Bronchipret^® syrup containing thyme and ivy extracts suppresses bronchoalveolar inflammation and goblet cell hyperplasia in experimental bronchoalveolitis

^a Preclinical R&D, Bionorica SE, Kerschensteinerstr. 11-15, D-92318 Neumarkt, Germany
^b Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, D-07743 Jena, Germany
^c Saint-Petersburg Institute of Pharmacy, Leningrad Region, Vsevolozhsky District, 188663, Kuzmolovo P 245, Russia

Received 12 January 2015, Revised 12 August 2015, Accepted 2 September 2015, Available online 1 October 2015

doi:10.1016/j.phymed.2015.09.001

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Abstract

Background/purpose

Acute bronchitis (AB) is a common lung condition characterized by inflammation of the large bronchi in response to infection. Bronchipret^® syrup (BRO), a fixed combination of thyme and ivy extracts has been effectively used for the treatment of AB. Combining in vivo and mechanistic in vitro studies we aimed to provide a better understanding of the therapeutic potential of BRO on key aspects of AB and to identify potential mechanisms of action.

Methods

Bronchoalveolitis in rats was induced by intratracheal LPS instillation. BRO was administered p.o. once daily at 1- to 10-fold equivalents of the human daily dose. Animals were sacrificed 24–72 h post LPS challenge to analyze leukocyte numbers in lung tissue, bronchoalveolar lavage fluid (BALF) and blood as well as goblet cells in bronchial epithelium. Inhibitory effects of BRO analogue on leukotriene (LT) production were determined in human neutrophils and monocytes as well as on isolated 5-lipoxygenase (5-LO).

Results

BRO significantly reversed the LPS-induced increase in leukocyte numbers in lung tissue, BALF and blood as well as goblet cell numbers in bronchial epithelium. In vitro, BRO analogue suppressed cellular release of LTB₄ (IC₅₀ = 36 µg⋅ml⁻¹) and cysLT (IC₅₀ = 10 µg⋅ml⁻¹) and inhibited the activity of isolated 5-LO (IC₅₀ = 19 µg⋅ml⁻¹).

Conclusion

BRO exerts significant anti-inflammatory effects and attenuates goblet cell metaplasia in LPS-induced bronchoalveolitis in vivo potentially via interference with 5-LO/LT signaling. These effects may contribute to its observed clinical efficacy in AB.

Graphical abstract

Keywords

Acute bronchitis;
Thyme;
Ivy;
Anti-inflammatory;
Goblet cells;
5-lipoxygenase

Abbreviations

AA, arachidonic acid;
AB, acute bronchitis;
5-LO, 5-lipoxygenase;
BALF, bronchoalveolar lavage fluid;
BLT, LTB₄ receptor;
BRO, Bronchipret^® syrup;
LT, leukotriene;
COX, cyclooxygenase;
DER, drug extract ratio;
EtOH, ethanol;
I_max, maximal inhibition;
IC₅₀, calculated concentration of half-maximal inhibition;
LPS, lipopolysaccharide;
RT, room temperature

: Corresponding author. Tel.: +49 (0) 9181/231 309; fax: +49 (0) 9181/231 6309.

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Saturday, 12 December 2015