Thyme Extract/Hedera Extract

Hypersecretion of viscous mucus is one of the hallmark symptoms of acute and chronic bronchitis and typically develops secondary to an inflammation of the airway epithelium. Bronchipret^® TP film-coated tablets (BRO), a herbal medicinal product containing a fixed combination of thyme herb and primula root extracts, has been successfully used clinically for the treatment of acute bronchitis for more than two decades. However, the underlying pharmacological mechanisms of action have not been fully understood so far. We investigated the anti-inflammatory and mucus-regulatory effects of orally administered BRO in an animal model of pulmonary inflammation that was experimentally induced by intratracheal LPS instillation. BRO was administered once daily for up to three days following the induction of inflammation. Treatment with BRO effectively inhibited polymorphonuclear cell influx into the lung as well as the increase in mucin 5ac (MUC5AC) protein. Furthermore, the LPS-induced increase of goblet cell numbers was significantly attenuated by BRO treatment. Subsequent in vitro investigations with IL-13 stimulated human primary respiratory epithelium and the Calu-3 respiratory epithelial cell line in air-liquid-interface culture confirmed the effects on mucus production and goblet cell numbers observed in the in vivo studies. They further suggest that the reduction of MUC5AC protein secretion by BRO is associated with reduced MUC5AC mRNA expression as assessed by quantitative Real-Time PCR. Our studies provide evidence that BRO exerts both anti-inflammatory and mucus-regulatory activity and that BRO's effect on mucin production is partially independent from its anti-inflammatory activity. These results contribute to the understanding of the modes of action underlying the clinical efficacy of BRO in acute bronchitis patients.

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.

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).

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)).

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.