Mechanism of Magnoliae Flos and Xanthii Fructus herb pair in treatment of allergic rhinitis based on network pharmacology

Yu-Qiang Lu,Hui Ding,Zhao-Lin Shi,Hai-Bo Lin,Guo-Cheng Zhang,*

1Shaanxi University of Chinese Medicine,Xianyang 712046,China.2Children's Hospital,The Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712046,China.

Abstract Objective:To explore the molecular mechanism of Magnoliae Flos and Xanthii Fructus herb pair for allergic rhinitis based on network pharmacology.Methods:From the Traditional Chinese Medicine Systems Pharmacology database,Uniprot database,and Gene Cards database,the relevant chemical constituents information,pharmacokinetic information and hub target of allergic rhinitis were obtained.The protein-protein interaction network was constructed by STRING online database,analyzed and showed by the Cytoscape software.The screened target information was analyzed by the Metascape database for Gene Ontology biological function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.Results:Main components of Magnoliae Flos and Xanthii Fructus herb pair,such as aloe-emodin,stigmasterol,beta-sitosterol and Yangambin,depend on the interaction of Nitric Oxide Synthase 3,Tumor Necrosis Factor,Caspase-3 and other functions involve G protein-coupled (amine) receptor activity,RNA polymerase II basic transcription factor binding,protease binding,heme binding,and integrin binding; can regulate calcium signal pathway,serotonergic synapse,Kyoto Encyclopedia of Genes and Genomes signal pathway,tryptophan inflammatory mediator regulation pathway,estrogen signal pathway alone or in combination,and play a role in the treatment of allergic rhinitis.Conclusion:Magnoliae Flos combined with Xanthii Fructus can regulate biomolecular network in multiple targets and pathways to treat allergic rhinitis.

Keywords:network pharmacology;allergic rhinitis;Magnoliae Flos and Xanthii Fructus herb pair;target prediction;mechanism of action

Background

Allergic rhinitis (AR) is a chronic inflammatory nasal mucosal lesions characterized by episotic sneezing,runny nose and nasal obstruction,which is mediated by immunoglobulin (IgE) and immunoactive cells and cytokines after the body is exposed to allergens,the main symptoms are itching,stuffy nose,runny nose and sneezing [1].AR is a global health problem,it is a common disease worldwide,affecting about 10–50% of the population,especially children,the prevalence rate is increasing [2].With the development of society and the change of living conditions,its incidence rate is gradually increasing.Recent studies have shown that the pathogenesis of AR is mainly due to the imbalance of Th1 and Th2 cells [3].According to the diagnosis and treatment guidelines,the treatment of western medicine for this disease mainly includes allergen avoidance,oral drug therapy,specific immunotherapy and anti-IgE therapy [4].The symptoms can be controlled quickly in a short time,but it is easy to occur repeatedly after drug withdrawal,seriously affecting children's daily life,learning,sleep,growth and development [5].According to traditional Chinese medicine,AR belongs to the category of“Biqiu”.Doctor Zhang Zhongjing pointed out that the disease is caused by the invasion of cold evil,the loss of lung qi and the loss of body fluid,and emphasizes that the pathogenic factor is wind-cold.However,with the progress of the times,combined with their own clinical experience and different understanding of the disease,doctors of all ages have proposed that dryness,heat,dampness and other factors can also lead to the attack of AR.

Traditional Chinese medicine (TCM) is a treasure handed down from generation to generation of the Chinese nation,which is characterized by the emphasis on the overall concept,syndrome differentiation and treatment,and obvious advantages in clinical diagnosis and treatment.Through the analysis of the law of the use of traditional Chinese medicine in the treatment of infantile rhinitis,it can be found thatMagnoliae FlosandXanthii Fructusas classic drugs,both of them have the effects of dispelling wind,dispelling cold and dredging nose orifices,and are often used alone,compatible or compatible with other drugs.Xanthium sibiricum and Magnolia sibirica have anti-inflammatory,antibacterial and anti-allergic effects[6–8].However,as a single herb,although it has a considerable curative effect in the treatment of AR,its effect is relatively weak;and the combination of them has many advantages in the treatment of AR,such as rich components,diverse targets and broad signaling pathways,which greatly increases the therapeutic effect of AR.Professor Ren Baocheng,a famous and veteran TCM doctor in Tianjin,often uses theMagnoliae FlosandXanthii Fructusherb pair as the basis,and adds medicine for dispelling wind and promoting lungs to treat AR according to symptoms and signs [9].Professor Luo Enxiang in Beijing advocated the treatment of AR from wind pathogen,with magnolia and Xanthium as the main drugs,adding or decreasing with the syndrome to effectively improve the clinical symptoms of the patients [10].The clinical effect is definite.Hence,Magnoliae FlosandXanthii Fructusherb pair is usually used in the treatment of AR.Therefore,further exploration of the mechanism of theMagnoliae FlosandXanthii Fructusherb pair drug pair has practical significance for clinical treatment.The concept of network pharmacology was proposed in 2007,and its definition mainly refers to the use of network methods to analyze the“multicomponent-multitarget-multipathway”between drugs,diseases and targets [11].And it has the three characteristics of holistic,systematic,and focusing on the interaction between herbs,which coincides with the holistic concept and syndrome differentiation of TCM [12].Therefore,this study uses network pharmacology as a method to analyze the possible mechanisms of treatment of AR by obtaining the effective compounds and targets of theMagnoliae FlosandXanthii Fructusherb pair.

