Application of ginseng-bile powder prepared based on network pharmacology and molecular docking technology in preparation of drugs for preventing and treating diabetic cardiomyopathy

Abstract

The application provides application of ginseng-bovine-bezoar compatibility in preparation of a medicine for preventing and treating diabetic cardiomyopathy based on network pharmacology and molecular docking technology. A method for obtaining ginseng-bovine-bezoar compatibility based on network pharmacology and molecular docking technology comprises the following steps: screening active ingredients of ginseng-bovine-bezoar and corresponding target points of the active ingredients; constructing a diabetic cardiomyopathy disease target point library; performing intersection analysis on the target points corresponding to the active ingredients of ginseng-bovine-bezoar and the diabetic cardiomyopathy target points to obtain potential treatment target points; constructing a traditional Chinese medicine-component-target point network; constructing a protein-protein interaction network based on the potential treatment target points; analyzing the protein-protein interaction network to screen out core target points; performing GO and KEGG enrichment analysis on the potential treatment target points; and performing molecular docking experiments on the core target points and the active ingredients of the medicine. The technical scheme of the application can screen out effective active ingredients and core target points of a new traditional Chinese medicine compound ginseng-bovine-bezoar for effectively preventing and treating diabetic cardiomyopathy.

Description

Technical Field

[0001] This invention relates to network pharmacology and molecular docking technology, belonging to the field of biomedicine, and specifically to a method for screening the active ingredients and core targets of ginseng-bezoar medicine for the prevention and treatment of diabetic cardiomyopathy. Background Technology

[0002] Diabetes has become one of the major diseases threatening human health. It can cause various complications affecting the cardiovascular, neurological, and renal systems, among which diabetic cardiomyopathy (DCM) is particularly prominent, characterized by high incidence and significant harm. DCM refers to the impairment of myocardial contractility and / or diastolic function in diabetic patients, with its main pathological features being ventricular hypertrophy and myocardial fibrosis, ultimately leading to heart failure. The risk of heart failure in diabetic patients is more than twice that of non-diabetic individuals, and approximately 39% of diabetic patients eventually develop heart failure. DCM has become one of the main factors contributing to the rising mortality rate among diabetic patients.

[0003] Studies have found a close link between mitochondrial dysfunction, inflammatory responses, and oxidative stress and the occurrence and development of myocardial infarction (DCM). Western medicine typically employs symptomatic treatments such as blood sugar control, lipid-lowering, and improvement of heart failure. However, these treatments are unlikely to fundamentally reverse myocardial damage, and many Western medicines may have significant side effects on liver and kidney function. Currently, Western medicine lacks a unified and effective treatment method targeting the complex pathological mechanisms of DCM.

[0004] In recent years, Traditional Chinese Medicine (TCM) has received widespread attention in the treatment of deep cardiac muscular dystrophy (DCM). Multiple effective components of TCM alleviate myocardial damage through different pathways and multiple targets, providing strong support for the development of new drugs for DCM. According to TCM records, ginseng is warm in nature, sweet and slightly bitter in taste, and enters the spleen, lung, and heart meridians. It has the effects of greatly replenishing vital energy, tonifying the spleen and lungs, promoting body fluid production and calming the mind, invigorating qi and raising yang, and nourishing qi and blood. Calculus bovis, on the other hand, is slightly bitter then sweet, neutral in nature, and has the effects of relieving fever, detoxifying, calming the nerves, and strengthening the heart. Both ginseng and calculus bovis regulate glucose and lipid metabolism and reduce myocardial damage; their combination can achieve a synergistic effect. Summary of the Invention

[0005] To address the aforementioned technical problems, the first aspect of this application provides a method for obtaining ginseng-bezoar combination based on network pharmacology and molecular docking technology, comprising:

[0006] Step S1: Screen the active ingredients of ginseng and bezoar and their corresponding targets from the ginseng-bezoar component database according to specific conditions;

[0007] Step S2: Extract disease target information related to diabetic cardiomyopathy from several disease target databases and construct a diabetic cardiomyopathy disease target database;

[0008] Step S3: Perform an intersection analysis between the target points corresponding to the active ingredients of ginseng-bezoar and the target points of diabetic cardiomyopathy to obtain the common target points of the drug and the disease, i.e., potential therapeutic targets.

