Xiu Chunmei, Luo Hua, Huang Weixing, Fan Shaohua, Yuan Chiting, Chen Jiangjie, Xu Chenghao, Yao Can, Hong Dun, Zhang Liwei
Institute of Bone Metabolism, Taizhou Hospital of Zhejiang Province, School of Medicine, Zhejiang University, Taizhou, 317000, People's Republic of China.
Department of Clinical Medicine, Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou, 310015, People's Republic of China.
Drug Des Devel Ther. 2025 Jun 3;19:4689-4715. doi: 10.2147/DDDT.S515930. eCollection 2025.
To investigate the therapeutic potential of lobetyolin (LBT), a bioactive compound derived from , against bone loss in postmenopausal osteoporosis (PMOP).
To investigate the therapeutic potential of LBT in osteoporosis, a multifaceted approach involving network pharmacology and molecular docking was employed to identify relevant targets and elucidate mechanisms of action. In vitro experiments evaluated LBT's impact on osteoclastogenesis, bone resorption, and osteoblast differentiation using bone marrow macrophages (BMMs) and bone marrow mesenchymal stromal cells (BMSCs). The inhibition of RANKL-activated NF-κB signaling and downstream NFATc1/c-Fos pathways was analyzed via Western blot and immunofluorescence. Additionally, an in vivo ovariectomy (OVX)-induced osteoporosis mouse model was utilized to examine the effects of LBT on bone architecture, assessed through micro-CT imaging and histological analyses.
LBT effectively suppressed RANKL-driven osteoclast differentiation in vitro without cytotoxic effects, reducing osteoclast numbers, size, and resorptive function. It also downregulated osteoclast-specific genes expressions, inhibited ROS production, and disrupted the NF-κB signaling cascade by blocking p50/p65 nuclear translocation. Moreover, LBT mitigated LPS-induced osteogenic impairment, enhancing osteoblast differentiation and mineralization. In the OVX mouse model, LBT treatment improved bone microstructure. Histological analyses further corroborated LBT's role in reducing osteoclast activity and promoting bone formation.
LBT exerts a dual effect on bone remodeling, simultaneously inhibiting osteoclast-mediated bone resorption and promoting osteoblast-driven bone formation. By targeting key pathways such as NF-κB/NFATc1/c-Fos and reducing inflammatory responses, LBT emerges as a potential therapeutic agent for managing PMOP and other conditions associated with excessive bone loss, offering a safer alternative to current treatments.
研究从[来源未提及]中提取的生物活性化合物洛贝蒂林（LBT）对绝经后骨质疏松症（PMOP）骨质流失的治疗潜力。
为研究LBT在骨质疏松症中的治疗潜力，采用了一种多方面的方法，包括网络药理学和分子对接，以确定相关靶点并阐明其作用机制。体外实验使用骨髓巨噬细胞（BMMs）和骨髓间充质基质细胞（BMSCs）评估LBT对破骨细胞生成、骨吸收和成骨细胞分化的影响。通过蛋白质免疫印迹法和免疫荧光分析RANKL激活的NF-κB信号通路及下游NFATc1/c-Fos通路的抑制情况。此外，利用体内卵巢切除（OVX）诱导的骨质疏松小鼠模型，通过显微CT成像和组织学分析来检测LBT对骨骼结构的影响。
LBT在体外有效抑制RANKL驱动的破骨细胞分化，且无细胞毒性作用，减少了破骨细胞数量、大小和吸收功能。它还下调破骨细胞特异性基因表达，抑制活性氧生成，并通过阻断p50/p65核转位破坏NF-κB信号级联反应。此外，LBT减轻了LPS诱导的成骨损伤，增强了成骨细胞分化和矿化。在OVX小鼠模型中，LBT治疗改善了骨微观结构。组织学分析进一步证实了LBT在降低破骨细胞活性和促进骨形成方面的作用。
LBT对骨重塑具有双重作用，同时抑制破骨细胞介导的骨吸收并促进成骨细胞驱动的骨形成。通过靶向NF-κB/NFATc1/c-Fos等关键通路并减少炎症反应，LBT有望成为治疗PMOP和其他与过度骨质流失相关病症的潜在治疗药物，为当前治疗提供了更安全的替代方案。
