Zhang Dazhen, Qu Xinzhe, Chu Fuchao, Wang Zhenxin, Mou Jie, Yuan Feng
Key Laboratory of Bone Tissue Regeneration and Digital Medicine, Xuzhou Medical University, Xuzhou 221006 Jiangsu, China; Department of Orthopedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006 Jiangsu, China; Xuzhou Medical University, Xuzhou 221006 Jiangsu, China.
Key Laboratory of Bone Tissue Regeneration and Digital Medicine, Xuzhou Medical University, Xuzhou 221006 Jiangsu, China; Xuzhou Medical University, Xuzhou 221006 Jiangsu, China.
Int J Pharm. 2025 Feb 25;671:125226. doi: 10.1016/j.ijpharm.2025.125226. Epub 2025 Jan 20.
Heterotopic ossification (HO) is characterized by abnormal bone formation outside the skeleton following injury or inherited disease, leading to limb dysfunction and neurological deficits. Current treatment options for HO are largely ineffective.
A network pharmacological analysis was conducted to identify the active ingredients and protein targets in Astragalus and Cinnamon Twig Five-Substance Decoction (ACTFSD) on HO. Protein-protein interaction analysis and Gene Ontology Enrichment Analysis were used to investigate the key genes associated with the target proteins. Molecular docking was employed to validate the interactions between the core components and targets of ACTFSD. Kaempferol was encapsulated in liposomes synthesized via the thin-film dispersion method. In vitro and in vivo experiments were conducted to evaluate the therapeutic effects of kaempferol liposomes.
Kaempferol, an active ingredient in ACTFSD, effectively inhibits the PTGS2\ NF-κB pathway, regulates macrophage immune responses, and reduces cytokine released by macrophages induce abnormal osteogenesis in tendon stem cells (TDSCs), thereby slowing the formation of HO. Kaempferol liposomes demonstrate better therapeutic effect than kaempferol alone.
This study indicates that targeting macrophages may represent an effective therapeutic strategy for HO. Furthermore, kaempferol liposomes appear to be a promising treatment for trauma-induced HO. These findings provide potential new directions for future HO treatment strategies.
异位骨化（HO）的特征是在受伤或遗传性疾病后骨骼外出现异常骨形成，导致肢体功能障碍和神经功能缺损。目前针对HO的治疗选择大多无效。
进行网络药理学分析，以确定黄芪桂枝五物汤（ACTFSD）对HO的活性成分和蛋白质靶点。使用蛋白质-蛋白质相互作用分析和基因本体富集分析来研究与靶蛋白相关的关键基因。采用分子对接来验证ACTFSD核心成分与靶点之间的相互作用。将山奈酚包裹在通过薄膜分散法合成的脂质体中。进行体外和体内实验以评估山奈酚脂质体的治疗效果。
山奈酚是ACTFSD中的一种活性成分，可有效抑制PTGS2\NF-κB通路，调节巨噬细胞免疫反应，并减少巨噬细胞释放的细胞因子诱导肌腱干细胞（TDSCs）异常成骨，从而减缓HO的形成。山奈酚脂质体显示出比单独使用山奈酚更好的治疗效果。
本研究表明，靶向巨噬细胞可能是治疗HO的有效策略。此外，山奈酚脂质体似乎是治疗创伤性HO的一种有前景的疗法。这些发现为未来HO治疗策略提供了潜在的新方向。
