ArticlePloS one2024
Inhibition of CFTR-mediated intestinal chloride secretion by nornidulin: Cellular mechanisms and anti-secretory efficacy in human intestinal epithelial cells and human colonoids.
Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Secretory diarrhea, a major global health concern, particularly among young children, is often characterized by excessive chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) channel. Nornidulin, a fungus-derived natural product from Aspergillus unguis, has previously been shown to inhibit cAMP-induced Cl- secretion in T84 cells (human intestinal cell lines). However, the cellular mechanism of nornidulin in inhibiting cAMP-induced Cl- secretion and its anti-secretory efficacy is still unknown especially in a human colonoid model, a preclinical model recapitulating intestinal physiology in humans. This research study aimed to examine the mechanism of nornidulin to inhibit cAMP-induced chloride secretion and assess its ability to reduce fluid secretion in both T84 cells and human colonoid models. Apical Cl- current analyses showed that nornidulin inhibited CFTR-mediated Cl- current in T84 cells with IC50 of ~1.5 μM. Nornidulin treatment had no effect on CFTR protein expression. Additionally, the inhibitory effects of nornidulin on CFTR-mediated chloride currents were unaffected by the presence of compounds that inhibit negative regulators of CFTR function, such as protein phosphatases, AMP-activated protein kinases, and phosphodiesterases. Interestingly, nornidulin suppressed the increase in intracellular cAMP levels caused by forskolin, an activator of adenylate cyclases, in T84 cells. Using human colonoid models, we found that nornidulin significantly suppressed the forskolin and cholera toxin-induced fluid secretion, indicating that nornidulin exerted an anti-secretory effect in human intestinal epithelia. Collectively, nornidulin represents a novel class of fungus-derived inhibitors of CFTR-mediated Cl- secretion, potentially making it a promising candidate for the development of anti-secretory treatments.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.