Xu Yier, Chen Shuilin, Yu Tao, Qiao Jiutao, Sun Guicai
Laboratory of Pharmacology, Research & Development Center of Harbin Pharmaceutical Group, The South of Zhuhai Road, the East of Harbin-Yinchun Highway, Limin Development Zone, Harbin, China.
Department of orthopaedics, The Fourth Hospital attached to Nanchang University, No. 133, Guangchang South Road, Xihu District, Nanchang, Jiangxi 330003, China.
Phytomedicine. 2018 Dec 1;51:68-76. doi: 10.1016/j.phymed.2018.09.235. Epub 2018 Oct 6.
Osteoporosis has brought about heavy socio-economic burden in the morbidity and medical expenses associated with osteoporosis treatment and various restrictions on behavior of their social roles. Oleanolic acid (OA) is an anti-osteoporosis natural product, but molecular mechanisms of therapeutic effect are not still well known.
In this study, we explore anti-osteoporosis activity of oleanolic acid and predict the underlying mechanisms by metabolomics strategy.
SD rats were intraperitoneal injection with prednison for once to establish osteoporosis model. Using metabolomics strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight/ mass spectrometry (UPLC-TOF/MS), serum samples of 24 rats were analyzed to seek differential metabolites and pathway associated with OA treatment of osteoporosis. In addition, the effect of OA on osteoporosis rats was also evaluated by clinical biochemistry indicators and bone density analysis.
Clinical biochemistry indicators and bone density of lumbar and femur were reversed by OA treatment. A total of 25 potential biomarkers were identified in the rats model of glucocorticoid-induced osteoporosis, and oleanolic acid have a regulatory effect on 17 of them that related to some vital metabolic pathway such as linoleic acid metabolism, valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis as well as cysteine and methionine metabolism. The ingenuity pathway analysis (IPA) platform is applied to further understanding the relationship between metabolic changes and therapeutic effect of OA, which the disordered state carbohydrate metabolism, molecular transport and lipid metabolism in glucocorticoid-induced osteoporosis rats are mainly ameliorated by oleanolic acid.
Metabolomics provides a novel method to investigate the anti-osteoporosis effects of OA and probe into the potential mechanisms, and will contributes to the development of new drugs.
骨质疏松症在发病率、骨质疏松症治疗相关医疗费用以及对患者社会角色行为的各种限制方面带来了沉重的社会经济负担。齐墩果酸（OA）是一种具有抗骨质疏松作用的天然产物，但其治疗作用的分子机制尚不清楚。
本研究通过代谢组学策略探讨齐墩果酸的抗骨质疏松活性并预测其潜在机制。
对SD大鼠一次性腹腔注射泼尼松建立骨质疏松模型。采用基于超高效液相色谱-四极杆飞行时间质谱联用（UPLC-TOF/MS）的代谢组学策略，分析24只大鼠的血清样本，寻找与OA治疗骨质疏松相关的差异代谢物和代谢途径。此外，还通过临床生化指标和骨密度分析评估OA对骨质疏松大鼠的影响。
OA治疗可逆转腰椎和股骨的临床生化指标及骨密度。在糖皮质激素诱导的骨质疏松大鼠模型中，共鉴定出25种潜在生物标志物，齐墩果酸对其中17种有调节作用，这些生物标志物与一些重要代谢途径有关，如亚油酸代谢、缬氨酸、亮氨酸和异亮氨酸生物合成、苯丙氨酸、酪氨酸和色氨酸生物合成以及半胱氨酸和蛋氨酸代谢。应用 Ingenuity Pathway Analysis（IPA）平台进一步了解OA代谢变化与治疗效果之间的关系，结果表明齐墩果酸主要改善了糖皮质激素诱导的骨质疏松大鼠体内紊乱的碳水化合物代谢、分子转运和脂质代谢状态。
代谢组学为研究OA的抗骨质疏松作用及潜在机制提供了一种新方法，将有助于新药开发。
