In vitro study shows promising results

The mechanism of action of butterbur extract Ze 339 for the treatment of allergic rhinitis and its anti-inflammatory potential against viral upper respiratory tract exacerbations are still unknown. An in vitro study reveals very interesting details about the mechanism of action of Ze 339 and gives indications for possible additional indications.

Ze 339

Ze 339 is a standardized extract from the leaves of butterbur, Petasites hybridus, obtained by a special process using supercritical_CO2. Butterbur is an ancient medicinal plant, which was also used in the Middle Ages to ward off the plague (name!). For many years butterbur preparations were used mainly for pain. Because of the pyrrolizidine alkaloids contained in petasites, which can have a liver-toxic effect with prolonged use, only pyrrolizidine-free butterbur extracts have been permitted in Switzerland for several years. Thanks to the use of a special Petasites hybridus cultivar and the aforementioned extraction with supercritical CO2, Ze 339 contains no detectable amounts of pyrrolizidine alkaloids.

Allergic rhinitis

Ze 339 has been approved for the treatment of seasonal allergic rhinitis, hay fever, since 2003. This effect has been proven with several clinical studies [1–4]. In patients suffering from allergic rhinitis, Ze 339 locally inhibits the formation of IL-8 and of eicosanoid LTB4. Until now, however, it was not known how this inhibition takes place. To elucidate the exact mechanism of action, a team of researchers conducted an in vitro study [5] using primary epithelial cells from the nose of individuals who had turbinoplastic surgery performed on them.

Method

For this study, human nasal epithelial cells (HNEC) were stimulated with the TLR3 ligand PolyIC, with poly(I:C)-LuyVec, with R-848, with a CpG oligonucleotide, with a Pseudomonas aeruginosa flagellin, with the lipoprotein Pam-3CSK4, and with interleukin, either together with Ze 339 or without this extract.

Results

The following results were found:

1. Ze 339 and the isoforms of petasin present in this extract decrease IL-8 formation induced by PolyIC and chemotaxis of neutrophils, a model of the virus-stimulated inflammatory response.
2. The additive action of the three isoforms of petasin present in Ze 339 are mediators of the anti-inflammatory effect of Ze 339.
3. Ze 339 decreases pro-inflammatory cytokines as well as chemokine response to viral pathogen associated patterns (PAMP).
4. In contrast to the inhibitory effect in models of virus-stimulated inflammatory response, Ze 339 does not decrease the pro-inflammatory cytokine/chemokine response to bacteria
5. Ze 339 promotes IL-4-, IFN-gamma-, and IL-6-induced formation of pro-inflammatory mediators.
6. Ze 339 decreases cytokine-induced STAT3 and STAT6 signaling and cytokine-induced nuclear translocation of STAT molecules.

Interpretation of these results

From these complex results, the study authors drew the following conclusions: Ze 339 has a broader mechanism of action than previously thought and can potentially be used to treat acute viral respiratory infections. In addition to the known and clinically relevant effect for the treatment of seasonal allergic rhinitis and the anti-chemotactic property in virally stimulated models, Ze 339 seems to have a broad anticytokine effect by interfering with the nuclear translocation of STAT molecules by this butterbur extract. Thus, Ze 339 offers itself as a potential agent suitable for the treatment of decreased immune response associated with ongoing cytokine-induced inflammation and inflammatory diseases such as sinusitis.
 

Literature:

1. Schapowal A: Randomised controlled trial of butterbur and cetirizine for treating seasonal allergic rhinitis, MBJ 2002; 324: 144-146.
2. Schapowal A on behalf of Petasites study group: Treating intermittent allergic rhinitis: a prospective, randomized, placebo and antihistaminic-controlled study of Butterbur extract Ze 339, Phytother Res 2005(6); 19: 530-537.
3. Käufeler R, et. al: Efficacy and safety of butterbur herbal extract Ze 339 in seasonal allergic rhinitis: postmarketing surveillance study, Adv Ther 2006(2); 23: 373-384.
4. Dumitr A.F. et al: Petasol butenoate complex (Ze339) relieves allergic rhinitis-induced nasal obstruction more effectively than desloratadine, J Allergy Clin Immunol 2001 (6); 127: 1515-1521.
5. Steiert S.A. Et al: Anti-inflammatory effects of the petasin phyto drug Ze 339 are mediated by inhibition of the STAT pathway, Biofactors, 2017. 31.01. doi: 10.1002/biof.1349.
    

HAUSARZT PRAXIS 2017; 12(4): 2-5