pick To:Traditional Chinese medicine emphasizes the unity, integrity and connection of things themselves. It is a discipline that takes the "overall concept" and "syndrome differentiation and treatment" as the guiding theory, and carries out clinical treatment based on the principles of "treating different diseases with the same treatment" and "treating different diseases with the same treatment". Network pharmacology is to explore the correlation between drugs and diseases as a whole. Its integrity, systematicness and emphasis on the interaction between drugs and targets are consistent with the basic characteristics of traditional Chinese medicine. It is a new discipline that reveals the regulatory effect of traditional Chinese medicine on the body network from the system level. Network pharmacology uses computer simulation and various databases to screen drug molecular targets, predict their signaling pathway and mechanism of action, and uses relevant software to carry out compound-Target-The path network is visualized, and the key nodes are screened through topology parameter analysis. It has saved the cost for the research and development of new drugs, and can solve the problem of "single component" in the research of traditional Chinese medicine to a certain extent-Single target-Limitations of "single pathway". This paper summarizes the research thinking methods, innovation points, application and challenges of network pharmacology in the field of traditional Chinese medicine at home and abroad, in order to improve the application of network pharmacology in the field of traditional Chinese medicine, and provide a new direction for the research of traditional Chinese medicine.
Traditional Chinese medicine mainly includes2Three aspects: Traditional Chinese medicine and traditional Chinese medicine. Traditional Chinese medicine is a subject based on the theory of traditional Chinese medicine and combined with practical experience. It studies the transformation law of human life activities, health and disease, as well as its prevention, diagnosis, treatment, rehabilitation and health care. It pays attention to the overall concept and syndrome differentiation and treatment; Traditional Chinese medicine is a discipline that studies the basic theory of traditional Chinese medicine and the relevant knowledge of the source, collection, performance, efficacy and clinical application of various traditional Chinese medicines. The basic theory mainly includes the performance, efficacy and compatibility laws of traditional Chinese medicine. However, the two are not separated. They form traditional Chinese medicine on the basis of traditional Chinese medicine theory. Traditional Chinese medicine cannot be separated from the material basis of traditional Chinese medicine, and traditional Chinese medicine cannot be separated from the theoretical guidance of traditional Chinese medicine[1]. At present, network pharmacology is widely used in the field of traditional Chinese medicine.
While Li Zao et al[2]It is proposed that traditional Chinese medicine is to grasp the relationship between life, health, disease and drugs from the perspective of integrity, dynamics and syndrome differentiation. Its characteristics are "heaven and man correspond", overall coordination, syndrome differentiation and treatment, and natural drugs through the compatibility of monarch, minister, assistant and envoy to achieve the overall comprehensive effect of the prescription. The characteristics of the holistic view and syndrome differentiation system of traditional Chinese medicine, such as large-scale system, openness to the environment and emphasis on interaction, as well as the holistic, living and dynamic observation mode, are the source of its complexity. Li Zao et al[2]For the first time in China2002In, it was proposed to analyze complex systems through bioinformatics. Bioinformatics is a science that uses computers as tools to store, retrieve, analyze, process and comprehensively utilize biological information in the research of life sciences. It can penetrate the laws hidden in the data through massive data. Therefore, it will play a powerful role in the exploration of the characteristic connotation and laws of traditional Chinese medicine, such as prescriptions and syndromes, and in the complexity depiction of traditional Chinese medicine moving towards the micro level and coordinating and integrating at the same time.
Traditional Chinese medicine focuses on the pathogenic mechanism and the changing law of diseases, while the components of traditional Chinese medicine are complex, and each component cooperates or antagonizes with each other, acting on the same or different targets, and using the same or different pharmacodynamic ways to exert its efficacy, and the traditional Chinese medicine compound pays attention to the principle of "monarch, minister, assistant, and seven emotions compatibility". Therefore, network pharmacology is introduced to study traditional Chinese medicine, study its integrity, systematization, and the interaction between components, and build a "multi-component-Multitarget-.
