A combination of thyme and ivy exerts potent anti-inflammatory and mucus-normalizing activity in vivo and inhibits 5-LO and PDE4

Aim: A fixed combination of thyme (THY) and ivy extracts (Bronchipret ® syrup (BRO)) is used for the treatment of acute bronchitis. 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 acute bronchitis and to identify potential mechanisms of action. Methods: Bronchoalveolitis in rats was induced by intratracheal LPS instillation. BRO was given p.o. daily at 1-10-fold equivalents of the human daily dose. Animals were sacrificed up to 72 h post LPS challenge to analyze lung inflammation, goblet cell numbers and MUC5AC expression. Inhibitory effects of BRO on leukotriene production were determined in human neutrophils and monocytes as well as on isolated 5-lipoxygenase (5-LO). Inhibition of isolated phosphodiesterase 4B (PDE4B) activity was determined radiometrically. Results: BRO significantly reversed the LPS-induced increase in goblet cell numbers and MUC5AC expression. It furthermore reduced interleukin (IL)-1β, IL-6 and prostaglandin E 2 levels in bronchoalveolar lavage fluid. BRO and THY suppressed cellular release of LTB 4 (IC 50 = 40 and 25 μg/mL) and cysLT (IC 50 = 8 and 12 μg/mL) and inhibited the activity of isolated 5-LO (IC 50 = 20 and 12 μg/mL). PDE4B activity was also blocked by BRO and THY with IC 50 = 24 and 33 µg/mL. Conclusion: A herbal medicinal product containing a combination of thyme and ivy extracts (Bronchipret ® ) exerts anti-inflammatory and mucus-normalizing effects in LPS-induced bronchoalveolitis in vivo , potentially via inhibition of 5-LO and PDE4 activities. These effects may contribute to the observed clinical efficacy in acute bronchitis.