[0009] Step S4: Construct a traditional Chinese medicine-component-target network based on the potential therapeutic targets of ginseng and bezoar for diabetic cardiomyopathy and their corresponding active pharmaceutical ingredients;

[0010] Step S5: Construct a protein-protein interaction network based on potential therapeutic targets;

[0011] Step S6: Analyze the protein-protein interaction network to further screen core targets from potential therapeutic targets;

[0012] Step S7: Perform GO and KEGG enrichment analysis on potential therapeutic targets to obtain the receptor signaling pathways involved in the treatment of diabetic cardiomyopathy with ginseng-bezoar.

[0013] Step S8: Perform molecular docking experiments on the core target corresponding to the receptor signaling pathway and the active pharmaceutical ingredient corresponding to the core target, and screen out the docking modes with stable docking results.

[0014] Further, step S1 includes: First, according to the Lipinski five rules, ginseng and bezoar components are screened from the TCMID, ITCM, ETCM, HERB, and TCMSP databases based on drug similarity DL ≥ 0.1 and oral bioavailability OB ≥ 20%; Second, based on the SMILES structural formula provided by PubChem, a secondary screening is performed using the SwissADME and ChemSpider platforms to select components with high gastrointestinal absorption and meeting ≥ 2 types of drug properties as active ingredients of ginseng and bezoar; Finally, the targets corresponding to the above active ingredients are obtained using the SwissTargetPrediction tool, and targets with a prediction probability greater than 0.1 are selected.

[0015] Step S2 includes: searching the GeneCards, OMIM, GEO, and MaLaCard databases respectively using "diabetic cardiomyopathy" as the keyword to extract disease target information related to diabetic cardiomyopathy; then, summarizing the target information in the above databases, and taking the disease targets with 3 or more intersections in the four databases to construct a diabetic cardiomyopathy disease target library.

[0016] Step S3 includes: importing the target points corresponding to the obtained ginseng and bezoar active ingredients and the target points of diabetic cardiomyopathy into the Venny 2.1.0 online platform for intersection analysis and constructing a Venn diagram to obtain the common target points of the drug and the disease, i.e. potential therapeutic targets;

[0017] Step S4 includes: based on the potential therapeutic targets for diabetic cardiomyopathy in ginseng and bezoar, and the corresponding traditional Chinese medicines and active ingredients, a "traditional Chinese medicine-ingredient-target" network is constructed and a network diagram is drawn using Cytoscape 3.9.1 software. Traditional Chinese medicines refer to ginseng and / or bezoar. After deleting 3 unrelated nodes, the "traditional Chinese medicine-ingredient-target" network diagram consists of 99 nodes and 401 edges. The nodes are interconnected by edges to show the interaction between traditional Chinese medicines, ingredients, diseases, and targets. The 99 nodes include 2 traditional Chinese medicine nodes, namely ginseng nodes and bezoar nodes, 42 active ingredient nodes, and 56 potential therapeutic targets.

[0018] Step S5 includes: importing potential therapeutic targets into the STRING database, limiting the species to "Homosapiens", setting the confidence score to ≥0.4, and constructing a PPI network diagram; subsequently, using Cytoscape 3.9.1 software for further visualization, i.e., constructing a potential therapeutic target network analysis diagram;

[0019] Step S6 includes: using the Centiscape 2.2 plugin of Cytoscape 3.9.1 software to further screen core targets from potential therapeutic targets, and taking the top 10 targets with the highest Degree values ​​as core targets;

[0020] Step S7 includes: uploading potential therapeutic targets to the Metascape platform for GO and KEGG enrichment analysis: in the GO analysis, the top 5 targets for biological processes, cellular composition, and molecular function are selected based on the count value; in the KEGG analysis, the top 10 targets are selected based on the p-value after FDR correction; subsequently, bar charts and bubble charts are plotted on the MicroBio platform to visualize the results of the GO and KEGG enrichment analysis; the results show that ginseng-bezoar treatment of diabetic cardiomyopathy involves signaling pathways such as AGE-RAGE and Toll-like receptors.

