The study of the mechanism of Xuduan promoting fracture healing based on network pharmacology and molecular docking

doi:10.3969/j.issn.1006-7795.2022.02.019

Abstract

Abstract: Objective To analyze the mechanism of Xuduan promoting fracture healing by network pharmacology and molecular docking technology. Methods The active components of Xuduan were acquired through traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database by setting the oral drug bioavailability (OB)≥30% and drug like index (DL)≥0.18 as screening criteria, and the target genes of the active components were obtained. The bone fracture related genes were obtained by searching TTD, OMIM, Genecards, Drugbank and PharmGkb databases. The main target genes were obtained by matching the target genes of Xuduan active components with fracture related genes. The results were visualized by EVenn. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of main target genes were analyzed by DAVID database and protein interaction network was constructed by STRING databases. Key genes in main target genes were obtained by degree and betweenness algorithms. Finally, Pymol and Autoduck softwares were used for molecular docking and calculating the minimum binding energy, binding site and fixed active pocket. Results Totally 8 active components and 63 target genes of Xuduan were screened by TCMSP database, and 53 target genes were obtained by deleting repeated target genes. Totally 5 115 genes related to bone fracture were obtained from TTD, OMIM, GeneCards, DrugBank and PharmGkb databases. Totally 34 main target genes were obtained by matching and intersection analysis. The 34 target genes were enriched in 76 biological processes, 20 cellular components and 20 molecular functions through DAVID database analysis. The protein interaction network was constructed by STRING database. A total of 34 genes and 79 connections were included. The average degree parameter was 4.65. Xuduan promoting bone healing key genes were PTGS2, HSP90AA1 and MAPK14 by calculating degree and betweenness in Cytoscape software. The active components with optimal bioavailability, as (E,E)-3,5-Di-O-caffeoylquinic acid, Gentisin and Sylvestroside Ⅲ_qt could bind with the key genes PTGS2, HSP90AA1 and MAPK14 at a less than 0 energy. The binding sites were obtained by Pymol and Autoduck software. Conclusion Through network pharmacology and molecular docking technology, the possible potential mechanism of Xuduan promoting fracture healing were clarified, and its effective components and key genes were predicted.

Key words: Xuduan, fracture healing, network pharmacology, molecular docking

CLC Number:

Zhang Jin, Wang Dong. The study of the mechanism of Xuduan promoting fracture healing based on network pharmacology and molecular docking[J]. Journal of Capital Medical University, 2022, 43(2): 275-283.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2022.02.019

