Journal of Shandong University (Health Sciences) ›› 2026, Vol. 64 ›› Issue (8): 35-47.doi: 10.6040/j.issn.1671-7554.0.2026.0025

• Preclinical Medicine • Previous Articles    

Mechanism of Gubao Capsule in the treatment of osteoporosis by regulating the nuclear factor-κB signaling pathway to inhibit osteocyte apoptosis and promote osteogenic differentiation

YAN Xiaolong1, CHEN Dongfeng2, GUAN Donghui2, ZHAO Canbin3, SHAO Jiang2, WANG Huixi4, LUO Zhengwei4, XU Boyang4, ZHAN Haozhi4   

  1. 1. Orthopedics Department, Jinan Changqing District Peoples Hospital/University Town Hospital, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250300, Shandong, China;
    2. Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China;
    3. The First Clinical Medical College, Guangxi University of Traditional Chinese Medicine, Nanning 530200, Guangxi, China;
    4. The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong, China
  • Published:2026-08-14

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Abstract: Objective To explore the mechanism by which Gubao Capsule treats osteoporosis by regulating the nuclear factor-kappa B(NF-κB)signaling pathway to inhibit osteocyte apoptosis and promote osteogenic differentiation. Methods Network pharmacology was used to retrieve targets related to the active ingredients of Gubao Capsule, osteogenic differentiation, and osteoporosis, and their overlapping targets were obtained. A protein-protein interaction(PPI)network was constructed using the STRING database, and topological analysis was performed with Cytoscape 3.8.0. Core targets(degree values above the median)were selected for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses. In animal experiments, 36 SD rats were divided into three groups: control group(no treatment, n=12), model group(ovariectomy-induced osteoporosis, n=12), and treatment group(Gubao Capsule gavage based on the model group, n=12). After intervention, hematoxylin-eosin, Sirius red, toluidine blue, and safranin O-fast green staining were performed to observe bone pathological changes. TUNEL and immunofluorescence assays were used to detect osteocyte apoptosis. Panoramic pathological analysis evaluated NF-κB pathway activation. Immunohistochemistry detected the expression of osteogenic proteins: bone morphogenetic protein 2(BMP2), osteopontin(OPN), osterix, and runt-related transcription factor 2(RUNX2). Results A total of 643 targets of Gubao Capsule, 2,998 osteogenic differentiation-related targets, and 7,707 osteoporosis-related targets were retrieved, with 266 overlapping targets. Among them, 132 core targets with degree values above the median were identified. KEGG enrichment showed that the core targets were mainly enriched in osteogenic differentiation and NF-κB signaling pathways; GO analysis revealed that theenrichment in biological processes such as apoptosis and programmed cell death.Animal experiments showed that compared with the control group, the model group exhibited severe bone tissue destruction, trabecular fracture, and loss of fibrin and proteoglycans. Meanwhile, NF-κB p65 and Caspase3 expression were significantly upregulated(P<0.05), accompanied by a marked increase in osteocyte apoptosis rate(P<0.05). Panoramic pathological analysis confirmed abnormal activation of the NF-κB pathway and significantly decreased osteogenic protein expression in the model group(P<0.05). All these abnormalities were significantly reversed after Gubao Capsule intervention. Conclusion Gubao Capsule can treat osteoporosis by inhibiting abnormal activation of the NF-κB signaling pathway in trabecular bone tissue, reducing osteocyte apoptosis, upregulating osteogenic protein expression, and promoting osteogenic differentiation.

Key words: Gubao Capsule, Nuclear factor-kappa B, Signaling pathway, Osteocyte apoptosis, Osteogenic differentiation, Osteoporosis

CLC Number: 