Network pharmacology is2007By a pharmacologist from the University of Dundee, EnglandHopkinsIt was first proposed based on the theory of systems biology, integrating the technology and content of multidirectional pharmacology, bioinformatics, computer science and other disciplines to carry out the "disease phenotype-gene-Target-The construction of multi-level networks such as "drugs", explore the correlation between drugs and diseases, guide the research and development of new drugs, clarify the mechanism of drug action, its integrity, systematicness and the interaction between drug components, "multi-component-Multitarget-Through the analysis of topological parameters and the visualization of protein interaction network diagram, histogram, bubble diagram, etc., the drug acting on the target, the mechanism of action and various physiological and pathological processes are clarified clearly, which coincides with the characteristics of traditional Chinese medicine[3]The innovation of applying it to the research of traditional Chinese medicine is based on the classic compound traditional Chinese medicine and traditional Chinese medicine, which are used in the research and development of new drugs, to test the disease with drugs, and to mine the disease mechanism with traditional medicine as the disease target. Its core technology is to reveal the mechanism of complex diseases and the discovery of preventive drugs, that is, to predict the mechanism of action of a disease treated with a known traditional Chinese medicine or traditional Chinese medicine compound, and to screen the mechanism of action of a known drug without knowing its therapeutic effect, so as to screen drugs for the prevention of a certain kind of disease or find new therapeutic effects of drugs[4]This paper will mainly summarize the research ideas and analysis routes of network pharmacology, its application in the field of traditional Chinese medicine at home and abroad and the challenges it faces..the research of network pharmacology is reviewed...The research of network pharmacology is based on the following aspects: the research of network pharmacology, the research of network pharmacology, the research of network pharmacology, the research of network.
1 Introduction to network pharmacology
1.1 Common databases of network pharmacology、Software and related functions
Network pharmacology is the comprehensive analysis, screening and construction of network diagram using a variety of databases and software. The main databases, software and related functions are as follows: TCM System Pharmacology database and analysis platform(TCMSP); General protein database(Uniprot)For the search and screening of target protein genes; Biological activity database of organic small molecules(Pubchem/OMIM)For pharmaceutical compounds2D、3DStructure search; Human gene database(GeneCards)For disease gene search screening; The online Wayne diagram reflects the intersection genes of drug screening target genes and disease genes; (STRING)Used to construct protein interaction networks(PPI); Biological information annotation database(DAVID v 6.8)ForGOTaxonomic enrichment andKEGGPathway enrichment analysis; Online cloud platform(Omicshare)Mainly used forGOTaxonomic enrichment analysis andKEGGBubble plot of pathway analysis results;GraphPad Prism 6Drawing software is mainly used forGOTaxonomic enrichment analysis andKEGGThe results of pathway analysis were plotted as a histogram; Network topology attribute analysis softwareCytoscapeVersion 3.6.1Mainly used to construct "ingredients-Target-Pathway "network[5]。
1.2 Research ideas of network pharmacology
Network pharmacology is a high-throughput branch and overall screening through various databases and software. First, the static compound small molecule screening of drugs is carried out, and the corresponding target protein macromolecules are screened. Then, the protein gene screening is carried out. Then, the branch is screened from the disease target protein gene, and then, the integrated screening of intersection genes is carried out. The gene level connection between drugs and diseases is carried out. Finally, the protein interaction and signaling pathway, that is, the mechanism of action research, is carried out-The two branches of "disease" begin and end with their interaction. It is summarized as "taking the network as the core, developing network construction, network visualization, and network analysis technology" to analyze traditional Chinese medicine as a whole[6]。
1.3 Analysis route of network pharmacology
Network pharmacology is commonly used to predict the mechanism of action of drugs in the treatment of diseases. Its technical route is generally to first obtain the active compounds through the traditional Chinese medicine composition database, then obtain the target information through the compound target relational database, annotate the target through the gene information database, obtain the potential target by intersection of the drug target protein and the target protein in the disease database, and then analyze the function of the potential target, integrate the relationship between the potential target and drug molecules, diseases, pathways, etc., and build a complex network. In this network, the connection proximity of proteins, drug molecules and pathways in the network is scored by the connection effective algorithm, and the network topology parameters are analyzed. Then the important nodes are screened out through these parameters, so as to mine the mechanism of drug action. By summarizing the literature, the general network pharmacology analysis route is shown in Fig1。
