Mechanisms of action that contribute to the efficacy of ivy leaves dry extract EA 575®
Mechanisms of action that contribute to the efficacy of ivy leaves dry extract EA 575®
dc.contributor.advisor | Häberlein, Hanns | |
dc.contributor.author | Schulte-Michels, Janka | |
dc.date.accessioned | 2020-04-25T13:46:02Z | |
dc.date.available | 2020-04-25T13:46:02Z | |
dc.date.issued | 11.12.2018 | |
dc.identifier.uri | https://hdl.handle.net/20.500.11811/7678 | |
dc.description.abstract | The ivy leaves dry extract EA 575® is an approved cough remedy distributed in more than 100 countries worldwide. The modes of action for its bronchospasmolytic, secretolytic, and anti-inflammatory effects remain poorly understood. Therefore, this work focuses on a contribution to these mechanisms. Within this work it is shown that the former investigated inhibition of β2-adrenergic receptor internalization arrives from an indirect inhibition of receptor phosphorylation by GRK2. Also the recruitment of β-arrestin2 to the β2-adrenergic receptor (β2AR) is shown to be diminished after EA 575® pre-treatment under stimulating conditions. With respect to anti-inflammatory effects, EA 575® reduces IL-6 secretion from murine macrophages after LPS stimulation. This effect is explained by a reduced NFκB transcriptional activity measured by a reporter gene assay based on luciferase activity in HEK and THP-1 cells. As assessed by immunostaining, the translocation of NFκB into the nucleus under stimulating conditions is also impaired, which is explained by a higher amount of bound NFκB to its inhibitor IκBα detected by a protein fragment complementation assay. This result is underlined with a lowered phosphorylation of IκBα and a heightened phosphorylation of NFκB subunit RelA at Ser536 after EA 575® pre-treatment and TNFα stimulation. Finally, it is demonstrated in HEK Nanoluc-PEST cells that NFκB transcriptional activity is diminished by β2-adrenergic stimulation and synergistically inhibited by EA 575® pre-incubation. Interestingly, this effect is shown to be β-arrestin dependent. Whether or not this crosstalk contributes to the efficacy of EA 575® requires further investigation. | |
dc.language.iso | eng | |
dc.rights | In Copyright | |
dc.rights.uri | http://rightsstatements.org/vocab/InC/1.0/ | |
dc.subject | Efeu | |
dc.subject | Entzündung | |
dc.subject | beta-arrestin | |
dc.subject | beta-2-adrenerger Rezeptor | |
dc.subject | Ivy | |
dc.subject | inflammation | |
dc.subject | beta-2-adrenergic receptor | |
dc.subject.ddc | 615 Pharmakologie, Therapeutik | |
dc.title | Mechanisms of action that contribute to the efficacy of ivy leaves dry extract EA 575® | |
dc.type | Dissertation oder Habilitation | |
dc.publisher.name | Universitäts- und Landesbibliothek Bonn | |
dc.publisher.location | Bonn | |
dc.rights.accessRights | openAccess | |
dc.identifier.urn | https://nbn-resolving.org/urn:nbn:de:hbz:5n-52787 | |
ulbbn.pubtype | Erstveröffentlichung | |
ulbbnediss.affiliation.name | Rheinische Friedrich-Wilhelms-Universität Bonn | |
ulbbnediss.affiliation.location | Bonn | |
ulbbnediss.thesis.level | Dissertation | |
ulbbnediss.dissID | 5278 | |
ulbbnediss.date.accepted | 27.11.2018 | |
ulbbnediss.institute | Mathematisch-Naturwissenschaftliche Fakultät : Fachgruppe Pharmazie / Pharmazeutisches Institut | |
ulbbnediss.fakultaet | Mathematisch-Naturwissenschaftliche Fakultät | |
dc.contributor.coReferee | Kostenis, Evi |
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