Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5845687 | Pulmonary Pharmacology & Therapeutics | 2015 | 7 Pages |
Abstract
The bronchospasmolytic and secretolytic effects of ivy leaves dry extracts can be explained by an increased β2-adrenergic responsiveness of the bronchi. Recently, it was shown that α-hederin inhibits the internalization of β2-adrenergic receptors (Ã2AR) under stimulating conditions. α-Hederin pretreated alveolar type II cells and human airway smooth muscle cells revealed an increased Ã2AR binding and an elevated intracellular cAMP level, respectively. In order to identify whether additional compounds also mediate an increased β2-adrenergic responsiveness, we examined the ingredients of an ivy leaves dry extract (EA 575) protocatechuic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, kaempferol-3-O-rutinoside, 3,4-, 3,5- and 4,5-dicaffeoylquinic acid, hederacoside B, and β-hederin. Within all the tested substances, only β-hederin inhibited the internalization of GFP-tagged Ã2AR in stably transfected HEK293 cells. Using fluorescence correlation spectroscopy β-hederin (1 μM, 24 h) pretreated HASM cells showed a statistically significant increase in the Ã2AR binding from 33.0 ± 8.9% to 44.1 ± 11.5% which was distributed with 36.0 ± 9.5% for Ïbound1 and 8.1 ± 2.6% for Ïbound2, respectively (n = 8, p < 0.05). The increased binding was selectively found for the receptor-ligand complex with unrestricted lateral mobility (Ïbound1 of 0.9 ± 0.1 ms, D1 = 9.1 ± 0.2 μm2/s, n = 8), whereas the binding of Ã2AR with hindered lateral mobility (Ïbound2 of 64.2 ± 47.6 ms, D2 = 0.15 ± 0.02 μm2/s, n = 8) was not affected. Compared to control cells, a statistically significant increase of 17.5 ± 6.4% (n = 4, p < 0.05) and 24.2 ± 5.8% (n = 4, p < 0.001) in the cAMP formation was found for β-hederin pretreated HASM cells after stimulation with 10 μM of terbutaline and simultaneous stimulation with 10 μM terbutaline and 10 μM forskolin, respectively. Within this systematic study focusing on the influence of the ingredients of an ivy leaves dry extract on HASM cells it was possible to identify β-hederin as further component presumably responsible for the β2-mimetic effects.
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Authors
Christian Greunke, Anne Hage-Hülsmann, Thomas Sorkalla, Nelli Keksel, Felix Häberlein, Hanns Häberlein,