1.4 The core theory of network pharmacology
1.4.1 "Network target" theory The core theory of network pharmacology is the establishment of target network. In the organism, various signaling pathways form an intricate signaling network. Blocking any one of them will cause other pathways to be activated or inhibited feedback. . Including biomolecule based protein interaction network, signaling pathway network, metabolic network, gene regulation networkmiRNANetwork, biological process network, organization network, etc[7-8]The nodes of the network include genes, pathways, diseases, compounds, protein domains, biological processes, proteins, metabolites, drugs, endogenous small molecules, etc. . Different nodes and edges constitute a rich biological network. The common network is "compound-Target-Gene "network," compounds-Target-Pathway "network," compounds-Target "network. Network analysis usually includes network topology information calculation, random network generation and comparison, and network stratification and clustering[9]Common network topology analysis contents include degree(degree), betweenness(betweenness)(shortestpath)(bottleneck)(hub), module(moldule)(chokepoint)[10-12]Et al. The larger the betweenness of a node is, the more data packets flow through it, which means that it is more prone to congestion, becoming the bottleneck of the network and the key node of the network. Degree and betweenness are the most concerned in network analysis. High degree and betweenness nodes are the focus of new drug discovery and target prediction. Most of the literature used in this paper is based onCytoscapeSoftwareNetwork AnalysisTools for network analysis.Lietc.[13](ASPD)Significantly less than that between TCM targets and randomly selected disease genesASPD, this finding confirms the rationality of traditional Chinese medicine in the treatment of specific diseases. Network pharmacology is consistent with the treatment concept of complex diseases with its "multi gene, multi-target" characteristics, through the elaboration of drugs-Target-gene-The complex network relationship of diseases, new drug research and development and drug action mechanism research.
1.4.2 Theory of "network pharmacology of traditional Chinese medicine" Traditional Chinese medicine system pharmacology is a new discipline developed in recent years. It studies the mechanism of disease under the guidance of the basic theory of traditional Chinese medicine, so as to provide new methods and ideas for the treatment of complex diseases. It focuses on the overall concept. System Pharmacology is a discipline that studies the interaction between drugs and human body and its laws and essence at various levels, from cells, molecules, networks to tissues and organs. By combining experiments and theoretical calculations, it can quickly screen effective drug molecules, determine their biological targets at the molecular level of human body, predict the possible adverse reactions of drugs and their mechanisms, and study the pathogenesis of diseases, so as to achieve the purpose of improving drug efficacy, reducing adverse reactions and treating diseases by regulating the complex biological network in cells. It studies the multi-component, multi-target, multi-channel, multi-function and compatibility of traditional Chinese medicine, which reflects the characteristics of single component corresponding to multi-target, multi regulating signaling pathway and the synergistic effect of multiple components acting on the same target or signaling pathway, thus well interpreting the integrity of traditional Chinese medicine[14]。
2 Application of network pharmacology in the field of traditional Chinese Medicine
2.1 Study on the mechanism of single herb
Network pharmacology is a new discipline based on the theory of systems biology, which analyzes the network of biological systems and selects specific signal nodes for multi-target drug molecular design. It emphasizes the multi-channel regulation of the signaling pathway, improves the therapeutic effect of drugs, reduces adverse reactions, so as to improve the success rate of clinical trials of new drugs, save the cost of drug research and development, and make drug design more rational. It can rapidly predict the effective components of drugs and disease mechanism of action using various databases and software. Among them, Xu Ya et al[15]Network pharmacology was used to study the antihypertensive mechanism of Semen Plantaginis, and it was found that there were6Chemical active ingredients, corresponding to157Targets, corresponding after mapping90Hypertension targets, throughKEGGPathway enrichment analysis, obtained36Information on pathways that play a role in reducing blood pressure; Ma Xincheng et al[16]Network pharmacology was also used to study the mechanism of Gouteng in the treatment of hypertension, and it was found that there were11Potential active ingredients,29Targets,6Signaling pathway. The two herbs have antihypertensive effect. Through network pharmacology research, it was found that the common active ingredients are quercetin, kaempferol and sitosterol, with common targetsPTGS1、PTGS2It can be found that different medicinal materials treat the same disease, and their pharmacodynamic components, targets and signaling pathways have many similarities.
