Target Prediction of Xinyi San for Nasal Polyposis Based on Network Pharmacology ()
1. Introduction
Nasal polyposis is a nasal disease with high incidence rate. The main clinical manifestations are nasal obstruction, runny nose, dizziness, headache and diminished olfaction. It seriously affects the quality of life of patients and is difficult to treat. It is easy to relapse [1]. The occurrence of nasal polyposis is closely related to allergy, bacterial infection, fungal infection, aspirin intolerance, genetics and other factors, but the related pathogenesis is not clear [2] [3]. Modern medicine mainly treats nasal polyposis with drugs and surgery. It is easy to repeat after stopping drugs, and the side effects of drugs are large. Traditional Chinese medicine has great advantages in treating nasal polyposis.
Xinyi San is a classic famous prescription, which originates from Yan’s Jisheng prescription [4] written by Yan Yonghe in the Song Dynasty. The whole prescription is composed of 10 drugs such as xinyi, xixin, gaoben, shengma, chuanxiong, mutong, fangfeng, qianghuo, gancao and baizhi. It has the function of evacuating wind cold and dredging nose orifices. The clinical pathology of nasal polyposis is complex, but the mechanism of Xinyi San in treating nasal polyposis is not clear. Network pharmacology can construct a complex network between drug component target disease to explore the mechanism of drug action. Therefore, based on network pharmacology, this study explored the pharmacodynamic material basis and potential mechanism of Xinyi San in treating nasal polyposis, so as to provide reference for clinical application.
2. Materials and Methods
2.1. Screened for Active Components and Targets of Xinyi San
The active components and targets were screened with xinyi, xixin, gaoben, shengma, chuanxiong, mutong, fangfeng, qianghuo, gancao and baizhi as keywords through TCMSP (http://tcmspw.com/tcmsp.php), in which OB ≥ 30% and DL ≥ 0.18 (OB: oral bioavailability; DL: drug properties). Then converted the target proteins to gene name through UniProt (https://www.uniprot.org/).
2.2. Screened Disease Targets
We searched for disease targets with “nasal polyposis” as the keyword through genecards (https://www.genecards.org). The total targets were obtained by eliminating the repeated targets.
2.3. Constructed Disease-Single Drug-Ingredient-Target Network
Based on the above results, Cytoscape 3.7.2 software builded the network model of “disease-single drug-component-target”. Nodes represented diseases, single drugs, components and targets, and edges were used to show the relationship between them.
2.4. Constructed PPI Network
The active component targets of Xinyi San and the disease targets of nasal polyposis were introduced into Venny analysis platform (https://bioinfogp.cnb.csic.es/tools/venny/) to obtain the potential targets of Xinyi San in treating nasal polyposis. Imported intersection targets into String (https://string-db.org), the species was limited to “Homo sapiens”, the isolated targets were removed, and the PPI network was constructed with a confidence of 0.4 as the screening condition.
2.5. Gene Enrichment Analysis
GO functional enrichment analysis and KEGG pathway enrichment analysis were performed on R4 1.1 software for the main components of Xinyi San (P ≤ 0.05). The top 20 biological processes and pathways were selected.
3. Results
3.1. Screened Active Components of Xinyi San
We screened 97 potential active components of Xinyi San by TCMSP platform, including 12 xinyi, 6 xixin, 1 gaoben, 7 shengma, 6 chuanxiong, 8 mutong, 14 fangfeng, 10 qianghuo, 85 gancao and 13 baizhi. The basic information of some active components was as follows (see Table 1).
3.2. Constructed “Disease-Single Drug-Ingredient-Target” Network
The disease, single drug, active ingredients and targets were introduced into Cytoscape to construct the “disease-single drug-component-target” network (see Figure 1), including 222 nodes (1 disease node, 10 drug nodes, 142 active
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Figure 1. Network diagram of “disease-single drug-component-target”.
