ArticlePloS one2014
Identification of resveratrol oligomers as inhibitors of cystic fibrosis transmembrane conductance regulator by high-throughput screening of natural products from chinese medicinal plants.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Rhinorrhea and increased chloride secretion through the CFTR chloride channel-a systematic review.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2023Pooled it
- Characterization of Some Stilbenoids Extracted from Two Cultivars of Lambrusco-Molecules (Basel, Switzerland) · 2023Article
- Comprehensive Analysis of Chemical Structures That Have Been Tested as CFTR Activating Substances in a Publicly Available Database CandActCFTR.Frontiers in pharmacology · 2021Article
- Creating and screening natural product libraries.Natural product reports · 2020Review
- Discovery of Clinically Approved Agents That Promote Suppression of Cystic Fibrosis Transmembrane Conductance Regulator Nonsense Mutations.American journal of respiratory and critical care medicine · 2016Article
- Effects of ε-viniferin, a dehydrodimer of resveratrol, on transepithelial active ion transport and ion permeability in the rat small and large intestinal mucosa.Physiological reports · 2016Article
- Natural Compounds as Therapeutic Agents in the Treatment Cystic Fibrosis.Journal of genetic syndromes & gene therapy · 2016Article
- Role of Quercetin in Modulating Chloride Transport in the Intestine.Frontiers in physiology · 2016Article
- Evidence against resveratrol as a viable therapy for the rescue of defective ΔF508 CFTR.Biochimica et biophysica acta · 2015Article
- Article
- Modulation of Chloride Channel Functions by the Plant Lignan Compounds Kobusin and Eudesmin.Frontiers in plant science · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibitors of cystic fibrosis transmembrane conductance regulator (CFTR) have been widely used for characterizing CFTR function in epithelial fluid transport and in diseases such as secretory diarrhea, polycystic kidney disease and cystic fibrosis. Few small molecule CFTR inhibitors have been discovered so far from combinatorial compound library. In the present study, we used a high throughput screening (HTS)-based natural product discovery strategy to identify new CFTR inhibitors from Chinese medicinal herbs. By screening 40,000 small molecule fractions from 500 herbal plants, we identified 42 positive fractions from 5 herbs and isolated two compounds that inhibited CFTR conductance from Chinese wild grapevine (Vitis amurensis Rupr). Mass spectrometry (MS) and nuclear magnetic resonance (NMR) studies determined the two active compounds as trans-ε-viniferin (TV) and r-2-viniferin (RV), respectively. Both compounds dose-dependently blocked CFTR-mediated iodide influx with IC50 around 20 μM. Further analysis by excised inside-out patch-clamp indicated strong inhibition of protein kinase A (PKA)-activated CFTR chloride currents by TV and RV. In ex vivo studies, TV and RV inhibited CFTR-mediated short-circuit Cl- currents in isolated rat colonic mucosa in a dose-dependent manner. In a closed-loop mouse model, intraluminal applications of TV (2.5 μg) and RV (4.5 μg) significantly reduced cholera toxin-induced intestinal fluid secretion. The present study identified two resveratrol oligomers as new CFTR inhibitors and validates our high-throughput screening method for discovery of bioactive compounds from natural products with complex chemical ingredients such as herbal plants.
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