CN113593717A - Research method of action mechanism of angelica sinensis and six-yellow decoction for treating ulcerative colitis - Google Patents

Research method of action mechanism of angelica sinensis and six-yellow decoction for treating ulcerative colitis Download PDF

Info

Publication number
CN113593717A
CN113593717A CN202110751851.XA CN202110751851A CN113593717A CN 113593717 A CN113593717 A CN 113593717A CN 202110751851 A CN202110751851 A CN 202110751851A CN 113593717 A CN113593717 A CN 113593717A
Authority
CN
China
Prior art keywords
target
decoction
angelica
screening
network
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202110751851.XA
Other languages
Chinese (zh)
Other versions
CN113593717B (en
Inventor
李静荣
苏薇薇
梁冰宜
高永坚
林碧珊
曾杉
陈锦霞
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sun Yat Sen University
Sinopharm Group Guangdong Medi World Pharmaceutical Co Ltd
Original Assignee
Sun Yat Sen University
Sinopharm Group Guangdong Medi World Pharmaceutical Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sun Yat Sen University, Sinopharm Group Guangdong Medi World Pharmaceutical Co Ltd filed Critical Sun Yat Sen University
Priority to CN202110751851.XA priority Critical patent/CN113593717B/en
Publication of CN113593717A publication Critical patent/CN113593717A/en
Application granted granted Critical
Publication of CN113593717B publication Critical patent/CN113593717B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H70/00—ICT specially adapted for the handling or processing of medical references
    • G16H70/40—ICT specially adapted for the handling or processing of medical references relating to drugs, e.g. their side effects or intended usage
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B5/00—ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/90—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to alternative medicines, e.g. homeopathy or oriental medicines
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
    • Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Landscapes

  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Medical Informatics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Primary Health Care (AREA)
  • Toxicology (AREA)
  • Biotechnology (AREA)
  • Chemical & Material Sciences (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Physiology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Evolutionary Biology (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Theoretical Computer Science (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

The invention relates to a research method of an action mechanism of angelica sinensis Liuhuang decoction for treating ulcerative colitis. And analyzing by databases such as TCMSP and uniprot to obtain the intersection target of the active ingredient and the disease. A protein-protein interaction (PPI) network is constructed based on String, and important modules and core targets in the PPI network are visually analyzed by applying Cytoscape software to the result. And (3) carrying out gene GO and KEGG channel enrichment analysis on the target by adopting Metascape to obtain a visual graph of components, the target, gene functions, the channel and diseases, and analyzing an action mechanism. The method provides a new method for researching the drug-target interaction mechanism of the angelica six-yellow decoction for treating the ulcerative colitis; solves the problems of large quantity of interaction between multiple active components and multiple target proteins and difficult screening, and has important application significance for guiding the research and development of Chinese herbal compound.