[0021] Step S8 includes: selecting the top 10 core targets corresponding to the AGE-RAGE pathway by degree ranking and their corresponding active pharmaceutical ingredients for molecular docking experiments: First, the 2D structures of the active ingredients are obtained from the PubChem and TCMSP databases, and after energy minimization and 3D transformation using Chem3D software, they are preprocessed using AutoDockTools; Second, the 3D structures of the core targets are obtained from the PDB database, and then processed using PyMOL 2.2.0 and AutoDockTools, including the removal of water molecules, small molecule ligands, and hydrogenation, and the docking file format is converted using OpenBabel software; Finally, docking is performed using AutoDockVina 1.1.2 software, the results are presented in the form of binding energy, and the docking results are visualized using PyMOL 2.2.0 software; Stable docking core targets and their corresponding active ingredients of ginseng and / or bezoar are screened out.

[0022] Furthermore, in step S1, the active ingredients of ginseng-bezoar include 44 pharmaceutical active ingredients, as shown in the table below:

[0023]

[0024] .

[0025] Furthermore, the active pharmaceutical ingredients are ursodeoxycholic acid, porcine deoxycholic acid, and ginsenoside Rh1.

[0026] Furthermore, in step S3, the potential therapeutic targets include 56, as shown in the table below.

[0027]

[0028] .

[0030] Furthermore, in step S6, the core targets are interleukin-6, interleukin-1β, tumor necrosis factor, albumin, protein kinase Bα, estrogen receptor 1, mitogen-activated protein kinase 3, cAMP response element binding protein, AP-1 transcription factor subunit, and Jun proto-oncogene.

[0031] Further, in step S8, the stable docking modes selected include: chenodeoxycholic acid-CASP3, chenodeoxycholic acid-JUN, ursodeoxycholic acid-CASP3, ursodeoxycholic acid-IL1B, ursodeoxycholic acid-NOS3, cholic acid-CASP3, cholic acid-IL6, ginsenoside Rb1-IL6, sugaenoside-AKT1, sugaenoside-IL6, sugaenoside-TNF, ginsenoside Rh2-IL1B, ginsenoside Rh2-IL6, ginsenoside Rh2-TNF, ginsenoside Rh1-CASP3, ginsenoside Rh1-JUN, ginsenoside Rh1-TNF, ginsenoside F1-IL1B, ginsenoside F1-IL6, ginsenoside F1-NOS3, ginsenoside F4- IL1B, Ginsenoside F4-NOS3, Ginsenoside Ia-CASP3, Ginsenoside Ia-IL1B, Ginsenoside Ia-TNF.

[0032] The second aspect of this application provides the application of the ginseng-bezoar combination obtained by the method described above in the preparation of drugs for the prevention and treatment of diabetic cardiomyopathy. The effective components of the ginseng-bezoar combination include 34 kinds of ginseng and 10 kinds of bezoar, as detailed in the table below:

[0033]

[0034] .

[0035] Furthermore, the core targets corresponding to the effective components of ginseng-bezoar include IL-6, IL1B, TNF, ALB, AKT1, ESR1, MAPK3, CREB1, FOS, and JUN.

[0036] Furthermore, the optimal docking modes between the active pharmaceutical ingredient and the core target include: chenodeoxycholic acid-CASP3, ursodeoxycholic acid-NOS3, porcine deoxycholic acid-TNF, ginsenoside Ia-IL1B, ginsenoside F4-IL1B, and ginsenoside Rh1-CASP3.

[0037] After adopting the above technical solution, this application has the following technical effects:

[0038] This invention utilizes network pharmacology and molecular docking technology to screen out the effective active ingredients and core targets of a novel traditional Chinese medicine compound, ginseng-bezoar, which can effectively prevent and treat diabetic cardiomyopathy. It can prevent and treat diabetic cardiomyopathy through a synergistic mechanism involving multiple components, multiple targets, and multiple pathways. Among them, ginsenoside Rh1, porcine deoxycholic acid, and ursodeoxycholic acid are more suitable as effective ingredients for the development of drugs to treat diabetic cardiomyopathy.

