes, Dalhousie University, Canada Received January 31, 2012; Accepted April 30,