Medication pattern and mechanism of marine traditional Chinese medicine in the treatment of osteoporosis

doi:10.12307/2025.646

Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (17): 3713-3723.doi: 10.12307/2025.646

Previous Articles Next Articles

Medication pattern and mechanism of marine traditional Chinese medicine in the treatment of osteoporosis

Lai Yue1, Lin Xuan2, Xu Miao3, Liu Huan4, Shen Jianlin5, Huang Wenhua1, 6

1The First Clinical Medical School, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China; 2Department of Environmental and Biological Engineering, Putian University, Putian 351100, Fujian Province, China; 3School of Basic Medicine, Fujian Medical University, Fuzhou 350100, Fujian Province, China; 4Department of Orthopaedics, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, China; 5Central Laboratory, the Affiliated Hospital of Putian University, Putian 351100, Fujian Province, China; 6Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, Southern Medical University, Guangzhou 510515, Guangdong Province, China

Received:2024-04-11 Accepted:2024-06-15 Online:2025-06-18 Published:2024-11-07
Contact: Shen Jianlin, Associate professor, Central Laboratory, the Affiliated Hospital of Putian University, Putian 351100, Fujian Province, China Co-corresponding author: Huang Wenhua, Professor, The First Clinical Medical School, Guangdong Medical University, Zhanjiang 524023, Guangdong Province, China; Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, Southern Medical University, Guangzhou 510515, Guangdong Province, China
About author:Lai Yue, Master candidate, The First Clinical Medical School, Guangdong Medical University, Zhanjiang 524002, Guangdong Province, China
Supported by:
the National Natural Science Foundation of China, No. 82301785 (to SJL)

Abstract

Abstract: BACKGROUND: Marine traditional Chinese medicine offers a potentially effective and less adverse treatment for osteoporosis.
OBJECTIVE: To explore the pharmacological regulations and procedures of traditional Chinese medicine in treating osteoporosis through data mining and network pharmacology techniques.
METHODS: Data mining and network pharmacology methods were used to study the medication pattern and mechanism of marine Chinese medicine patented prescriptions approved by China National Intellectual Property Administration for the treatment of osteoporosis, and special attention was paid to the core Chinese medicine constituents of these prescriptions. The core constituents of the compound drug group composed of oyster-Dipsacus asper-epimedium were comprehensively identified and analyzed by using ultra-high-performance liquid chromatography tandem mass spectrometry.
RESULTS AND CONCLUSION: (1) We collected 381 authorized compound patents for the treatment of osteoporosis from the database inception to April 1, 2024. Among these, 48 patent groups utilized marine traditional Chinese medicine. These prescriptions contained 183 Chinese herbal medicines, of which 13 marine traditional Chinese medicines were used 574 times in total, and the number of flavors used in a single patented formula ranged from 2 to 41. (2) Oyster was the most frequently used marine ingredient, while Dipsacus asper, epimedium, Rehmannia glutinosa, Eucommia ulmoides Oliv. were the most frequent non-marine components. Association rule analysis identified oyster, Dipsacus asper, and epimedium as the core drug group. Network pharmacology analysis revealed that the core targets of this group for the treatment of osteoporosis included ALB, AKT1, TP53, PPARG, and SRC. Sitosterol, liquiritigenin, japonine, luteolin, and kaempferol were identified as the core components within the marine traditional Chinese medicine prescriptions. (3) The GO and KEGFG enrichment analyses suggested a potential association between the mechanism of the core drug group and the rap1/mapk signaling pathway in the treatment of osteoporosis. (4) The molecular docking verified the beneficial interactions between core components and core targets. (5) The ultra-high-performance liquid chromatography tandem mass spectrometry analysis of the compound medicine confirmed the presence of luteolin, sitosterol, kaempferol, and other components, aligning with the drug components identified by network pharmacology. Quantitative analysis indicated that flavonoids, terpenes, and alkaloids constituted a significant proportion of the compound medicine’s components.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: osteoporosis, marine traditional Chinese medicine, data mining, network pharmacology, molecular docking

CLC Number:

Lai Yue, Lin Xuan, Xu Miao, Liu Huan, Shen Jianlin, Huang Wenhua. Medication pattern and mechanism of marine traditional Chinese medicine in the treatment of osteoporosis[J]. Chinese Journal of Tissue Engineering Research, 2025, 29(17): 3713-3723.