Subjects

Data collection of chemical constituents of TCM

Taking the Traditional Chinese Medicine Systems Pharmacology(TCMSP) database (Developed by Professor Wang Yonghua’s research group from Northwest A&F University,http://tcmspw.com/tcmsp.php) as the research scope,the information of chemical composition and pharmacokinetics (absorption,distribution,metabolism and excretion) ofMagnoliae FlosandXanthii Fructuswere collected respectively.

Collection of disease targets gene data of AR

Searching for gene targets from different sources with the UniProtKB search function in the Uniprot database (http://www.uniprot.org) to obtain official gene symbols of all targets;using the Gene Cards database (The Human Gene Database,https://www.genecards.org/)as the research scope,searching keywords“AR”to obtain the target gene of AR for subsequent analysis.

Methods

Screening of effective chemical components of Chinese medicines

Based on absorption,distribution,metabolism,excretion information,the effective components of traditional Chinese medicines were screened to determine the key compounds with high activity.The screening criteria are:Oral bioavailability (OB) ≥ 30%,Drug-likeness(DL) ≥ 18% [13].

Combined with the literature,the OB and DL were further combined to screen the target protein and try to predict the pharmacokinetics of compounds.

Target protein gene name transformation

Taking the target protein as the research object,and using the UniProt database (http://www.uniprot.org) as the research scope to convert the target protein name into the target gene name.

Target prediction

Research methods based on ligand prediction (chemical similarity search and pharmacophore model):[6,7] 1) Taking the TCMSP database as the research scope,target genes corresponding to chemical compositions of the drug were collected and duplicates were removed;2) Taking the Gene Cards database (The Human Gene Database,https://www.genecards.org/) as the research scope,searching for the keyword“AR”,and clicking the search to obtain the target genes of AR.

Matching the target ofMagnoliae FlosandXanthii Fructusto the target genes of AR,and using Excel to delete duplicates to screen out the common targets of them,and then predicting the potential targets of this drug for the treatment of AR.

The construction of an interaction network (PPI)

In order to explore the interaction between target proteins,the relevant action targets ofMagnoliae FlosandXanthii Fructusin the treatment of AR were uploaded to the online STRING database(http://stringdb.org).The species was selected as“Homo sapiens”,and the minimum interaction threshold was set as“medium confidence”.Combined score was not screened,and the Tab-separated values (TSV) file was downloaded and imported into Cytoscape 3.7.2 software for visualization.The core target was finally screened out.

Construction of“Drug-Component-Target”intersection network

The target genes ofMagnoliae FlosandXanthii Fructusscreened by Excel were mapped with disease target genes of AR to screen out the common active target.

The Cytoscape 3.7.2 software was used to obtain the active ingredient ofMagnoliae FlosandXanthii Fructus–target network map.

Importing the TSV file successfully matched with the STRING database in the early stage into Cytoscape 3.7.2 software,conducting network topology analysis,and saving it for subsequent analysis.

GO function enrichment analysis and KEGG pathway enrichment analysis based on Metascape

Entering the core target genes of the selected“Magnoliae FlosandXanthii Fructusherb pair”into the Metascape database(https://metascape.org/gp/index.html),checking the“Multiple Gene List”,and selecting the species as“H.sapiens”,selecting“Custom Analyze”,after downloading,the data of GO enrichment analysis and KEGG enrichment analysis are obtained.These data are imported into Wei sheng xin (http://www.bioinformatics.com.cn/) and the enrichment analysis map is obtained.