Description

Research method of action mechanism of angelica sinensis and six-yellow decoction for treating ulcerative colitis
Technical Field
The invention relates to pharmacological research of a traditional Chinese medicine compound, in particular to a method for researching an action mechanism of angelica sinensis Liuhuang decoction for treating ulcerative colitis.
Background
Ulcerative Colitis (UC) is an idiopathic chronic inflammatory disease of the colonic mucosa with a worldwide increasing incidence. By 2025, it is expected that the global prevalence will be as high as 3000 million people, and the U pathogenesis is multifactorial, involving genetic susceptibility, epithelial barrier defects, dysregulated immune responses and environmental factors, among others.
Currently, there is a lack of effective drugs and methods for the treatment of ulcerative colitis. Traditional corticosteroids and aminosalicylic anti-inflammatory drugs remain the major drugs in use today. In recent years, it has been found that chronic inflammatory diseases such as ulcerative colitis, whose pathogenesis is much more complex than originally expected, are usually not the result of a single gene or target defect, but rather are caused by multiple gene or target abnormalities, constitute a "Cellular or phenotypic network" (Cellular or phenotypic network) of pathogenesis, and thus interference from a single gene or target may not achieve a therapeutic effect. The traditional Chinese medicine compound comprises more than a plurality of Chemical components to form a Chemical Space Network (Chemical Space Network), can effectively interfere a plurality of gene targets of an organism at the same time, and can be an effective method for treating complex polygenic diseases. However, it is difficult to perform an experimental one-to-one screening because the number of all possible pairwise interactions between compounds and proteins, and between proteins and proteins, is too large.
The Chinese angelica-six-yellow decoction is a classic traditional Chinese medicine prescription consisting of Chinese angelica, radix rehmanniae recen, prepared rehmannia root, baical skullcap root, amur corktree bark, golden thread and astragalus. The book of lan ventricular secretary edited by the Jindai famous Li Gao (also known as Li Dongyuan) records "Dang Gui Liu Huang Tang" on page 79, and notes that the book is a holy prescription for treating night sweat, and has the following main functional indications: nourishing yin, purging fire, consolidating superficial resistance and arresting sweating. The modern medicine is mainly used for treating various diseases such as menopause, hyperthyroidism, diabetes, autoimmune diseases and the like in clinic. When 48 cases of chronic nonspecific ulcerative colitis are treated by angelica sinensis Liuhuang decoction reported by Zhuqing and the like, symptoms such as abdominal pain, diarrhea, tenesmus and the like of a person who takes the traditional Chinese medicine angelica sinensis Liuhuang decoction are found to disappear or improve quickly, stool characters are higher than those of a control group, physical strength and mental state are obviously improved, and no report about an action mechanism of the angelica sinensis Liuhuang decoction for treating ulcerative colitis is reported at present.
Disclosure of Invention
The invention discloses a research method of an action mechanism of an active ingredient of angelica and six-yolk decoction for treating ulcerative colitis.
The technical scheme of the invention comprises the following steps:
1. screening the active ingredients of the angelica six-yellow decoction: according to a traditional Chinese medicine system pharmacological analysis platform, active ingredients of the whole components of the angelica six-yellow decoction in a database are screened under the conditions that the bioavailability is more than or equal to 30%, the drug property index is more than or equal to 0.1 and the Caco-2 cell permeability is more than or equal to 0.4;
2. screening the action target of the active ingredients: screening action targets of the active ingredients of the angelica sinensis Liuhuang decoction by using a TCMSP online database, and carrying out normalization and standardized naming on target data through a UniProt database to finally obtain 407 potential targets of the active ingredients of the seven medicinal materials of the angelica sinensis Liuhuang decoction;
3. screening candidate targets for ulcerative colitis: searching and screening a disease target gene as a candidate target of the disease in a disease target database, and screening an intersection gene of a potential target of an active component of the angelica Liuhuang decoction and the disease target as a candidate target of the angelica Liuhuang decoction for treating ulcerative colitis;
4. constructing an active component of the angelica six-yellow decoction, namely a disease target point-UC network: establishing a D-U network by corresponding the action target of the active ingredients of the angelica Liuhuang decoction to a candidate target of the angelica Liuhuang decoction for treating ulcerative colitis, calculating the connection number by using the analysis of a Cytoscape3.7.2 software system, and screening the first six ingredients according to the degree value, wherein the six ingredients are respectively beta-sitosterol, lutein, wogonin, stigmasterol, baicalein and coptisine;
