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Bioprocess 2025
柚皮苷治疗股骨头坏死作用机制的网络药理学研究
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Abstract:
该研究以网络药理学为研究对象，探讨在股骨头坏死(ONFH)治疗中柚皮苷(NR)的潜在作用机理。方法：NR的简化分子式及其靶点预测信息是通过TCMSP和Switzerl and Target Prediction数据库获得的，然后将靶点信息通过Uniprot数据库转换成人类基因名。随后利用GeneCards、OMIM及PharmGkb数据库提取与ONFH有关的靶点，并借助R软件筛选药物与疾病之间的交集靶点(版本：4.3.1)。然后将目标靶点导入STRING数据库，获取蛋白–蛋白相互作用(PPI)信息，用Cytoscape软件(版本：3.8.0)选出核心目标超过所有条件平均值，最终通过R软件(版本：4.3.1)进行富集分析。结果：识别109个作用靶点的柚子苷、1632个与ONFH有关的基因、18个与NR-ONFH有关的靶点和7个核心靶点。GO功能富集分析得到了1107个结果(P < 0.05)，KEGG通路富集分析得到38个通路(P < 0.05)，这些信号通路涉及p53、IL-17、细胞凋亡、TNF及坏死性凋亡等。结论：柚皮苷可能为ONFH的治疗提供了潜在的新策略。
Objective: This study aims to explore the potential mechanism of naringin (NR) in the treatment of femoral head necrosis (ONFH) through online pharmacology. Methods: The simplified molecular formula and target prediction information of NR were obtained through TCMSP and Swiss Target Prediction databases, and the target information was converted into human gene names using Uniprot database. Next, targets related to ONFH were extracted using GeneCards, OMIM and PharmGkb databases, and the intersection targets of drugs and diseases were identified with the help of R software (version: 4.3.1). The intersection targets were input into the STRING database to obtain protein-protein interaction (PPI) information, and the core targets greater than the average of all conditions were screened using Cytoscape software (version: 3.8.0). Finally, enrichment analysis was conducted using R software (version: 4.3.1). Results: 109 targets of naringin, 1632 genes related to ONFH, 18 NR-ONFH-related targets and 7 core targets were selected. GO functional enrichment analysis obtained 1107 results (P < 0.05), and KEGG pathway enrichment analysis obtained 38 signaling pathways (P < 0.05), which involved p53, IL-17, cell apoptosis, TNF and necrotic apoptosis. Conclusion: Naringin may provide a potential new strategy for the treatment of ONFH.
| [1] | Liu, B., Yang, F., Wei, X., Zhang, X., Zhang, Y., Wang, B., et al. (2019) An Exploratory Study of Articular Cartilage and Subchondral Bone Reconstruction with Bone Marrow Mesenchymal Stem Cells Combined with Porous Tantalum/Bio-Gide Collagen Membrane in Osteonecrosis of the Femoral Head. Materials Science and Engineering: C, 99, 1123-1132. https://doi.org/10.1016/j.msec.2019.02.072 |
| [2] | Zhao, D., Zhang, F., Wang, B., Liu, B., Li, L., Kim, S., et al. (2020) Guidelines for Clinical Diagnosis and Treatment of Osteonecrosis of the Femoral Head in Adults (2019 Version). Journal of Orthopaedic Translation, 21, 100-110. https://doi.org/10.1016/j.jot.2019.12.004 |
| [3] | Seamon, J., Keller, T., Saleh, J. and Cui, Q. (2012) The Pathogenesis of Nontraumatic Osteonecrosis. Arthritis, 2012, Article ID: 601763. https://doi.org/10.1155/2012/601763 |