Results

Screening results of effective chemical components

The TCMSP database was searched and supplemented with the website (http://www.swisstargetprediction.ch/),colleting a total of 295 chemical constituents ofMagnoliae FlosandXanthii Fructus,including 184 components ofMagnoliae Flosand 111 ofXanthii Fructus.With OB ≥ 30% and DL ≥ 0.18 as the standard,30 compounds with theoretically higher OB and higher self-activity were screened out,including 19 species ofMagnoliae Flosand 11 species ofXanthii Fructus.According to the current database searched,the two herbs have no common active ingredients.As shown in Table 1.

Table 1 Effective components of Magnoliae Flos and Xanthii Fructus

Gene name transformation of target protein

The protein names of the action targets of the above 30 compounds were transformed into gene target names by Uniprot database.Among the 19 active compounds ofMagnoliae Flos(replaced by XY in the table),the corresponding gene targets could be found for 15 of them,and 145 gene target information were obtained.Corresponding gene targets could be found for 7 of the 11 active components ofXanthii Fructus(replaced by CEZ in the table),and 113 gene target information were obtained.

Target prediction

After deleting the duplicates of the above transformed gene targets by Excel,88 related gene targets were remained.A total of 1,404 Gene targets related to AR were obtained from Gene Cards database.By comparing and analyzing the related targets ofMagnoliae FlosandXanthii Fructuswith the disease targets collected,19 core targets for the treatment of AR were obtained as shown in See Table 2 for more details.

Table 2 Core targets and frequency

Protein interaction network (PPI)

Entering the information of 19 specific targets for the treatment of AR into the STRING platform to construct a protein interaction network.There are 19 target protein nodes in the PPI network,74 target proteins are connected to each other,and the average value is 7.79,intermediate number is 0.725;Cytoscape 3.7.2 software was used to construct the core target network diagram of the disease of AR–components ofMagnoliae FlosandXanthii Fructus,as shown in Figure 1.

Figure 1 PPI network diagram of Magnoliae Flos and Xanthii Fructus herb pair in treatment of AR target protein. The blue circle represents the core disease target corresponding to the active component of Xanthii Fructus,the pink circle represents Magnoliae Flos,and the line represents the mutual relationship.

Establishment of“Drug-Active Ingredient-Target”intersection network

The relevant information of the active ingredient and target of the herb was imported into Cytoscap 3.7.2 software to draw the network diagram of“drug-active ingredient-target”(as shown in Figure 2).As can be seen from the figure:the darker the color of the node and the denser the connection indicate that the target is more important and more likely to be the core target.From this,the interaction between each active component and the target can be clearly seen.In addition,it can be found from the figure that there is not a one-to-one correspondence between the active components and targets of the herb pair,but a complex network system,which reveals the multi-component and multi-target interaction relationship between them.

Biofunction and pathway enrichment analysis

GO biological function enrichment analysisThe selected target information was used for GO biofunctional enrichment analysis through Metascape database.Min Overlap 3,P-value <0.01 and Min Enrichment 1.5 were set for analysis.Finally,GO enrichment analysis was obtained,which were imported into Wei sheng xin(http://www.bioinformatics.com.cn/),18 functional information related Biological process,3 related Cellular components and 5 pathways related Molecular Function were obtained (Figure 3).Biological processes involve mitogen-activated protein kinases(MAPK) cascade regulation,negative regulation of cell proliferation,regulation of blood pressure,cell response to drugs,glial cell apoptosis,heat production,cell response to toxic substances,the decomposition reaction of cells to hypoxia,positive regulation of migration of vascular endothelial cells,regulation of cell-cell adhesion,prostaglandin biosynthesis process,protein deproteinization,cell response to organic ring compounds,rhythmic process,negative regulation of intracellular signal transduction,regulation of purine nucleotide metabolism,regulation of autophagy,etc.The cell components involved membrane rafts,nuclear membranes,dissolved vacuoles,etc.Molecular functions involved G-protein coupled (amine) receptor activity,RNA polymerase II base transcription factor binding,protease binding,heme binding,integrin binding,etc.

KEGG pathway enrichment analysisMetascape database was screened withP<0.01,the data were imported into Wei sheng xin(http://www.bioinformatics.com.cn/) and 7 signaling pathways were obtained (Figure 4).Some of them are related to disease:calcium signaling pathway,serotonergic synapse,VEGF signaling pathway,TRP inflammatory mediator regulatory pathway,and estrogen signaling pathway.It is suggested that the effective components of the herbs can be used to treat AR by regulating the above signaling pathway.