5. GO functional annotation and KEGG pathway enrichment analysis: performing gene body function annotation and KEGG pathway enrichment analysis on the intersection gene through a metascape online database, determining a biological function related to a potential target, importing a KEGG pathway enrichment result and intersection target gene information into Cytoscape3.7.2 software, constructing a 'target-pathway' enrichment network, realizing visualization of an enrichment analysis result, and prompting that the regulating function of the Angelica sinensis Liuhuang decoction on tumor, inflammation and immunity is related to ulcerative colon;
6. construction of protein-protein interaction PPI networks: uploading the obtained intersection target genes to a String database, selecting various proteins, wisdom and confidence 0.9 options, obtaining protein-protein interaction PPI network data of the intersection target genes, and performing visual analysis on the result by using cytoscape3.7.2 software;
7. core gene and key compound screening and evaluation: the method comprises the steps of determining the first 10 core genes by using an MCC method in a 'cytoHubba' plug-in unit of Cytoscape3.7.2 software, carrying out GO and KEGG path analysis on the core genes through a metascape database, and revealing the relationship between the core genes and possible treatment components; according to PPI network discovery, the 10 core genes including IL6, JUN, TNF, AKT1, MYC, TP53, VEGFA, CXCL8, STAT3 and HSP90AA1 are closely related to diseases; the active ingredients of the angelica six-ingredient decoction corresponding to the core gene in DGLHD are identified to mainly comprise beta-sitosterol, lutein, wogonin, stigmasterol, baicalein and coptisine, and the wogonin of the scutellaria baicalensis can be a key active ingredient aiming at most of the central genes.
The invention has the beneficial effects that:
compared with the prior art, the invention firstly establishes a 'component-target-disease' system network diagram of the active component of the angelica six-yellow decoction (DGLHD) for treating UC based on the network pharmacological technology, and analyzes and determines how the DGLHD plays a role through a 'multi-activity, multi-target and multi-channel' network system. The results show that: modulation of tumor, inflammation and immunity may be the primary mechanism by DGLHD for treatment of UC. The method provides a new idea and a new method for researching the drug-target interaction mechanism of the angelica and six-yolk decoction for treating the ulcerative colitis. The systematic and network information research methods are helpful for solving the problems that the interaction quantity between multiple active ingredients and multiple target proteins of the traditional Chinese medicine compound is too large, and the one-to-one screening is difficult to perform experimentally, and have important significance for guiding the research and development of the traditional Chinese medicine compound
Description of the drawings:
FIG. 1 is a network diagram of DANGGUILIHUANG decoction-active compound-target-UC;
FIG. 2 is a schematic diagram of GO functional annotation analysis of intersection target genes of Angelica sinensis Liuhuang decoction and UC;
FIG. 3 is a schematic diagram of KEGG pathway enrichment network of intersection target gene of Angelica sinensis Liuhuang decoction and UC;
FIG. 4 is a PPI network diagram of intersection target genes of DANGGUILIUHUANG decoction and UC;
FIG. 5A is a diagram of identifying important blocks in a PPI network, and FIG. 5B is a diagram of a core gene network;
FIG. 6 is a network diagram of the components-target-pathway-disease of the Angelica sinensis Liuhuang decoction;
FIG. 7 is a flow chart of the procedure of the study of the Dangguang Liuhuang decoction for treating ulcerative colitis.
Detailed Description
The present invention is further illustrated by the following specific examples.
The flow chart of the main steps of the study of this example is shown in fig. 7.
1. Screening of active ingredients of angelica sinensis Liuhuang decoction and prediction of action target thereof
1-1, screening method and analysis platform
According to a traditional Chinese medicine system pharmacology analysis platform (TCMSP) (https:// tcmspw.com/tcmsp.php), all chemical components of the six medicinal materials are searched by taking Chinese angelica, prepared rehmannia root, scutellaria root, astragalus root, phellodendron bark and coptis root as keywords, and a Chinese angelica six-yellow decoction (DGLHD) chemical component database is established.
Oral Bioavailability (OB) refers to the relative amount of a drug reaching the systemic circulation after oral administration, and high oral bioavailability is an important indicator of whether a drug has biological activity; the drug-like property represents the similarity of a compound with a known drug; caco-2 cells are structurally and functionally similar to differentiated small intestinal epithelial cells, and the bioavailability of the drug absorbed by a human body is determined by the permeability of the Caco-2 cells. According to the research, an active ingredient database of the angelica sinensis Liuhuang decoction is established by selecting a compound with high biological activity by evaluating the in vivo process of the compound by taking the oral bioavailability threshold OB of more than or equal to 30%, the drug property similarity of more than or equal to 0.1 and the Caco-2 cell permeability of more than or equal to 0.4 as screening conditions. Potential action targets of the active ingredients are searched by a TCMSP database, target data are passed through a UniProt database (https:// www.uniprot.org /), and a species human is selected for normalization and standardization naming.
1-2, results and analysis