Figures/Tables 14

挖掘结果，选择置信度最高的牡蛎、续断和淫羊藿进行网络药理学分析。该软件的可视化工具被用来生成一个描述这些高频中药之间关联的网络，线条的粗细表示关联频率(图2)。 2.2 网络药理学分析结果 2.2.1 核心药组的药物作用靶点获取及疾病靶点筛选在所选的3种中药中共鉴定出35种(淫羊藿22种、续断8种和牡蛎5种)独特的药物成分，见表6。去除重复序列后，这些药物共537个药物靶点。从GeneCards、OMIM、TTD、Pharmgkb数据库中查询“osteoporosis”，以确定骨质疏松的靶点，检索得5 741，45，29，3个骨质疏松的潜在靶点。为了确定相关性高的靶点，通过选择相关性得分超过中位数2倍的GeneCards数据库结果，排除相关性低的疾病靶点，共产生1 650个潜在靶点。通过Cytoscape软件(3.10.1版)可以创建出一个完整的药物成分靶点网络图，如图3所示。 2.2.2 药物-疾病共同靶点获取及蛋白质-蛋白质相互作用网络的构建结果通过建立蛋白质-蛋白质相互作用网络系统，能够更好地理解药品与其他疾病的作用。为了实现这一目标，需要在Venn图(图4)中引用0.4的中等置信阈值，使用Cytoscape(版本3.10.1)对蛋白质-蛋白质相互作用网络实现可视化，如图5所示。拓扑分析显示ALB为最高值，提示其有可能成为研究药物治疗干预的关键靶点，AKT1、TP53和其他靶点也具有潜在的重要性。 2.2.3 核心靶点获取为了探究核心组方对骨质疏松的治疗作用机制，将127个交集靶点导入Cytoscape 3.10.1，运用插件Centiscape 2.2分析网络的拓扑参数，构建蛋白质-蛋白质相互作用网络。该网络包括127个节点和1 207条边，度中心性、紧密中心性和中介中心性分别为 19.008，0.004和 131.575。以度中心性≥2 倍作为筛选标准，经筛选后得到关键核心靶点10个(图6)及10个核心靶点信息(表7)。基于拓扑分析确定了核心蛋白质-蛋白质相互作用网络。在蛋白质-蛋白质相互作用网络中，节点大小、颜色与目标度数呈正比。 2.2.4 核心成分获取使用Cytoscape软件(3.10.1版)构建药物成分靶网络(图7)。利用Cytoscape插件CytoNCA研究网络拓扑参数，包括度中心性、紧密中心性、特征向量中心性和中介中心性。参数值超过平均值的组件被视为核心成分。表8列出了前10个核心组成部分，谷甾醇作为具有最高拓扑值，表明其是高频药组发挥疗效的主要成分；甘草素、臭山羊碱、木犀草素、山奈酚也被鉴定为潜在的重要成分。 2.2.5 GO 与 KEGG 富集分析结果为阐明核心药组治疗骨质疏松症的作用机制，对127个已鉴定的靶基因进行了GO富集分析。结果表明，在1 407个生物过程、76个细胞成分和136个分子功能中均有富集。根据P值显著性选择每个类别(生物过程、细胞成分和分子功能)中前20个富集项，并在气泡图中显示(图8A)。为了清晰起见，以柱状图(图8B)突出呈现每个类别中P值最低的一个项目共30"

