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Planta Med 2015; 81(08): 670-678
DOI: 10.1055/s-0034-1383408
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Modulation of Calcium Signaling of Angiotensin AT1, Endothelin ETA, and ETB Receptors by Silibinin, Quercetin, Crocin, Diallyl Sulfides, and Ginsenoside Rb1

Ruba Bahem
1   Research Group of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
,
Anja Hoffmann
1   Research Group of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
,
Arnaud Azonpi
1   Research Group of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
,
Catherina Caballero-George
2   Unit of Molecular Pharmacology and Pharmacognosy, Institute for Scientific Research and High Technology Services, Clayton, Panama, Republic Panama
,
Patrick Vanderheyden
1   Research Group of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium
› Author Affiliations
Further Information

Publication History

received 11 August 2014
revised 14 October 2014

accepted 19 November 2014

Publication Date:
17 December 2014 (online)

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Abstract

Angiotensin II and endothelin-1 are potent vasoconstrictive peptides that play a central role in blood pressure regulation. Both peptides exert their pleiotropic effects via binding to their respective G-protein-coupled receptors, i.e., angiotensin AT1 and endothelin type A and type B receptors. In the present study, we have selected six structurally different plant-derived compounds with known cardioprotective properties to evaluate their ability to modulate calcium signaling of the above-mentioned receptors. For this purpose, we used and validated a cellular luminescence-based read-out system in which we measured intracellular calcium signaling in Chinese hamster ovary cells that express the calcium sensitive apo-aequorin protein. Firstly, silibinin, a flavanolignan that occurs in milk thistle (Silybum marianum), was investigated and found to be an antagonist for the human angiotensin AT1 receptor with an affinity constant of about 9 µM, while it had no effect on endothelin type A or type B receptor activation. Quercetin and crocin partially impeded intracellular calcium signaling resulting in a non-receptor-related reduction of the responses recorded for the three investigated G-protein-coupled receptors. Two organosulfur compounds, diallyl disulfide and diallyl trisulfide, as well as the triterpene saponin ginsenoside Rb1 did not affect the activation of the angiotensin AT1 and endothelin type A and type B receptors. In conclusion, we were able, by using a nonradioactive cellular read-out system, to identify a novel pharmacological property of the flavanolignan silibinin.

Key words

angiotensin II - endothelin-1 - G-protein coupled receptors - silibinin - calcium signaling
 

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