  • R274
[1] Ensrud K E, Crandall C J. Osteoporosis[J]. Ann Intern Med, 2024, 177(1): 1-16.
[2] Ye C, Ebeling P, Kline G. Osteoporosis[J]. Lancet, 2025, 406(10514): 2003-2016.
[3] Wang Y, Tao Y, Hyman M E, et al. Osteoporosis in China[J]. Osteoporos Int, 2009, 20(10): 1651-1662.
[4] Liu Y, Huang X, Tang K, et al. Prevalence of osteoporosis and associated factors among Chinese adults: a syste-matic review and modelling study[J]. J Glob Health, 2025, 15: 04009. DOI:10.7189/jogh.15.04009
[5] Gao Y, Chen N, Fu Z, et al. Progress of wnt signaling pathway in osteoporosis[J]. Biomolecules, 2023, 13(3): 483. DOI:10.3390/biom13030483
[6] Zhang C, Li H, Li J, et al. Oxidative stress: a common pathological state in a high-risk population for osteoporosis[J]. Biomed Pharmacother, 2023, 163: 114834. DOI:10.1016/j.biopha.2023.114834
[7] Gao Z, Gao Z, Zhang H, et al. Targeting STING: from antiviral immunity to treat osteoporosis[J]. Front Immunol, 2023, 13: 1095577. DOI:10.3389/fimmu.2022.1095577
[8] Li P, Xu T Y, Yu A X, et al. The role of ferroptosis in osteoporosis and advances in Chinese herbal interventions[J]. Biology(Basel), 2025, 14(4): 367. DOI:10.3390/biology14040367
[9] Subarajan P, Arceo-Mendoza R M, Camacho P M. Postmenopausal osteoporosis: a review of latest guidelines[J]. Endocrinol Metab Clin North Am, 2024, 53(4): 497-512.
[10] Aibar-Almazán A, Voltes-Martínez A, Castellote-Caballero Y, et al. Current status of the diagnosis and management of osteoporosis[J]. Int J Mol Sci, 2022, 23(16): 9465. DOI:10.3390/ijms23169465
[11] Ramchand S K, Leder B Z. Sequential therapy for the long-term treatment of postmenopausal osteoporosis[J]. J Clin Endocrinol Metab, 2024, 109(2): 303-311.
[12] Cao G, Hu S, Ning Y, et al. Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity[J]. Front Pharmacol, 2024, 15: 1370900. DOI:10.3389/fphar.2024.1370900
[13] Tan M, Li Q, Yang B, et al. Insight of Chinese herbal medicine in treating osteoporosis: achievements from 2013 to 2023[J]. Am J Chin Med, 2024, 52(5): 1303-1328.
[14] 贾泽涛. 基于 “肾主骨” 理论探讨骨宝胶囊联合经皮穿刺椎体后凸成形术治疗Ⅰ、Ⅱ期Kümmell病的临床疗效[D]. 济南:山东中医药大学, 2024: 1-2.
[15] 赵灿斌. 骨宝胶囊联合 InterTAN 治疗老年股骨粗隆间骨折的临床疗效观察及实验验证[D]. 济南:山东中医药大学, 2024: 12-13.
[16] 王群. 骨宝胶囊治疗老年男性原发性骨质疏松症的临床观察 [D]. 济南:山东中医药大学, 2016: 5-9.
[17] 朱高明. 骨宝胶囊通过 p53 信号通路抑制成骨细胞凋亡促进成骨防治 PMOP 的机制研究 [D]. 济南:山东中医药大学, 2024: 36-38.
[18] 马德欣. 骨宝胶囊治疗肝肾亏虚型早期酒精性股骨头坏死的临床观察 [D]. 济南:山东中医药大学, 2022: 7-14.
[19] 胡亚楠,杜海涛,于洋,等. 鹿角胶体内分布及入血入骨成分的示踪动力学分析 [J]. 中国组织工程研究,2024, 28(28): 4441-4446. Hu Yanan, Du Haitao, Yu Yang, et al. In vivo distribution of Cornus cervi Colla and tracer kinetic analysis of its components that enter the blood and bone[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(28): 4441-4446.
[20] 孙铁锋, 赵玉, 王平, 等. 基于细胞膜色谱技术的鹿角胶肽段筛选及鉴定 [J]. 山东科学, 2024, 37(5): 1-9. Sun Tiefeng, Zhao Yu, Wang Ping, et al. To explore the pharmacodynamic substance basis of Cervi Cornus colla based on cell membrane chromatography[J]. Shandong Science, 2024, 37(5): 1-9.
[21] 李娜, 胡亚楠, 王晓雪, 等. 鹿角胶化学成分、药理作用及质量控制研究进展 [J]. 中药材,2021, 44(7): 1777-1783. Li Na, Hu Yanan, Wang Xiaoxue, et al. Research progress on chemical composition, pharmacological action and quality control of antler glue[J]. Journal of Chinese Medicinal Materials, 2021, 44(7): 1777-1783.
[22] 陆包伟, 王能, 何清湖. 鹿角胶的最新研究进展 [J]. 光明中医, 2021, 36(17): 2881-2884. Lu Baowei, Wang Neng, He Qinghu. The latest research progress of antler gum[J]. Guangming Journal of Chinese Medicine, 2021, 36(17): 2881-2884.