Because network pharmacology has the characteristics of measuring disease by medicine, it may be found that treating another disease or treating this disease requires many ways to complete in the study of the mechanism of action of some traditional Chinese medicine in the treatment of diseases, and then prodrugs or lead compounds for the treatment of new diseases can appear. Gao Sijia et al[17]Network pharmacology was used to predict the mechanism of action of Pueraria lobata in relieving muscle and fever. Finally, Pueraria lobata was screened out to have13Active ingredients203Targets19Signaling pathway. Some of the signaling pathways are related to inflammatory response; [18]This method was also used to study the mechanism of Pueraria lobata in the treatment of coronary heart disease, and the results showed that70Active ingredients,18Three targets and multiple biological processes, including inflammatory response, reflect the characteristics of treating different diseases with the same treatment of traditional Chinese medicine, while Gaoyuan et al[19]Network pharmacology was used to study the anti-inflammatory mechanism of Astragalus complanatus11Active ingredients,50,261There are biological processes and pathways of this model, which also include inflammatory reaction. These two medicinal materials both pass the biological pathway of inflammatory reaction when they exert different effects. It can be seen that many diseases may be associated with inflammation in the body, which can provide new ideas for anti-inflammatory and antipyretic diseases.
2.2 Study on the mechanism of compatibility of traditional Chinese Medicine
. Zhang Sixuan et al[20]Network pharmacology was used to study the "Rhizoma Atractylodis-The mechanism of "Phellodendron amurense" compatibility in the treatment of gout, screening"Rhizoma Atractylodis" related to gout treatment-Phellodendron amurense "drug pair" active ingredient-Potential targets "network contains17The key target involved estrogen receptor1, prostaglandin endoperoxide synthase1、2And phosphatidylinositol3-Kinases et al,KEGGPathway enrichment analysis obtained23Pathways, such as tumor necrosis factor signaling pathway, osteoclast differentiation pathway, etc. Initially explored the "Rhizoma Atractylodis-The mechanism of "Phellodendron amurense" in the treatment of gout. It just proves that compatible drugs should follow the principle of "seven emotions" and complement each other and work together. Zhang Xuezhu et al[21]Network pharmacology was used to analyze the effect of "Atractylodes macrocephala Koidz-The mechanism of action of "Poria cocos" drug pair was analyzed, and the22Candidate compound molecules, corresponding targets61, related diseases135Species, and the disease systems with higher degrees are tumors29Species and cardiovascular diseases22Species and neurological diseases17This is a typical example of the innovation of network pharmacology, which can predict the disease and mechanism of action of compatible drugs with the characteristics of multi-component, multi-target and multi-channel synergy. [22]Bupleurum chinense was treated with network pharmacology-The molecular mechanism of treating different diseases of Radix Paeoniae Alba with the same treatment was analyzed, and it was found that Radix Bupleuri-Radix Paeoniae Alba20Active ingredients193Potential targets7Biological processes and67Article signaling pathway, which predicts its therapeutic effect on gastrointestinal inflammation, nervous system, cancer and other diseases, as well as the material basis and molecular mechanism of its efficacy. It can be seen that it can explain Bupleurum-Mechanism of compatibility of Radix Paeoniae Alba with different diseases. Network pharmacology was used to solve the problem of complex chemical components and unknown mechanism of action in the compatibility of traditional Chinese medicine.
