An intergated serum and urinary metabonomic research based on UPLC-MS and therapeutic effects of Gushudan on prednisolone-induced osteoporosis rats

An intergated serum and urinary metabonomic research based on UPLC-MS and therapeutic effects of Gushudan on prednisolone-induced osteoporosis rats
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DOI:
10.1016/j.jchromb.2016.05.019
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发表时间:
2016-08-01
影响因子:
3
通讯作者:
Xiong, Zhili
Xiong, Zhili
中科院分区:
医学3区
文献类型:
--
作者:
Huang, Yue;Bo, Yunhai;Xiong, Zhili

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骨疏丹是以中医理论为基础,专为治疗骨质疏松症而设计的中药复方。然而,其体内干预的有效机制还不是很清楚。本研究建立了基于UPLC-MS技术的血、尿综合代谢组学策略,以期加深对骨质疏松症代谢特点的认识,并探讨骨疏丹对强的松龙诱导的骨质疏松症大鼠模型的整体治疗作用。采用主成分分析(PCA)对正常对照组、强的松龙骨质疏松症模型组和骨疏丹治疗组大鼠的代谢谱进行比较,并将3组大鼠的代谢谱进行了明确的区分。此外,从尿液中鉴定出17个潜在生物标志物,从血清中鉴定出10个潜在生物标志物,初步与氨基酸代谢、能量代谢、脂肪代谢、肠道菌群代谢和肾脏损害有关。骨疏丹通过调节多种代谢途径对骨质疏松大鼠有治疗作用。值得一提的是,本研究首次发现了一些与骨质疏松症相关的新生物标志物,如3-甲氧基多巴、2,8-二羟基腺嘌呤等。本研究为深入了解强的松龙诱导的骨质疏松症的代谢组学机制和评价骨疏丹对骨质疏松大鼠的疗效提供了有用的途径。研究还表明,代谢组学方法在中药复方的药效和作用机制研究中具有广阔的应用前景。(C)2016爱思唯尔B.V.保留所有权利。
Gushudan, a Chinese compound formulation based on the theory of traditional Chinese medicine and desgined to treat osteoporosis. However, its intergated intervention effective mechanism in vivo is not well understood. In this study, an intergated serum and urinary metabonomic strategy based on UPLC-MS technique have been developed to increase the understanding of the metabolism characters of osteoporosis and to investigate the holistic therapeutic efficacy of Gushudan on prednisolone-induced osteoporosis rat model. Principle component analysis (PCA) was utilized to identify differences in metabolic profiles of rats in the control group, prednisolone-induced osteoporosis model group and Gushudan-treatment group and clear separation was achieved among three groups. Furthermore, 17 potential biomarkers from urine and 10 potential biomarkers from serum were identified, primiarily related to amino acid metabolism, energy metabolism, lipid metabolism, intestinal flora metabolism and kidney damage. Gushudan has therapeutic effects on rat with osteoporosis via the regulation of multiple metabolic pathways. It's worth mentioning that some new biomarkers associated with osteoporosis such as 3-methoxydopa, 2,8-digydroxyadenine have been discovered in this study for the first time. This study provides a useful approach to get insight into the intergated metabonomic mechanism of prednisolone-induced osteoporosis and to assess the efficacy of Gushudan on osteoporotic rats. The work also shows that the metabonomics method is a promising tool in the efficacy and mechanism research of traditional Chinese compound medicines. (C) 2016 Elsevier B.V. All rights reserved.