title: Modulation of Calcium Signaling of Angiotensin AT1, Endothelin ETA, and ETB Receptors by Silibinin, Quercetin, Crocin, Diallyl Sulfides, and Ginsenoside Rb1.
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.
authors.affiliation: Research Group of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Ruba
authors.initials: R
authors.lastname: Bahem
authors.affiliation: Research Group of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Anja
authors.initials: A
authors.lastname: Hoffmann
authors.affiliation: Research Group of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Azonpi
authors.affiliation: Unit of Molecular Pharmacology and Pharmacognosy, Institute for Scientific Research and High Technology Services, Clayton, Panama, Republic Panama.
authors.forename: Catherina
authors.initials: C
authors.lastname: Caballero-George
authors.affiliation: Research Group of Molecular and Biochemical Pharmacology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Vanderheyden
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology; D000804:Angiotensin II / Q000187:drug effects; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology*; D000809:Angiotensins / Q000187:drug effects; D000818:Animals; D016466:CHO Cells; D020013:Calcium Signaling / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology*; D019332:Endothelin-1 / Q000187:drug effects; D016232:Endothelins / Q000187:drug effects*; D005260:Female; D036145:Ginsenosides / Q000494:pharmacology; D006801:Humans; D011794:Quercetin / Q000494:pharmacology; D011945:Receptors, Angiotensin / Q000187:drug effects; D017466:Receptors, Endothelin / Q000187:drug effects; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D013440:Sulfides / Q000494:pharmacology
chemical_list: D000498:Allyl Compounds; D057911:Angiotensin Receptor Antagonists; D000809:Angiotensins; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D016232:Endothelins; D036145:Ginsenosides; D011945:Receptors, Angiotensin; D017466:Receptors, Endothelin; D012838:Silymarin; D013440:Sulfides; D000804:Angiotensin II; D002338:Carotenoids; D000077385:Silybin; C038491:allyl sulfide; C442759:ginsenoside Rb1; C029036:crocin; D011794:Quercetin