个。GO富集分析结果表明，核心药物群主要影响与激素反应、细胞对脂质和肽的反应相关的生物过程，并涉及膜筏、受体复合物和膜微区等细胞成分；此外，核受体和配体激活转录因子，而分子功能与转录因子的活性相关联。对127个交集靶点进行KEGG通路富集分析。结果显示，177条通路的靶标具有较高的富集程度，其中前20条通路的P值最高(图9A)，绘制了基于KEGG富集分析的前20条通路的KEGG类型(图9B)。KEGG通路富集分析结果表明，丝裂原活化蛋白激酶、Rap1、环磷酸腺苷和松弛素信号通路可能与核心药物组对骨质疏松症的治疗作用有关。 2.3 分子对接结果选取靶点 ALB (PBDID：7VR0)、AKT1(PBDID：7NH5)、TP53(PBDID：6SL6)、PPARG (PBDID：8FKC)、SRC(PBDID：1FMK)与核心成分谷甾醇、甘草素、臭山羊碱、木犀草素、山奈酚进行分子对接。核心成分与其靶蛋白之间的对接分数(结合能)范围为-22.8至-46.3 kJ/mol(图10)。较低的结合能表明更强的相互作用，例如谷甾醇与ALB的对接能为-39.9 kJ/mol(图11)，表明其与靶蛋白结合良好(使用PyMOL进行可视化)。 2.4 超高效液相色谱串联质谱定性定量分析结果使用Analyst 1.6.3软件处理质谱数据。图12描述了复合药物组的总离子电流色谱图以及MRM代谢物检测多峰图(也称为提取离子色谱图)。X轴表示代谢物检测的保留时间，Y轴表示检测到的离子电流强度。以下部分介绍了从该分析中获得的结果。利用本地代谢数据库，使用质谱进行代谢产物定性和定量分析。图13显示了多反应监测代谢物检测多峰色谱图，展现了样品中的可检测物质，每个色谱峰以颜色区分，对应于一个不同的检测代谢物。使用三重四极杆质谱仪分离每个代谢物的特征离子，并通过检测器记录其信号强度(每秒计数，CPS)。数据采集后，使用Multi Quant软件处理原始质谱文件，以整合和校正色谱峰。每个峰的峰面积代表相应代谢物的相对丰度。最后，将"