[23] 曹策, 李玲美, 訾明杰, 等. 医学研究中动物实验样本量的确定方法 [J]. 中国比较医学杂志, 2023, 33(2): 99-105. Cao Ce, Li Lingmei, Zi Mingjie, et al. Methods for determining sample size in animal experiments of medical research [J]. Chinese Journal of Comparative Medicine, 2023, 33(2): 99-105.
[24] 黄继汉, 黄晓晖, 陈志扬, 等. 药理试验中动物间和动物与人体间的等效剂量换算 [J]. 中国临床药理学与治疗学, 2004, 9(9): 1069-1072. Huang Jihan, Huang Xiaohui, Chen Zhiyang, et al. Dose conversion among different animals and healthy volunteers in pharmacological study[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(9): 1069-1072.
[25] 郭金星, 田增辉, 盛夏, 等. 骨宝胶囊对糖皮质激素诱导骨质疏松大鼠骨密度、骨微结构的影响 [J]. 中医药信息, 2024, 41(1): 12-17. Guo Jinxing, Tian Zenghui, Sheng Xia, et al. Effect of gubao capsule on bone mineral density and bone microstructure in rats with glucocorticoid-induced osteoporosis[J]. Information on Traditional Chinese Medicine, 2024, 41(1): 12-17.
[26] 葛继荣, 赵咏芳, 王金榜, 等. 中医药防治原发性骨质疏松症专家共识(2025)[J]. 中国骨质疏松杂志, 2026, 32(3): 313-325. Ge Jirong, Zhao Yongfang, Wang Jinbang, et al. Traditional Chinese medicine expert consensus on the prevention and treatment of primary osteoporosis(2025)[J]. Chinese Journal of Osteoporosis, 2026, 32(3): 313-325.
[27] 牛黎明, 邴雅珺. 老年骨质疏松症的中医治疗研究进展 [J]. 中外医药研究, 2025, 4(19): 165-167. Niu Liming, Bing Yajun. Research progress on traditional Chinese medicine treatment of senile osteoporosis[J]. Journal of Chinese and Foreign Medicine and Pharmacy Research, 2025, 4(19): 165-167.
[28] 王寒. 骨宝胶囊治疗老年骨质疏松症合并认知功能障碍(肝肾亏虚证)的临床疗效观察[D]. 济南:山东中医药大学, 2022: 12-20.
[29] 刘立君. 骨宝胶囊治疗老年骨质疏松症合并甲状腺功能减退临床观察[D]. 济南: 山东中医药大学, 2021:12-20.
[30] Fischer V, Haffner-Luntzer M. Interaction between bone and immune cells: implications for postmenopausal osteoporosis[J]. Semin Cell Dev Biol, 2022, 123: 14-21. DOI:10.1016/j.semcdb.2021.05.014
[31] Yao Z, Getting S J, Locke I C. Regulation of TNF-induced osteoclast differentiation[J]. Cells, 2021, 11(1): 132. DOI:10.3390/cells11010132
[32] Xiao Y, Xie X, Chen Z, et al. Advances in the roles of ATF4 in osteoporosis[J]. Biomed Pharmacother, 2023, 169: 115864. DOI:10.1016/j.biopha.2023.115864
[33] 姜子晗, 芦兴晨, 孙露, 等. NR4A1 通过 IκBα/NF-κB 通路调控过氧化氢诱导人脐静脉内皮细胞凋亡的机制 [J]. 山东大学学报(医学版), 2024, 62(3): 11-19. Jiang Zihan, Lu Xingchen, Sun Lu, et al. Mechanism of NR4A1 regulating hydrogen peroxide-induced apoptosis of human umbilical vein endothelial cells through IκBα/NF-κB pathway [J]. Journal of Shandong University(Health Sciences), 2024, 62(3): 11-19.
[34] Guo Q, Jin Y, Chen X, et al. NF-κB in biology and targeted therapy: new insights and translational implications[J]. Signal Transduct Target Ther, 2024, 9(1): 53. DOI:10.1038/s41392-024-01757-9
[35] 陈秉雄, 何明, 陈秉虎, 等. 黄芪有效成分调控骨保护素 /核转录因子-κB 受体活化因子配体/核转录因子-κB 受体活化因子信号通路预防骨质疏松症的研究进展 [J]. 中医临床研究, 2025, 17(29): 135-140. Chen Bingxiong, He Ming, Chen Binghu, et al. A review on active components of Huangqi in preventing osteoporosis by regulating OPG/RANKL/RANK signaling pathway[J]. Clinical Journal of Chinese Medicine, 2025, 17(29): 135-140.
[36] 梁雄波. 基于NF-κB/IκBα信号通路对银杏双黄酮抗骨质疏松的机制研究[D]. 桂林:桂林医科大学, 2025: 5-7.
[37] 蹇秀林. 壮骨止痛胶囊对成骨细胞NF-κB信号通路中NF-κB p65和IκBα蛋白的影响[D]. 长沙:湖南中医药大学, 2019: 22-23.
[38] 姚媛, 李娜, 孙娇瑞, 等. 中药调控 NF-κB 信号通路治疗糖尿病骨质疏松的研究进展 [J]. 山西中医药大学学报, 2024, 25(6): 698-703. Yao Yuan, Li Na, Sun Jiaorui, et al. Research progress on the regulation of NF-κB signaling pathway by Chinese herbs in the treatment of diabetic osteoporosis[J]. Journal of Shanxi University of Chinese Medicine, 2024, 25(6): 698-703.