Figure 2 Magnoliae Flos and Xanthii Fructus herb pair compound-target network diagram.The blue circle represents the Xanthii Fructus composition,the pink circle represents the Magnoliae Flos composition,the green is the target of the two drugs,and the big green circle is the unique target of the Magnoliae Flos.

Figure 3 Histogram of GO function enrichment analysis.BP,Biological process;CC,Cellular components;MF,Molecular Function.

Figure 4 Pathway enrichment information involving key targets of Magnoliae Flos and Xanthii Fructus herb pair in treatment of AR.

Discussion

Magnoliae Flos and Xanthii Fructusherb pair has a complex network relationship in the treatment of AR.AR is an allergic disease induced by the interaction of genes and environment,which can lead to many complications,thus resulting in the loss of labor force of patients and aggravating the burden on family and society.The incidence of AR is increasing,so it has become a disease of global concern,and the investment is increasing gradually in its mechanism research and new drug research and development.TCM has a good effect on the treatment of AR.With the further development of the research,the role of Chinese medicine in AR treatment has attracted more and more attention.Among them,the research is also gradually intensive on the effect and mechanism of the classical prescription“Magnoliae FlosandXanthii Fructus”herb pair.Cangqizhiqiu soup is a self-created prescription of Liu Xiaowei,containingXanthii Fructus,Hedysarum Multijugum Maxim,Magnoliae Flos,Saposhnikoviae Radix,the effect of four drugs can eliminate pathogenic,cultivating the soil to promote the growth of gold.Play the role of treatment of AR lung empty feeling cold syndrome,and the total effective rate is greater than the control group of western medicine treatment [14].

According to pharmacodynamics experiments,it was concluded that the combined decoction ofMagnoliae Flos and Xanthii Fructushave a detoxification effect and significantly increase the effect on anti-inflammation compared with single decoction [15].Studies have shown thatXanthii Fructushas good anti allergy,anti-inflammatory and analgesic effects,it can reduce the frequency of sneezing and nasal itching symptoms.Magnoliae Floshas pharmacological effects such as anti allergy,anti-inflammatory,angiogenesis,anti proliferation,Ca2+channel antagonism and anti microbial activity.The combination of the two drugs has a synergistic inhibitory effect on allergic and inflammatory reactions [16-17].Studies have confirmed thatMagnoliae Flos and Xanthii Fructuscan enhance the anti-inflammatory effect and reduce the toxic effect ofXanthii Fructus,in addition,studies have found that the combination of the two TCM can synergistically inhibit the allergic reaction of the skin,reduce the pathological changes of nasal mucosa of AR guinea pigs and improve the behavioral symptoms of the nose [18–20].From the perspective of the micro-molecular mechanism of modern medicine,the molecular mechanism of a single medicine to play a specific therapeutic role is varied,and the mechanism of the composition of the herb pair is more complicated after the compound prescription based on the prescription compatibility theory.Therefore,to identify the specific components and targets of TCM related to the treatment of AR,and combined with relevant theories to integrate the application,is an effective way to accurately use and give full play to the role of TCM in the treatment of AR.Based on this,the network pharmacological analysis method was used in this study to explore the molecular mechanism of the active ingredients contained in the herb pair of“Magnoliae FlosandXanthii Fructus”and its role in the treatment of AR.It was first found in Shennong Materia Medica,and has the effect of dispelling wind and dispersing cold,and promoting nose.It is often used in clinical treatment of headache,congestion and other diseases caused by wind and cold [21].

