Pharmacology of Cimicifuga racemosa extract BNO 1055 in rats: bone, fat and uterus

Objectives: Hormone replacement therapy (HRT) has therapeutic effects on climacteric complaints and prevents osteoporosis. Owing to the increased risks of breast cancer and cardiovascular diseases, patients look for alternatives. Cimicifuga racemosa (CR) preparations might be an alternative, because they proved to reduce climacteric complaints as efficiently as conjugated estrogens without exerting estrogenic effects in the uterus. Whether CR has positive effects on bone and in fat tissue is currently unknown. Therefore, osteoprotective effects of the CR extract BNO 1055 and an influence on fat tissue were studied in ovariectomized rats. Methods: Bone mineral density (BMD) of the tibia of ovariectomized (ovx) rats was determined by computer-assisted tomography (CT). CT scans of fat depots were perimetrically quantified. Bone turnover (osteocalcin, crosslaps) and lipocyte activity (leptin) were also determined. Uterine weights were measured and gene expression of estrogen-regulated uterine genes (IGF-1, ERβ) was determined by RT-PCR. Results: Treatment of the ovx rats over a period of 3 months with E2 and the CR extract BNO 1055 showed osteoprotective effects; both significantly reduced the loss of BMD in tibia. Serum osteocalcin levels were significantly reduced by both treatments, whereas only E2, but not BNO 1055, reduced serum crosslaps. A paratibial fat depot and serum leptin concentration were also significantly reduced. In contrast to E2, the CR extract showed no effect on uterine weight and gene expression of E2-regulated genes. Conclusion: The CR extract BNO 1055 exerted estrogenic effects in the bone (particularly in osteoblasts) and in fat tissue, but not in the uterus of ovx rats. The extract appears to contain rat organ-specific selective estrogen receptor modulators (SERMs), and if these findings can be approved in human it may be an alternative to HRT. [Copyright &y& Elsevier]