Through TCMSP search, 125 angelica sinensis, 76 rehmannia glutinosa, 143 scutellaria baicalensis, 87 astragalus membranaceus, 140 phellodendron amurense and 48 coptis chinensis are found, the total components are removed, and 395 related chemical components of the angelica sinensis Liuhuang decoction are all found. Some components are shared by 2 or more than 2 medicines, the shared components are removed, and 80 active compounds are found to meet the screening conditions in total, wherein 4 angelica sinensis, 25 phellodendron amurense, 9 coptis chinensis, 15 astragalus mongholicus (astragalus polysaccharide and astragalus saponin are derived from active components of astragalus mongholicus reported in literature), 36 scutellaria baicalensis, 7 rehmannia glutinosa and 4 prepared rehmannia roots are included. See table 1.
TABLE 1
Figure BDA0003144770960000041
Figure BDA0003144770960000051
Figure BDA0003144770960000061
The potential action targets of 80 active ingredients are searched through a TCMSP database, target data are normalized and named in a standardized way through a UniProt database, 407 potential targets of seven active ingredients of the medicinal materials are finally obtained, and from results, the fact that a plurality of compounds are predicted to aim at the same protein target can be seen. The active Compound and the potential target protein generate (C-T) network diagram, which has 494 nodes and 1870 edges.
2. Target screening of ulcerative colitis
2-1, screening method and database platform
In a drug bank and Genecard online database, the UC disease related target gene is searched by taking 'Ulcerative colitis' as a keyword. Drug bank is a network database containing comprehensive molecular information about drugs, mechanisms, interactions and their targets. Drug bank searches for known UC drugs/drug-like compounds approved for clinical trials by the U.S. Food and Drug Administration (FDA). GeneCards is a comprehensive database that automatically integrates data for approximately 125 network-derived genes (including genomic, transcriptomics, proteomics, etc.). Finally, the common target shared by the two databases is retained as the UC-related target, while the other targets are deleted.
2-2 screening results and analysis
In the drug bank database and the Genecards database, 1235 UC disease-related target genes are screened out in total. Combining the obtained UC disease target with the target of the compound active ingredient obtained in the item 1.1, and carrying out Venn map mapping intersection treatment by using http:// www.bioinformatics.com.cn (biological on-line tool) to obtain the active ingredient target-intersection target genes of ulcerative colitis, wherein the intersection target genes are regarded as the potential target of the angelica sinensis Liuhuang decoction for treating UC. According to the angelica six-yellow decoction target database and the UC related target database, 137 intersection genes are discovered together, and the genes are considered as potential action targets of the angelica six-yellow decoction for treating UC.
3. Construction of Angelica sinensis Liuhuang decoction active Compound-target-UC network (D-U network)
Visual analysis method of 3-1D-U network
A cytoscape3.7.2 software is utilized to construct an angelica six-yellow decoction (DGLHD) -compound-target-UC (D-U) network, and the relationship between an active compound and a potential target in DGLHD is clarified.
3-2, results and analysis
To better understand the complex relationship between all bioactive compounds in DGLHD and UC-associated targets, a D-U network was constructed, as shown in FIG. 1. As shown in figure 1, according to network analysis, 66 active ingredients in the Angelica sinensis Liuhuang decoction are found to correspond to 137 potential targets, and 225 nodes are formed, and 717 interaction is performed. The number of connections was calculated using the analysis tool "NetworkAnalyzer" in Cytoscape 3.7.2. The first six ingredients are beta-sitosterol, lutein, wogonin, stigmasterol, baicalein, and coptisine. Details of the D-U network are shown in table 2.
TABLE 2
Figure BDA0003144770960000071
Figure BDA0003144770960000081
Figure BDA0003144770960000091
Figure BDA0003144770960000101
Figure BDA0003144770960000111
Figure BDA0003144770960000121
Figure BDA0003144770960000131
Figure BDA0003144770960000141
Figure BDA0003144770960000151
Figure BDA0003144770960000161
Figure BDA0003144770960000171
Figure BDA0003144770960000181
Figure BDA0003144770960000191
Figure BDA0003144770960000201
Figure BDA0003144770960000211
Figure BDA0003144770960000221
Figure BDA0003144770960000231
Figure BDA0003144770960000241
4. GO functional annotation and KEGG pathway enrichment
4-1, analytical method and database
To investigate biological functions associated with potential targets, we performed Gene Ontology (GO) functional annotation and KEGG pathway enrichment analysis via the metascape online database (https:// metascape. org /). Metascape is a powerful gene function annotation analysis tool that can help us to apply the currently popular bioinformatics analysis method to the analysis of genes and proteins in batches. Among them, GO enrichment analysis was used to interpret and annotate genes by three-dimensional dimensions, including Cellular Component (CC), Molecular Function (MF), and Biological Process (BP) analysis. KEGG pathway enrichment is used primarily for pathway analysis. In addition, the species defined as "Human" contains at least three genes, and p values of 0.05 or less are considered to have statistical significance. And (4) reserving enrichment items with q values (namely corrected P values) less than 0.05, sorting the enrichment items according to the q values, and outputting a histogram. And (3) importing the KEGG passage enrichment result and intersection target gene information into Cytoscape3.7.2 software, and constructing a target-passage enrichment network to realize the visualization of the enrichment analysis result.
