Luo Duosheng, Li Jingbiao, Chen Kechun, Rong Xianglu, Guo Jiao
Key Unit of Modulating Liver to Treat Hyperlipemia SATCM (State Administration of Traditional Chinese Medicine), Guangdong Pharmaceutical University, Guangzhou, China.
Guangdong Metabolic Disease Research Center of Integrated Chinese and Western Medicine, Guangzhou, China.
Front Pharmacol. 2019 Jan 8;9:1483. doi: 10.3389/fphar.2018.01483. eCollection 2018.
Fufang Zhenzhu Tiaozhi (FTZ), as an effective traditional Chinese medicine, has been prescribed for more than 20 years. It has proven clinical efficacy as a prescription for patients with dyslipidemia, glucocorticoid- and high-fat-induced osteoporosis, but its effect on osteoporosis induced by aging is still unclear. The aim of this study was to investigate the anti-osteoporosis effect of FTZ in aging mice and revealed its biochemical action mechanism using metabolomics. Model of primary osteoporosis induced by aging was established. The mice in treatment group received a therapeutic dose of oral FTZ extract once daily during the experiment. The model and control groups received the corresponding volume of oral normal saline solution. Plasma samples of all three groups were collected after 12 weeks. Clinical biochemical parameters and biomechanics were determined in the osteoporosis model induced by normal aging to evaluate anti-osteoporosis effect of FTZ. Ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was used to analyze metabolic changes. The changes of histomorphometric and biomechanic parameters of femurs, as well as osteoblast and osteoclast activity indicated that FTZ administration reduced the risk of osteoporosis. Partial least squares discriminant analysis (PLS-DA) score plot revealed a clear separation trend between model and controls. Moreover, PLS-DA score plot indicated the anti-osteoporosis effect of FTZ with sphingosine 1-phosphate, LPA (16:0) and arachidonic acid (AA) among key biomarkers. The pivotal pathways revealed by pathway analysis including sphingolipid metabolism, glycerophospholipid metabolism, and AA metabolism. The mechanism by which FTZ reduces the risk of primary age-related osteoporosis in mice might be related to disorders of the above-mentioned pathways. FTZ has a protective effect against osteoporosis induced by aging, which may be mediated via interference with sphingolipid, glycerophospholipid, and AA metabolisms in mice.
复方珍珠调脂（FTZ）作为一种有效的中药，已被应用20多年。它作为治疗血脂异常、糖皮质激素和高脂诱导的骨质疏松症患者的处方，已被证明具有临床疗效，但其对衰老诱导的骨质疏松症的作用仍不清楚。本研究旨在探讨FTZ对衰老小鼠的抗骨质疏松作用，并利用代谢组学揭示其生化作用机制。建立衰老诱导的原发性骨质疏松症模型。治疗组小鼠在实验期间每天口服一次治疗剂量的FTZ提取物。模型组和对照组口服相应体积的生理盐水溶液。12周后收集三组小鼠的血浆样本。在正常衰老诱导的骨质疏松症模型中测定临床生化参数和生物力学指标，以评估FTZ的抗骨质疏松作用。采用超高效液相色谱-四极杆飞行时间质谱联用（UPLC-QTOF/MS）分析代谢变化。股骨组织形态计量学和生物力学参数的变化，以及成骨细胞和破骨细胞活性表明，FTZ给药降低了骨质疏松症的风险。偏最小二乘判别分析（PLS-DA）得分图显示模型组和对照组之间有明显的分离趋势。此外，PLS-DA得分图表明FTZ在关键生物标志物中对鞘氨醇1-磷酸、LPA（16:0）和花生四烯酸（AA）具有抗骨质疏松作用。通路分析揭示的关键通路包括鞘脂代谢、甘油磷脂代谢和AA代谢。FTZ降低小鼠原发性年龄相关性骨质疏松症风险的机制可能与上述通路紊乱有关。FTZ对衰老诱导的骨质疏松症具有保护作用，这可能是通过干扰小鼠的鞘脂、甘油磷脂和AA代谢介导的。