References

[1] AIBAR-ALMAZÁN A, VOLTES-MARTÍNEZ A, CASTELLOTE-CABALLERO Y, et al. Current Status of the Diagnosis and Management of Osteoporosis. Int J Mol Sci. 2022;23(16):9465.
[2] HARRIS K, ZAGAR CA, LAWRENCE KV. Osteoporosis: Common Questions and Answers. Am Fam Physician. 2023;107(3): 238-246.
[3] LORENC R, GŁUSZKO P, FRANEK E, et al. Guidelines for the diagnosis and management of osteoporosis in Poland : Update 2017. Endokrynol Pol. 2017;68(5): 604-609.
[4] LANGDAHL BL. Overview of treatment approaches to osteoporosis. Br J Pharmacol. 2021;178(9):1891-1906.
[5] COSMAN F, LANGDAHL B, LEDER BZ. Treatment Sequence for Osteoporosis. Endocr Pract. 2024;30(5):490-496.
[6] REID IR, BILLINGTON EO. Drug therapy for osteoporosis in older adults. Lancet. 2022;399(10329):1080-1092.
[7] 郑熙,朱敏,甘露,等.60岁以上人群骨质疏松性骨折发病特点及转归分析[J].老年医学与保健,2017,23(6):499-501.
[8] 张云飞,安军伟,龚幼波,等.原发性骨质疏松症的中医药防治研究进展[J].中国骨质疏松杂志,2019,25(4):554-558.
[9] 秦昆明,史大华,董自波,等.海洋中药资源综合开发利用现状与对策研究[J].中草药,2020,51(19):5093-5098.
[10] 侯小涛,刘婧曦,吴东阳,等.我国海洋生物废弃物药用研究现状与策略[J].广西科学,2021,28(6):577-587.
[11] 龚世禹,刘艺琳,李世明,等.海洋中药的研究进展[J].安徽农业科学,2020,48(8): 26-29.
[12] 范星华. 骨痿骨折的中医病机探讨 [J]. 中医正骨, 2022, 34(9): 67-68.
[13] 卞琴,沈自尹,王拥军.骨髓间充质干细胞在中医理论中的归属[J].中国中医基础医学杂志,2011,17(7):794-797.
[14] 付先军, 王振国, 王长云, 等. 海洋中药的内涵与外延探讨 [J]. 世界科学技术-中医药现代化,2016,18(12):2034-2042.
[15] 陆洁航,李正言,杜国庆,等.骨松宝制剂治疗原发性骨质疏松症的系统评价与Meta分析[J].中国中药杂志,2023, 48(11):3086-3096.
[16] 姜耘宙,汪正明,王瑞,等.β-谷甾醇改善绝经后骨质疏松的实验研究[J].浙江中医药大学学报,2024,48(2):131-137,146.
[17] 邢如温,李双进.甘草素对乳腺癌内分泌治疗后继发性骨质疏松大鼠Wnt/β-catenin信号通路作用的研究[J].世界中西医结合杂志,2023,18(8):1566-1574.
[18] 许勇,谢贤斐,颜威,等.木犀草素调控PI3K/AKT通路改善绝经后骨质疏松症大鼠模型骨丢失的机制[J].热带医学杂志, 2022,22(5):639-643,688,封4.
[19] 杨启培,陈锋,崔伟,等.山奈酚活性单体治疗骨质疏松症的相关信号通路[J].中国组织工程研究,2024,28(26):4242-4249.
[20] YU T, YOU X, ZHOU H, et al. p53 plays a central role in the development of osteoporosis. Aging (Albany NY). 2020; 12(11):10473-10487.
[21] SUSVA M, MISSBACH M, GREEN J. Src inhibitors: drugs for the treatment of osteoporosis, cancer or both? Trends Pharmacol Sci. 2000;21(12):489-495.
[22] JAISWAL N, GAVIN MG, QUINN WJ, et al. The role of skeletal muscle Akt in the regulation of muscle mass and glucose homeostasis. Mol Metab. 2019;28:1-13.
[23] KAWAMURA N, KUGIMIYA F, OSHIMA Y, et al. Akt1 in osteoblasts and osteoclasts controls bone remodeling. PLoS One. 2007;2(10):e1058.
[24] SUGATANI T, HRUSKA KA. Akt1/Akt2 and mammalian target of rapamycin/Bim play critical roles in osteoclast differentiation and survival, respectively, whereas Akt is dispensable for cell survival in isolated osteoclast precursors. J Biol Chem. 2005; 280(5):3583-3589.
[25] LEE SE, WOO KM, KIM SY, et al. The phosphatidylinositol 3-kinase, p38, and extracellular signal-regulated kinase pathways are involved in osteoclast differentiation. Bone. 2002;30(1):71-77.
[26] MOON JB, KIM JH, KIM K, et al. Akt induces osteoclast differentiation through regulating the GSK3β/NFATc1 signaling cascade. J Immunol. 2012;188(1):163-169.
[27] SUZUKI E, OCHIAI-SHINO H, AOKI H, et al. Akt activation is required for TGF-β1-induced osteoblast differentiation of MC3T3-E1 pre-osteoblasts. PLoS One. 2014; 9(12):e112566.
[28] CHEN LS, ZHANG M, CHEN P, et al. The m6A demethylase FTO promotes the osteogenesis of mesenchymal stem cells by downregulating PPARG. Acta Pharmacol Sin. 2022;43(5):1311-1323.
[29] 李哲立,严孙杰.糖尿病患者血清白蛋白、血红蛋白与骨质疏松的关系[C].中华医学会糖尿病学分会第二十次全国学术会议论文集,2016:573-574.
[30] 董紫怡,宋程威,崔亚宁,等.膜微区相关结构模型及甾醇成像技术的研究进展[J].电子显微学报,2019,38(5):542-549.
[31] 卢义钦,沈士弼.“膜筏”的国际规范定义[J].中国科技术语,2007,9(4):38.
[32] XIE Y, SHI X, SHENG K, et al. PI3K/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (Review). Mol Med Rep. 2019;19(2):783-791.
[33] PAN BL, TONG ZW, LI SD, et al. Decreased microRNA-182-5p helps alendronate promote osteoblast proliferation and differentiation in osteoporosis via the Rap1/MAPK pathway. Biosci Rep. 2018; 38(6):BSR20180696.

