Division of Endocrinology, Council of Scientific and Industrial Research-Central Drug Research Institute, Chattar Manzil Palace, Lucknow, India.
Menopause. 2012 Dec;19(12):1336-46. doi: 10.1097/gme.0b013e318256b6ae.
The aim of this study was to evaluate the skeletal effects of an extract made from the leaves and pods of Dalbergia sissoo (butanol-soluble standardized fraction [BSSF]) on ovariectomized rats, a model for postmenopausal osteopenia.
Adult Sprague-Dawley rats were ovariectomized and administered BSSF (50 and 100 mg/kg per day) or 17β-estradiol orally for 12 weeks. The sham-operated group and the ovariectomy + vehicle group served as controls. Bone microarchitecture, bone turnover markers (serum osteocalcin and C-telopeptide fragment of collagen type I), biomechanical strength, new bone formation (based on mineral apposition rate and bone formation rate), and skeletal expressions of osteogenic and resorptive gene markers were studied. Uterine histomorphometry was used to assess estrogenicity. Bioactive marker compounds in BSSF were analyzed by high-performance liquid chromatography. One-way analysis of variance was used to test the significance of effects.
In comparison with ovariectomized rats treated with vehicle, BSSF treatment in ovariectomized rats resulted in an improved trabecular microarchitecture of the long bones, increased biomechanical strength parameters of the vertebra and femur, decreased bone turnover markers (osteocalcin and type I collagen) and expression of skeletal osteoclastogenic genes, and increased new bone formation and expression of osteogenic genes in the femur. Overall, the osteoprotective effects of BSSF were comparable to those of 17β-estradiol. BSSF did not exhibit uterine estrogenicity. Analysis of marker compounds revealed the presence of osteogenic methoxyisoflavones, including caviunin 7-O-[β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside] (a novel compound), biochanin A, and pratensin.
Oral doses of BSSF in the preclinical setting are effective in preventing estrogen deficiency-induced bone loss by dual action: inhibition of bone resorption and stimulation of new bone formation.
本研究旨在评估从印度黄檀的叶和荚中提取的一种提取物（丁醇可溶标准化级分 [BSSF]）对去卵巢大鼠（绝经后骨质疏松症模型）的骨骼影响。
成年 Sprague-Dawley 大鼠行卵巢切除术，并给予 BSSF（50 和 100 mg/kg/天）或 17β-雌二醇口服治疗 12 周。假手术组和卵巢切除术+载体组作为对照。研究了骨微结构、骨转换标志物（血清骨钙素和 I 型胶原 C 端肽片段）、生物力学强度、新骨形成（基于矿化沉积率和骨形成率）以及成骨和破骨基因标志物的骨骼表达。子宫组织形态计量学用于评估雌激素活性。通过高效液相色谱法分析 BSSF 中的生物活性标志物化合物。采用单因素方差分析检验效应的显著性。
与接受载体治疗的卵巢切除大鼠相比，BSSF 治疗可改善长骨的小梁微结构，增加椎体和股骨的生物力学强度参数，降低骨转换标志物（骨钙素和 I 型胶原）和骨骼破骨基因的表达，并增加股骨的新骨形成和成骨基因的表达。总体而言，BSSF 的骨保护作用与 17β-雌二醇相当。BSSF 不具有子宫雌激素活性。标志物化合物分析显示存在成骨甲氧基异黄酮，包括棘叶素 7-O-[β-D-阿戊呋喃糖基-(1→6)-β-D-吡喃葡萄糖苷]（一种新化合物）、大豆苷元和普替森。
在临床前环境中，BSSF 的口服剂量通过抑制骨吸收和刺激新骨形成的双重作用，有效预防雌激素缺乏引起的骨丢失。