4-2, results and analysis
In order to further verify whether the biological functions of the candidate targets are related to UC, GO and KEGG enrichment analysis is carried out through a metascape online database. Three GO entries were analyzed, including CC, MF, and BP, with the top 10 enrichment results for each entry shown in fig. 2. Total 2294 entries (q value < 0.05) were obtained by GO functional annotation analysis, including 2090 bioprocesses, 72 cellular constituents, 164 molecular functions. Analysis shows that the biological process of the intersection target mainly relates to the reaction to inflammation, apoptosis signal reaction, the reaction of cells to chemical stress, oxidative stress and the like; cellular components relate to membrane rafts, extracellular matrix, cytoplasmic perikaryocytic regions, etc.; molecular functions are mainly focused on transcription factor binding, heme binding, protein kinase binding, receptor modulating activity, and the like.
In addition, 292 KEGG pathways were found. The KEGG enrichment analysis indicates that 137 potential targets are closely related to several key pathways related to UC, such as "tumor pathway", "endocrine resistance", "NF-kB signaling pathway", "Th 17 cell differentiation", and the like. The first 20 abundant KEGG signal pathways are shown in figure 3. These findings suggest that modulation of tumor, inflammation and immunity may be the primary mechanism by DGLHD in the treatment of UC. And constructing a component-target-pathway-disease diagram of the angelica six-yolk decoction according to the results for visual analysis, and referring to fig. 6.
5. Construction of protein-protein interaction (PPI) networks and screening of core targets
5-1, analysis method and database platform
Protein-protein interactions (PPI) are crucial in the regulation of biological systems, uploading the intersection target genes obtained in item 1.2 above to the String database. The result of selecting the option of Multiple proteins, setting the species as Homo sapiens and the confidence as 0.9, and selecting the hidden nodes to obtain the protein-protein interaction (PPI) network data of the intersection target genes is beneficial to understanding the mechanism related to the occurrence and development of diseases. String is an online PPI analysis database that currently has the largest number of organisms (5090) and proteins (2460 million) and has a very broad and diverse baseline data source. Studies have shown that a small fraction of PPI networks with highly connected regions (subnetworks) have a higher probability of participating in bioregulation, while those nodes that are lightly connected do not play a critical role in the integrity of the entire network. Therefore, the result of the PPI network is imported into Cytoscape software for visual analysis, and all targets are clustered and analyzed by means of the MCODE plug-in unit to find important modules (subnets) in the network. The MCODE selection criteria were: cut-of value 2, node cut-of value 0.2, maximum depth 100, and k-score 2. MCODE can detect densely connected regions in a large protein-protein interaction network that may represent molecular complexes. The method is based on vertex weighting of local neighborhood density and outward traversal of local compact seed protein, and compact regions are separated according to given parameters. Compared to other graph clustering methods, the algorithm has a directed pattern, allowing fine-tuning of clusters of interest without regard to the rest of the network, and allowing the inter-cluster connectivity associated with the protein network to be examined.
In addition, gene silencing experiments further confirm that the hub genes (core genes) in the module are often significantly related to the disease state, and the capture of the hub genes from the PPI network is more meaningful than a single gene without network information screening. Cytohubba ranks nodes in a network mainly through network functions, and provides 11-medium topology analysis methods including degree, maximum neighborhood components and the like, and MCC has better performance in the precision of predicting necessary protein from PPI network. To further identify the central genes in potential targets, we identified the top 10 (hub) central genes using the MCC method in "cytoHubba" of the cytoscape3.7.2 software. Meanwhile, GO and KEGG path analysis is carried out on the core gene through a metascape database. Gene counts >3 and p values below 0.05 were considered as cutoff criteria. To reveal the relationship between the central genes and the possible therapeutic components, the compounds corresponding to the central genes were included in the morqui map.
5-2, results and analysis
The PPI network diagram of the intersection target gene of the angelica six-yellow decoction and the UC is shown in figure 4, and the PPI network diagram contains 114 nodes and 532 edges in total. Two important modules (modules 1 and 2) with scores ≧ 5 were screened by MCODE, see FIGS. 5A and 5B. And (4) calculating the ranking through the MCC function in the 'cytoHubba' plug-in, and determining the top ten core nodes. The ten major core genes include IL6, JUN, TNF, AKT1, MYC, TP53, VEGFA, CXCL8, STAT3, HSP90AA 1. For example, IL-6 is involved in "immune response", "cell response to lipopolysaccharide" and "inflammatory bowel disease", all of which are closely related to UC.six components of β -sitosterol, lutein, wogonin, stigmasterol, baicalein, and coptisine, corresponding to the central genes, were identified in DGLHD, and in particular, wogonin from Scutellaria baicalensis may be directed against most of the central genes.

