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Abstract Title:

Phloretin, An Apple Polyphenol, Inhibits Pathogen-Induced Mucin Overproduction.

Abstract Source:

Mol Nutr Food Res. 2020 Nov 20:e2000658. Epub 2020 Nov 20. PMID: 33216464

Abstract Author(s):

Rahel L Birru, Kiflai Bein, Heather Wells, Natalya Bondarchuk, Aaron Barchowsky, Y Peter Di, George D Leikauf

Article Affiliation:

Rahel L Birru

Abstract:

SCOPE: Bacterial infection induces mucus overproduction, contributing to acute exacerbations and lung function decline in chronic respiratory diseases. A diet enriched in apples may provide protection from pulmonary disease development and progression. We examined whether phloretin, an apple polyphenol, inhibits mucus synthesis and secretion induced by the predominant bacteria associated with chronic respiratory diseases.

METHODS AND RESULTS: We analyzed expression of the mucus constituent mucin 5AC (MUC5AC) in FVB/NJ mice and NCI-H292 epithelial cells. Nontypeable Haemophilus influenzae (NTHi)-infected mice developed increased MUC5AC mRNA, which a diet containing phloretin inhibited. In NCI-H292 cells, NTHi, Moraxella catarrhalis, Streptococcus pneumoniae, and Pseudomonas aeruginosa increased MUC5AC mRNA, which phloretin inhibited. Phloretin also diminished NTHi-induced MUC5AC protein secretion. NTHi-induced increased MUC5AC required toll-like receptor 4 (TLR4) and NADH oxidase 4 (NOX4) signaling and subsequent activation of the epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) pathway. Phloretin inhibited NTHi-induced TLR4/NOX4 and EGFR/MAPK signaling, thereby preventing increased MUC5AC mRNA. EGFR activation can also result from increased EGFR ligand synthesis and subsequent ligand activation by matrix metalloproteinases (MMPs). In NCI-H292 cells, NTHi increased EGFR ligand and MMP1 and MMP13 mRNA, which phloretin inhibited.

CONCLUSIONS: In summary, phloretin is a promising therapeutic candidate for preventing bacterial-induced mucus overproduction. This article is protected by copyright. All rights reserved.

Study Type : In Vitro Study

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