The Mechanisms of Action of Zuogui Pill on Osteoporosis in Ovariectomized Rats

Traditional Chinese medicine recommends kidney-tonifying treatment for osteoporosis. Zuogui pill is one such treatment composed of eight well characterized Chinese medicinal herbs (Radix rehmanniae preparata, Fructus lycii, Rhizoma dioscoreae, F. corni, Semen cuscutae, Colla cornus cervi, C. carapacis et Plastri testudinis, and R. achyranthis bidentatae). The aim of the study is to evaluate the effects of the Zuogui pill on osteoporosis in ovariectomized rats and to identify the signaling pathways that mediate its action on the bones. A total of 46 6-month-old female Sprague-Dawley rats were divided into four groups: sham-operated control, bilaterally ovariectomized, ovariectomized rats receiving diethylstilbestrol (the positive control group), and ovariectomized rats receiving the Zuogui pill. By the end of 8-week treatments, the following parameters were assessed: (a) bone mineral density and trabecular histomorphology, (b) the expression levels of receptor activator of nuclear factor kappa B ligand and osteoprotegerin in rat tibial osteoblasts and (c) bone marrow stromal cells. The Zuogui pill treatment elevated the trabecular bone area and trabecular thickness and reduced the trabecular spacing in rats with ovariectomy-induced osteoporosis. Compared to the ovariectomized group, the Zuogui pill treatment significantly increased the levels of bone mineral density and osteoprotegerin and suppressed the level of receptor activator of the nuclear factor kappa B ligand. These data led us to conclude that the Zuogui pill regulates bone metabolism and improves osteoporosis symptoms possibly through the osteoprotegerin/receptor activator of the nuclear factor kappa B ligand/receptor activator of the nuclear factor kappa B signaling pathway.