2.3 Study on the mechanism of traditional Chinese medicine compound
Because the traditional Chinese medicine compound has the characteristics of multi-component, multi-target and multi-channel synergy[23]Therefore, it is difficult to clearly study its mechanism of action. Its efficacy is independent and unified. The independence is reflected in the direct or indirect influence or action of a certain drug component on a certain target. Its unity is reflected in the synergistic or antagonistic effect between multiple components, and the treatment of disease as a whole. Therefore, the introduction of network pharmacology to study traditional Chinese medicine compounds as a whole, at multiple levels and at multiple levels can clearly analyze the therapeutic pathways and mechanisms of traditional Chinese medicine compounds, and can be visualized through the network[24]Among them, Ruan Yi et al[25]Network pharmacology was used to study the mechanism of action of amaranth ginseng mixture against exercise-induced fatigue15Active ingredients172Targets17Biological processes and12. Huang Shuai et al[26]The mechanism of action of Pushen capsule in the treatment of hyperlipidemia was analyzed and studied, and the active ingredients were screened out75PCs, main targets261, key targets are associated with inflammatory response, and also throughKEGGAccording to pathway enrichment analysis, the main signaling pathways of activating blood circulation and removing blood stasis, nourishing yin and removing turbidity are5Finally, the effect of the capsule on hyperlipidemia was obtainedThe treatment is through inhibiting the occurrence and development of chronic inflammation. Yangmengdie et al[27]Network pharmacology was used to study the mechanism of "treating different diseases with the same treatment" of Yiguanjian, which screened out49Active ingredients200Target proteins and264Disease prediction, mainly the best treatment effect for cancer, afterGOBiological analysis andKEGGThe results of pathway analysis are helpful to explore the mechanism of "treating different diseases at the same time" in the treatment of kidney yin deficiency syndrome with Yiguanjian, and provide certain clues for the discovery of new clinical indications and potential drugs. Therefore, it can be seen that network pharmacology in the study of traditional Chinese medicine compound can not only clarify its therapeutic mechanism, but also predict its comprehensive effect and discover new ways of action or new thinking. [28]Network pharmacology method was used to predict the action targets of the main components in Yangyin Qingfei oral liquid, and its action pathways were predicted. The prediction results showed that it may play a role through anti-inflammatory and anti-oxidation. Based on this result, the lung tissue injury model of smoke and haze exposed mice was used to verify the protective effect of Yangyin Qingfei oral liquid on liver injury. The results showed that this may be related to the related pathways of anti-inflammatory and anti-oxidation. . There are also studies on traditional Chinese medicine compounds published internationally,Tongetc.[29]Target prediction regression model based on NetworkDrugIPHER, revealing the treatment of Gegen Qinlian Decoction2Type 2 diabetic19Active ingredients and their mechanism of action. Gegen Qinlian decoction was prepared by4. Studies have shown that Radix Puerariae and Radix ScutellariaeLiantang right2Type 2 diabetes has good clinical effect, and the anti diabetic activity of Gegen Qinlian Decoction in vivo and in vitro was studied[29-30]。Although studies have shown that Gegen Qinlian decoction, which is composed of a variety of bioactive compounds, is a kind of effective drug for the treatment of chronic hepatitis B.the drug has been used to treat chronic hepatitis B.the drug can be used to treat chronic hepatitis B.the drug can be used to treat chronic hepatitisagentContribute to2Type 2 diabeticTreatment, but due to its complex nature and the lack of appropriate methods, the mechanism of this formulation is still unknown. thereforeLietc.[31]Using the comprehensive analysis based on the TCM network pharmacology platform, Gegen Qinlian decoction was calculatedagentright2Type 2 diabetes mellitusThe antidiabetic activity of the candidate ingredients was experimentally verified by insulin secretion assay and insulin resistance model calculation. Network target analysis showed that Gegen Qinlian DecoctionagentCan adjust2Type 2 diabetes mellitusKey biological processes in development, such as glucose homeostasis and response to insulin stimulation. In addition, the study also found that the core components of Pueraria lobata4-Hydroxytolytoin participated in Gegen Qinlian Decoction.The study of the effect of hydroxytolytoin on the quality of Pueraria baicalensis Georgi Decoction in rats and rats was carried out..the results showed that the effect of hydroxytolytoin on the quality of Pueraria baicalensisagentIt can stimulate endogenous insulin secretion and improve3T3-L1Insulin resistance in a model of type 2 insulin resistance.
