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齐墩果酸和齐墩果酸与熊果酸混合物均可模拟女贞子对去卵巢大鼠骨特性和循环 1,25-二羟胆钙化醇的作用。

Both Oleanolic Acid and a Mixture of Oleanolic and Ursolic Acids Mimic the Effects of Fructus ligustri lucidi on Bone Properties and Circulating 1,25-Dihydroxycholecalciferol in Ovariectomized Rats.

机构信息

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China.

Department of Nutrition Science, Purdue University, West Lafayette, IN.

出版信息

J Nutr. 2018 Dec 1;148(12):1895-1902. doi: 10.1093/jn/nxy242.

Abstract

BACKGROUND

Oleanolic acid (OA) and ursolic acid (UA) are major chemical constituents found in Fructus ligustri lucidi (FLL), a Chinese herb previously shown to increase bone properties and modulate calcium-vitamin D metabolism in rats. OA and UA have been reported to exert osteoprotective effects in vitro.

OBJECTIVE

The present study was designed to determine whether OA or OA + UA mimicked the effects of FLL on bone and calcium homeostasis using ovariectomized rats.

METHODS

Three-month-old ovariectomized Sprague-Dawley rats were stabilized for 2 mo and randomly assigned to 4 groups offered the same amount (15-17 g/d) of a control diet or experimental diets containing FLL (18.8 g/kg), OA (0.67 g/kg), or OA (0.67 g/kg) + UA (0.22 g/kg) for 6 wk. Serum was obtained for measurement of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] and bones were collected for micro-CT analysis. Calcium balance was measured at weeks 1 and 6. A calcium kinetic study using 45Ca was conducted at week 6 and modeled using WinSAAM software.

RESULTS

Compared with the control group, rats fed the FLL-, OA-, and OA + UA-enriched diets had better bone properties and 51%, 31%, and 27% higher serum 1,25(OH)2D3 concentrations at week 6, respectively. These variables did not differ between the treatments. Calcium balance was not affected by diet at either week 1 or week 6. Kinetic modeling predicted that FLL and OA + UA diet-fed rats had 9% and 15% less endogenous excretion of calcium, respectively, compared with the control group. All 3 treatments resulted in a higher calcium mass of compartment 3 because of changes in transfer rate between compartments 2 and 3, and were positively associated with the serum 1,25(OH)2D3 concentration (R2 = 0.28; P < 0.01).

CONCLUSION

Similar to FLL, OA and OA + UA increase bone properties, serum 1,25(OH)2D3 concentration, and calcium use in ovariectomized rats, suggesting their potential role in management of osteoporosis.

摘要

背景

齐墩果酸(OA)和熊果酸(UA)是女贞子(Fructus ligustri lucidi,FLL)中的主要化学成分,既往研究显示女贞子可改善大鼠的骨特性并调节钙-维生素 D 代谢。OA 和 UA 已被报道具有体外护骨作用。

目的

本研究旨在通过去卵巢大鼠模型确定 OA 或 OA+UA 是否可模拟 FLL 对骨和钙稳态的作用。

方法

3 月龄去卵巢 Sprague-Dawley 大鼠稳定 2 个月后,随机分为 4 组,分别给予相同量(15-17 g/d)的对照饮食或含有 FLL(18.8 g/kg)、OA(0.67 g/kg)或 OA(0.67 g/kg)+UA(0.22 g/kg)的实验饮食 6 周。采集血清以检测 1,25-二羟胆钙化醇[1,25(OH)2D3],收集骨骼进行 micro-CT 分析。在第 1 周和第 6 周测量钙平衡。第 6 周进行 45Ca 钙动力学研究,使用 WinSAAM 软件建模。

结果

与对照组相比,6 周时,给予 FLL、OA 和 OA+UA 饮食的大鼠具有更好的骨特性,血清 1,25(OH)2D3 浓度分别升高 51%、31%和 27%。各组间这些变量无差异。第 1 周和第 6 周时,饮食均未影响钙平衡。动力学模型预测,与对照组相比,FLL 和 OA+UA 饮食组大鼠的内源性钙排泄分别减少 9%和 15%。所有 3 种治疗方法均导致 3 号 compartment 的钙质量增加,这是由于 2 号 compartment 和 3 号 compartment 之间的转移率发生变化,并且与血清 1,25(OH)2D3 浓度呈正相关(R2=0.28;P<0.01)。

结论

与 FLL 相似,OA 和 OA+UA 可增加去卵巢大鼠的骨特性、血清 1,25(OH)2D3 浓度和钙利用率,提示其在骨质疏松症管理中的潜在作用。

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