Claims (1)

1. A research method for an action mechanism of angelica sinensis Liuhuang decoction for treating ulcerative colitis is characterized by comprising the following steps:
1.1 screening active ingredients of the angelica six-yellow decoction: according to a traditional Chinese medicine system pharmacological analysis database platform, screening active ingredients of the whole components of the angelica six-yellow decoction in a database under the conditions that the bioavailability is more than or equal to 30%, the drug property index is more than or equal to 0.1 and the Caco-2 cell permeability is more than or equal to 0.4;
1.2 screening the action target of the active ingredients: screening action targets of the active ingredients of the angelica sinensis Liuhuang decoction by using a TCMSP online database, and carrying out normalization and standardized naming on the target data through a UniProt database to finally obtain 407 potential targets of the active ingredients of the seven medicinal materials of the angelica sinensis Liuhuang decoction;
1.3 screening candidate targets for ulcerative colitis: searching and screening a disease target gene as a candidate target of the disease in a disease target database, and screening an intersection gene of a potential target of an active component of the angelica Liuhuang decoction and the disease target as a candidate target of the angelica Liuhuang decoction for treating ulcerative colitis;
1.4 the active ingredients of the angelica six-yellow decoction, namely a disease target point and a UC network are constructed: establishing a D-U network by corresponding the action target of the active ingredients of the angelica Liuhuang decoction to a candidate target of the angelica Liuhuang decoction for treating ulcerative colitis, analyzing and calculating the connection number by using a Cytoscape3.7.2 software system, and screening the first six ingredients according to a degree value, wherein the six ingredients are respectively beta-sitosterol, lutein, wogonin, stigmasterol, baicalein and coptisine;
1.5GO functional annotation and KEGG pathway enrichment analysis: performing gene body function annotation and KEGG pathway enrichment analysis on the intersection gene through a metascape online database, determining a biological function related to a potential target, importing a KEGG pathway enrichment result and intersection target gene information into Cytoscape3.7.2 software, constructing a 'target-pathway' enrichment network, realizing visualization of an enrichment analysis result, and prompting that the regulating function of the Angelica sinensis Liuhuang decoction on tumor, inflammation and immunity is related to ulcerative colon;
1.6 construction of protein-protein interaction PPI networks: uploading the obtained intersection target genes to a String database, selecting various proteins, wisdom and confidence 0.9 options, obtaining protein-protein interaction PPI network data of the intersection target genes, and performing visual analysis on the result by using cytoscape3.7.2 software;
1.7 core genes and key compounds screening and evaluation: the method comprises the steps of determining the first 10 core genes by using an MCC method in a 'cytoHubba' plug-in unit of Cytoscape3.7.2 software, carrying out GO and KEGG path analysis on the core genes through a metascape database, and revealing the relationship between the core genes and possible treatment components; according to PPI network discovery, the 10 core genes including IL6, JUN, TNF, AKT1, MYC, TP53, VEGFA, CXCL8, STAT3 and HSP90AA1 are closely related to diseases; the active ingredients of the angelica six-ingredient decoction corresponding to the core gene are identified in DGLHD and mainly comprise beta-sitosterol, lutein, wogonin, stigmasterol, baicalein and coptisine, and the wogonin of the scutellaria baicalensis can be a key active ingredient aiming at most of the core gene.
CN202110751851.XA 2021-07-03 2021-07-03 Research method of action mechanism of angelica sinensis and six-yellow decoction for treating ulcerative colitis Active CN113593717B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202110751851.XA CN113593717B (en) 2021-07-03 2021-07-03 Research method of action mechanism of angelica sinensis and six-yellow decoction for treating ulcerative colitis

