TY - JOUR
T1 - Inhibition of human complement by β-glycyrrhetinic acid
AU - Kroes, B. H.
AU - Beukelman, C. J.
AU - Van Den Berg, A. J.J.
AU - Wolbink, G. J.
AU - Van Dijk, H.
AU - Labadie, R. P.
PY - 1997
Y1 - 1997
N2 - Licorice, the root extract of Glycyrrhiza glabra L., is used as a medicine for various diseases. Antiinflammatory as well as anti-allergic activities have been attributed to one of its main constituents, glycyrrhizin. These activities are mainly ascribed to the action of the aglycone, β-glycyrrhetinic acid. β-Glycyrrhetinic acid has a steroid-like structure and is believed to have immunomodulatory properties. To determine whether interference with complement functions may contribute to the immunomodulatory activity of β-glycyrrhetinic acid, its effects on the classical and alternative activation pathways of human complement were investigated. We found that β-glycyrrhetinic acid is a potent inhibitor of the classical complement pathway (IC50 = 35 μM), whereas no inhibitory activity was observed towards the alternative pathway (IC50 > 2500 μM). The anticomplementary activity of β-glyrrhetinic acid was dependent on its conformation, since the a-form was not active. It was also established that naturally occurring steroids, e.g. hydrocortisone and cortisone, did not inhibit human complement activity under similar conditions. Detailed mechanistic studies revealed that β-glycyrrhetinic acid acts at the level of complement component C2.
AB - Licorice, the root extract of Glycyrrhiza glabra L., is used as a medicine for various diseases. Antiinflammatory as well as anti-allergic activities have been attributed to one of its main constituents, glycyrrhizin. These activities are mainly ascribed to the action of the aglycone, β-glycyrrhetinic acid. β-Glycyrrhetinic acid has a steroid-like structure and is believed to have immunomodulatory properties. To determine whether interference with complement functions may contribute to the immunomodulatory activity of β-glycyrrhetinic acid, its effects on the classical and alternative activation pathways of human complement were investigated. We found that β-glycyrrhetinic acid is a potent inhibitor of the classical complement pathway (IC50 = 35 μM), whereas no inhibitory activity was observed towards the alternative pathway (IC50 > 2500 μM). The anticomplementary activity of β-glyrrhetinic acid was dependent on its conformation, since the a-form was not active. It was also established that naturally occurring steroids, e.g. hydrocortisone and cortisone, did not inhibit human complement activity under similar conditions. Detailed mechanistic studies revealed that β-glycyrrhetinic acid acts at the level of complement component C2.
UR - http://www.scopus.com/inward/record.url?scp=0031014294&partnerID=8YFLogxK
U2 - https://doi.org/10.1046/j.1365-2567.1997.00131.x
DO - https://doi.org/10.1046/j.1365-2567.1997.00131.x
M3 - Article
C2 - 9038721
SN - 0019-2805
VL - 90
SP - 115
EP - 120
JO - Immunology
JF - Immunology
IS - 1
ER -