Bitto A, Burnett B P, Polito F, Marini H, Levy R M, Armbruster M A, Minutoli L, Di Stefano V, Irrera N, Antoci S, Granese R, Squadrito F, Altavilla D
Section of Pharmacology, Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy.
Br J Pharmacol. 2008 Nov;155(6):896-905. doi: 10.1038/bjp.2008.305. Epub 2008 Aug 11.
Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis.
Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg(-1) s.c.); alendronate (0.003 and 0.03 mg kg(-1) s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.); 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology.
Genistein (10 mg kg(-1)) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels.
The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.
染料木黄酮苷元对绝经后女性的骨质流失有积极影响，但骨质质量数据仍很缺乏。为阐明这一点，我们在已建立的骨质疏松动物模型中研究了染料木黄酮与阿仑膦酸钠、雷洛昔芬和雌二醇相比的效果。
卵巢切除术后6个月，将96只去卵巢（OVX）大鼠分为8个相等的组，随机接受治疗（染料木黄酮苷元（1和10 mg kg⁻¹皮下注射）；阿仑膦酸钠（0.003和0.03 mg kg⁻¹皮下注射）；盐酸雷洛昔芬（0.05和0.5 mg kg⁻¹皮下注射）；17-α-乙炔基雌二醇（0.003和0.03 mg kg⁻¹皮下注射）），持续12周。未治疗的OVX大鼠（n = 12）和假手术OVX大鼠（n = 12）用作对照。在治疗开始和结束时评估骨密度（BMD）和骨矿物质含量（BMC）。在实验结束时，测定钙、磷、骨碱性磷酸酶（b-ALP）、胶原蛋白C末端肽（CTX）、骨保护素（OPG）和核因子κB受体活化因子配体可溶性受体（sRANKL）。取出股骨并测试其断裂强度和组织学。
染料木黄酮（10 mg kg⁻¹）在BMD（与OVX相比，P < 0.0001）和BMC方面的增加均大于所有其他治疗。此外，与所有剂量水平的其他治疗相比，染料木黄酮显著提高了断裂强度、骨质质量、b-ALP（与OVX相比，P < 0.0001）和OPG，并降低了CTX和sRANKL。
结果强烈表明，染料木黄酮苷元可能是治疗人类绝经后骨质疏松症的一种新疗法。
