Petasins in the treatment of allergic diseases: results of preclinical and clinical studies.

Plant extracts are causing an increased interest in the treatment of many chronic diseases, including asthma and other allergic diseases. Several laboratories characterized petasins (petasin, isopetasin, and neopetasin) isolated from extracts of butterbur (Petasites hybridus) as pharmacologically active components, which inhibit leukotriene synthesis in leukocytes. The molecular mechanisms by which petasins abrogate inflammatory effector cell functions have, at least partially, been identified. In vitro studies revealed that petasins may have several intracellular targets and this may depend on the stereoisomer used. In an open clinical trial in patients suffering from allergic rhinitis, a reduction of leukotriene and histamine levels in nasal fluids was associated with the butterbur extract administration. To better evaluate the clinical value in this particular allergic disease, the clinical efficacy of the drug was compared with an established antihistamine treatment scheme in a double-blind study; no significant difference was observed between the two treatment groups. In this article, we critically review recently published work and summarize the current stage in the pharmacological characterization of butterbur extracts.

Role of petasin in the potential anti-inflammatory activity of a plant extract of petasites hybridus.

A large production of leukotrienes (LTs) can be induced in human eosinophils or neutrophils by priming with granulocyte-macrophage colony-stimulating factor and subsequent stimulation with platelet-activating factor (PAF) or the anaphylatoxin C5a. Here, we investigated the effects of a plant extract of petasites hybridus (Ze339) and its isolated active sesquiterpene ester petasin in these two in vitro cell models. Zileuton, a 5-lipoxygenase inhibitor, was used as a positive control. All compounds inhibited both cysteinyl-LT synthesis in eosinophils and LTB(4) synthesis in neutrophils. In contrast, only Ze339 and petasin, but not zileuton, abrogated PAF- and C5a-induced increases in intracellular calcium concentrations. These data suggest that Ze339 and petasin may block, compared to zileuton, earlier signalling events initiated by G protein-coupled receptors in granulocytes, perhaps at the level of or proximal to phospholipase C(beta). Taken together, petasin appears to be one major active compound of petasites hybridus extract, since it demonstrates the same inhibitory activities on calcium fluxes and subsequent LT generation in both eosinophils and neutrophils as Ze339 does.