| [4] | Wei, Q., Hong, G., Yuan, Y., Chen, Z., Zhang, Q. and He, W. (2019) Huo Xue Tong Luo Capsule, a Vasoactive Herbal Formula Prevents Progression of Asymptomatic Osteonecrosis of Femoral Head: A Prospective Study. Journal of Orthopaedic Translation, 18, 65-73. https://doi.org/10.1016/j.jot.2018.11.002 |
| [5] | Wang, A., Ren, M. and Wang, J. (2018) The Pathogenesis of Steroid-Induced Osteonecrosis of the Femoral Head: A Systematic Review of the Literature. Gene, 671, 103-109. https://doi.org/10.1016/j.gene.2018.05.091 |
| [6] | Migliorini, F., Maffulli, N., Baroncini, A., Eschweiler, J., Tingart, M. and Betsch, M. (2021) Failure and Progression to Total Hip Arthroplasty among the Treatments for Femoral Head Osteonecrosis: A Bayesian Network Meta-Analysis. British Medical Bulletin, 138, 112-125. https://doi.org/10.1093/bmb/ldab006 |
| [7] | Swarup, I., Lee, Y., Chiu, Y., Sutherland, R., Shields, M. and Figgie, M.P. (2018) Implant Survival and Patient-Reported Outcomes after Total Hip Arthroplasty in Young Patients. The Journal of Arthroplasty, 33, 2893-2898. https://doi.org/10.1016/j.arth.2018.04.016 |
| [8] | 邓攀, 王星, 纪海, 杨乐. 桃红四物汤加减对股骨头坏死临床疗效及部分机制探讨[J]. 世界中医药, 2019, 14(9): 2339-2343. |
| [9] | 李凯杰, 李慧英, 孟东方. 健步虎潜丸加减对气滞血瘀型股骨头坏死患者的临床疗效[J]. 时珍国医国药, 2020, 31(10): 2419-2422. |
| [10] | Wang, H., Li, C., Li, J., Zhu, Y., Jia, Y., Zhang, Y., Zhang, X., Li, W., Cui, L., Li, W., et al. (2017) Naringin Enhances Osteogenic Differentiation through the Activation of ERK Signaling in Human Bone Marrow Mesenchymal Stem Cells. Iranian Journal of Basic Medical Sciences, 20, 408-414. |
| [11] | Huang, D., Li, Z., Chen, B., Fang, G., Sun, X., Li, F., et al. (2017) Naringin Protects against Steroid-Induced Avascular Necrosis of the Femoral Head through Upregulation of PPARγ and Activation of the Notch Signaling Pathway. Molecular Medicine Reports, 17, 3328-3335. https://doi.org/10.3892/mmr.2017.8247 |
| [12] | Xu, Z., Li, N., Wooley, P.H., Yang, S. and Jiang, Y. (2013) Naringin Promotes Osteoblast Differentiation and Effectively Reverses Ovariectomy-Associated Osteoporosis. Journal of Orthopaedic Science, 18, 478-485. https://doi.org/10.1007/s00776-013-0362-9 |
| [13] | Xu, T., Wang, L., Tao, Y., Ji, Y., Deng, F. and Wu, X. (2016) The Function of Naringin in Inducing Secretion of Osteoprotegerin and Inhibiting Formation of Osteoclasts. Evidence-Based Complementary and Alternative Medicine, 2016, Article ID: 8981650. https://doi.org/10.1155/2016/8981650 |
| [14] | 黄俊波, 王世勇, 张晓敏, 李根, 姬菩忠, 赵红斌. 载柚皮苷复合支架对兔骨软骨缺损修复的实验研究[J]. 中国修复重建外科杂志, 2017, 31(4): 489-496. |
| [15] | Chen, K., Lin, K., Chen, Y. and Yao, C. (2013) A Novel Porous Gelatin Composite Containing Naringin for Bone Repair. Evidence-Based Complementary and Alternative Medicine, 2013, Article ID: 283941. https://doi.org/10.1155/2013/283941 |
