Bioactivity-guided fractionation of an antidiarrheal Chinese herb Rhodiola kirilowii (Regel) Maxim reveals (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate as inhibitors of cystic fibrosis transmembrane conductance regulator

PloS One
Lei ChenHong Yang

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is the principal apical route for transepithelial fluid transport induced by enterotoxin. Inhibition of CFTR has been confirmed as a pharmaceutical approach for the treatment of secretory diarrhea. Many traditional Chinese herbal medicines, like Rhodiola kirilowii (Regel) Maxim, have long been used for the treatment of secretory diarrhea. However, the active ingredients responsible for their therapeutic effectiveness remain unknown. The purpose of this study is to identify CFTR inhibitors from Rhodiola kirilowii (Regel) Maxim via bioactivity-directed isolation strategy. We first identified fractions of Rhodiola kirilowii (Regel) Maxim that inhibited CFTR Cl- channel activity. Further bioactivity-directed fractionation led to the identification of (-)-epigallocatechin-3-gallate (EGCG) as CFTR Cl- channel inhibitor. Analysis of 5 commercially available EGCG analogs including (+)-catechins (C), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin-3-gallate (ECG) and EGCG revealed that ECG also had CFTR inhibitory activity. EGCG dose-dependently and reversibly inhibited CFTR Cl- channel activity in transfected FRT cells with an IC50 value around 100 μM. In ex v...Continue Reading

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Citations

May 15, 2015·Expert Opinion on Therapeutic Patents·Hong Yang, Tonghui Ma
Jul 30, 2019·Pharmaceutical Biology·Zoltán Péter ZomborszkiWieland Peschel
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Dec 10, 2016·Frontiers in Physiology·Bo YuHong Yang
Mar 5, 2019·Metabolomics : Official Journal of the Metabolomic Society·Rafael Teixeira FreireJoëlle Quetin-Leclercq
Jul 27, 2021·Biochemistry Research International·Alexander M ZakharenkoKirill S Golokhvast

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Methods Mentioned

BETA
fluorescence assay
column chromatography

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