Method for analyzing anti-rheumatoid arthritis osteoclast mechanism of rhizoma curculiginis and herba epimedii medicines
Through network pharmacology and molecular docking technology, the core active ingredients and mechanism of the Xianmao-Epimedium drug in the treatment of bone destruction of rheumatoid arthritis were analyzed, and the problem of unknown functional components and mechanism of action was solved, providing a theoretical basis and improving its clinical application and marketing effect.
Patent Information
- Application Number
- CN202411614935.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-13
- Publication Date
- 2025-03-28
AI Technical Summary
The effective components of Xianmao-Epimedium in the treatment of bone destruction of rheumatoid arthritis are not clear, and its mechanism of action has not been clarified, which limits its clinical application, market share and international promotion.
Through network pharmacology and molecular docking technology, the core active ingredients and mechanisms of celestial macadamia and epimedium drugs for the treatment of bone destruction of rheumatoid arthritis were screened and analyzed, and the Chinese medicine-component-target-disease network was constructed, and the protein-protein interaction network construction, GO and KEGG enrichment analysis and molecular docking verification were carried out.
The effective components and mechanism of Xianmao-Epimedium in the treatment of RA bone destruction were clarified, and the theoretical basis for clinical use was provided, and reference was provided for subsequent research and new drug development, which improved the scientific application and marketing effect of its related preparations.
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Abstract
Description
Technical Field
[0001] The invention relates to the technical field of traditional Chinese medicine network pharmacology analysis, and in particular to a method for analyzing the mechanism of curculigo and epimedium in resisting bone destruction in rheumatoid arthritis. Background Art
[0002] Rheumatoid arthritis (RA) is an autoimmune disease with symmetrical polyarthritis as the main clinical manifestation, characterized by progressive destruction of joints. Its clinical symptoms are prone to recurrence, and there is still a lack of ideal therapeutic drugs. The 5-year disability rate can be as high as 30-50%, which is one of the main diseases causing loss of labor force. At present, the treatment goal of RA has changed from the initial simple relief of joint swelling and pain to the relief of the disease and the prevention of joint bone destruction, so as to achieve deep relief in which patients have no joint swelling and pain, no synovial inflammation, and no bone destruction progression. In recent years, the types of RA treatment drugs have been continuously enriched, from traditional treatments (such as methotrexate) to targeted treatments (JAK inhibitors, such as tofacitinib), and the prognosis of patients has been greatly improved, but there is still the possibility of patient intolerance, many adverse drug reactions, and drug resistance. Therefore, finding safer drugs that can control symptoms and prevent the progression of bone destruction is the key and difficulty to improve the treatment rate and prognosis of RA patients.
[0003] Liu Boling, a modern master of traditional Chinese medicine, proposed the academic idea that "the kidney governs the bones, and treating the kidney also treats the bones". He believed that kidney deficiency is an intrinsic factor of RA, and that the disease is caused by the invasion of evil spirits such as wind, cold, and dampness. Therefore, he proposed the treatment principles of "tonifying the kidney and strengthening the bones" and "eliminating evil and removing numbness", and achieved remarkable results in the clinical prevention and treatment of RA.
[0004] The Curculigo-Epimedium drug pair was first recorded in Compendium of Materia Medica and included in ancient books of Ming and Qing Dynasties such as Wanbing Huichun and Huizhitang Experience Prescription. It is not only a classic warming and nourishing kidney yang drug pair, but also a commonly used drug in orthopedics of traditional Chinese medicine. The two drugs complement each other and enhance the effects of nourishing the kidney and strengthening the tendons, dispelling wind and dampness.
