α-Hederin, but Not Hederacoside C and Hederagenin fromHedera helix, Affects the Binding Behavior, Dynamics, and Regulation of β₂-Adrenergic Receptors

Abstract

Hederacoside C, alpha-hederin, and hederagenin are saponins of dry extracts obtained from the leaves of ivy (Hedera helix L.). Internalization of beta(2)-adrenergic receptor-GFP fusion proteins after stimulation with 1 microM terbutaline was inhibited by preincubation of stably transfected HEK293 cells with 1 microM alpha-hederin for 24 h, whereas neither hederacoside C nor hederagenin (1 microM each) influenced this receptor regulation. After incubation of A549 cells with 5 nM Alexa532-NA, two different diffusion time constants were found for beta(2)AR-Alexa532-NA complexes by fluorescence correlation spectroscopy. Evaluation of the autocorrelation curve revealed diffusion time constants: tau(bound1) = 1.4 +/- 1.1 ms (n = 6) found for receptor-ligand complexes with unrestricted lateral mobility, and tau(bound2) = 34.7 +/- 14.1 ms (n = 6) for receptor-ligand complexes with hindered mobility. The distribution of diffusion time constants was 24.3 +/- 2.5% for tau(bound1) and 8.7 +/- 4.3% for tau(bound2) (n = 6). A549 cells pretreated with 1 microM alpha-hederin for 24 h showed dose-dependent alterations in this distribution with 37.1 +/- 5.5% for tau(bound1) and 4.1 +/- 1.1% for tau(bound2). Simultaneously, the level of Alexa532-NA binding was significantly increased from 33.0 +/- 6.8 to 41.2 +/- 4.6%. In saturation experiments, alpha-hederin did not influence the beta(2)-adrenergic receptor density (B(max)), whereas the K(D) value for Alexa532-NA binding decreased from 36.1 +/- 9.2 to 24.3 +/- 11.1 nM. Pretreatment of HASM cells with alpha-hederin (1 microM, 24 h) revealed an increased intracellular cAMP level of 13.5 +/- 7.0% under stimulating conditions. Remarkably, structure-related saponins like hederacoside C and hederagenin did not influence either the binding behavior of beta(2)AR or the intracellular cAMP level.

Protective Effects of Glycyrrhizin against .BETA.2-Adrenergic Receptor Agonist-Induced Receptor Internalization and Cell Apoptosis

“…20) Additionally, glycyrrhizin injection attenuates the development of carrageenan-induced lung injury in CD mice. 21) Recently, Sieben et al 22) found that pre-incubation for 24 h with the saponin compound R-hed-erin could inhibit the terbutaline-stimulated internalization of the b 2 AR, which is in agreement with the fact that saponins are cholesterol-complexing agents and that cholesterol depletion is known to inhibit receptor internalization. [23][24][25][26] Chemically, glycyrrhizin is a triterpenoid saponin glycoside, therefore, we hypothesized that glycyrrhizin may have a positive effect on the regulation of b 2 AR agonist-induced internalization of b 2 ARs.…”

The Phytochemical Constitution of Maltese Medicinal Plants – Propagation, Isolation and Pharmacological Testing

“…Typical reported activities include anti-inflammatory [78,79], antiviral [80], antifungal [81], antibacterial, mucolytic, antispasmodic agent and in vitro bronchodilatory [82,83].…”

Medical Herbalism and Frequency of Use

“…The most frequently www.intechopen.com mentioned indications were urogenital tract disorders, respiratory system disorders, gastrointestinal tract disorders, skin ailments, blood system disorders, nervoussystem disorders, cardiovascular system disorders, and rheumatism (ˇSari´c-Kundali´c et al, 2010). Ivy leaf contains spooning which are considered to have mucolytic, spasmolytic, bronchodilatory and antibacterial effects (Sieben et al, 2009;Gepdiremen et al, 2005). Despite widespread use of ivy leaf extracts, the effectiveness for the treatment of acute cough is not well established (Holzinger & Chenot, 2011).…”

“…More and more physicians are either referring patients to herbal practitioners or practising phytotherapy themselves (Gepdiremen et al, 2005). US sales figures for herbal remedies have risen almost exponentially and, in 1997, exceeded $US350 million (Sieben et al, 2009). HMPs are used to treat a large variety of conditions as well as for 'maintenance of health', i.e.…”