Journal Article

Euphorbium compositum SN improves the innate defenses of the airway mucosal barrier network during rhinovirus infection

Seilheimer, Bernd, Sajjan, Umadevi, Ganjian, Haleh, Weyer, Kathrin, Muruganandam, Ganesh, Rajput, Charu, Dannenmaier, Julia

2024

Overview

Background Rhinoviruses (RV) are the major cause of common colds in healthy individuals and are associated with acute exacerbations in patients with chronic lung diseases. Yet, no vaccines or effective treatment against RV are available. This study investigated the effect of Euphorbium compositum SN (ECSN6), a multicomponent, multitarget medication made from natural ingredients, on the mucosal barrier network during RV infection. Methods Mucociliary-differentiated airway epithelial cell cultures were infected with RV or sham, and treated with 20% ECSN6 or placebo twice daily. Barrier integrity was assessed by measuring transepithelial resistance (TER), permeability to inulin, and expression and localization of intercellular junctions proteins (IJ). Ciliary beat frequency (CBF), expression of pro-inflammatory cytokines, antiviral interferons and mucins, and viral load were also measured. C57BL/6 mice were infected intranasally with RV or sham and treated with 40% ECSN6 or placebo twice daily. Inflammation of sinunasal mucosa, localization of E-cadherin, viral load and mucin gene expression were determined. Results ECSN6-treated, uninfected cell cultures showed small, but significant increase in TER over placebo, which was associated with enhanced localization of E-cadherin and ZO-1 to IJ. In RV-infected cultures, treatment with ECSN6, but not placebo prevented RV-induced (1) reduction in TER, (2) dissociation of E-cadherin and ZO-1 from the IJ, (3) mucin expression, and (4) CBF attenuation. ECSN6 also decreased RV-stimulated expression of pro-inflammatory cytokines and permeability to inulin. Although ECSN6 significantly increased the expression of some antiviral type I and type III interferons, it did not alter viral load. In vivo, ECSN6 reduced RV-A1-induced moderate inflammation of nasal mucosa, beneficially affected RV-A1-induced cytokine responses and Muc5ac mRNA expression and prevented RV-caused dissociation of E-cadherin from the IJ of nasal mucosa without an effect on viral clearance. Conclusions ECSN6 prevents RV-induced airway mucosal barrier dysfunction and improves the immunological and mucociliary barrier function. ECSN6 may maintain integrity of barrier function by promoting localization of tight and adherence junction proteins to the IJ. This in turn may lead to the observed decrease in RV-induced pro-inflammatory responses in vitro. By improving the innate defenses of the airway mucosal barrier network, ECSN6 may alleviate respiratory symptoms caused by RV infections.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Airway management / Animals / Apical junctional complex / Asthma / Beat frequencies / Biotechnology industry / Cell culture / Cell differentiation / Cells, Cultured / Chronic obstructive pulmonary disease / Cilia beat frequency / Ciliary beat frequency / Colds / Composition / Control / Cytokines / E-cadherin / Epithelial cells / Epithelium / Euphorbia / Evaluation / Experiments / Gene expression / Health aspects / Humans / Immunity, Innate - drug effects / Immunology / Infection / Inflammation / Integrity / Interferon / Inulin / Localization / Lung diseases / Medicine / Medicine & Public Health / Mice / Mice, Inbred C57BL / Mucin / Mucins / Mucosa / Multicomponent / Multitarget / Nasal Mucosa - drug effects / Nasal Mucosa - immunology / Nasal Mucosa - metabolism / Nasal Mucosa - virology / Permeability / Physiological aspects / Picornaviridae Infections - drug therapy / Picornaviridae Infections - immunology / Picornaviridae Infections - metabolism / Picornaviridae Infections - virology / Placebos / Plant Extracts - isolation & purification / Plant Extracts - pharmacology / Plant Extracts - therapeutic use / Pneumology/Respiratory System / Prescription drugs / Proteins / Pulmonary manifestations of general diseases / Respiratory Mucosa - drug effects / Respiratory Mucosa - immunology / Respiratory Mucosa - metabolism / Respiratory Mucosa - virology / Respiratory tract / Rhinitis / Rhinovirus / Rhinovirus - drug effects / Rhinovirus - physiology / Rhinoviruses / RNA / Sinusitis / Sodium / Throat / Transepithelial resistance / Vaccines / Viral infections / Viruses / Zonula occludens-1 protein