Modern pharmacological studies have found that the active components ofXanthii Fructushave anti-inflammatory,analgesic and anti-allergic effects,and pointed out that the active components of it are mainly water-soluble glycosides,sesquiterpene lactones,volatile oils,fatty oils,phenolic acids and other compounds [22-23].Magnoliae Flosbelongs to the Magnolia subfamily of Magnolia family.It has the effect of removing wind and cold,and freeing nasal orifices.The main chemical components ofMagnoliae Flosinclude lipid-soluble and water-soluble,which can be classified into volatile oil,lignans and alkaloids.In this study,the chemical components,active targets and coverage signal pathways ofMagnoliae Flos and Xanthii Fructuswere analyzed through network pharmacology.Applying the TCMSP database platform,we screened out 30 compounds with high OB and self-activity,including 19 species ofMagnoliae Flosand 11 species ofXanthii Fructus.According to Table 1 and Figure 2,it can be seen that some compounds contained a relatively large number of targets:Mol000358 (Beta-Sitosterol),Mol000449 (Stitmasterol),Mol000471 (Aloe-Emodin) ofXanthii Fructusand Mol012123 (Denudanolide A),Mol012124 (Denudanolide B),Mol012125 (Denudanolide C),Mol012126 (Denudanolide D),and Mol007563 (Yangambin) ofMagnoliae Flos.We searched related literatures and found that Denudanolide A,Denudanolide B,Denudanolide C,Denudanolide D almost did not involve AR.Therefore,the main components ofMagnoliae Flos and Xanthii Fructusin treating AR are Beta-Sitosterol,Stitmasterol,Aloe-Emodin and Yangambin.Studies have shown that β-sitosterol can protect acute lung injury by inhibiting the release of Tumor Necrosis Factor(TNF) and down-regulating the activation of NF-κB signal transduction pathway [24].

Stigmasterol,a typical representative of phytosterol,exists in various plant oils and seeds.Sosterol has a wide range of pharmacological effects,such as anti-oxidation,anti-tumor,anti-inflammation,and reducing cholesterol disease [25].PANDITH et al.concluded that stigsterol found in Siamese weed extract has obvious anti-inflammatory effect,the main mechanism is to reduce the release of prostagland E2 and Nitric Oxide (NO) by inhibiting the mRNA expression of Cyclooxygenase-2(COX-2) and inducible Nitric Oxide Synthase (iNOS) induced by Lipopolysaccharide [26].Beta-sitosterol and stigmasterol can reduce inflammatory cytokines to improve the symptoms of AR [27].Studies have shown that aloe-emodin,an anthraquinone compound isolated from plant roots,can exert anti-inflammatory effects by inhibiting the mRNA expression of iNOS without affecting the activity of NOS,and it can also inhibit the expression of COX-2 [28].Yangambin,as one of the seven tetrahydrofuran lignans,has the function of platelet activating factor antagonist,shows antiallergic and analgesic effects,and can effectively inhibit the inflammatory reaction of AR and sinusitis [29].According to the analysis of its pharmacology and component target diagram,it was found that many effective chemical components contained inMagnoliae FlosandXanthii Fructusplayed an important role in the occurrence and development of AR.These effective active ingredients play a therapeutic role in the form of multi-component,multi-target and multi-pathway,which reflects the holistic concept of TCM diagnosis and syndrome differentiation and treatment.By analyzing the“component-target diagram”and“targets-pathway diagram”,we found that the 19 core targets screened in this study were involved in multiple biological processes such as signal transduction,cell cycle and immune system,which were closely related to the occurrence of AR.NO is a molecular messenger and regulatory factor produced by macrophages and other phagocytes mediated by inflammatory factors.It can promote mast cells to release transmitters,causing smooth muscle cells and distended blood vessels,which further leads to swelling of the nasal cavity and a series of AR symptoms such as nasal congestion.Nitric Oxide Synthase (NOS),an enzyme used to catalyze Nitric Oxide production,is regulated by genes and affected by a variety of factors,and can be expressed by a variety of cells in the body.NOS can be divided into iNOS,endothelial NOS (eNOS) and neuronal NOS (nNOS).In this study,the main targets were endothelial and induced types (NOS3 and NOS2).As can be seen from Figure 1,the color and line segment reflect that the first three main targets in the core target are NOS3,TNF,CASP3.The target of NOS3 has the darkest color and the most dense lines passing through this node,so it may be the most core target.The first discovery of NO in human exhalation was in 1991 [30].At present,NO has become a consensus as a marker reflecting the degree of inflammation of the lower respiratory tract,and has become increasingly important in the diagnosis,treatment and monitoring of AR.Suojalehto et al.respectively detected nNO in the control group,AR group and NAR group,and the results showed that the concentration of nNO in the AR group was higher than that in the other two groups.After further analysis of the results,they proposed the idea that high level of NO could be used as a marker of hypereosinophils in the nasal cavity [31].Zhang Shaojie took 152 patients with moderate or severe AR and 108 patients with Non-allergic rhinitis (NAR) as experimental group,125 healthy subjects as control group.They checked the nNO concentration respectively and found that nNO concentration in patients with AR group is (693.64 ± 236.62) ppb,(430.04 ± 92.15)ppb in NAR group,(400.17 ± 102.59) ppb in control group,concentration of nNO in Allergic rhinitis (AR) group was obviously higher than that of the NAR group and the control group.Moreover,the total serum IgE in AR group was significantly higher than that in the other two groups [32].This is consistent with the conclusion of this study.TNF is an inflammatory mediator produced by macrophages and lymphocytes.It participates in the Th1-mediated inflammatory response and can activate NF-κB,inducing the expression of cytokines and immune receptors and further participating in the inflammatory response.Wang Jinlei et al.found that the expression of NF-κB in lung tissue decreased,and the airway inflammation and lung type I epithelial injury in asthmatic rats were significantly improved [33].Studies have shown that macrophages can release a large amount of TNF-α,which activates neutrophils and the adhesion receptors of and endothelial cells and mediated the release of inflammatory factors when the body is in the inflammatory response [34].Zhang Min et al.found that NF-κB can adjust ratio of Th1/Th2 to reach a balance state between them,and then down-regulate the expression of IgE,which plays an important role in the occurrence and development of AR [35].CASP3 is a member of cysteine aspartic protease family,which participates in the regulation of inflammation and apoptosis,and plays an important anti-inflammatory role in the treatment of AR [36].

