title: Bronchipret® syrup containing thyme and ivy extracts suppresses bronchoalveolar inflammation and goblet cell hyperplasia in experimental bronchoalveolitis.
abstract: OBJECTIVE
  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)).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Preclinical R&D, Bionorica SE, Kerschensteinerstr. 11-15, D-92318 Neumarkt, Germany . Electronic address: jan.seibel@bionorica.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Seibel
authors.affiliation: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, D-07743 Jena, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pergola
authors.affiliation: Chair of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich-Schiller-University Jena, Philosophenweg 14, D-07743 Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.affiliation: Saint-Petersburg Institute of Pharmacy, Leningrad Region, Vsevolozhsky District, 188663, Kuzmolovo P 245, Russia.
authors.forename: Kirill
authors.initials: K
authors.lastname: Kryshen
authors.affiliation: Preclinical R&D, Bionorica SE, Kerschensteinerstr. 11-15, D-92318 Neumarkt, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Wosikowski
authors.affiliation: Preclinical R&D, Bionorica SE, Kerschensteinerstr. 11-15, D-92318 Neumarkt, Germany.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Lehner
authors.affiliation: Preclinical R&D, Bionorica SE, Kerschensteinerstr. 11-15, D-92318 Neumarkt, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Haunschild
mesh_terms: D000818:Animals; D001991:Bronchitis / Q000188:drug therapy*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020397:Goblet Cells / Q000187:drug effects*; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000188:drug therapy*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013943:Thymol / Q000494:pharmacology*; D046930:Thymus Plant / Q000737:chemistry; D004338:Drug Combinations
chemical_list: D007975:Leukotriene B4; D016859:Lipoxygenase Inhibitors; D010936:Plant Extracts; D013943:Thymol; C475160:thyme extract and ivy extract drug combination; D004338:Drug Combinations
keywords: 5-lipoxygenase; Acute bronchitis; Anti-inflammatory; Goblet cells; Ivy; Thyme