Heetc.[32]The comprehensive network pharmacology method successfully identified the45Active ingredients,45Active ingredients were163And2Type 2 diabetes related potential target hits.10The predicted components (quercetin, kaempferol, sitosterolβ-Glutasterol, cardulenone, diosgenin, glutathioneC, hedragenin, garcianoneB, isoflavonol) are involved in anti-inflammatory, anti oxidative stress and reductionβCell damage. adoptAGE-RAGEsignaling pathway、TNFSignaling pathway andNF-κBsignaling pathway, Liuwei Dihuang pill may play an important role in2Type 2 diabetes and its complications (atherosclerosis and nephropathy) play a role in the treatment. The results of the above two cases show that different drugs for the same disease may be a certain compound, action related target and pathway, which plays a key role in the key target; However, there are also different components that act synergistically on the same target and also play a hypoglycemic role. Thus, it explains that TCM network pharmacology can understand the scientific basis of TCM compound prescription or compatibility from the molecular level and system perspective.
Guoetc.[33]Network pharmacology was used to study Jinzhen oral liquid, a classical traditional Chinese medicine formula for the treatment of children's lung diseases. However, the effective components of Jinzhen oral liquid are still unclear. In this study, itsUPLC-Q-TOF/MSThe lung injury rat model was used to study the protective effect of Jinzhen oral liquid. according toUPLC-Q-TOF/MSAnalyzed, identified, or preliminarily identified31Prototypical components of species uptake and41. Selected24The three core targets often participate in the metabolic process of reactive oxygen species, dopaminergic synaptic pathway, etc., which may play an important role in the mechanism of Jinzhen oral liquid in the treatment of lung injury.Zhaietc.[34]To study the mechanism of ursodeoxycholic acid capsules in alleviating atherosclerotic plaque formed by thoracic artery in rats, including network pharmacology analysis and biochemical validation based on hemolytic components, usingUPLC-Q-TOF/MSMethods the components of ursodeoxycholic acid capsules dissolved in blood were determined, and then the obtained components were used for network pharmacological analysis to predict the key components and targets of ursodeoxycholic acid capsules. ELISAandWestern blottingMethods the predicted targets were validated.Ouetc.[35]A comprehensive method combining HPLC with quadrupole time-of-flight mass spectrometry and network pharmacology was used to screen out the components of Rhodiola crenulata L53Compounds, and combinedUPLC/Q-TOF-MS/MSConduct detection and determination, determine its composition, and screen out40Bioactive ingredients33Target proteins (includingPTGS2andPTGS1Etc.) and68Three important signaling pathways (such as inflammatory pathway, apoptosis pathway, etc.) have played an important role in regulating the treatment of acute mountain sickness.Sun[36]Et al. Screened the ingredients of Dachengqi decoction which can effectively treat acute pancreatitis through network pharmacology, and verified its potential molecular mechanism through in vivo and in vitro experiments. The study confirmed the feasibility of exploring the material basis and mechanism of action of Dachengqi Decoction in the treatment of acute pancreatitis based on network pharmacology, and also laid the foundation for the in-depth study of the compounds with obvious pharmacological effects but not yet confirmed in this prescription and their related transcription factors. In foreign countries, network pharmacology is used to study traditional Chinese medicine and Chinese patent medicine. It not only studies its active ingredients, but also uses liquid phase or liquid mass spectrometry technology to study the identification of chemical components screened through network pharmacology database and the activity verification by in vivo and in vitro experiments. However, few people determine the content of its active ingredients. The effectiveness of traditional Chinese medicine is closely related to the dose of active ingredients, and the minimum effective blood concentration must be achieved to exert the efficacy. Therefore, it is far from enough to identify the active ingredients screened by network pharmacology, and the content of its active ingredients should also be determined.
Shengetc.[37]The pharmacological mechanism of compound Xueshuantong capsules against thrombosis was analyzed by network pharmacology. The effects of the active ingredients of the compound on coagulation, fibrinolysis and platelet aggregation were revealed. And using lipopolysaccharide(LPS)InducedDIC. The mechanism of action was not only studied theoretically from network pharmacology, but also verified by in vivo animal experiments.