[0005] However, the effective components of the Curculigo-Epimedium drug pair for treating RA bone destruction are still unclear, and the mechanism of action of the effective components has not been elucidated, which limits the clinical scientific application, market share and international promotion of its related preparations. Therefore, the purpose of the present invention is to provide a method for analyzing the mechanism of bone destruction of the Curculigo-Epimedium drug pair in treating rheumatoid arthritis based on network pharmacology and molecular docking technology. Summary of the invention
[0006] In order to solve the above technical problems, the purpose of the present invention is to provide a method for analyzing the mechanism of bone destruction of rheumatoid arthritis against Curculigo and Epimedium. The present invention screens and analyzes the core active ingredients and their mechanism of action of the Curculigo-Epimedium drug pair for treating bone destruction in rheumatoid arthritis by network pharmacology and molecular docking technology, clarifies the effective ingredients and their mechanism of action contained in the Curculigo-Epimedium drug pair for treating RA bone destruction, provides a theoretical basis for the clinical use of the Curculigo-Epimedium drug pair for treating RA bone destruction, and also has reference significance for the subsequent research and new drug development of the Curculigo-Epimedium drug pair.
[0007] The technical solution of the present invention to solve the above technical problems is as follows:
[0008] The first object of the present invention is to provide a method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis, comprising the following steps:
[0009] S1. Screening of active ingredients and targets of Curculigo-Epimedium drug pair
[0010] The chemical components of Curculigo and the chemical components of Epimedium were retrieved through the TCMSP database, and the active components of Curculigo and the active components of Epimedium were screened from the chemical components of Curculigo and the chemistry of Epimedium using the Lipinski five drug principles; the canonical SMILES number of the active components of Curculigo and the canonical SMILES number of the active components of Epimedium were queried through the Pubchem database, and the canonical SMILES number of the active components of Curculigo and the canonical SMILES number of the active components of Epimedium were searched and removed in the Swiss Target Predicti on database to obtain the predicted targets of the active components of Curculigo and the predicted targets of the active components of Epimedium;
[0011] S2. Collect RA bone destruction disease-related targets
[0012] In the Genecard database, RA bone destruction disease targets were collected by keyword search;
[0013] S3. Construction of Traditional Chinese Medicine-Ingredient-Target-Disease Network
[0014] The predicted targets of the active ingredients of Curculigo, the predicted targets of the active ingredients of Epimedium, and the RA bone destruction disease targets were imported into the Venny 2.1 online platform to obtain the intersection targets of the Curculigo-Epimedium drug pair for treating RA bone destruction, and the active ingredients of Curculigo, the active ingredients of Epimedium, and the intersection targets were imported into the Cytoscape 3.7.2 software for topological analysis to obtain the core components of the Curculigo-Epimedium drug pair, and a traditional Chinese medicine-ingredient-target-disease network was drawn;
[0015] S4. Construction of protein-protein interaction network
[0016] The intersection targets were uploaded to the STRING database, a PPI network was constructed for the intersection targets and saved in TSV format, and then the TSV format was imported into Cytoscape 3.7.2 software for visualization analysis to obtain a PPI network diagram, and the Network Analyzer plug-in was used to perform topological analysis on the PPI network diagram to obtain core targets;
[0017] S5, GO and KEGG enrichment analysis
[0018] The intersection targets were input into the Metascape database for GO and KEGG enrichment analysis, and a bubble chart was made using the Microbiological Information Platform to visualize the analysis results;
[0019] S6. Molecular docking verification
[0020] The 3D structure of the core target was downloaded from the PDB database; the 3D structure of the core component of the Curculigo-Epimedium drug pair was downloaded from the PubChem database; the 3D structure of the core target and the 3D structure of the core component were preprocessed respectively, the binding site was predicted using POCASA 1.1, molecular docking was performed using AutoDock Vina1.1.2, and visualization analysis was performed using PyMOL2.3.0 to obtain a docking map between the core target and the core component of the Curculigo-Epimedium drug pair.
[0021] The beneficial effect of the present invention is that the present invention screens and analyzes the core active ingredients and their action mechanisms of the "Curculigo-Epimedium" drug for treating rheumatoid arthritis bone destruction mechanism through network pharmacology and molecular docking technology, clarifies the effective ingredients and their action mechanisms contained in the Curculigo-Epimedium drug for treating RA bone destruction, and improves the clinical scientific application, market share and international promotion of its related preparations.
[0022] Based on the above technical solution, the present invention can also be improved as follows.