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202110751851.XA CN113593717B (en) 2021-07-03 2021-07-03 Research method of action mechanism of angelica sinensis and six-yellow decoction for treating ulcerative colitis

Publications (2)

Publication Number Publication Date
CN113593717A true CN113593717A (en) 2021-11-02
CN113593717B CN113593717B (en) 2023-06-02

Family

ID=78245612

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202110751851.XA Active CN113593717B (en) 2021-07-03 2021-07-03 Research method of action mechanism of angelica sinensis and six-yellow decoction for treating ulcerative colitis

Country Status (1)

Country Link
CN (1) CN113593717B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114438190A (en) * 2022-01-14 2022-05-06 中国人民解放军空军军医大学 Opening and closing nerve soothing soup-autism core effect gene target and screening method thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103028001A (en) * 2011-09-29 2013-04-10 中国中医科学院西苑医院 Traditional Chinese medicine prescription for relieving asthma, relieving cough and resisting inflammatory, preparation method and application thereof
CN103356845A (en) * 2012-03-29 2013-10-23 湖南中医药大学 Formula and preparation process of traditional Chinese medicine for treating ulcerative colitis
CN110556166A (en) * 2018-12-27 2019-12-10 刘存 New integrated pharmacological method and application thereof in treatment of breast cancer by using astragalus membranaceus
CN112201365A (en) * 2020-11-10 2021-01-08 南宁市第二人民医院 Method for analyzing action mechanism of pachyman against glandular cystitis based on network pharmacology

