Evaluation of bioactive saponins and triterpenoidal aglycons for their binding properties on human endothelin ETA and angiotensin AT1 receptors.
Different types of triterpenes including saponins and aglycons were evaluated for their ability to inhibit [3H] BQ-123 and [3H] angiotensin II binding to the human endothelin 1 ETA and angiotensin II AT1 receptors, respectively. Selectivity for only one of the two receptors was exhibited by asiatic acid and its saponins (ETA) and oleanolic acid (AT1). To a lesser extent betulinic acid, beta-amyrin and friedelin also showed selectivity for the ETA receptor. To address the question whether the effect of saponins on cell membranes might interfere with the normal binding of specific radioligands to their receptors, the activity of saponins with different haemolytic properties were compared. Highly haemolytic saponins such as alpha-hederin and beta-escine showed partial (60%) inhibition of radioligand-binding to the ETA receptor and complete inhibition (100%) to the AT1 receptor. Moreover, the haemolytically inactive kryptoescine, at the same concentration, caused complete inhibiton of radioligand-binding to both receptors, indicating that inhibition of receptor binding was not related to the membrane-interacting properties of saponins.
Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, B-2610, Belgium.
C
C
Caballero-George
P M L
PM
Vanderheyden
Y
Y
Okamoto
T
T
Masaki
Z
Z
Mbwambo
S
S
Apers
M P
MP
Gupta
L
L
Pieters
G
G
Vauquelin
A
A
Vlietinck
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D010946:Plants, Medicinal; D011869:Radioligand Assay; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects*; D044022:Receptor, Endothelin A / Q000187:drug effects*; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology; D014315:Triterpenes / Q000008:administration & dosage / Q000494:pharmacology
D010936:Plant Extracts; D044140:Receptor, Angiotensin, Type 1; D044022:Receptor, Endothelin A; D012503:Saponins; D014315:Triterpenes