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2022/V43/I2/275

References

[1] Wang D, Wang J Y, Zhou J L, et al. The role of adenosine receptor a2a in the regulation of macrophage exosomes and vascular endothelial cells during bone healing[J]. J Inflamm Res, 2021, 14: 4001-4017.
[2] 王东, 周君琳. 免疫调控紊乱与骨不连的关系研究进展[J]. 中国医刊, 2021, 56(4): 375-378.
[3] Wang D, Liu Y, Lv W R, et al. Repetitive brief ischemia accelerates tibial shaft fracture healing: a 5-years prospective preliminary clinical trial (PCT)[J]. BMC Musculoskelet Disord, 2021, 22(1): 631.
[4] Barbosa J S, Mendes R F, Figueira F, et al. Bone tissue disorders: healing through coordination chemistry[J]. Chemistry, 2020, 26(67): 15416-15437.
[5] Goodman S B, Maruyama M. Inflammation, bone healing and osteonecrosis: from bedside to bench[J]. J Inflamm Res, 2020, 13: 913-923.
[6] ElHawary H, Baradaran A, Abi-Rafeh J, et al. Bone healing and inflammation: principles of fracture and repair[J]. Semin Plast Surg, 2021, 35(3): 198-203.
[7] Dumic-Cule I, Peric M, Kucko L, et al. Bone morphogenetic proteins in fracture repair[J]. Int Orthop, 2018, 42(11): 2619-2626.
[8] Lopez C D, Bekisz J M, Corciulo C, et al. Local delivery of adenosine receptor agonists to promote bone regeneration and defect healing[J]. Adv Drug Deliv Rev, 2019, 146: 240-247.
[9] Mediero A, Wilder T, Shah L, et al. Adenosine A_2A receptor (A2AR) stimulation modulates expression of semaphorins 4D and 3a, regulators of bone homeostasis[J]. FASEB J, 2018, 32(7): 3487-3501.
[10] 冯汪银, 周涛, 肖承鸿, 等. 续断的本草整理及现代研究概况[J]. 中药材, 2018, 41(9): 2236-2240.
[11] 廖楚, 李恒飞, 李晓东. 基于网络药理学及分子对接探讨芍药甘草汤治疗乙型病毒性肝炎肝损伤的作用机制[J]. 药物评价研究, 2021, 44(9): 1852-1861.
[12] Wang Y X, Zhang S, Li F C, et al. Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics[J]. Nucleic Acids Res, 2020, 48(D1): D1031-D1041.
[13] Amberger J S, Hamosh A. Searching online mendelian inheritance in man (OMIM): a knowledgebase of human genes and genetic phenotypes[J]. Curr Protoc Bioinformatics, 2017, 58: 1.2.1-1.2.12.
[14] Stelzer G, Rosen N, Plaschkes I, et al. The GeneCards suite: from gene data mining to disease genome sequence analyses[J]. Curr Protoc Bioinformatics, 2016, 54: 1.30.1-1.30.33.
[15] Wishart D S, Feunang Y D, Guo A C, et al. DrugBank 5.0: a major update to the DrugBank database for 2018[J]. Nucleic Acids Res, 2018, 46(D1): D1074-D1082.
[16] Tilleman L, Weymaere J, Heindryckx B, et al. Contemporary pharmacogenetic assays in view of the PharmGKB database[J]. Pharmacogenomics, 2019, 20(4): 261-272.
[17] Chen T, Zhang H Y, Liu Y, et al. EVenn: easy to create repeatable and editable Venn diagrams and Venn networks online[J]. J Genet Genomics, 2021, 48(9): 863-866.
[18] Huang D W, Sherman B T, Lempicki R A. Systematic and integrative analysis of large gene lists using David bioinformatics resources[J]. Nat Protoc, 2009, 4(1): 44-57.
[19] Huang D W, Sherman B T, Lempicki R A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists[J].Nucleic Acids Res, 2009,37(1):1-13.
[20] Szklarczyk D, Gable A L, Nastou K C, et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets[J]. Nucleic Acids Res, 2021, 49(D1): D605-D612.
[21] Szklarczyk D, Morris J H, Cook H, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible[J]. Nucleic Acids Res, 2017, 45(D1): D362-D368.
[22] Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks[J]. Genome Res, 2003, 13(11): 2498-2504.
[23] Otasek D, Morris J H, Bouças J, et al. Cytoscape automation: empowering workflow-based network analysis[J]. Genome Biol, 2019, 20(1): 185.
[24] Karuppasamy M P, Venkateswaran S, Subbiah P. PDB-2-PBv3.0: an updated protein block database[J]. J Bioinform Comput Biol, 2020, 18(2): 2050009.
[25] Seeliger D, De Groot B L. Ligand docking and binding site analysis with PyMOL and Autodock/Vina[J]. J Comput Aided Mol Des, 2010, 24(5): 417-422.
[26] Kong L C, Wang Y, Wang H X, et al. Conditioned media from endothelial progenitor cells cultured in simulated microgravity promote angiogenesis and bone fracture healing[J]. Stem Cell Res Ther, 2021, 12(1): 47.
[27] Camal Ruggieri I N, Cícero A M, Issa J P M, et al. Bone fracture healing: perspectives according to molecular basis[J]. J Bone Miner Metab, 2021, 39(3): 311-331.
[28] Sharma R, Wu X H, Rhodes S D, et al. Hyperactive Ras/MAPK signaling is critical for tibial nonunion fracture in neurofibromin-deficient mice[J]. Hum Mol Genet, 2013, 22(23): 4818-4828.
[29] 陈建泉, 许建文, 桂裕昌, 等. 基于网络药理学探讨女贞子治疗骨质疏松性骨折的作用机制[J]. 广西医科大学学报, 2021, 38(5): 969-974.