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Inhibition of tanshinone IIA on renin activity protected against osteoporosis in diabetic mice

丹参酮Ⅱa对糖尿病小鼠肾素活性的抑制作用

  • 影响因子:2.43
  • DOI:10.1080/13880209.2020.1738502
  • 作者列表:"Jingjing Zhang","Zixuan Cai","Min Yang","Lijuan Tong","Yan Zhang
  • 发表时间:2020-04-02
Abstract

Context: Salvia miltiorrhiza Bge. (Labiatae) (SMB) is applied clinically for management of diabetic osteoporosis in China, and research results has suggested its potential action on renin–angiotensin system (RAS). Objective: This study screens and explores naturally occurring bioactive constituents from the root of SMB acting on renin activity and evaluates its osteoprotective efficacy in diabetic mice. Materials and methods: Human embryonic kidney (HEK) 293 cells, engineered to express human renin, were used as an in vitro model to identify bioactive compound, tanshinone IIA, inhibiting renin activity. The C57BL/6 mice (n = 10 in each group) with diabetes induced by streptozotocin (STZ) were intraperitoneally injected with tanshinone IIA (10 and 30 mg/kg). The mice without STZ treatment and the diabetic mice treated with aliskiren were used as non-diabetic control and positive control, respectively. Results: Tanshinone IIA was found to display inhibitory effects on renin activity of HEK-293 cells; moreover, it down-regulated protein expression of ANG II in human renin-expressed HEK-293 cells. Treatment of diabetic mice with tanshinone IIA with both doses could significantly decrease ANG II level in serum (from 16.56 ± 1.70 to 10.86 ± 0.68 and 9.14 ± 1.31 pg/mL) and reduce ANG II expression in bone, consequently improving trabecular bone mineral density and micro-structure of proximal tibial end and increasing trabecular bone area of distal femoral end in diabetic mice. Conclusions: This study revealed beneficial effects of tanshinone IIA on bone of diabetic mice, and potentially suggested the application of Salvia miltiorrhiza in the treatment of osteoporosis and drug development of tanshinone IIA as a renin inhibitor.

摘要

背景:丹参。在我国临床上已应用于糖尿病性骨质疏松症的治疗,研究结果提示其对肾素-血管紧张素系统(RAS)具有潜在的作用。目的:筛选和探讨丹参根中天然活性成分对肾素活性的影响,评价其对糖尿病小鼠的骨保护作用。材料与方法:以人胚肾(HEK)293细胞表达人肾素为模型,体外鉴定抑制肾素活性的生物活性物质丹参酮Ⅱa。用链脲佐菌素(STZ)诱导的C57BL/6小鼠(每组10只)腹腔注射丹参酮Ⅱa(10和30毫克/千克)。分别以未经STZ治疗的小鼠和aliskiren治疗的糖尿病小鼠作为非糖尿病对照组和阳性对照组。结果:丹参酮Ⅱa对HEK-293细胞肾素活性有抑制作用,并下调人肾素表达HEK-293细胞ANGⅡ蛋白表达。两种剂量丹参酮Ⅱa治疗糖尿病小鼠均能显著降低血清ANGⅡ水平(从16.56±1.70降至10.86±0.68和9.14±1.31μg/mL),降低骨ANGⅡ表达,从而改善糖尿病小鼠胫骨近端小梁骨密度和微结构,增加股骨远端小梁骨面积。结论:丹参酮Ⅱa对糖尿病小鼠有良好的骨保护作用,提示丹参酮Ⅱa作为肾素抑制剂在治疗骨质疏松症和药物开发中的应用。

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来源期刊:Food & function
DOI:10.1039/c9fo01817d
作者列表:["Galán MG","Weisstaub A","Zuleta A","Drago SR"]

METHODS::Apparent calcium absorption, total bone mineral content and density, and mineral contents of the right femur were studied using a growing rat model. Twenty-four male Wistar rats were fed with diets based on extruded whole grain red (RSD) or white sorghum (WSD), and control diet (CD) up to 60 days. The animals fed with sorghum diets consumed less and gained less weight compared to those fed with CD, but the efficiency of all diets was similar. Calcium intake was lower in animals fed with sorghum diets, related to the lower total intake of these animals. Apparent calcium absorption in animals fed with RSD was lower than in those fed with CD (CD: 72.7%, RSD: 51.0%, WSD: 64.8%). No significant differences in bone mineral density of total body, spin, femur, distal femur, tibia and proximal tibia were observed among the groups. However, Ca and P contents in the right femur of the rats consuming RSD were lower, indicating a certain imbalance in the metabolism of these minerals.

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影响因子:1.50
发表时间:2020-01-24
来源期刊:Skeletal radiology
DOI:10.1007/s00256-020-03378-z
作者列表:["Schaffler-Schaden D","Kneidinger C","Schweighofer-Zwink G","Flamm M","Iglseder B","Pirich C"]

METHODS:OBJECTIVE:Controversy exists about the impact of bone mineral density (BMD) and fracture risk in newly diagnosed patients with breast cancer (BC). It is presumed that there are differences in BMD between women with BC and healthy controls. BMD is therefore considered as a potential marker to predict BC risk. This study was conducted to investigate the association of BMD, trabecular bone score (TBS) and fracture risk in younger postmenopausal women with hormone responsive BC. METHODS:Overall, 343 women were examined. Women with BC were matched to a control group of the general population. Forty-nine women and fifty-nine controls were included in the final analysis. All subjects underwent dual energy x-ray absorptiometry (DXA) of the lumbar spine, femoral neck, and the total hip to evaluate bone mineral density. The 10-year fracture risk for a major osteoporotic fracture was assessed using the FRAX-score and the TBS-adjusted FRAX-Score, respectively. RESULTS:Lumbar and femoral neck BMD were similar in BC patients and controls. No difference was found for TBS of the spine (1.38 ± 0.1 vs.1.36 ± 0.09) in the BC and the control group, respectively (p = 0.19). The 10- year probability for a major osteoporotic fracture (MoF) or femoral neck (FN) fracture was 6.1 (± 2.6%) and 0.9 (± 1.2%) in the BC group vs. 6.7 (± 3.5%) (p = 0.33) and 0.9 (± 1.1%) (p = 0.73) in the control group. CONCLUSION:Postmenopausal women younger than 60 years with breast cancer do not show any differences in baseline BMD, TBS, or TBS adjusted FRAX in comparison to controls.

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影响因子:5.97
发表时间:2020-01-27
DOI:10.1002/adhm.201901385
作者列表:["Gurumurthy B","Tucci MA","Fan LW","Benghuzzi HA","Pal P","Bidwell GL","Salazar Marocho SM","Cason Z","Gordy D","Janorkar AV"]

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