Zhu Liming, Wang Yeqing, Zhu Zhongxin, Yao Xiaocong, Zhang Ruijuan, Xia Yujie, Liu Minbo
Department of Osteoporosis Care and Control Xiaoshan Affiliated Hospital of Wenzhou Medical University Zhejiang Hangzhou China.
Department of Pharmacy Xiaoshan Affiliated Hospital of Wenzhou Medical University Zhejiang Hangzhou China.
Food Sci Nutr. 2025 Jan 14;13(1):e4604. doi: 10.1002/fsn3.4604. eCollection 2025 Jan.
Osteoporosis (OP) is a prevalent metabolic bone disease globally. Currently, the development of Traditional Chinese Medicine (TCM) resources to unblock joints, strengthen bones, and enhance muscle function to regulate anti-osteogenic and anabolic metabolism and thus reshape intraosseous homeostasis was an effective way to alleviate OP. The F-E-D formula, comprising Fructus Psoraleae, Eucommia, and Drynariae Rhizoma, has shown efficacy in treating OP. However, its complex natural components necessitate the screening and simplification of bioactive compounds to further elucidate their therapeutic mechanisms and enhance therapeutic efficacy. In this study, we first used drug-target binding to produce different effects, which in turn exhibited different retention characteristics on the stationary phase. Using osteoblasts and osteoclasts as stationary phases, a chromatographic system (Solid-phase Bio-cell Chromatography, SBC) had been constructed to mimic the drug-target interaction, and the separation, analysis, and bioactivity screening of the chemical components of F-E-D had been performed. Then, the above collected eluates were analyzed by fine metabolomics, and 95 effective metabolites were initially screened and combined with database screening to finally select betaine, L-fucose, and itaconic acid as potentially active candidate compound monomers for the interaction with osteoblast-osteoclast in F-E-D. In terms of cell validation experiments, we found that the screened active monomers significantly inhibited the formation of osteoclasts, and the itaconic acid-treated group played a significant inhibitory effect on the expression of inflammatory factors TNF-α and IL-6. The above experimental data showed that the monomeric active ingredients in TCM could be effectively screened by solid-phase bio-chromatography and HPLC-MS, and the in vitro cellular experiments verified that the active monomers of TCM slowed down the progression of OP by inhibiting osteoclast production and alleviating the expression of inflammation.
骨质疏松症（OP）是一种在全球范围内普遍存在的代谢性骨病。目前，开发传统中药（TCM）资源以疏通关节、强健骨骼并增强肌肉功能，从而调节抗成骨和合成代谢，进而重塑骨内稳态，是缓解OP的有效途径。由补骨脂、杜仲和骨碎补组成的F-E-D配方已显示出治疗OP的功效。然而，其复杂的天然成分需要对生物活性化合物进行筛选和简化，以进一步阐明其治疗机制并提高治疗效果。在本研究中，我们首先利用药物-靶点结合产生不同的效应，进而在固定相上表现出不同的保留特性。以成骨细胞和破骨细胞作为固定相，构建了一种色谱系统（固相生物细胞色谱，SBC）以模拟药物-靶点相互作用，并对F-E-D的化学成分进行了分离、分析和生物活性筛选。然后，通过精细代谢组学对上述收集的洗脱液进行分析，初步筛选出95种有效代谢物，并结合数据库筛选，最终选择甜菜碱、L-岩藻糖和衣康酸作为F-E-D中与成骨细胞-破骨细胞相互作用的潜在活性候选化合物单体。在细胞验证实验方面，我们发现筛选出的活性单体显著抑制破骨细胞的形成，衣康酸处理组对炎症因子TNF-α和IL-6的表达具有显著抑制作用。上述实验数据表明，通过固相生物色谱和HPLC-MS可以有效地筛选中药中的单体活性成分，体外细胞实验证实中药活性单体通过抑制破骨细胞生成和减轻炎症表达减缓了OP的进展。