[39] Sadati S, Khalaji A, Bonyad A, et al. NF-κB and apoptosis: colorectal cancer progression and novel strategies for treatment[J]. Eur J Med Res, 2025, 30(1): 616. DOI:10.1186/s40001-025-02734-w
[40] Gao L, Zhang W, Shi X H, et al. The mechanism of linear ubiquitination in regulating cell death and correlative diseases[J]. Cell Death Dis, 2023, 14(10): 659. DOI:10.1038/s41419-023-06183-3
[41] Han J H, Park J, Kang T B, et al. Regulation of Caspase-8 activity at the crossroads of pro-inflammation and anti-inflammation[J]. Int J Mol Sci, 2021, 22(7): 3318. DOI:10.3390/ijms22073318
[42] Zou X, Xu H, Qian W. Macrophage polarization in the osteoarthritis pathogenesis and treatment[J]. Orthop Surg, 2025, 17(1): 22-35.
[43] Hu Q, Zhang W, Wu Z, et al. Baicalin and the liver-gut system: pharmacological bases explaining its therapeutic effects[J]. Pharmacol Res, 2021, 165: 105444. DOI:10.1016/j.phrs.2021.105444
[44] Christian F, Smith E L, Carmody R J. The regulation of NF-κB subunits by phosphorylation[J]. Cells, 2016, 5(1): 12. DOI:10.3390/cells5010012
[45] Fischer V, Haffner-Luntzer M. Interaction between bone and immune cells: implications for postmenopausal osteoporosis[J]. Semin Cell Dev Biol, 2022, 123: 14-21. DOI:10.1016/j.semcdb.2021.05.014
[46] Szabó L, Gere Á, Kovács ZM, et al. The beneficial effects of marine plant-derived compounds on the musculoskeletal system[J]. Int J Mol Sci, 2026, 27(2): 1032. DOI:10.3390/ijms27021032
[47] Liu G, Ma C, Wang P, et al. Pilose antler peptide potentiates osteoblast differentiation and inhibits osteoclastogenesis via manipulating the NF-κB pathway[J]. Biochem Biophys Res Commun, 2017, 491(2): 388-395.
[48] 李时斌, 夏天, 章晓云, 等. 淫羊藿活性单体成分调控骨质疏松症相关信号通路影响骨吸收与骨形成的稳态 [J]. 中国组织工程研究, 2022, 26(11): 1772-1779. Li Shibin, Xia Tian, Zhang Xiaoyun, et al. Active monomer components of Epimedium regulate osteoporosis-related signaling pathways and affect the homeostasis of bone resorption and bone formation[J]. Chinese Journal of Tissue Engineering Research, 2022, 26(11): 1772-1779.
[49] 徐翀, 申利民, 苑文杰. 当归多糖通过Wnt/β-catenin 信号通路抑制骨关节炎软骨细胞氧化应激损伤与炎症反应 [J]. 陕西中医, 2022, 43(6): 700-703. Xu Chong, Shen Limin, Yuan Wenjie. Angelica sinensis polysaccharide inhibits oxidative stress injury and inflammatory response of osteoarthritis chondrocytes via Wnt/β-catenin signaling pathway[J]. Shaanxi Journal of Traditional Chinese Medicine, 2022, 43(6): 700-703.
[50] 赵向绒, 王海芳, 刘杨, 等. 白芍总苷对小鼠成骨细胞增殖、分化和矿化的影响 [J]. 中国中西医结合杂志, 2019, 39(10): 1230-1233. Zhao Xiangrong, Wang Haifang, Liu Yang, et al. Effects of total glucosides of paeony on proliferation, differentiation and mineralization of mouse osteoblasts[J]. Chinese Journal of Integrated Traditional and Western Medicine, 2019, 39(10): 1230-1233.
[51] 陈婷婷, 彭涛. 中医药治疗骨质疏松症的研究进展 [J]. 实用中医内科杂志, 2024, 38(8): 141-143. Chen Tingting, Peng Tao. Research progress of traditional Chinese medicine in treating osteoporosis[J]. Journal of Practical Traditional Chinese Internal Medicine, 2024, 38(8): 141-143.
[52] 任可心. 中药治疗骨质疏松症的研究进展 [J]. 内蒙古中医药,2024, 43(6): 161-163. Ren Kexin. Research progress of traditional Chinese medicine in treating osteoporosis[J]. Inner Mongolia Journal of Traditional Chinese Medicine, 2024, 43(6): 161-163.
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