Gautam Jyoti, Kumar Padam, Kushwaha Priyanka, Khedgikar Vikram, Choudhary Dharmendra, Singh Divya, Maurya Rakesh, Trivedi Ritu
1Endocrinology Division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India 2Medicinal and Process Chemistry Division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India.
Menopause. 2015 Nov;22(11):1246-55. doi: 10.1097/GME.0000000000000453.
Dalbergiphenol (DGP) is a neoflavonoid isolated from heartwood of Dalbergia sissoo. Effects of DGP on skeletal health remain to be elucidated. The objective of the present study was to investigate the biological effects of DGP on bone loss in ovariectomized mice.
Adult BALB/c mice were ovariectomized and administered DGP (1 and 5 mg/kg/d) or 17β-estradiol (E2) orally for 6 weeks. The sham group and the ovariectomy (OVX) + vehicle group served as controls. Eight female BALB/c mice were taken for each group. Uterine estrogenicity, bone microarchitecture, biomechanical strength, new bone formation (based on bone formation rate and mineral apposition rate), and skeletal expression of osteogenic and resorptive gene markers were studied.
OVX resulted in a marked increase in body weight and a decrease in femoral and vertebral trabecular bone volume that were prevented by DGP or E2 treatment. DGP treatment increased bone biomechanical strength and new bone formation rate in ovariectomized mice, comparable with E2 treatment. However, increase in uterine weight and estrogenicity were observed in E2-treated ovariectomized mice, but not in response to DGP treatment. Treatment with DGP increased messenger RNA expression of runt-related transcription factor 2, osterix, and collagen type I, and decreased messenger RNA expression of tartrate-resistant acid phosphatase and the osteoprotegerin-to-receptor activator of nuclear factor-κB ligand ratio in the femur of ovariectomized mice.
Overall findings suggest that DGP treatment can effectively prevent OVX-induced increase in bone loss and decrease in bone strength possibly by increasing osteoblastic activities and by decreasing osteoclastic activities.
黄檀酚(DGP)是从印度黄檀心材中分离出的一种新黄酮类化合物。DGP对骨骼健康的影响尚待阐明。本研究的目的是探讨DGP对去卵巢小鼠骨质流失的生物学效应。
将成年BALB/c小鼠去卵巢,然后分别口服给予DGP(1和5毫克/千克/天)或17β-雌二醇(E2),持续6周。假手术组和去卵巢(OVX)+赋形剂组作为对照。每组取8只雌性BALB/c小鼠。研究子宫雌激素活性、骨微结构、生物力学强度、新骨形成(基于骨形成率和矿物质沉积率)以及成骨和吸收基因标志物的骨骼表达。
OVX导致体重显著增加,股骨和椎骨小梁骨体积减少,而DGP或E2治疗可预防这种情况。DGP治疗可增加去卵巢小鼠的骨生物力学强度和新骨形成率,与E2治疗相当。然而,E2治疗的去卵巢小鼠子宫重量和雌激素活性增加,而DGP治疗则无此反应。DGP治疗可增加去卵巢小鼠股骨中与 runt相关转录因子2、osterix和I型胶原蛋白的信使核糖核酸表达,并降低抗酒石酸酸性磷酸酶的信使核糖核酸表达以及骨保护素与核因子κB受体激活剂配体的比例。
总体研究结果表明,DGP治疗可能通过增加成骨细胞活性和降低破骨细胞活性,有效预防OVX诱导的骨质流失增加和骨强度降低。