Ma Yong-Sheng, Hou Zhan-Jiang, Li You, Zheng Beng-Beng, Wang Jia-Ming, Wang Wen-Bo
The Second Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
The Emergency Surgery Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Pharmacol. 2020 Aug 26;11:1316. doi: 10.3389/fphar.2020.01316. eCollection 2020.
Postmenopausal osteoporosis (PMOP) is a common metabolic bone disease in postmenopausal women in the Worldwide, and seriously affects the quality of life of middle-aged and elderly women. Therefore, there is an urgent need to discover a highly effective drug for PMOP treatment. In this study, ultra-high performance liquid tandem quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to analyze the urine metabolic profiling and potential biomarkers, the relevant metabolic network of PMOP rats, and further to evaluate the intervention effect of Eleutheroside E (EE) against PMOP. Using multivariate statistical analysis combined with UPLC-Q/TOF-MS, a total of 27 biomarkers were identified, which related with 16 metabolic pathways, mainly involving steroidogenesis, beta oxidation of very long chain fatty acids, glutathione metabolism, carnitine synthesis, estrone metabolism, oxidation of branched chain fatty acids, etc. After treatment of EE, these biomarkers were markedly regulated, mainly involving steroid hormone biosynthesis, arachidonic acid metabolism, primary bile acid biosynthesis, indicating that EE had the therapeutic effect on PMOP. This study identified the potential urine metabolic markers and related metabolic pathways of the PMOP, explained the metabolic effect and pharmacological mechanisms of EE against PMOP, and provided a basis for the pharmacological study of EE.
绝经后骨质疏松症(PMOP)是全球绝经后女性常见的代谢性骨病,严重影响中老年女性的生活质量。因此,迫切需要发现一种治疗PMOP的高效药物。本研究采用超高效液相色谱串联四极杆飞行时间质谱(UPLC-Q/TOF-MS)分析尿液代谢谱和潜在生物标志物、PMOP大鼠的相关代谢网络,并进一步评估刺五加苷E(EE)对PMOP的干预效果。通过多元统计分析结合UPLC-Q/TOF-MS,共鉴定出27种生物标志物,涉及16条代谢途径,主要包括类固醇生成、超长链脂肪酸的β氧化、谷胱甘肽代谢、肉碱合成、雌酮代谢、支链脂肪酸氧化等。EE治疗后,这些生物标志物受到明显调节,主要涉及类固醇激素生物合成、花生四烯酸代谢、初级胆汁酸生物合成,表明EE对PMOP具有治疗作用。本研究确定了PMOP潜在的尿液代谢标志物及相关代谢途径,阐释了EE对PMOP的代谢作用和药理机制,为EE的药理研究提供了依据。