[0039] Traditional Chinese medicine (TCM) possesses a holistic regulatory advantage in treating complex chronic diseases, characterized by "multiple components, multiple targets, and multiple pathways." Ginseng, traditionally considered a key tonic for replenishing qi, has seen innovative applications in cardiovascular diseases, primarily shifting from macroscopic "replenishing vital energy and restoring pulse" to a deeper understanding and application of microscopic, multi-target, and multi-pathway molecular mechanisms. Calculus bovis (ox gallstone) has a clear, fragrant aroma, a slightly bitter taste followed by sweetness, and is neutral in nature. It can be used for antipyretics, detoxification, and calming the nerves. Calculus bovis exhibits pharmacological activities such as improving cardiac function, dilating peripheral blood vessels, constricting coronary arteries, and significantly and persistently lowering blood pressure. The combined application of ginseng and calculus bovis is a model of integrating TCM theory with modern pharmacology, embodying a treatment strategy that combines "tonifying qi" with "clearing heat," aiming to synergistically address the complex pathogenesis of diabetic cardiomyopathy. Attached Figure Description

[0040] The above and other objects, features and advantages of the present invention will become more apparent from the more detailed description of the embodiments of the present invention in conjunction with the accompanying drawings. The accompanying drawings are used to provide a further understanding of the embodiments of the present invention and form part of the specification. They are used together with the embodiments of the present invention to explain the present invention and do not constitute a limitation thereof. In the accompanying drawings, the same reference numerals generally represent the same parts or steps.

[0041] Figure 1 This is a Venn diagram of the drug and disease co-targets in an embodiment of the present invention.

[0042] Figure 2 This is a network diagram of "Traditional Chinese Medicine - Components - Targets" in an embodiment of the present invention;

[0043] Figure 3 This is a flowchart illustrating the core target screening process in an embodiment of the present invention;

[0044] Figure 4 This is a GO enrichment analysis diagram from an embodiment of the present invention;

[0045] Figure 5 This is a KEGG enrichment analysis diagram from an embodiment of the present invention;

[0046] Figure 6 This is a diagram of the AGE-RAGE signal path according to an embodiment of the present invention;

[0047] Figure 7 This is a Toll-like signal path diagram according to an embodiment of the present invention;

[0048] Figure 8 This is a thermal diagram of molecular docking binding energy according to an embodiment of the present invention;

[0049] Figure 9 This is an example of a molecular docking mode diagram according to an embodiment of the present invention. Detailed Implementation

[0050] The advantages of the present invention are further illustrated below with reference to the accompanying drawings and specific embodiments. Those skilled in the art should understand that the following detailed description is illustrative rather than restrictive and should not be construed as limiting the scope of protection of the present invention.

[0051] This embodiment provides a method for screening ginseng-bezoar active ingredients and core targets for the treatment of diabetic cardiomyopathy based on network pharmacology and molecular docking technology, including steps S1-S8.

[0052] Step S1: Screen the active ingredients of ginseng and bezoar and their corresponding targets from the ginseng-bezoar component database according to specific conditions;

[0053] Based on the Lipinski five rules, components of ginseng and bezoar were screened from the TCMID, ITCM, ETCM, HERB, and TCMSP databases according to drug similarity (DL) ≥ 0.1 and oral bioavailability (OB) ≥ 20%. Secondly, based on the SMILES structural formulas provided by PubChem, a secondary screening was performed using the SwissADME and ChemSpider platforms. Components with high gastrointestinal absorption and meeting ≥ 2 drug activity rules were selected as the active ingredients of ginseng and bezoar, resulting in 44 active pharmaceutical ingredients. The ranking of Degree values ​​based on network pharmacology analysis is shown in Table 1. Finally, the targets corresponding to the above active ingredients were obtained using the SwissTargetPrediction tool, and targets with a prediction probability greater than 0.1 were selected.

[0054] Table 1: 44 active pharmaceutical ingredients: , , .

[0055] Step S2: Extract disease target information related to diabetic cardiomyopathy from several disease target databases and construct a diabetic cardiomyopathy disease target database;

[0056] We searched the GeneCards, OMIM, GEO, and MaLaCard databases using "diabetic cardiomyopathy" as the keyword to extract disease target information related to diabetic cardiomyopathy. Then, we summarized the target information from the above databases and selected disease targets with three or more intersections from the four databases to construct a diabetic cardiomyopathy disease target library.

[0057] Step S3: Perform an intersection analysis between the target points corresponding to the active ingredients of ginseng-bezoar and the target points of diabetic cardiomyopathy to obtain the common target points of the drug and the disease, i.e., potential therapeutic targets.