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Table 1. The basic information of some active components in Xinyi San.
ingredient nodes and 69 action target nodes) and 995 edges. The degree value of the node represents the number of the edges connected with the node, and the compound nodes with large degree value were screened. These compounds may be the key compounds of Xinyi San in treating nasal polyposis. The results showed that the top 7 compounds were quercetin, kaempferol, wogonin, beta-sitosterol, 7-Methoxy-2-methyl isoflavone, licochalcone a and isorhamnetin, which could connect with 56, 24, 17, 15, 12, 12 and 12 targets respectively.
3.3. Constructed PPI Network
Searched “nasal polyposis” in Genecards database to obtain 2062 disease targets, and mapped the intersection with 120 potential active component targets through Venn analysis, that was, 69 targets of Xinyi San in treating nasal polyposis (see Figure 2). Imported the 69 intersection targets into the String database to build the PPI network (see Figure 3). The top 30 targets were processed with R language to obtain the core target map (see Figure 4). The corresponding targets of these proteins with a large degree value may be the key targets of Xinyi San in treating nasal polyposis.
3.4. GO Enrichment Analysis
A total of 88 functional enrichments were obtained through R software analysis, and the top 20 with the greatest significance were made into a bar graph (see
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Figure 2. Venn diagram of intersection target of Xinyi San and nasal polyposis.
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Figure 3. PPI network of Xinyi San in treating nasal polyposis.
Figure 5). DNA-binding transcription factor binding, ubiquitin-like protein ligase binding, ubiquitin protein ligase binding, nuclear receptor activity, ligand-activated transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor binding, etc.
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Figure 5. GO enrichment analysis of Xinyi San.
3.5. KEGG Pathway Analysis
We got 135 KEGG pathways (P < 0.05), the top of 20 were plotted as a bar graph (see Figure 6). The results showed that the effective mechanism of Xinyi San in treating nasal polyposis mainly involves Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, Kaposi sarcoma-associated herpesvirus infection, Hepatitis B, Human cytomegalovirus infection and other pathways.
4. Discussion
Although the pathogenesis of nasal polyposis is not clear, the current etiological theory believes that the root cause of nasal polyposis is the inflammatory reaction caused by environmental or allergic stimuli or nasal infection [5].
The construction results of “disease-single drug-component-target” network showed that quercetin, kaempferol, wogonin, beta sitosterol, 7-methoxy-2-methyl isoflavone, Licochalcone a and isorhamnetin may be the key compounds of Xinyi San in treating nasal polyposis. It was found that [6] quercetin could significantly inhibit the infiltration of eosinophils in nasal mucosa of rhinitis rats, and significantly improved nasal mucosal edema, vasodilation and gland hyperplasia. Kaempferol could inhibit TNF in nasal mucosa-α and the expression level of IL-4, reducing the infiltration of eosinophils in nasal mucosa [7]. Chalcone had many pharmacological activities, such as anti-inflammatory, antifungal, anti ulcer, anti-oxidation, anti-virus and anti-tumor. Especially in terms
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Figure 6. KEGG pathway enrichment analysis of Xinyi San.
of anti-inflammatory, some chalcone compounds had very significant biological activities [8].
The PPI network showed that the key targets of Xinyi San in treating nasal polyposis were RAF1, RB1, PARP1, HSPB1, ESR2, IKBKB, NR3C1, ICAM1, NFE2L2 and GSK3B. The results of GO analysis showed that the active components of Xinyi San mainly involved in biological processes such as cell response, inflammatory response and immune response, suggesting that Xinyi San might act on a variety of cytokines, anti-inflammatory and inhibit cytokine storm in treating nasal polyposis. KEGG pathway enrichment mainly involved Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, Kaposi sarcoma-associated herpesvirus infection, Hepatitis B, Human cytomegalovirus infection, etc.
5. Conclusion
The study used network pharmacology to analyze the action mechanism of Xinyi San in treating nasal polyposis, and confirmed the complex action mechanism of multi-component, multi-target and multi-channel of Xinyi San, which laid a foundation for its in-depth research.
Funding
This study was funded by Scientific Research Project of Hebei Administration of Traditional Chinese Medicine (No.2022437).