[0023] Furthermore, the conditions for using the five principles of Lipinski drugs in step S1 to screen the active ingredients of Curculigo and Epimedium from the chemical components of Curculigo and the chemistry of Epimedium are as follows: relative molecular mass (MW) ≤ 500; lipid-water partition coefficient (AlogP) ≤ 5; number of hydrogen bond donors (Hdon) ≤ 5; number of hydrogen bond acceptors (Hacc) ≤ 10.
[0024] Furthermore, the specific steps of searching and removing duplicates in the SwissTargetPrediction database in step S1 are: selecting the species as "Homo sapiens", setting the condition as "Probability>0", and performing search and removing duplicates.
[0025] Furthermore, in step S2, the search keyword for RA bone destruction disease-related targets collected and retrieved in the Genecard database is "bone destruction in rheumatoid arthritis".
[0026] Furthermore, the active ingredients of the Curculigo, the active ingredients of the Epimedium and the intersection targets were imported into the Cytoscape 3.7.2 software, and the Network Analyzer plug-in was used to perform topological analysis parameters, wherein the parameters included betweenness centrality, closeness centrality and degree value, and the core components of the Curculigo-Epimedium drug pair with the top 5 association values were obtained, and a traditional Chinese medicine-ingredient-target-disease network was drawn in the Cytoscape 3.7.2 software.
[0027] Further, the specific steps of step S4 are as follows:
[0028] The intersection targets were uploaded to the STRING database (https: / / cn.string-db.org / ), and a PPI network was constructed for the intersection targets. The species was set to Homo sapiens, the lowest confidence was set to highestconfidence 0.900, free targets in the network were deleted, and the network was saved in TSV format. The TSV format was then imported into Cytoscape 3.7.2 software for visualization analysis to obtain a PPI network diagram, and the degree value was calculated using the Network Analyzer plug-in. The core targets were sorted according to the degree value.
[0029] Furthermore, the core targets in step S4 are the targets ranked in the top 10 by degree value.
[0030] Further, step S5 is specifically as follows:
[0031] The intersection targets were input into the Metascape database (https: / / metascape.org / ) for GO and KEGG enrichment analysis, and the species was set as Homo sapiens; the statistical significance threshold was set to P < 0.01, and the microbial information platform (https: / / www.bioinformatics.com.cn / ) was used to create a bubble chart.
[0032] Further, the specific steps of the pre-processing in step S6 are as follows:
[0033] The 3D structure of the core component of the Curculigo-Epimedium drug pair was downloaded from PubChem data, and the structure was imported into ChemBio3D Ultra 14.0 for energy minimization to obtain an optimized small molecule, and the optimized small molecule was imported into AutodockTools-1.5.6 for hydrogenation, charge calculation, charge distribution, setting of rotatable bonds, and then saved;
[0034] The 3D structure of the core target was downloaded from the PDB database, and the protein structure of the core target was obtained by preprocessing with Pymol2.3.0. The protein structure was imported into AutoDocktools-1.5.6 for hydrogenation, charge calculation, charge assignment, atomic type assignment, and saving.
[0035] Furthermore, in step S6, the binding strength standard for molecular docking using AutoDock Vina1.1.2 is: binding energy Affinity (kJ / mol) ≤ -7.0 kJ / mol. BRIEF DESCRIPTION OF THE DRAWINGS
[0036] Figure 1 is a Venn diagram of Embodiment 1 of the present invention;
[0037] Figure 2 The network diagram of the traditional Chinese medicine-ingredient-target-disease of Example 1 of the present invention;
[0038] Figure 3 This is a PPI network diagram of Example 1 of the present invention;
[0039] Figure 4 This is the GO analysis diagram of Example 1 of the present invention;
[0040] Figure 5 This is a KEGG pathway analysis diagram of Example 1 of the present invention;
[0041] Figure 6 is a heat map of the molecular docking matrix of Example 1 of the present invention;
[0042] Figure 7 This is a molecular docking visualization diagram of Example 1 of the present invention. DETAILED DESCRIPTION
[0043] The principles and features of the present invention are described below, and the examples are only used to explain the present invention and are not used to limit the scope of the present invention. If no specific technology or conditions are specified in the embodiments, the technology or conditions described in the literature in this field or the product instructions are used. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased through regular channels.
