Zhang Ai-Hua, Ma Zhi-Ming, Sun Hui, Zhang Ying, Liu Jian-Hua, Wu Fang-Fang, Wang Xi-Jun
National TCM Key Laboratory of Serum Pharmacochemistry, Laboratory of Metabolomics, Department of Pharmaceutical Analysis, National Chinmedomics Research Center, Sino-America Chinmedomics Technology Collaboration Center, Heilongjiang University of Chinese Medicine, Harbin, China.
National Engineering Laboratory for the Development of Southwestern Endangered Medicinal Materials, Guangxi Botanical Garden of Medicinal Plant, Nanning, China.
Front Pharmacol. 2019 May 29;10:553. doi: 10.3389/fphar.2019.00553. eCollection 2019.
Postmenopausal osteoporosis (PMOP) is a common clinical illness in postmenopausal women, but there is no effective drug at present. Metabolomics approach was used to explore the potential biomarkers of PMOP and evaluate the efficacy and therapeutic targets of total lignans in the stem of Acanthophanax senticosus (ASSL) on the ovariectomized osteoporosis model rats. UPLC/MS and pattern recognition methods were used for serum metabolites discovery to illustrate the pathological mechanism of PMOP model rats, and then revealing the intervention effect of ASSL. The pattern recognition result showed that serum metabolic profiles of the sham operation group and the model group were clustered clearly, and 16 potential biomarkers were finally identified (7 in positive ion mode and 9 in negative ion mode), and they are involved in 15 related metabolic pathways. After oral administration of ASSL, 10 biomarkers were found to be significantly up-regulated and mainly regulated metabolic pathways include unsaturated fatty acid biosynthesis, linoleic acid metabolism, and arachidonic acid metabolism, primary bile acid synthesis, tyrosine metabolism, etc. Our study demonstrated that the ASSL could affect the endogenous metabolites related metabolic mechanism, provides a pharmacological basis of the ASSL for PMOP treatment.
绝经后骨质疏松症（PMOP）是绝经后女性常见的临床疾病，但目前尚无有效药物。采用代谢组学方法探索PMOP的潜在生物标志物，并评价刺五加茎总木脂素（ASSL）对去卵巢骨质疏松模型大鼠的疗效及治疗靶点。运用超高效液相色谱/质谱联用技术（UPLC/MS）和模式识别方法发现血清代谢物，以阐明PMOP模型大鼠的病理机制，进而揭示ASSL的干预作用。模式识别结果显示，假手术组和模型组血清代谢谱聚类明显，最终鉴定出16个潜在生物标志物（正离子模式下7个，负离子模式下9个），它们参与15条相关代谢途径。口服ASSL后，发现10个生物标志物显著上调，主要调节的代谢途径包括不饱和脂肪酸生物合成、亚油酸代谢、花生四烯酸代谢、初级胆汁酸合成、酪氨酸代谢等。我们的研究表明，ASSL可影响内源性代谢物相关代谢机制，为ASSL治疗PMOP提供了药理学依据。
