Zhang Yan, Diao Teng-Yue, Wang Liang, Che Chun-Tao, Wong Man-Sau
State Key Laboratory of Dairy Biotechnology, Bright Dairy Research Institute, Shanghai 200436, China; Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai 200093, China.
Center for Systems Biomedical Sciences, University of Shanghai for Science and Technology, Shanghai 200093, China.
J Ethnopharmacol. 2014 Dec 2;158 Pt A:239-45. doi: 10.1016/j.jep.2014.10.025. Epub 2014 Oct 30.
Fructus Ligustri Lucidi (FLL), the fruit of Ligustrum lucidum Ait, is a commonly prescribed herb to nourish the endocrine and renal systems and to strengthen the bones in Traditional Chinese Medicine. This study was aimed to determine the effects of water fraction of FLL ethanol extract (WF-EE) on urinary calcium excretion and trabecular bone properties in type 1 diabetic mice.
The DBA/2J mice with type 1 diabetes induced by streptozotocin injection were orally administered with WF-EE. After 6 weeks of treatment, the level of biomarkers, including serum calcium, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) and urine calcium, was measured. Micro-CT was performed to detect trabecular bone properties of the proximal tibial metaphysis. The expression of active calcium transporting proteins in kidney and duodenum was determined by RT-PCR, immunoblotting and immunostaining.
Type 1 diabetes induced hypercalciuria and trabecular bone deterioration. The WF-EE could significantly inhibit hypercalciuria and ameliorate the micro-structure of trabecular bone as well as increase serum PTH and FGF-23 levels in type 1 diabetic mice. The gene expressions of active calcium transporting proteins in duodenum were up-regulated, and the gene and protein expressions of calcium-sensing receptor (CaSR) in kidney were dramatically down-regulated in diabetic mice in response to the treatment with WF-EE.
The present study demonstrated the protective effects of the water fraction of Fructus Ligustri Lucidi ethanol extract against hypercalciuria and trabecular bone deterioration in experimentally type 1 diabetic mice, and the underlying mechanism may be attributed to its regulations on duodenal calcium transporting proteins and renal CaSR.
女贞子（Fructus Ligustri Lucidi，FLL）是女贞（Ligustrum lucidum Ait）的果实，是一种在传统中医中常用于滋养内分泌和肾脏系统以及强健骨骼的草药。本研究旨在确定女贞子乙醇提取物的水相部分（WF-EE）对1型糖尿病小鼠尿钙排泄和小梁骨特性的影响。
将通过注射链脲佐菌素诱导1型糖尿病的DBA/2J小鼠口服给予WF-EE。治疗6周后，测量包括血清钙、甲状旁腺激素（PTH）、成纤维细胞生长因子23（FGF-23）和尿钙在内的生物标志物水平。进行显微CT检测胫骨近端干骺端的小梁骨特性。通过逆转录聚合酶链反应（RT-PCR）、免疫印迹和免疫染色测定肾脏和十二指肠中活性钙转运蛋白的表达。
1型糖尿病导致高钙尿症和小梁骨退化。WF-EE可显著抑制1型糖尿病小鼠的高钙尿症，改善小梁骨的微观结构，并提高血清PTH和FGF-23水平。十二指肠中活性钙转运蛋白的基因表达上调，而糖尿病小鼠肾脏中钙敏感受体（CaSR）的基因和蛋白表达在接受WF-EE治疗后显著下调。
本研究证明了女贞子乙醇提取物的水相部分对实验性1型糖尿病小鼠的高钙尿症和小梁骨退化具有保护作用，其潜在机制可能归因于其对十二指肠钙转运蛋白和肾脏CaSR的调节作用。