[0058] The targets corresponding to the ginseng-bezoar active ingredients and the targets of diabetic cardiomyopathy were imported into the Venny2.1.0 online platform for intersection analysis and Venn diagram construction to obtain the common targets of the drug and the disease, i.e. potential therapeutic targets.

[0059] Based on steps S1, S2, and S3, the active ingredients of ginseng and bezoar in this invention correspond to 42 and 206 target sites, respectively. After removing duplicates, the number of target sites for the active ingredients is 237; the number of target sites for DCM is 675; and the number of target sites for the combined action of the drug and the disease is 56. See Figure 1 See Table 2.

[0060] Table 2. Targets of 56 drugs and diseases acting together: , .

[0061] Step S4: Construct a traditional Chinese medicine-component-target network based on the potential therapeutic targets of ginseng and bezoar for diabetic cardiomyopathy and their corresponding active pharmaceutical ingredients;

[0062] Based on the potential therapeutic targets of ginseng and bezoar against DCM, and the corresponding traditional Chinese medicines and active ingredients, a "traditional Chinese medicine-ingredient-target" network was constructed and visualized using Cytoscape 3.9.1 software. See [link / reference]. Figure 2 After deleting three unrelated nodes, the "Traditional Chinese Medicine-Ingredient-Target" network diagram constructed in this invention consists of 99 nodes (2 Traditional Chinese Medicine nodes, 42 active ingredient nodes, and 56 therapeutic targets) and 401 edges. The outer purple cone-shaped nodes represent the active ingredients of Traditional Chinese Medicine, the middle orange circular nodes represent potential therapeutic targets, and the two light green rhombus-shaped nodes represent the Traditional Chinese Medicines ginseng and bezoar, respectively. The nodes are connected to each other through edges, clearly showing the complex interaction between Traditional Chinese Medicine, ingredients, diseases, and targets.

[0063] Step S5: Construct a protein-protein interaction network based on potential therapeutic targets;

[0064] Potential therapeutic targets were imported into the STRING database, with the species limited to "Homosapiens" and the confidence score set to ≥ 0.4, to construct a PPI network diagram. Subsequently, Cytoscape 3.9.1 software was used for further visualization, i.e., to construct a potential therapeutic target network analysis diagram.

[0065] Step S6: Analyze the protein-protein interaction network to further screen core targets from potential therapeutic targets;

[0066] The Centiscape 2.2 plugin of Cytoscape 3.9.1 software was used to further screen core targets from potential therapeutic targets. The top 10 targets with the highest Degree values ​​were selected as core targets, and a core target screening flowchart was constructed.

[0067] Based on steps (5) and (6), this invention constructs a PPI network and a potential therapeutic target analysis network based on 56 potential therapeutic targets. The core target screening process is described in [link to core target screening process]. Figure 3 The 10 core targets, ranked by degree, are interleukin-6 (IL-6, degree=86), interleukin-1β (IL1B, degree=84), tumor necrosis factor (TNF, degree=84), albumin (ALB, degree=82), protein kinase Bα (AKT1, degree=80), estrogen receptor 1 (ESR1, degree=74), mitogen-activated protein kinase 3 (MAPK3, degree=70), cAMP response element binding protein (CREB1, degree=70), AP-1 transcription factor subunit (FOS, degree=70), and Jun proto-oncogene (JUN, degree=66).

[0068] Step S7: Perform GO and KEGG enrichment analysis on potential therapeutic targets to obtain the receptor signaling pathways involved in the treatment of diabetic cardiomyopathy with ginseng-bezoar.

[0069] Potential therapeutic targets were uploaded to the Metascape platform for GO and KEGG enrichment analysis to explore the potential mechanism of ginseng-bezoar in treating DCM. In the GO analysis, the top 5 targets for biological processes (BP), cellular composition (CC), and molecular function (MF) were selected based on the count value. In the KEGG analysis, the top 10 targets were selected based on the p-value after FDR correction. Subsequently, bar charts and bubble charts were plotted on the MicroBio platform to visualize the results of the GO and KEGG enrichment analysis.

