Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo Models

<b>Background:</b> The efficacy of EA575 in the treatment of respiratory diseases is described in various clinical studies, improving patients’ disease-related symptoms. However, mechanistic in vivo data proving its beneficial effects are limited. <b>Methods:</b> Focusing on...

Full description

Saved in:
Bibliographic Details
Main Authors: Matthias Hufnagel, André Rademaekers, Anika Weisert, Hanns Häberlein, Sebastian Franken
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/13/7/1673
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849407698430328832
author Matthias Hufnagel
André Rademaekers
Anika Weisert
Hanns Häberlein
Sebastian Franken
author_facet Matthias Hufnagel
André Rademaekers
Anika Weisert
Hanns Häberlein
Sebastian Franken
author_sort Matthias Hufnagel
collection DOAJ
description <b>Background:</b> The efficacy of EA575 in the treatment of respiratory diseases is described in various clinical studies, improving patients’ disease-related symptoms. However, mechanistic in vivo data proving its beneficial effects are limited. <b>Methods:</b> Focusing on the treatment of acute airway inflammation and accompanying cough, this study aimed to elucidate antitussive and mucoactive properties of EA575, applying two animal models. Animals were treated orally twice daily for 7 days, resulting in 43, 215.2, or 430.5 mg/kg bw/d of EA575. Antitussive effects were investigated within an acute lung inflammation model of bleomycin-treated guinea pigs after citric acid exposure. Hereby, the number of coughs, enhanced pause (penH), and bronchoalveolar lavage fluid (BALF) were investigated. Mucoactivity of EA575 was assessed within a murine model, determining phenol red concentration in BALF. <b>Results:</b> EA575 treatment within the acute lung inflammation model reduced cough events up to 56% while reducing inflammatory cell influx in BALF dose-dependently, e.g., reducing neutrophils in BALF up to 70.9%. This suggests a strong connection between anti-inflammatory and antitussive properties of EA575. Furthermore, penH decreased in a dose-dependent manner, suggesting an ease in respiration. Mucoactivity was shown by a dose-dependent increase in phenol red concentration in BALF up to 38.9%. Notably, EA575/salbutamol co-administration resulted in enhanced phenol red secretion compared to respective single administrations. <b>Conclusions:</b> These data highlight the benefits of EA575 in treating cough-related respiratory diseases, particularly when accompanied by sputum, as EA575 has been shown to obtain mucoactivity. Furthermore, the combinatory effect of EA575/salbutamol treatment provides a foundation for future research in the treatment of chronic respiratory diseases.
format Article
id doaj-art-0a829ca5cb374b4085f224ed25c847f5
institution Kabale University
issn 2227-9059
language English
publishDate 2025-07-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj-art-0a829ca5cb374b4085f224ed25c847f52025-08-20T03:35:58ZengMDPI AGBiomedicines2227-90592025-07-01137167310.3390/biomedicines13071673Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo ModelsMatthias Hufnagel0André Rademaekers1Anika Weisert2Hanns Häberlein3Sebastian Franken4Engelhard Arzneimittel GmbH & Co. KG, 61138 Niederdorfelden, GermanyEngelhard Arzneimittel GmbH & Co. KG, 61138 Niederdorfelden, GermanyEngelhard Arzneimittel GmbH & Co. KG, 61138 Niederdorfelden, GermanyInstitute of Biochemistry and Molecular Biology, Medical Faculty, University of Bonn, 53115 Bonn, GermanyDepartment of Natural Sciences, Institute for Functional Gene Analytics, Bonn-Rhein-Sieg University of Applied Sciences, 53359 Rheinbach, Germany<b>Background:</b> The efficacy of EA575 in the treatment of respiratory diseases is described in various clinical studies, improving patients’ disease-related symptoms. However, mechanistic in vivo data proving its beneficial effects are limited. <b>Methods:</b> Focusing on the treatment of acute airway inflammation and accompanying cough, this study aimed to elucidate antitussive and mucoactive properties of EA575, applying two animal models. Animals were treated orally twice daily for 7 days, resulting in 43, 215.2, or 430.5 mg/kg bw/d of EA575. Antitussive effects were investigated within an acute lung inflammation model of bleomycin-treated guinea pigs after citric acid exposure. Hereby, the number of coughs, enhanced pause (penH), and bronchoalveolar lavage fluid (BALF) were investigated. Mucoactivity of EA575 was assessed within a murine model, determining phenol red concentration in BALF. <b>Results:</b> EA575 treatment within the acute lung inflammation model reduced cough events up to 56% while reducing inflammatory cell influx in BALF dose-dependently, e.g., reducing neutrophils in BALF up to 70.9%. This suggests a strong connection between anti-inflammatory and antitussive properties of EA575. Furthermore, penH decreased in a dose-dependent manner, suggesting an ease in respiration. Mucoactivity was shown by a dose-dependent increase in phenol red concentration in BALF up to 38.9%. Notably, EA575/salbutamol co-administration resulted in enhanced phenol red secretion compared to respective single administrations. <b>Conclusions:</b> These data highlight the benefits of EA575 in treating cough-related respiratory diseases, particularly when accompanied by sputum, as EA575 has been shown to obtain mucoactivity. Furthermore, the combinatory effect of EA575/salbutamol treatment provides a foundation for future research in the treatment of chronic respiratory diseases.https://www.mdpi.com/2227-9059/13/7/1673ivy leaf dry extractEA575antitussiverespiratory diseasecoughmucoactive agent
spellingShingle Matthias Hufnagel
André Rademaekers
Anika Weisert
Hanns Häberlein
Sebastian Franken
Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo Models
Biomedicines
ivy leaf dry extract
EA575
antitussive
respiratory disease
cough
mucoactive agent
title Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo Models
title_full Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo Models
title_fullStr Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo Models
title_full_unstemmed Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo Models
title_short Efficacy of EA575 as an Antitussive and Mucoactive Agent in Preclinical In Vivo Models
title_sort efficacy of ea575 as an antitussive and mucoactive agent in preclinical in vivo models
topic ivy leaf dry extract
EA575
antitussive
respiratory disease
cough
mucoactive agent
url https://www.mdpi.com/2227-9059/13/7/1673
work_keys_str_mv AT matthiashufnagel efficacyofea575asanantitussiveandmucoactiveagentinpreclinicalinvivomodels
AT andrerademaekers efficacyofea575asanantitussiveandmucoactiveagentinpreclinicalinvivomodels
AT anikaweisert efficacyofea575asanantitussiveandmucoactiveagentinpreclinicalinvivomodels
AT hannshaberlein efficacyofea575asanantitussiveandmucoactiveagentinpreclinicalinvivomodels
AT sebastianfranken efficacyofea575asanantitussiveandmucoactiveagentinpreclinicalinvivomodels