Seidlová-Wuttke D, Jarry H, Becker T, Christoffel V, Wuttke W
Department of Clinical and Experimental Endocrinology, University of Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
Maturitas. 2003 Mar 14;44 Suppl 1:S39-50. doi: 10.1016/s0378-5122(02)00347-x.
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.
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, ERbeta) was determined by RT-PCR.
Treatment of the ovx rats over a period of 3 months with E(2) 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 E(2), but not BNO 1055, reduced serum crosslaps. A paratibial fat depot and serum leptin concentration were also significantly reduced. In contrast to E(2), the CR extract showed no effect on uterine weight and gene expression of E(2)-regulated genes.
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.
激素替代疗法(HRT)对更年期症状具有治疗作用,并可预防骨质疏松症。由于乳腺癌和心血管疾病风险增加,患者在寻求替代疗法。总状升麻(CR)制剂可能是一种替代选择,因为它们已被证明在减轻更年期症状方面与结合雌激素同样有效,且不会对子宫产生雌激素样作用。目前尚不清楚CR对骨骼和脂肪组织是否具有积极作用。因此,在去卵巢大鼠中研究了CR提取物BNO 1055的骨保护作用及其对脂肪组织的影响。
通过计算机辅助断层扫描(CT)测定去卵巢(ovx)大鼠胫骨的骨密度(BMD)。对脂肪储存部位的CT扫描进行周长定量分析。还测定了骨转换指标(骨钙素、交联C端肽)和脂肪细胞活性指标(瘦素)。测量子宫重量,并通过逆转录聚合酶链反应(RT-PCR)测定雌激素调节的子宫基因(IGF-1、雌激素受体β)的基因表达。
用E₂和CR提取物BNO 1055对ovx大鼠进行为期3个月的治疗显示出骨保护作用;两者均显著减少了胫骨骨密度的损失。两种治疗均显著降低了血清骨钙素水平,而只有E₂降低了血清交联C端肽水平,BNO 1055则无此作用。胫骨旁脂肪储存部位和血清瘦素浓度也显著降低。与E₂不同,CR提取物对子宫重量和E₂调节基因的基因表达没有影响。
CR提取物BNO 1055在去卵巢大鼠的骨骼(特别是成骨细胞)和脂肪组织中发挥雌激素样作用,但在子宫中无此作用。该提取物似乎含有大鼠器官特异性选择性雌激素受体调节剂(SERM),如果这些发现能在人体中得到证实,它可能成为HRT的替代疗法。