[0070] The GO analysis results of this invention showed a total of 2223 bars, including BP (1954 bars), CC (108 bars), and MF (161 bars). Based on the bar chart results, it can be inferred that the BP effect of ginseng-bezoar in treating DCM mainly involves positive regulation of miRNAs, transcriptional regulation, and miRNA transcriptional regulation; in CC, euchromatin, endoplasmic reticulum, and luminal RNA polymerase ranked in the top three; MF mainly involves lipid localization regulation of cellular responses to lipopolysaccharides and cellular responses to bacterial-derived molecules, etc. (See...) Figure 4KEGG enrichment analysis identified 180 pathways and biological processes. Larger bubbles indicate a greater number of targets involved in that pathway; smaller P-values ​​and a color closer to red indicate more significant enrichment of that pathway. (See attached image) Figure 5 By excluding irrelevant pathways, ginseng-bezoar treatment for DCM mainly involves signaling pathways such as AGE-RAGE and Toll-like receptors. Figure 6 , Figure 7 ).

[0071] Step S8: Perform molecular docking experiments on the core target corresponding to the receptor signaling pathway and the active pharmaceutical ingredient corresponding to the core target, and screen out the docking modes with stable docking results.

[0072] Molecular docking between active ingredients and core targets was performed as follows: The top 10 core targets corresponding to the AGE-RAGE pathway and their corresponding active pharmaceutical ingredients (24 pairs in total) were selected for molecular docking experiments. First, the 2D structures of the active ingredients were obtained from the PubChem and TCMSP databases. After energy minimization and 3D transformation using Chem3D software, they were preprocessed using AutoDockTools. Second, the 3D structures of the core targets were obtained from the PDB database and then processed using PyMOL 2.2.0 and AutoDockTools, including the removal of water molecules, small molecule ligands, and hydrogenation. The docking file format was converted using OpenBabel software. Finally, docking was performed using AutoDockVina 1.1.2 software, and the results were presented in the form of binding energy. The docking results were visualized using PyMOL 2.2.0 software.

[0073] The molecular docking results showed that the binding energies of the top 10 major active ingredients to the core targets were all less than -5 kcal / mol, indicating good binding ability between the active ingredients of ginseng and bezoar and the key targets. Furthermore, the binding energies of the core targets CASP3, TNF, and NOS3 to the active ingredients were mostly between -5 kcal / mol and -8 kcal / mol, exhibiting high affinity and extremely strong interactions. Among them, the active ingredient in bezoar, hyodeoxycholic acid, had the strongest affinity for the target TNF, with a binding energy of -7.82 kcal / mol. Moreover, the active ingredients in ginseng, ginsenoside Rh2, ginsenoside F1, ginsenoside F4, and ginsenoside Ia, bound stably to IL1B. All of these active ingredients formed hydrogen bonds with the core targets. In molecular docking, the smaller the binding energy, the tighter the binding between the receptor and ligand, and the more stable the interaction. A binding energy below -5.0 kcal / mol indicates a high binding affinity between the acceptor and ligand; a binding energy below -7.0 kcal / mol indicates an extremely strong bond. The heatmap of the 24 molecular docking pairs in this invention is shown below. Figure 8 .

[0074] By screening out the active ingredients that showed the best docking results with each target, and selecting the target sites with the best docking results for each active ingredient, a total of molecular docking patterns were screened. (See example of the molecular docking pattern diagram.) Figure 9 .

[0075] In summary, this study, employing network pharmacology and molecular docking techniques, screened 46 active ingredients (34 from ginseng and 12 from bezoar), 241 drug targets, 675 disease targets, and 56 drug-disease intersection targets. The core targets included 10: IL-6, IL-1B, TNF, ALB, AKT1, ESR1, MAPK3, CREB1, FOS, and JUN. GO enrichment analysis identified the top 5 targets for BP, CC, and MF, while KEGG analysis showed enrichment in AGE-RAGE signaling pathways. Molecular docking analysis indicated that the active ingredients of ginseng and bezoar bind well to key targets in treating DCM. Ursodeoxycholic acid, porcine deoxycholic acid, and ginsenoside Rh1 showed the most stable binding and were suitable as active drug ingredients. This novel traditional Chinese medicine compound, ginseng-bezoar, prevents and treats DCM through multi-component, multi-target, and multi-pathway interactions.

[0076] It should be noted that the embodiments of the present invention have better implementability and are not intended to limit the present invention in any way. Any person skilled in the art may use the above-disclosed technical content to change or modify it into equivalent effective embodiments. However, any modifications or equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention shall still fall within the scope of the technical solution of the present invention.