| [16] | Song, N., Zhao, Z., Ma, X., Sun, X., Ma, J., Li, F., et al. (2017) Naringin Promotes Fracture Healing through Stimulation of Angiogenesis by Regulating the VEGF/VEGFR-2 Signaling Pathway in Osteoporotic Rats. Chemico-Biological Interactions, 261, 11-17. https://doi.org/10.1016/j.cbi.2016.10.020 |
| [17] | Shangguan, W., Zhang, Y., Li, Z., Tang, L., Shao, J. and Li, H. (2017) Naringin Inhibits Vascular Endothelial Cell Apoptosis via Endoplasmic Reticulum Stress-and Mitochondrial-Mediated Pathways and Promotes Intraosseous Angiogenesis in Ovariectomized Rats. International Journal of Molecular Medicine, 40, 1741-1749. https://doi.org/10.3892/ijmm.2017.3160 |
| [18] | Li, L., Zeng, Z. and Cai, G. (2011) Comparison of Neoeriocitrin and Naringin on Proliferation and Osteogenic Differentiation in MC3T3-E1. Phytomedicine, 18, 985-989. https://doi.org/10.1016/j.phymed.2011.03.002 |
| [19] | Schulman, R.C., Weiss, A.J. and Mechanick, J.I. (2011) Nutrition, Bone, and Aging: An Integrative Physiology Approach. Current Osteoporosis Reports, 9, 184-195. https://doi.org/10.1007/s11914-011-0079-7 |
| [20] | Wu, J., Yang, Y., He, Y., Li, Q., Wang, X., Sun, C., et al. (2019) EFTUD2 Gene Deficiency Disrupts Osteoblast Maturation and Inhibits Chondrocyte Differentiation via Activation of the P53 Signaling Pathway. Human Genomics, 13, Article No. 63. https://doi.org/10.1186/s40246-019-0238-y |
| [21] | Abdi, A., Sadraie, H., Dargahi, L., Khalaj, L. and Ahmadiani, A. (2010) Apoptosis Inhibition Can Be Threatening in Aβ-Induced Neuroinflammation, through Promoting Cell Proliferation. Neurochemical Research, 36, 39-48. https://doi.org/10.1007/s11064-010-0259-3 |
| [22] | 刘海, 李林福, 施伟梅, 杨建琼, 吴龙火. 雌激素受体在骨形成代谢中的研究进展[J]. 基因组学与应用生物学 2016, 35(7): 1656-1661. |
| [23] | 纪志华, 贾丙申, 于鹏, 付昆, 孟志斌, 云大科. 激素性股骨头坏死中MMP2作用的研究[J]. 海南医学, 2017, 28(14): 2245-2246. |
| [24] | 张国权, 范挽亭, 陈倩仪, 吕卫东, 赵琦, 黄盛兴. IL-17抗体对大鼠破骨细胞功能影响的体外研究[J]. 全科口腔医学电子杂志, 2018, 5(12): 7-10. |
| [25] | Tao, S., Yuan, T., Rui, B., Zhu, Z., Guo, S. and Zhang, C. (2017) Exosomes Derived from Human Platelet-Rich Plasma Prevent Apoptosis Induced by Glucocorticoid-Associated Endoplasmic Reticulum Stress in Rat Osteonecrosis of the Femoral Head via the Akt/Bad/Bcl-2 Signal Pathway. Theranostics, 7, 733-750. https://doi.org/10.7150/thno.17450 |
| [26] | Ichiseki, T., Ueda, S., Ueda, Y., Tuchiya, M., Kaneuji, A. and Kawahara, N. (2017) Involvement of Necroptosis, a Newly Recognized Cell Death Type, in Steroid-Induced Osteonecrosis in a Rabbit Model. International Journal of Medical Sciences, 14, 110-114. https://doi.org/10.7150/ijms.17134 |
| [27] | Dai, Q., Zhang, Y., Liao, X., Jiang, Y., Lv, X., Yuan, X., et al. (2020) Fluorofenidone Alleviates Renal Fibrosis by Inhibiting Necroptosis through RIPK3/MLKL Pathway. Frontiers in Pharmacology, 11, Article 534775. https://doi.org/10.3389/fphar.2020.534775 |
