女贞子活性成分防治骨质疏松症的分子机制  

Molecular mechanism of active ingredients of Ligustri Lucidi Fructus against osteoporosis

作　　者：王文驰 夏天[2] 武瑞骐 梁浩瀚 倪振扬 章震浩 李振兴[4] 陈广辉[4] 苏晗[4] Wang Wenchi;Xia Tian;Wu Ruiqi;Liang Haohan;Ni Zhenyang;Zhang Zhenhao;Li Zhenxing;Chen Guanghui;Su Han(Ruikang Hospital,Guangxi University of Chinese Medicine,Nanning 530000,Guangxi Zhuang Autonomous Region,China;Guangxi University of Chinese Medicine,Nanning 530000,Guangxi Zhuang Autonomous Region,China;Taihe Hospital of Wannan Medical College,Fuyang 236600,Anhui Province,China;First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530000,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西中医药大学附属瑞康医院,广西壮族自治区南宁市530000 [2]广西中医药大学,广西壮族自治区南宁市530000 [3]皖南医学院附属太和医院,安徽省阜阳市236600 [4]广西中医药大学第一附属医院,广西壮族自治区南宁市530000

出　　处：《中国组织工程研究》2025年第18期3856-3867,共12页Chinese Journal of Tissue Engineering Research

基　　金：广西医疗卫生适宜技术开发与推广应用项目(S2022053);广西高校中青年教师科研基础能力提升项目(2021KY0302);广西高水平中医药重点学科建设项目(2024016-02-04);广西中医药重点研究室建设项目-广西中医药经筋康复重点研究室(2024019-03);广西中医药重点培育学科建设项目(GZXK-Z-20-32);广西中医药大学高层次人才队伍建设项目-高层次人才培育创新团队(2022A006);2024年广西第七批全国老中医药专家学术经验继承工作项目,项目负责人:夏天;2024年广西中医药适宜技术开发与推广项目(GZSY22-39),项目负责人:夏天;2023年广西中医药大学博士科研启动基金项目(2023BS018),项目负责人:夏天。

摘　　要：背景:目前,中医药已被证实在抗骨质疏松方面具有显著作用,女贞子活性成分的抗骨质疏松有效性及作用机制逐渐得到学者们的关注。目的:分析总结女贞子活性成分在体内外发挥抗骨质疏松方面的研究进展。方法:检索中国知网及PubMed数据库收录的相关文献,中文检索词为“骨质疏松症,骨髓间充质干细胞,成骨细胞,破骨细胞,女贞子,信号通路”;英文检索词为“Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path”,并根据研究需要确立相应的标准,对所得文献进行筛选,最终纳入82篇文献进行综述。结果与结论:女贞子活性成分在体内外发挥抗骨质疏松作用主要涉及以下几种重要成分:①红景天苷通过抑制骨硬化蛋白(SOST)和Dickkopf相关蛋白1(Dkk1)的表达,激活了Wnt/β-catenin信号通路,该激活过程增强了去卵巢大鼠和原代成骨细胞中磷酸化低密度脂蛋白受体相关蛋白6(p-LRP6)的表达,同时降低了糖原合酶激酶3β的表达。进一步地,红景天苷促进了细胞核内β-catenin、特异性转录因子2(Runx2)和骨髓细胞瘤病毒癌基因(c-Myc)的表达,从而促进了成骨细胞的骨形成能力。红景天苷可直接作用于成骨细胞,促进骨形成,为骨质疏松症的治疗提供了新的策略。②橄榄苦苷显著提高了SD大鼠的骨密度,并通过降低终末白细胞介素6和碱性磷酸酶浓度来调节骨代谢。体外实验表明,橄榄苦苷促进了成骨细胞的增殖,并上调了骨保护素蛋白和mRNA的表达,同时抑制了核转录因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)蛋白和mRNA的表达。这一作用机制与调节骨保护素/RANKL系统的平衡密切相关,展现出能提高骨密度,又能通过调节骨代谢相关因子来维护骨骼健康的优势,但对Ca2+浓度无显著影响,可能限制了其在某些特定骨质疏松类型中的应用。③BACKGROUND:Traditional Chinese medicine has been proved to have a significant role in anti-osteoporosis,and the effectiveness and mechanism of Ligustri Lucidi Fructus and its the active ingredients against osteoporosis have gradually gained the attention of scholars.OBJECTIVE:To analyze and summarize the research progress of Ligustri Lucidi Fructus and its active ingredients against osteoporosis in vitro and in vivo.METHODS:We searched the relevant literature included in CNKI and PubMed databases using the search terms of“Osteoporosis,Bone marrow mesenchymal stem cells,Osteoblast,Osteoclast,Ligustri Lucidi Fructus,Signal path”in Chinese and English,respectively.According to the needs of the research,we established the corresponding criteria and screened the literature.A total of 82 papers were included in the final review.RESULTS AND CONCLUSION:(1)The active ingredients of Ligustri Lucidi Fructus that exert anti-osteoporotic effects in vitro and in vivo mainly involve the following:Salidroside activates the Wnt/β-catenin signaling pathway by inhibiting the expression of Sclerostin and Dickkopf-related protein 1.This activation process enhances the expression of phosphorylated low-density lipoprotein receptor-related protein 6 in ovariectomized rats and primary osteoblasts,while decreasing the expression of glycogen synthase kinase 3β.Further,it promotes the expression ofβ-catenin,runt-related transcription factor 2 and cellular myelocytomatosis oncogene in the nucleus,thereby promoting the bone formation capacity of osteoblasts.The advantage is that it acts directly on osteoblasts to promote bone formation,which provides a new strategy for the treatment of osteoporosis.(2)Olive bittersweet significantly increases bone mineral density and regulates bone metabolism by decreasing terminal interleukin-6 and alkaline phosphatase concentrations in Sprague-Dawley rats.In vitro experiments showed that olive bittersweet promotes the proliferation of osteoblasts and up-regulates the protein and mRNA expression of os

关 键 词：女贞子 骨质疏松症 氧化应激 骨吸收 成骨分化 信号通路 发病机制 综述 

分 类 号：R459.9[医药卫生—治疗学] R364[医药卫生—临床医学] R285