[0044] Example 1: Method for analyzing the mechanism of Curculigo and Epimedium against bone destruction in rheumatoid arthritis S1: Screening of active ingredients and targets of Curculigo-Epimedium drug pair
[0045] The chemical components of Curculigo and Epimedium were retrieved through TCMSP database (https: / / old.tcmsp-e.com / tcmsp.php), and the active components of Curculigo and Epimedium were screened from the chemical components of Curculigo and Epimedium using the Lipinski five-principle drug screening method. The following conditions should be met when screening using the Lipinski five-principle drug screening method: relative molecular mass (MW) ≤ 500; lipid-water partition coefficient (AlogP) ≤ 5; number of hydrogen bond donors (Hdon) ≤ 5; number of hydrogen bond acceptors (Hacc) ≤ 10 to obtain the active components; the canonical SMILES number of the active components of Curculigo and Epimedium and the canonical SMILES number of the active components of Epimedium were queried through Pubchem database (https: / / pubchem.ncbi.nlm.nih.gov / ), and the canonical SMILES number of the active components of Curculigo and Epimedium and the canonical SMILES number of the active components of Epimedium were searched in SwissTa The SwisstargetPrediction database (http: / / www.swisstargetprediction.ch / ) was used for retrieval and duplication removal, and the species was selected as "Homo sapiens" and the condition was set as "Probability>0" to obtain the predicted targets of the active ingredients of Curculigo and Epimedium.
[0046] Screening results and analysis:
[0047] Through the TCMSP database, the chemical components of Curculigo and Epimedium were screened according to the "Five Principles of Drug-likeness" standard, and a total of 108 qualified active ingredients were obtained, and 13 active ingredients without canonical SMILES were deleted. Combined with literature reports, curculigoside, an active ingredient in Curculigo, has a therapeutic effect on RA, so a total of 96 potential effective ingredients were screened. A total of 797 active ingredient targets were screened using the Swiss Target Pre diction database (Probability>0).
[0048] S2. Collect RA bone destruction disease-related targets
[0049] Using “bone destruction in rheumatoid arthritis” as the keyword, RA bone destruction disease targets were collected through searching the GeneCards database (https: / / www.genecards.org / );
[0050] Screening results and analysis:
[0051] A total of 3316 disease targets were obtained from the GeneCards database using the keyword "bone destruction in rheumatoid arthritis".
[0052] S3. Construction of Traditional Chinese Medicine-Ingredient-Target-Disease Network
[0053] The predicted targets of the active ingredients of Curculigo orchioides, the predicted targets of the active ingredients of Epimedium, and the RA bone destruction disease targets were imported into the Venny 2.1 online platform (https: / / bioinfogp.cnb.csic.es / tools / venny / ) to draw a Venn diagram, as shown in Figure 1 As shown in Table 1, the intersection target of the Curculigo-Epimedium drug pair for treating RA bone destruction was obtained, that is, the potential target of the Curculigo-Epimedium drug pair for treating RA bone destruction. The active ingredients of Curculigo, the active ingredients of Epimedium, and the intersection target were imported into Cytoscape 3.7.2 software, and the Network Analyzer plug-in was used for topological analysis, including parameters such as Betweenness Centrality, Closeness Central, and Degree, to obtain the core components of the Curculigo-Epimedium drug pair with the top 5 association values, as shown in Table 1, and drawn in Cytoscape 3.7.2 software as shown in Table 1. Figure 2 The “Traditional Chinese Medicine-Ingredient-Target-Disease Network” shown.
[0054] Results and analysis:
[0055] like Figure 1 As shown, by analyzing the Venn diagram drawn by the Venny 2.1 online platform, 424 intersection targets of the active targets of the Curculigo-Epimedium drug pair and the disease targets of RA bone destruction were obtained, that is, the potential targets of the Curculigo-Epimedium drug pair in the treatment of RA bone destruction.
[0056] The screened active ingredients and intersection targets were imported into Cytoscape 3.7.2 software, and the imported data were topologically analyzed using the plug-in Network Analyzer to obtain the top five key ingredients with the highest associated degree values, namely anhydroicaritin, Besigomsin, Liquiritigenin, apigenin, and magnoflorin e. The betweenness centrality, closeness centrality, and degree values of the above key ingredients are shown in Table 1.
