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| 新穿心莲内酯调控MAPK/NF-κB/PI3K-AKT和激活钙离子通路抑制骨量丢失 |
| Neoandrographolide inhibits bone loss by regulating MAPK/NF-κB/PI3K-AKT and activating of calcium pathway |
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| DOI：10.3969/j.issn.1006-7108.2026.03.002 |
| 中文关键词: 穿心莲 穿心莲内酯 骨质疏松症 破骨细胞分化 |
| 英文关键词:neoandrographolide andrographis paniculata (Burm. f.) Nees osteoporosis osteoclast differentiation |
| 基金项目:河南省中医药科学研究专项项目（20-21ZY1058，20-21ZY2243）；洛阳市公益性行业医疗卫生专项项目（2022008A） |
| 作者 | 单位 | | 栾继耀1 程启潮2 洪悦雯2,3,4 李海山2,3,4 邓威2,3,4 潘其鹏1 乔杨1 王文举1 孔凡国1* | 1.河南省洛阳正骨医院/河南省骨科医院,河南 郑州 450000
2.广州中医药大学,广东 广州 510006
3.广州中医药大学第二临床医学院/广州中医药大学附属第二医院/广东省中医院,广东 广州 510405
4.广州中医药大学岭南医学研究中心,广东 广州510006 |
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| 中文摘要: |
| 目的 骨质疏松症（osteoporosis，OP）是一种以骨微结构破坏和骨量减少为特征的老年代谢性骨病，其病理机制与破骨细胞（osteoclast，OC）骨吸收功能异常活跃密切相关。本研究旨在探究穿心莲的有效成分新穿心莲内酯（neoandrographolide，NEO）抑制破骨细胞分化及骨吸收的作用机制，为OP的药物开发提供理论依据。方法 通过体内外实验结合验证NEO对OC形成的作用浓度和机制，体外实验提取骨髓来源巨噬细胞（bone marrow-derived macrophages，BMMs）并在M-CSF和RANKL的作用下诱导分化为成熟OC，评估NEO（≤30 μmol/L）的细胞毒性及对破骨细胞分化的影响，运用TRAP染色、RT-PCR和Western Blot检测破骨细胞成熟标志物及相关信号通路变化；体内实验通过OP动物模型，分析NEO对骨量丢失的干预效果。结果 NEO在≤30 μmol/L浓度下对BMMs无显著细胞毒性。TRAP染色表明其可显著抑制成熟破骨细胞形成，RT-PCR及Western Blot显示NEO通过调控MAPK/NF-κB/PI3K-AKT/Ca2+信号通路的磷酸化水平，下调破骨细胞特异性基因（MMP9、NFATc1、c-Fos、CTSK）的表达。动物实验证实，NEO可有效缓解骨破坏并减少骨量丢失。结论 NEO通过介导多通路协同调控破骨细胞分化，抑制骨吸收功能，提示其具有治疗OP的潜在价值。本研究为中药单体靶向OC的研究提供了实验依据。 |
| 英文摘要: |
| Objective Osteoporosis (OP) is an age-related metabolic bone disease characterized by disrupted bone microstructure and reduced bone mineral density, primarily resulting from pathological hyperactivity of osteoclast (OC)-mediated bone resorption. This study investigated the mechanism by which neoandrographolide (NEO), a bioactive compound isolated from andrographis paniculata (Burm. f.) Nees, inhibited OC differentiation and bone resorption, thereby providing theoretical foundation for novel OP therapeutic development. Methods The inhibitory effects of NEO on OC formation were evaluated through comprehensive in vitro and in vivo approaches. Primary bone marrow-derived macrophages (BMMs) were isolated and differentiated into mature OC via macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-Β ligand (RANKL) stimulation. NEO concentrations (≤30 μmol/L) were assessed for cytotoxicity and anti-osteoclastogenic activity using tartrate-resistant acid phosphatase (TRAP) staining, RT-PCR, and Western blotting analyses to quantify OC-specific markers and associated signaling pathways. An established OP animal model was subsequently employed to validate NEO's therapeutic efficacy against pathological bone loss. Results NEO demonstrated no significant cytotoxicity toward BMMs at concentrations ≤30 μmol/L. TRAP staining revealed that NEO treatment significantly suppressed mature OC formation in a dose-dependent manner. Mechanistically, NEO significantly down-regulated OC-related genes (MMP9, NFATc1, c-Fos, CTSK) and modulated phosphorylation levels within MAPK, NF-κB, PI3K-AKT, and Ca2? signaling cascades. In the in vivo model, NEO effectively attenuated bone destruction and significantly mitigated bone mass reduction. Conclusion NEO inhibits osteoclastogenesis and subsequent bone resorption through coordinated regulation of multiple signaling pathways, demonstrating substantial therapeutic potential for OP treatment. This study provides compelling experimental evidence for targeting OC activity with botanical monomers derived from traditional Chinese medicine, opening new avenues for osteoporosis pharmacotherapy. |
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