Claims

1. A method for obtaining ginseng-bezoar compatibility based on network pharmacology and molecular docking technology, characterized in that, include: Step S1: Screen the active ingredients of ginseng and bezoar and their corresponding targets from the ginseng-bezoar component database according to specific conditions; Step S2: Extract disease target information related to diabetic cardiomyopathy from several disease target databases and construct a diabetic cardiomyopathy disease target database; Step S3: Perform an intersection analysis between the target points corresponding to the active ingredients of ginseng-bezoar and the target points of diabetic cardiomyopathy to obtain the common target points of the drug and the disease, i.e., potential therapeutic targets. Step S4: Construct a traditional Chinese medicine-component-target network based on the potential therapeutic targets of ginseng and bezoar for diabetic cardiomyopathy and their corresponding active pharmaceutical ingredients; Step S5: Construct a protein-protein interaction network based on potential therapeutic targets; Step S6: Analyze the protein-protein interaction network to further screen core targets from potential therapeutic targets; Step S7: Perform GO and KEGG enrichment analysis on potential therapeutic targets to obtain the receptor signaling pathways involved in the treatment of diabetic cardiomyopathy with ginseng-bezoar. Step S8: Perform molecular docking experiments on the core target corresponding to the receptor signaling pathway and the active pharmaceutical ingredient corresponding to the core target, and screen out the docking modes with stable docking results.

2. The method for obtaining ginseng-bezoar compatibility based on network pharmacology and molecular docking technology as described in claim 1, characterized in that, Step S1 includes: First, ginseng and bezoar components are screened from the TCMID, ITCM, ETCM, HERB, and TCMSP databases according to the Lipinski five rules, based on drug similarity DL ≥ 0.1 and oral bioavailability OB ≥ 20%; Second, based on the SMILES structural formulas provided by PubChem, a secondary screening is performed using the SwissADME and ChemSpider platforms to select components with high gastrointestinal absorption and meeting ≥2 types of drug properties as active ingredients of ginseng and bezoar; Finally, the targets corresponding to the above active ingredients are obtained using the SwissTargetPrediction tool, and targets with a prediction probability greater than 0.1 are selected. Step S2 includes: searching the GeneCards, OMIM, GEO, and MaLaCard databases respectively using "diabetic cardiomyopathy" as the keyword to extract disease target information related to diabetic cardiomyopathy; then, summarizing the target information in the above databases, and taking the disease targets with 3 or more intersections in the four databases to construct a diabetic cardiomyopathy disease target library. Step S3 includes: importing the target points corresponding to the obtained ginseng and bezoar active ingredients and the target points of diabetic cardiomyopathy into the Venny 2.1.0 online platform for intersection analysis and constructing a Venn diagram to obtain the common target points of the drug and the disease, i.e. potential therapeutic targets; Step S4 includes: based on the potential therapeutic targets for diabetic cardiomyopathy in ginseng and bezoar, and the corresponding traditional Chinese medicines and active ingredients, constructing a "traditional Chinese medicine-ingredient-target" network and drawing a network diagram using Cytoscape 3.9.1 software. Traditional Chinese medicines refer to ginseng and / or bezoar. After deleting 3 unrelated nodes, the "traditional Chinese medicine-ingredient-target" network diagram consists of 99 nodes and 401 edges. The nodes are interconnected by edges to show the interaction between traditional Chinese medicines, ingredients, diseases, and targets. The 99 nodes include 2 traditional Chinese medicine nodes, namely ginseng nodes and bezoar nodes, 42 active ingredient nodes, and 56 potential therapeutic targets. Step S5 includes: importing potential therapeutic targets into the STRING database, limiting the species to "Homosapiens", setting the confidence score to ≥0.4, and constructing a PPI network diagram; subsequently, using Cytoscape 3.9.1 software for further visualization, i.e., constructing a potential therapeutic target network analysis diagram; Step S6 includes: using the Centiscape 2.2 plugin of Cytoscape 3.9.1 software to further screen core targets from potential therapeutic targets, and taking the top 10 targets with the highest Degree values ​​as core targets; Step S7 includes: uploading potential therapeutic targets to the Metascape platform for GO and KEGG enrichment analysis: in the GO analysis, the top 5 targets for biological processes, cellular composition, and molecular function are selected based on the count value; in the KEGG analysis, the top 10 targets are selected based on the p-value after FDR correction; subsequently, bar charts and bubble charts are plotted on the MicroBio platform to visualize the results of the GO and KEGG enrichment analysis; the results show that ginseng-bezoar treatment of diabetic cardiomyopathy involves signaling pathways such as AGE-RAGE and Toll-like receptors. Step S8 includes: selecting the top 10 core targets corresponding to the AGE-RAGE pathway by degree ranking and their corresponding active pharmaceutical ingredients for molecular docking experiments: First, the 2D structures of the active ingredients are obtained from the PubChem and TCMSP databases, and after energy minimization and 3D transformation using Chem3D software, they are preprocessed using AutoDockTools; Second, the 3D structures of the core targets are obtained from the PDB database, and then processed using PyMOL 2.2.0 and AutoDockTools, including the removal of water molecules, small molecule ligands, and hydrogenation, and the docking file format is converted using OpenBabel software; Finally, docking is performed using AutoDockVina 1.1.2 software, the results are presented in the form of binding energy, and the docking results are visualized using PyMOL 2.2.0 software; Stable docking core targets and their corresponding active ingredients of ginseng and / or bezoar are screened out.

