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Resveratrol Dimer trans-ε-viniferin Prevents Rotaviral Diarrhea in Mice by Inhibition of the Intestinal Calcium-Activated Chloride Channel

Resveratrol Dimer trans-ε-viniferin Prevents Rotaviral Diarrhea in Mice by Inhibition of the Intestinal Calcium-Activated Chloride Channel

Bo Yu, Yu Jiang, Bo Zhang, Hong Yang, Tonghui Ma

Pharmacol Res. 2018 Mar;129:453-461.

PMID: 29155014

Abstract:

We previously identified, by a natural-product screen, resveratrol oligomers as inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Here, we report the resveratrol dimer trans-ε-viniferin (TV) and tetramer r-2-viniferin (RV) as inhibitors of the intestinal calcium-activated chloride channel (CaCC) and demonstrate their antisecretory efficacy in a neonatal mouse model of rotaviral diarrhea. Short-circuit measurements show inhibition of CaCC current in the human colonic cell line HT-29 by TV and RV with IC50∼1 and 20μM, respectively. TV primarily inhibited the physiologically relevant, long-term CaCC current following agonist stimulation, without effect on cytoplasmic Ca2+ signaling. TV and RV inhibited short-circuit current in mouse colon as well. In a neonatal mouse model of rotaviral secretory diarrhea produced by oral inoculation with rotavirus, 2μg TV or 11μg RV inhibited secretory diarrhea by >50%, without effect on the rotaviral infection. Our results support the antisecretory efficacy of non-toxic, natural-product resveratrol oligomers for diarrheas produced by CaCC activation. Because these compounds also inhibit the CFTR chloride channel, they may be useful for antisecretory therapy of a wide range of diarrheas.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP62218080	ε-Viniferin		62218-08-0	Price

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