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103028001A (en) * 2011-09-29 2013-04-10 中国中医科学院西苑医院 Traditional Chinese medicine prescription for relieving asthma, relieving cough and resisting inflammatory, preparation method and application thereof
CN103356845A (en) * 2012-03-29 2013-10-23 湖南中医药大学 Formula and preparation process of traditional Chinese medicine for treating ulcerative colitis
CN110556166A (en) * 2018-12-27 2019-12-10 刘存 New integrated pharmacological method and application thereof in treatment of breast cancer by using astragalus membranaceus
CN112201365A (en) * 2020-11-10 2021-01-08 南宁市第二人民医院 Method for analyzing action mechanism of pachyman against glandular cystitis based on network pharmacology

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114438190A (en) * 2022-01-14 2022-05-06 中国人民解放军空军军医大学 Opening and closing nerve soothing soup-autism core effect gene target and screening method thereof

Also Published As

Publication number Publication date
CN113593717B (en) 2023-06-02

Similar Documents

Publication Publication Date Title
Yang et al. A network pharmacology approach to uncover the molecular mechanisms of herbal formula ban‐Xia‐Xie‐Xin‐Tang
CN107437004A (en) A kind of system intelligently understood for tumour individuation genetic test
CN110556166A (en) New integrated pharmacological method and application thereof in treatment of breast cancer by using astragalus membranaceus
CN107423578A (en) Detect the device of somatic mutation
CN108038352A (en) Combination difference analysis and the method for association rule mining full-length genome key gene
Liang et al. Identification of active compounds of Mahuang Fuzi Xixin Decoction and their mechanisms of action by LC‐MS/MS and network pharmacology
Li et al. A preliminary inquiry into the potential mechanism of huang-lian-jie-du decoction in treating rheumatoid arthritis via network pharmacology and molecular docking
CN113593717A (en) Research method of action mechanism of angelica sinensis and six-yellow decoction for treating ulcerative colitis
Ma et al. Network Pharmacology‐Based Strategy for Predicting Active Ingredients and Potential Targets of Coptis chinensis Franchin Polycystic Ovary Syndrome
CN114783529A (en) Luteolin-autism related action gene target and screening method thereof
CN110751981A (en) Analysis method for explaining essence of traditional Chinese medicine syndrome based on system biology
US20120035855A1 (en) Method of network-based identification for drug action and/or synergy effect of medicine combination
CN110517732B (en) Radix astragali radiation damage resistance related gene screening and functional analysis method
Sun et al. Mining Important Herb Combinations of Traditional Chinese Medicine against Hypertension Based on the Symptom‐Herb Network Combined with Network Pharmacology
Sun et al. To Predict Anti‐Inflammatory and Immunomodulatory Targets of Guizhi Decoction in Treating Asthma Based on Network Pharmacology, Molecular Docking, and Experimental Validation
CN113506592A (en) Mechanism analysis method of traditional Chinese medicine for treating chronic bronchitis
Zou et al. Exploring the molecular mechanism of Tong Xie Yao Fang in treating ulcerative colitis using network pharmacology and molecular docking
Rani et al. Performance evaluation of drug synergy datasets using computational intelligence approaches
CN114438190A (en) Opening and closing nerve soothing soup-autism core effect gene target and screening method thereof
Li et al. Bioactive-Chemical Quality Markers Revealed: An Integrated Strategy for Quality Control of Chicory
Liu et al. A comprehensive quality evaluation method of different medicinal parts of Physalis Calyx seu Fructus by fingerprints, chemometrics, antioxidant activity, network pharmacology and molecular docking
Pan et al. Study on the active ingredients and mechanism of Jiaotai Pill in the treatment of primary insomnia based on network pharmacology and GEO statistics: A review
Wang et al. Targeted regulation of miR-17-5p on TMOD1 promotes the development of cardia cancer.
Han et al. Potential immune-related therapeutic mechanisms of multiple traditional Chinese medicines on type 2 diabetic nephropathy based on bioinformatics, network pharmacology and molecular docking
Su et al. Case study of network pharmacology and modernization of traditional Chinese medicine

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant