α-Hederin inhibits G protein-coupled receptor kinase 2-mediated phosphorylation of β2-adrenergic receptors

Schulte-Michels, Janka; Wolf, Anne; Aatz, Stefan; Engelhard, Katharina; Sieben, Anne; Martinez-Osuna, Manuel; Häberlein, Felix; Häberlein, Hanns

doi:10.1016/j.phymed.2015.12.001

Cited by 24 publications

(18 citation statements)

References 23 publications

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“…Ivy leaves dry extract EA 575 ® (DER 5-7.5:1, 30% ethanol) (Batch number CID-100048) was obtained from Engelhard Arzneimittel GmbH & Co. KG (Niederdorfelden, Germany). Chemical composition and pharmacological properties of relevant ingredients have been reported previously (Sieben et al 2009 ; Greunke et al 2015 ; Schulte-Michels et al 2016a , b ). For further characterization, EA 575 ® was dissolved in 50% EtOH in a concentration of 40.8 mg/ml.…”

Section: Methodsmentioning

confidence: 74%

“…Its bronchospasmolytic and secretolytic effects have been proven in clinical studies (Lang et al 2015). The mechanism of action is based on increased β 2 -adrenergic responsiveness of the respiratory tract mediated by inhibition of GRK2-mediated phosphorylation of activated β 2 -adrenergic receptors, resulting in decreased internalization of β 2 -adrenergic receptors under stimulating conditions (Sieben et al 2009; Schulte-Michels et al 2016b). The anti-inflammatory effect of EA 575 ® is less examined.…”

Section: Introductionmentioning

confidence: 99%

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Anti-inflammatory effects of ivy leaves dry extract: influence on transcriptional activity of NFκB

et al. 2018

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EA 575 is an ivy leaves dry extract (DER 5-7.5:1, 30% ethanol) used against diseases of the lower respiratory tract associated with productive cough. EA 575 improves symptoms associated with chronic inflammatory bronchial conditions. Compared to its bronchospasmolytic and secretolytic properties, the anti-inflammatory effects of EA 575 are mostly untried. Therefore, we addressed the question of whether the anti-inflammatory effect of EA 575 is due to an impact on the NFκB pathway. NFκB nuclear translocation was visualized by immunofluorescence in J774.2 as well as HEK293 cells. In the latter, a luciferase-based reporter was used to monitor NFκB transcriptional activity. Phosphorylation of RelA and its inhibitor IκB was measured by Western blot analysis. Additionally, changes in the stability of NFκB:IκB complex were shown by protein fragment complementation. Decreased transcriptional activity of NFκB under treatment with EA 575 was also shown for a human monocytic as well as a human lung epithelial cell line. EA 575 is able to inhibit NFκB transcriptional activity by partially inhibiting its translocation to the nucleus after stimulation with TNFα. Furthermore, phosphorylation of IκBα is reduced while phosphorylation of RelA is enhanced after pre-incubation with EA 575, leading to an enhanced stability of NFκB:IκBα complex. EA 575 has an regulatory impact on the NFκB pathway, possibly by switching specificity of IKK from IκBα to RelA, resulting in enhanced stability of NFκB:IκBα complex and reduced RelA translocation into the nucleus.

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Section: Methodsmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory effects of ivy leaves dry extract: influence on transcriptional activity of NFκB

et al. 2018

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“…Виявляючи мукокінетичну і секретолітичну дію, виразність якої порівнянна з такою у мукоактивних препаратів інших фармаколо гічних груп, сухий екстракт листя плюща вияв ляє ще й унікальний бронхоспазмолітичний ефект за рахунок специфічного метаболіту альфа гедерину, що утворюється із сапонінів. Доведено, що альфа гедерин оптимізує процеси рециклізації бета 2 адренорецепторів і збіль шення їх числа на поверхні міоцитів, підвищує кількість активних бета 2 адренорецепторів і підсилює їх чутливість до адреноміметиків [11,20,24,27]. Секретолітична дія препарату зумовлена наявністю в екстракті сапонінів, що викликають стимуляцію блукаючого нерва і збільшення вироблення секрету келихоподіб ними клітинами.…”

Section: сапоніни екстракту плюща виявляють протизапальну відхаркуваunclassified

Preparations with ivy extract for the treatment of cough with bronchitis in children

Mishchenko¹

2020

MPU

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Показано фізіологічну роль кашлю у роботі дихальної системи. Як патологічний стан кашель виникає при багатьох захворюваннях. Особливо актуальна проблема кашлю у дітей. Головним критерієм вибору препарату патогенетичної терапії кашлю у дітей є безпека. Серед препаратів, що застосовуються для лікування кашлю, у педіатрії перевага надається засобам рослинного походження, яким притаманні більш м'який, порівняно із синтетичними препаратами, фармакотерапевтичний ефект та краща переносимість. Завдяки багатому складу біологічно активних речовин, рослинні препарати від кашлю чинять комплексний вплив, коригуючи порушені фізіологічні функції організму. Екстракт листя плюща звичайного здавна застосовується для лікування кашлю. Безпечність та ефективність препаратів на основі плюща при захворюваннях верхніх дихальних шляхів, у тому числі у дітей, доведена результатами багатьох досліджень. Автор заявляє про відсутність конфлікту інтересів. Ключові слова: кашель, діти, лікування, екстракт листя плюща.

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“…While many medicines are being used today, undoubtedly not all therapeutics can fulfil the increased demand for high evidence of efficacy, the identification of the responsible active principles or the understanding of the mechanism of action. In this respect, the ivy leaves dry extract EA 575 stands out with over 20 published clinical trials and post-marketing studies, with documented clinical data with a total of >65 000 patients [6–8], in addition to preclinical data on the mode of action [9–11].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of two dosing schemes of a liquid containing ivy leaves dry extract EA 575versusplacebo in the treatment of acute bronchitis in adults

Schaefer¹,

Ludwig

Giannetti³

et al. 2019

ERJ Open Res

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IntroductionThe results of a clinical trial published in 2016 showed the efficacy of ivy leaves dry extract EA 575 versus placebo in the treatment of patients suffering from acute cough. A clinical trial with a very similar design was conducted to not only show the reproducibility of former results but also to investigate an alternative dosing scheme.MethodsThis randomised, placebo-controlled, multicentre, double-blind clinical trial was conducted to assess the efficacy and safety of a liquid containing EA 575 in the treatment of acute bronchitis. A total of 209 patients were treated with a liquid containing EA 575 as an active investigational medicinal product (verum) either two (7.5 mL) or three (5 mL) times a day or placebo in the respective dosing scheme for 1 week, with a total observational period of 2 weeks. The primary efficacy outcome was a change in Bronchitis Severity Score (BSS) of the pooled placebo and pooled verum groups between visits 1 and 5. Additional secondary parameters were assessed, including, for example, change in cough severity as assessed by a visual analogue scale (VAS) and the Verbal Category Descriptive (VCD) score.ResultsSuperiority of verum over placebo was during and at the end of treatment, as measured by BSS. No significant differences between the dosing schemes were observed. VCD scores and VAS measurements also showed the superiority of verum over placebo.ConclusionThe existing data on the clinical efficacy of EA 575 were confirmed. Furthermore, a new dosing scheme was shown to be noninferior to the currently used scheme while maintaining the safety and tolerability of the well-established cough liquid containing EA 575.

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α-Hederin inhibits G protein-coupled receptor kinase 2-mediated phosphorylation of β2-adrenergic receptors

Abstract: Taken together, these results indicate that α-hederin acts as an indirect GRK2 inhibitor leading to a reduced homologous desensitization of β2AR-GFP in HEK293 cells.

Cited by 24 publications

References 23 publications

Anti-inflammatory effects of ivy leaves dry extract: influence on transcriptional activity of NFκB

Anti-inflammatory effects of ivy leaves dry extract: influence on transcriptional activity of NFκB

Preparations with ivy extract for the treatment of cough with bronchitis in children

Efficacy of two dosing schemes of a liquid containing ivy leaves dry extract EA 575versusplacebo in the treatment of acute bronchitis in adults

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