3 Challenges faced by network pharmacology
Although network pharmacology can effectively make up for the defects of single target and low selectivity in previous studies of traditional Chinese medicine, and can be applied in many aspects of traditional Chinese medicine, it still faces some challenges in practical application(1)Network pharmacology is based on database and analysis software, but due to the current technical level, the database is not perfect, the data and analysis results provided byThe reliability of the results needs to be further verified, and the criteria for screening ingredients need to be optimized. For example, most of the current studies are based on oral bioavailability values(OB)≥30%, drug like(DL)≥0.18As criteria for screening ingredients[38],However, it lacks certain basis; The(2)The active ingredients screened by network pharmacology for diseases are not the main quality control ingredients in the current standards of traditional Chinese medicine or the ingredients with high content in traditional Chinese medicine. The existing experimental basis showed that network pharmacology was used to screen Scutellaria baicalensis Georgi-The active ingredients of Huaihua compound in the treatment of dysfunctional uterine bleeding include quercetin, wogonin and kaempferol, but there is no current standard quality control component of traditional Chinese medicine baicalin; β-But there was no paeoniflorin with high quality control content. Therefore, how to evaluate and deal with this difference needs further discussion; The(3)The efficacy of drugs is based on the effective substances[39], the effective substances must reach a certain dose or concentration to take effect. However, at present, few people in network pharmacology research have verified the efficacy by animal test or cell test. The accuracy of network pharmacology research results needs further investigation. The(4)The existing experimental basis shows that some components screened by network pharmacology have low content in the original medicinal materials or the original compound, such as baicalein, wogonin, quercetin, and Robinia pseudoacacia in Scutellaria baicalensis Georgi.The content of baicalein in the original compound is relatively low.The content of baicalein in Scutellaria baicalensis Georgi is relatively low............the content of baicale-The contents of Sophora japonica compound were0.45%、0.13%、0.11%、0.02%As the main effective component of the compound, it may only have theoretical significance, and this component can not really play the medicinal value of the traditional Chinese medicine in the clinic; The(5)Literature research found that network pharmacology was used to screen out some active ingredients with high similarity, such as quercetin, kaempferol andβ-Sitosterol has a wide range of activities. In the screening of different drugs or prescriptions, the screening results have a great degree of similarity, such as Han Zhuzhu, etc[40]Network pharmacology was used to treat Eucommia ulmoides Oliv-The mechanism of Cornus officinalis compatibility in the treatment of diabetes was studied. The results showed that the screened active ingredients included quercetin, kaempferol andβ-Sitosterol et al., while Liu Yan et al[41]Study on Astragalus membranaceus-The active ingredients screened from the seeds of lepidia in the treatment of heart failure were also kaempferol, quercetin andβ-Sitosterol, etc., the two are compatible with different medicinal materials, and the active ingredients screened for the treatment of different diseases are highly similar. Another example is Liu Dan[42-43]Quercetin and kaempferol are also the active ingredients screened from the studies on the chemical constituents of Ginkgo biloba leaves and the mechanism of treating gout. Obviously, this phenomenon needs further discussion.
4 epilogue
In recent years, network pharmacology has been widely used in the field of traditional Chinese medicine, Zhang Yu et al[44]This paper mainly introduces the application and existing problems of network pharmacology in the field of traditional Chinese medicine compound research from the aspects of pharmacodynamic material basis, mechanism of action, new drug research and development, new indications, and compatibility laws of traditional Chinese medicineThe research on the mechanism of action of traditional Chinese medicine compound provides a new direction. Xingxinrui et al[45]Network pharmacology was used to predict the mechanism of action of various diseases, which provided a new idea for solving the problems of unclear effective ingredients and unclear mechanism of action of traditional Chinese medicine. It plays an important role in the excavation and exploration of new indications[46],It can not only be applied to the study of active ingredients and mechanism of action of drugs in the treatment of diseases, but also be applied to the screening of active ingredients and action targets and pathways of known drugs, so as to discover new indications and related mechanisms of action of drugs, which can be used as anti-tumor, anti cardiovascular system and immune systemAnd other complex diseases to screen reasonable drugs for compatibility and targeted design research[46]carryIt also saves a lot of cost and time for new drug research and development.