[0057] Table 1 The top 5 key components of Curculigo-Epimedium drug pair in terms of degree value
[0058]
[0059]
[0060] S4. Protein-protein interaction (PPI) network construction
[0061] The intersection targets obtained from S3 were uploaded to the STRING database (https: / / cn.string-db.org / ) to construct the PPI network, the species was set to "Homo sapiens", the minimum confidence was set to "highest confidence (0.900)", the free targets in the network were deleted, and the network was saved in TSV format. The TSV format was imported into Cytoscape 3.7.2 software for visualization analysis. Figure 3 The PPI network diagram shown in the figure is used, and the Degree value is calculated using the Network Analyzer plug-in. The core targets are obtained by topological analysis based on the Degree value sorting.
[0062] Results and analysis:
[0063] like Figure 3As shown in the figure, there are 422 targets, 1274 edges and an average degree value of 6.04 in the network. The size and color of the nodes in the network represent the degree value of the target. The larger the node, the darker the color, indicating that the role is more critical. The top 10 targets in degree value are TP53, S RC, PIK3R1, PIK3CA, HSP90AA1, STAT3, PIK3CB, AKT1, PIK3CD, and EGFR, suggesting that they may be the core targets of Curculigo-Epimedium for the treatment of RA bone destruction.
[0064] S5, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis
[0065] The intersection targets were input into the Metascape database (https: / / metascape.org / ) for GO and KEGG enrichment analysis, and the species was set as “Homo sapiens”. GO gene function enrichment analysis, such as Figure 4 The results showed that KEGG enrichment analysis, the results are shown in Figure 5 The statistical significance threshold was set at P < 0.01, and the microbial information platform (https: / / www.bioinformatics.com.cn / ) was used to create a bubble chart to visualize the analysis results;
[0066] Results and Analysis:
[0067] (1) GO gene function enrichment analysis, such as Figure 4 The results show that Figure 4 It was found that in terms of biological processes (BP), the Curculigo-Epimedium pair could regulate stem cell proliferation, peptide decomposition process, positive regulation of transporter activity, regulation of cysteine endopeptidase activity during apoptosis, positive regulation of Notch signaling pathway, etc.; in terms of cellular components (CC), the proteins regulated by the Curculigo-Epimedium pair were mainly located in the Xie collateral-CA1 synapse, nuclear membrane cavity, Bcl-2 family protein complex, external components of membrane, microvilli, etc.; in terms of molecular functions (MF), it involved cyclin-dependent protein serine / threonine kinase regulator activity, peptide hormone binding, gated channel activity, growth hormone receptor binding, etc.
[0068] (2) KEGG enrichment analysis, the results are shown in Figure 5 .Depend on Figure 5 The results showed that the pathways closely related to the effect of Curculigo-Epimedium on the treatment of RA bone destruction include PI3K-AKT, RAS, Rap1, AGE-RAGE, MAPK, JAK-STAT, and Adipocytokine.
[0069] S6. Molecular docking
[0070] In order to further explore the influence of the core components with the highest degree value in the Curculigo-Epimedium drug pair on the core targets, we conducted a molecular docking study. The molecular docking binding energy matrix heat map is shown in Figure 6 .
[0071] The top five core components and core targets were selected from the TCM-component-target-disease network and PPI network according to the degree value for molecular docking. The 3D structure of the core component in SDF format was downloaded from PubChem data, and the structure was imported into ChemBio3D Ultra 14.0 for energy minimization. The optimized small molecules were imported into AutodockTools-1.5.6 for hydrogenation, charge calculation, charge assignment, setting rotatable bonds and saving. The core targets were obtained from the PDB database (https: / / www.rcsb.org / ), and Pymol2.3.0 was used to remove protein crystal water, original ligands, etc. The protein structure was imported into AutoDocktools for hydrogenation, charge calculation, charge assignment, specifying atom types and saving. POCASA 1.1 was used to predict protein binding sites, and AutoDock Vina1.1.2 was used for docking. The binding energy Affinity (kJ / mol) ≤ -7.0kJ / mol was selected as the strong binding standard, and PyMOL2.3.0 was used for visualization analysis.
