Mechanisms of action of antiosteoporotic effects of a special Cimicifuga racemosa (CR) extract: Inhibition of the RANK-RANKL-Osteoprotegerin triad
It is known that Estradiol-17ß (E2), testosterone (T) and the Cimicifuga racemosa extract CR BNO 1055 have antiosteoporotic effects. The histological structure of the bone and the mechanism of action of the substances their mechanisms of action remain largely unexplored. Receptor activator of nuclear factor κB (RANK), its ligand RANKL and the RANKL decoy receptor osteoprotegerin (OPG) form a protein triad of importance for maintenance of bone homeostasis.
Castrated rats were substituted with E2 (0.4mg/day/male or female), T (56.1mg/day/male) and CR BNO 1055 29.97mg/day/female and 35.6mg/day/malel) via soy free food for 3 months. Cancellous bone mineral density of the metaphysis of tibia was determined by qCT and its architecture studied histomorphometrically. Serum levels of RANKL, OPG, osteocalcin and the breakdown products of collagen 1α1, the CrossLaps, were determined by radioimmunoassay.
E2 and CR treated animals had the highest bone mineral density. In the castrated animals the trabecular structures were rarefied, an effect prevented by E2 and partially by CR but not by T. RANKL was suppressed by E2 and CR BNO 1055, while T suppressed RANKL levels in orx males only. OPG remained uneffected. In both sexes, osteocalcin was significantly reduced by E2. CrossLaps were reduced by E2 and CR BNO 1055. The histomorphometric and qCT data indicate that E2 and CR BNO 1055 have antiosteoporotic effects. These bone sparing effects of E2 and CR BNO 1055 are partly mediated by inhibition of RANKL production. Since compounds in CR BNO 1055 do not bind to any type of estrogen receptors, the mechanism of RANKL inhibition by CR BNO 1055 remains unknown.