Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea

Wan Namkung, Jay R. Thiagarajah, Puay Wah Phuan, A. S. Verkman

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

TMEM16A was found recently to be a calcium-activated Cl- channel (CaCC). CaCCs perform important functions in cell physiology, including regulation of epithelial secretion, cardiac and neuronal excitability, and smooth muscle contraction. CaCC modulators are of potential utility for treatment of hypertension, diarrhea, and cystic fibrosis. Screening of drug and natural product collections identified tannic acid as an inhibitor of TMEM16A, with IC50 ∼ 6 μM and ∼100% inhibition at higher concentrations. Tannic acid inhibited CaCCs in multiple cell types but did not affect CFTR Cl- channels. Structure-activity analysis indicated the requirement of gallic or digallic acid substituents on a macromolecular scaffold (gallotannins), as are present in green tea and red wine. Other polyphenolic components of teas and wines, including epicatechin, catechin, and malvidin-3-glucoside, poorly inhibited CaCCs. Remarkably, a 1000-fold dilution of red wine and 100-fold dilution of green tea inhibited CaCCs by >50%. Tannic acid, red wine, and green tea inhibited arterial smooth muscle contraction and intestinal Cl- secretion. Gallotannins are thus potent CaCC inhibitors whose biological activity provides a potential molecular basis for the cardioprotective and antisecretory benefits of red wine and green tea.

Original languageEnglish
Pages (from-to)4178-4186
Number of pages9
JournalFASEB Journal
Volume24
Issue number11
DOIs
Publication statusPublished - 2010 Nov 1

Fingerprint

Hydrolyzable Tannins
Wine
Insurance Benefits
Tea
Health
Tannins
Catechin
Muscle Contraction
Calcium
lissamine rhodamine B
Dilution
Smooth Muscle
Muscle
Intestinal Secretions
Cell Physiological Phenomena
Gallic Acid
Preclinical Drug Evaluations
Physiology
Bioactivity
Biological Products

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology
  • Medicine(all)

Cite this

Namkung, Wan ; Thiagarajah, Jay R. ; Phuan, Puay Wah ; Verkman, A. S. / Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. In: FASEB Journal. 2010 ; Vol. 24, No. 11. pp. 4178-4186.
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Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. / Namkung, Wan; Thiagarajah, Jay R.; Phuan, Puay Wah; Verkman, A. S.

In: FASEB Journal, Vol. 24, No. 11, 01.11.2010, p. 4178-4186.

Research output: Contribution to journalArticle

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