[0072] The lower the binding energy, the more stable the conformation, indicating that the component has a higher probability of binding to the target. Select binding energy ≤ -7.0 kJ / mol for visualization analysis. Figure 7 .
[0073] In summary, the present invention screened and analyzed the core active ingredients and their mechanism of action of the "Curculigo-Epimedium" drug pair for the treatment of rheumatoid arthritis bone destruction mechanism through network pharmacology and molecular docking technology. After analysis, the top five core active ingredients of anhydroicaritin, Besigomsin, Liquiritigenin, apigenin, and magnoflorine, as well as the top five core targets of TP53, SRC, PIK3R1, PIK3CA, and HSP90AA1, were obtained.
[0074] Through GO functional enrichment analysis, it can be concluded that the Curculigo-Epimedium pair can regulate stem cell proliferation, peptide decomposition process, positive regulation of transporter activity, regulation of cysteine endopeptidase activity in apoptosis, positive regulation of Notch signaling pathway, etc. In terms of cellular components (CC), the proteins regulated by the Curculigo-Epimedium pair are mainly located in Xie's collateral-CA1 synapse, nuclear membrane cavity, Bcl-2 family protein complex, external components of membrane, microvilli, etc. In terms of molecular function (MF), it involves cyclin-dependent protein serine / threonine kinase regulator activity, peptide hormone binding, gated channel activity, growth hormone receptor binding, etc. KEGG enrichment analysis showed that the pathways closely related to the Curculigo-Epimedium pair in the treatment of RA bone destruction include PI3K-AKT, RAS, Rap1, AGE-RAGE, and MAPK. The core active ingredients obtained by network pharmacology analysis were molecularly docked with key target proteins. From the results, it can be seen that the molecular docking experiment also shows that the core active ingredients have good binding energy with the key target proteins, and SRC and HSP90AA1 can spontaneously bind to the active ingredients and the binding conformation is stable. Among them, Liquiritigenin has the highest binding affinity with HSP90AA1, with a binding energy of -9.1kJ / mol, and TP53 and PIK3CA have poor affinity with the active ingredients.
[0075] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.
Claims
1. A method for analyzing the mechanism of Curculigo and Epimedium in combating bone destruction in rheumatoid arthritis, characterized in that: The method comprises the following steps: S1. Screening of active ingredients and targets of Curculigo-Epimedium drug pair The chemical components of Curculigo and the chemical components of Epimedium are retrieved through the TCMSP database, and the active components of Curculigo and the active components of Epimedium are screened from the chemical components of Curculigo and the chemistry of Epimedium by using the five principles of Lipinski drug classes; the canonical SMILES number of the active components of Curculigo and the canonical SMILES number of the active components of Epimedium are queried through the Pubchem database, and the canonical SMILES number of the active components of Curculigo and the canonical SMILES number of the active components of Epimedium are retrieved and deduplicated in the Swiss Target Predicti on database to obtain the predicted targets of the active components of Curculigo and the predicted targets of the active components of Epimedium; S2. Collect RA bone destruction disease-related targets In the Genecard database, RA bone destruction disease targets were collected by keyword search; S3. Construction of Traditional Chinese Medicine-Ingredient-Target-Disease Network Import the predicted targets of the active ingredients of Curculigo, the predicted targets of the active ingredients of Epimedium, and the RA bone destruction disease targets into the Venny 2.1 online platform to obtain the intersection targets of the Curculigo-Epimedium drug pair for treating RA bone destruction, import the active ingredients of Curculigo, the active ingredients of Epimedium, and the intersection targets into the Cytoscape 3.7.2 software for topological analysis, obtain the core components of the Curculigo-Epimedium drug pair, and draw a traditional Chinese medicine-ingredient-target-disease network; S4. Construction of protein-protein interaction network The intersection targets are uploaded to the STRING database, a PPI network is constructed for the intersection targets, and the network is saved in TSV format. The TSV format is then imported into Cytoscape 3.7.2 software for visualization analysis to obtain a PPI network diagram, and the Network Analyzer plug-in is used to perform topological analysis on the PPI network diagram to obtain core targets; S5, GO and KEGG enrichment analysis The intersection targets were input into the Metascape database for GO and KEGG enrichment analysis, and a bubble chart was made using the Microbiological Information Platform to visualize the analysis results; S6. Molecular docking verification The 3D structure of the core target was downloaded from the PDB database; the 3D structure of the core component of the Curculigo-Epimedium drug pair was downloaded from the PubChem database; the 3D structure of the core target and the 3D structure of the core component were preprocessed respectively, the binding site was predicted using POCASA 1.1, molecular docking was performed using AutoDock Vina1.1.2, and visualization analysis was performed using PyMOL2.3.0 to obtain a docking map between the core target and the core component of the Curculigo-Epimedium drug pair.