Zhengetc.[47]Proposed an innovative high-throughput research strategy, combined with the computational and experimental methods of network pharmacology, and selected22. In addition, it also includes25Three kinds of traditional Chinese medicine to eliminate pathogens were compared. Using network pharmacology analysis, it was found that the predicted targets of compounds in health enhancing traditional Chinese medicine were enriched in immune related and antitumor pathways, and their functions were similar to those of pathogen eliminating traditional Chinese medicine. Galopeptide, a compound in a health enhancing herb, Paeonia lactiflora (Paeonia lactiflora), has antitumor effects in vivo and in vitro. However, the inhibitory effect of compounds in pathogen eliminating traditional Chinese medicine on tumor cell proliferation was significantly stronger than that of health enhancing traditional Chinese Medicine(P<0.001). In addition, the percentage of detected compounds in health enhancing TCMs with predicted targets enriched in immune related pathways, such as natural killer cell-mediated cytotoxicity and antigen processing and presentation, was significantly higher than that in pathogen clearing TCMs(P<0.05). This finding was supported by high-throughput sequencing(HTS2). At the same time, it was also found that the compounds in the same traditional Chinese medicine may show the same or different mechanisms in cancer treatment, which was proved to be due to the compounds affecting the expression of pathway genes in the same or opposite direction. Such as acetylursolic acid and steno were really up-regulated in Ligustrum lucidum, a health enhancing herbTGene expression in the cell receptor signaling pathway. This study shows that compared with directly killing tumor cells, the potential of tumor immunity, microenvironment regulation and tumor prevention is greater.Guoetc.[48]Studies have shown that tumorigenesis is a complex process driven by the combination of genes and environmental factors; However, there is a lack of effective methods to identify functional networks disturbed by the process of tumorigenesis. Therefore, his team provided a comprehensive network-based strategy to systematically discover functional synergy modules that are causal determinants of inflammation induced tumorigenesis. This method prioritizes candidate genes by integrating clinical based and web-based genome-wide gene prediction methods, and determines the function based on combinationCRIS PR-Cas9Screened collaboration module. On the basis of candidate genes re inferred from experimental and computational methods to be involved in inflammation and cancer, existing transforming growth factors were usedβ1(TGFβ1)Induced transformation model of colonic epithelial cells and a new combinationCRIS PR-Cas9Screening strategies to construct inflammation induced differential genetic interaction networks. . Identified opposite differential genetic interactions for inflammation induced tumorigenesis——Synergistic promotion and inhibition. The synergistic promotion state is mainly caused by the deletion in the immune and metabolic modules; The synergistic inhibitory state is mainly caused by the deletion in the proliferation and immune module or the proliferation and metabolism module. These results provide insight into possible early combined targets and biomarkers of inflammation induced tumorigenesis, and highlight the synergistic effects that occur between immune, proliferative, and metabolic modules. In conclusion, this approach deepens the understanding of the underlying mechanisms leading to inflammation that potentially increases the risk of cancer in colonic epithelial cells and accelerates the translation to new functional modules or combinations of synergistic modules that regulate complex disease phenotypes. Cancer is one of the largest causes of human death, but its deterioration process is extremely complex. The above examples provide a new idea for the study of traditional Chinese medicine treatment or prevention of cancer. The combination of network pharmacology calculation and experimental verification is a relatively cutting-edge research direction.
In the era of rapid development of information technology, network pharmacology is used to comprehensively and systematically study traditional Chinese medicine. On the one hand, it is to analyze and study the pharmacological mechanism of traditional Chinese medicine, and on the other hand, it is to explore the mechanism of multi-component, multi-target and multi-channel synergy in the treatment of unknown diseases[49]However, network pharmacology has some defects, which need to be continuously improved and improved, such as the use of multidisciplinary technology and molecular docking technology[50], improve the content of the relevant database, re evaluate the reliability of the data in the database, formulate relevant standards, improve data analysis and visual processing software, evaluate and update the screening results of the database, determine the content of the screened active ingredients by HPLC or UV spectrophotometry, judge whether they reach the clinical efficacy concentration, and effectively combine them with pharmacology, pharmacokinetics, toxicology, pharmacodynamics and other experiments, so as to make the screened active ingredients and action mechanism more convincing.
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