Medication pattern and mechanism of marine traditional Chinese medicine in the treatment of osteoporosis

PDF

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 14

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Chen Shuai, Jin Jie, Han Huawei, Tian Ningsheng, Li Zhiwei . Causal relationship between circulating inflammatory cytokines and bone mineral density based on two-sample Mendelian randomization [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(8): 1556-1564.
[2]	Chen Yueping, Chen Feng, Peng Qinglin, Chen Huiyi, Dong Panfeng . Based on UHPLC-QE-MS, network pharmacology, and molecular dynamics simulation to explore the mechanism of Panax notoginseng in treating osteoarthritis [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(8): 1751-1760.
[3]	Jiang Qiyu, Zeng Huiyan. A novel analysis and prediction method for potential mechanisms of traditional Chinese medicine based on artificial intelligence and omics data-driven approach [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(35): 7552-7561.
[4]	Wang Tong, Zheng Yu, Jia Chengming, Yang Hu, Zhang Guangfei, Ji Yaoyao. Action mechanism of Gegenmaqi prescription in treatment of periarthritis of shoulder combined with type 2 diabetes based on TCMSP database [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(35): 7669-7678.
[5]	Yang Lei, Liu Sanmao, Sun Huanwei, Che Chao, Tang Lin. Comparison of six machine learning models suitable for use in medicine: support for osteoporosis screening and initial diagnosis [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(35): 7499-7510.
[6]	Fang Yuan, Qian Zhiyong, He Yuanhada, Wang Haiyan, Sha Lirong, Li Xiaohe, Liu Jing, He Yachao, Zhang Kai, Temribagen. Mechanism of Mongolian medicine Echinops sphaerocephalus L. in proliferation and angiogenesis of vascular endothelial cells [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(35): 7519-7528.
[7]	Zhou Rulin, Hu Yuanzheng, Wang Zongqing, Zhou Guoping, Zhang Baochao, Xu Qian, Bai Fanghui. Exploration of biomarkers for moyamoya disease and analysis of traditional Chinese medicine targets#br# #br# [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(32): 6927-6938.
[8]	Zhang Xin, Guo Baojuan, Xu Huixin, Shen Yuzhen, Yang Xiaofan, Yang Xufang, Chen Pei. Protective effects and mechanisms of 3-N-butylphthalide in Parkinson’s disease cell models [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(30): 6466-6473.
[9]	Ping Xingfeng, Huang Zongxuan, Li Kai, Xie Guangmin, Lyu Junying. Regularity of prescriptions for ischemic stroke based on latent structure combined with association rules [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(29): 6277-6284.
[10]	Wu Wangxiang, Ran Dongcheng, Xu Jiamu, Xu Jiafu, Chen Jingjing, Wang Chunqing. Long noncoding RNAs related to osteoporosis: current research status and developmental trends [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(29): 6360-6368.
[11]	Li Su, Wang Qinghua, Da Mengting, Yang Rui, Chen Daozhen. Action mechanism by which gambogic acid down-regulates expression of protein C receptor to kill triple negative breast cancer stem cells [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(23): 4888-4898.
[12]	Lyu Hao, Zhang Ge, Hu Zhimu, Wang Yan, Chu Qingsong, Zhou Yao, Jiang Ting, Wang Jiuxiang. Inflammation, metabolites and osteoporosis [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(17): 3697-3704.
[13]	Gu Yufeng, Deng Bingying, Li Niren, Zeng Yixuan, Lu Sifan, Zhu Chen, Chen Lei, Liu Yi. Mechanisms of total flavonoids from Sophora flavescens for the treatment of non-alcoholic fatty liver disease and experimental validation in zebrafish [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(14): 2969-2978.
[14]	Zhang Wensheng, Guo Haiwei, Weng Rui, Mo Ling, Song Zhenjie, Tian Han, Zhong Yelin, Wang Yuancheng, Tang Hanwu, Liu Caijun, Yuan Chao, Li Ying. Liquiritin inhibits osteoclast differentiation and alleviates bone loss [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(12): 2429-2437.
[15]	Chen Xinfei, Dai Yahui, Xie Bingying, Huang Xiaobin, Huang Huimin, Huang Jingwen, Li Shengqiang, Ge Jirong. Metabolomics analysis of the lumbar spine after alendronate sodium intervention in ovariectomized rats with osteoporosis [J]. Chinese Journal of Tissue Engineering Research, 2025, 29(11): 2277-2284.