2. The method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis according to claim 1, characterized in that: The conditions for using the five principles of Lipinski drugs in step S1 to screen the active ingredients of Curculigo and Epimedium from the chemical components of Curculigo and the chemistry of Epimedium are as follows: relative molecular mass ≤500; lipid-water partition coefficient ≤5; number of hydrogen bond donors ≤5; number of hydrogen bond acceptors ≤10.
3. The method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis according to claim 1, characterized in that: The specific steps of searching and removing duplicates in the SwissTargetPrediction database in step S1 are: selecting the species as "Homo sapiens" and setting the condition as "Probabilit y>0".
4. The method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis according to claim 1, characterized in that: The keyword in step S2 is "bone destruction in rheumatoid arthritis".
5. The method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis according to claim 1, characterized in that: The specific steps of the topological analysis in step S3 are as follows: the active ingredients of the Curculigo, the active ingredients of the Epimedium and the intersection targets are imported into the Cytoscape 3.7.2 software, and the topological analysis parameters are performed using the Network Analyzer plug-in, wherein the parameters include betweenness centrality, closeness centrality, and degree value, and the core components of the Curculigo-Epimedium drug pair with the top 5 association values are obtained, and a traditional Chinese medicine-ingredient-target-disease network is drawn in the Cytoscape 3.7.2 software.
6. The method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis according to claim 1, characterized in that: The specific steps of step S4 are as follows: The intersection targets were uploaded to the STRING database, and a PPI network was constructed for the intersection targets. The species was set to Homo sapiens, the lowest confidence was set to highest confidence 0.900, free targets in the network were deleted, and the network was saved in TSV format. The TSV format was then imported into Cytoscape 3.7.2 software for visualization analysis to obtain a PPI network diagram, and the degree values were calculated using the Network Analyzer plug-in. The core targets were sorted according to the degree values.
7. The method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis according to claim 6, characterized in that: The core targets in step S4 are the targets ranked in the top 10 by degree value.
8. The method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis according to claim 1, characterized in that: Step S5 is specifically as follows: The intersection targets were input into the Metascape database for GO and KEGG enrichment analysis, and the species was set as Homosapiens; the statistical significance threshold was set to P < 0.01, and a bubble chart was produced using the Microbial Information Platform.
9. The method for analyzing the mechanism of bone destruction of Curculigo and Epimedium against rheumatoid arthritis according to claim 1, characterized in that: The specific steps of the pre-processing in step S6 are as follows: The 3D structure of the core component of the Curculigo-Epimedium drug pair was downloaded from PubChem data, and the structure was imported into ChemBio3D Ultra 14.0 for energy minimization to obtain an optimized small molecule, and the optimized small molecule was imported into AutodockTools-1.5.6 for hydrogenation, charge calculation, charge distribution, setting of rotatable bonds, and then saved; The 3D structure of the core target was downloaded from the PDB database, and the protein structure of the core target was obtained by preprocessing with Pymol2.3.
0. The protein structure was imported into AutoDocktools-1.5.6 for hydrogenation, charge calculation, charge assignment, atomic type assignment, and saving.
10. The method for analyzing the mechanism of Curculigo and Epimedium in combating bone destruction in rheumatoid arthritis according to claim 1, characterized in that: The binding strength standard for molecular docking using AutoDock Vina1.1.2 in step S6 is: binding energy Affinity ≤ -7.0 kJ / mol.