Cellular evidence for EA 575 as an add-on therapy for chronic inflammations of the lower respiratory tract

Chronic inflammatory respiratory diseases associated with cough have a high prevalence and treatment options are limited. Acute forms such as acute bronchitis are often treated with expectorants. Chronic forms like asthma and chronic bronchitis are treated with anti-inflammatory corticosteroids and bronchospasmolytic ß₂-adrenergic agonists administered by inhalation. The use of the latter is limited by an induced ß₂ receptor desensitization and internalisation leading to drug tolerance.

EA 575® is a dry extract from ivy leaves with a well-established use as a treatment for diseases of the lower respiratory tract associated with productive cough. There is evidence that children with mild uncontrolled asthma might benefit from an add-on therapy with EA 575® [1]. It has been shown, that on a cellular level a) the bronchospasmolytic properties of EA 575® under stimulating conditions are based on a reduced internalization of the ß₂-adrenergic receptor [2] and that b) EA 575® is able to lower IL-6 secretion from LPS-stimulated murine macrophages [3]. Here we demonstrate that EA 575® exerts its anti-inflammatory properties by decreasing nuclear translocation and transcriptional activity of NFκB. Furthermore, we show that the crosstalk between the ß₂-adrenergic pathway and the NFκB pathway through ß-arrestin-2 can be influenced by EA 575® in-vitro. Therefore EA 575® might counteract a drug tolerance towards ß₂-sympathomimetic drugs and the use of corticosteroids might be reduced due to the additional anti-inflammatory effect. This dual mode of action makes EA 575® a promising candidate for an add-on therapy for chronic inflammatory diseases of the lower respiratory tract, such as asthma or chronic bronchitis.

[1] Zeil S, Schwanebeck U, Vogelberg C. Phytomedicine. 2014; 21:1216 – 20.

[2] Sieben A, Prenner L, Sorkalla T, et al. Biochemistry. 2009; 48:3477 – 82.

[3] Schulte-Michels J, Wolf A, Aatz S, et al. Phytomedicine. 2016; 23:52 – 7.