According to analyzing the KEGG pathway of target gene enrichment,this study found that the effect ofMagnoliae FlosandXanthii Fructusherb pair is mainly regulated by the Calcium signaling pathway,Serotonergic synapse,VEGF signaling pathway,Inflammatory mediator regulation of TRP channels,Estrogen signaling pathway and other signaling pathways,which play a role in the treatment of AR.

VEGF is one of the important signaling pathways,mainly because it is correlated with the release of NO.VEGF is a vascular endothelium-specific pro-vascular growth factor,which can promote the proliferation and migration of endothelial cells,regulate angiogenesis,increase vascular permeability,and induce mast cells and eosinophils to migrate to inflammatory sites.Many factors,such as estrogen and TNF,can affect the expression of VEGF.The estrogen signaling pathway mainly participates in the inflammatory response of the airway by regulating the synthesis and release of NO.Secondly,it can also promote the production of NO through the concentration of a variety of cells in the airway,so as to achieve the function of dilating blood vessels and relaxing tracheal smooth muscle.It is found that suppressing the expression of VEGF signal can reduce TNF [37].Some core targets ofMagnoliae FlosandXanthii Fructusmay be involved in the regulation of AR through VEGF signal pathway.In addition,estrogen can also activate MAPK to reduce the production of tissue-specific cortisol.MAPK,the main channel for extracellular signal transduction to the inside of the cell,exists widely in the organism and regulate gene expression and inflammatory factor transcription by regulating related transcription factors under exogenous stimuli such as cytokines and neurotransmitters.It plays an important role in the activation,maturation,differentiation and final immunity of inflammatory cells.Studies have shown that p38MAPK,a member of the MAPK family,plays a very important role in the occurrence and development of various airway inflammation [38].Jung et al.concluded that inhibition of phosphorylation of p38MAPK signaling pathway can significantly reduce the production and release of inflammatory transmitters,and the degree of nasal mucosal damage and inflammatory cell infiltration are also reduced [39].

To sum up,the main active ingredients of theMagnoliae FlosandXanthii Fructusherb pair include stigmasterol,aloe-emodin,etc.These active components interact with NOS3,TNF,CASP3 and other targets to regulate calcium signal pathway,serotonergic synapse,VEGF signal pathway,TRP inflammatory mediator regulation pathway,estrogen signal pathway,and finally play a role in the treatment of AR.

Conclusion

Based on the analysis method of network pharmacology,this study preliminarily screened the active components and targets ofMagnoliae FlosandXanthii Fructusherb pair in the treatment of AR,and explored the relationship between herb pair and different signal pathways.Through the analysis,we found that the selected core targets involved a number of biological processes related to the occurrence of AR such as signal transduction,cell cycle and immune system,which not only confirmed the accuracy of the therapeutic effect ofMagnoliae FlosandXanthii Fructusherb pair in the treatment of AR from the point of view of molecular biology,but also provided a theoretical and scientific basis for the treatment of TCM in AR from the micro level.It also laid a theoretical foundation for the later clinical and laboratory research of our team.We expect that the results of this study can provide new ideas and directions for the research and development of new clinical drugs for AR.