3. The method for obtaining ginseng-bezoar compatibility based on network pharmacology and molecular docking technology as described in claim 2, characterized in that, In step S1, the active ingredients of ginseng-bezoar include 44 pharmaceutical active ingredients, as shown in the table below: 。 4. The method for obtaining ginseng-bezoar compatibility based on network pharmacology and molecular docking technology as described in claim 3, characterized in that, The active pharmaceutical ingredients are ursodeoxycholic acid, porcine deoxycholic acid, and ginsenoside Rh1.

5. The method for obtaining ginseng-bezoar combination based on network pharmacology and molecular docking technology as described in claim 2, characterized in that, In step S3, there are 56 potential therapeutic targets, as shown in the table below: 。 6. The method for obtaining ginseng-bezoar compatibility based on network pharmacology and molecular docking technology as described in claim 2, characterized in that, In step S6, the core targets are interleukin-6, interleukin-1β, tumor necrosis factor, albumin, protein kinase Bα, estrogen receptor 1, mitogen-activated protein kinase 3, cAMP response element binding protein, AP-1 transcription factor subunit, and Jun proto-oncogene.

7. The method for obtaining ginseng-bezoar compatibility based on network pharmacology and molecular docking technology as described in claim 2, characterized in that, In step S8, the stable docking modes selected include: chenodeoxycholic acid-CASP3, chenodeoxycholic acid-JUN, ursodeoxycholic acid-CASP3, ursodeoxycholic acid-IL1B, ursodeoxycholic acid-NOS3, cholic acid-CASP3, cholic acid-IL6, ginsenoside Rb1-IL6, porcine deoxycholic acid-AKT1, porcine deoxycholic acid-IL6, porcine deoxycholic acid-TNF, and ginsenoside Rh2. -IL1B, Ginsenoside Rh2-IL6, Ginsenoside Rh2-TNF, Ginsenoside Rh1-CASP3, Ginsenoside Rh1-JUN, Ginsenoside Rh1-TNF, Ginsenoside F1-IL1B, Ginsenoside F1-IL6, Ginsenoside F1-NOS3, Ginsenoside F4-IL1B, Ginsenoside F4-NOS3, Ginsenoside Ia-CASP3, Ginsenoside Ia-IL1B, Ginsenoside Ia-TNF.

8. The application of the ginseng-bezoar combination obtained by the method according to any one of claims 1 to 7 in the preparation of drugs for the prevention and treatment of diabetic cardiomyopathy, characterized in that, The effective components of ginseng-bezoar are shown in the table below: 。 9. The application as described in claim 8, characterized in that, The core targets corresponding to the effective components of ginseng-bezoar include IL-6, IL1B, TNF, ALB, AKT1, ESR1, MAPK3, CREB1, FOS, and JUN.

10. The application as described in claim 9, characterized in that, The optimal docking modes between active pharmaceutical ingredients and core targets include: chenodeoxycholic acid-CASP3, ursodeoxycholic acid-NOS3, porcine deoxycholic acid-TNF, ginsenoside Ia-IL1B, ginsenoside F4-IL1B, and ginsenoside Rh1-CASP3.

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