Mechanism of Peitu Shengjin Formula Shenlingbaizhu Powder in Treating Bronchial Asthma and Allergic Colitis through Different Diseases with Simultaneous Treatment Based on Network Pharmacology and Molecular Docking

Background Shenlingbaizhu powder (SLBZP), one of the classic Earth-cultivating and gold-generating prescriptions of traditional Chinese medicine, is widely used to treat various diseases. However, the pharmacological mechanisms of SLBZP on bronchial asthma (BA) and allergic colitis (AC) remain to be elucidated. Methods Network pharmacology and molecular docking technology were used to explore the potential mechanism of SLBZP in treating BA and AC with the simultaneous treatment of different diseases. The potential active compounds of SLBZP and their corresponding targets were obtained from BATMAN-TCM, ETCM, SymMap TCM@TAIWAN, and TCMSP databases. BA and AC disease targets were collected through DisGeNET, TTD, GeneCards, PharmGKB, OMIM, NCBI, The Human Phenotype Ontology, and DrugBank databases. Common targets for drugs and diseases were screened by using the bioinformatics and evolutionary genomics platform. The analyses and visualizations of Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of common targets were carried out by R software. The key targets were screened by using the plug-in “cytoHubba” of Cytoscape software, and the “active compound-key target” network was constructed. Molecular docking analysis was performed using AutoDock software. The miRTarBase database was used to predict microRNAs (miRNAs) targeting key targets, and the key target-miRNA network was constructed. Result Through screening, 246 active compounds and 281 corresponding targets were obtained. Common targets were mainly enriched in 2933 biological processes and 182 signal pathways to play the role of treating BA and AC. There were 131 active compounds related to key targets. The results of molecular docking showed that the important active compounds in SLBZP had good binding ability with the key targets. The key target-miRNA network showed that 94 miRNAs were predicted. Conclusion SLBZP has played the role of treating different diseases with the same treatment on BA and AC through the characteristics of multicompound, multitarget, and multipathway of traditional Chinese medicine, which provides a theoretical basis for explaining the mechanism and clinical application of SLBZP treating different diseases with the same treatment in BA and AC.


Introduction
Asthma generally refers to bronchial asthma (BA). BA, one of the most common chronic noncommunicable diseases in children and adults, is characterized by variable respiratory symptoms and variable airflow limitation, which is the result of complex gene-environment interactions, and is heterogeneous in clinical manifestations and the type and intensity of airway inflammation and remodeling [1]. e goal of BA treatment is to achieve good asthma control, that is, to minimize the burden of symptoms and the risk of deterioration [2]. However, asthma attacks and hospitalizations are frequent, and the mortality rate remains high. Strategies need to be developed to change the natural history of BA and prevent serious deterioration and the decline of lung function [1]. Allergic colitis (AC), an inflammatory disease, is characterized by the infiltration of eosinophils into the colon wall and the presence of red blood in the stool of healthy breast-fed or formula-fed infants, which usually develops in the first few weeks or months of life and can be a benign and/or severe disease in infant gastrointestinal diseases [3][4]. To date, the most effective interventions are preventive methods, especially feeding strategies, to reduce the incidence of disease while establishing adequate growth and progression to enteral feeding [5]. However, their pathogenesis has not yet been fully clarified with some allergens unclear or unavoidable, and modern medicine lacks ideal preventive and therapeutic methods [6]. At present, modern medicine adopts allergen avoidance, desensitization, and symptomatic treatment, but some antihistamines and antileukotrienes need to be taken for a long time, which brings certain economic burden and psychological impact to patients and cannot completely cure allergic diseases with some deficiencies, such as side effects of drugs and easy recurrence after withdrawal [7][8][9]. In recent years, treating allergic diseases with traditional Chinese medicine has been more and more widely used in clinical practice with various methods, remarkable effects, less adverse reactions in longterm application, and good compliance, which is convenient for clinical promotion [10,11].
Network pharmacology, targeting biological networks, analyzes the connections between drugs, targets, and diseases in these networks. A comprehensive and systematic research on network pharmacology conforms to a holistic view, which is the main characteristic of many traditional medicines. Studies have shown that many traditional medicines exhibit synergistic effects by acting on multiple targets and pathways at different levels through network pharmacology [15]. is method effectively bridges the gap between modern medicine and traditional medicine and greatly promotes the research on the synergy of traditional medicine. Different diseases with simultaneous treatment means that the same pathogenesis appears in the occurrence and development of different diseases, and the same treatment can be adopted. SLBZP reinforces Earth to generate metal for treating BA and AC, which is in line with the concept of different diseases with simultaneous treatment.
is study comprehensively analyzed and explored the mechanism of SLBZP in treating BA and AC with simultaneous treatment of different diseases from compounds, targets, pathways, biological processes, etc., by network pharmacology and molecular docking, which conforms to the overall function of traditional Chinese medicine theory and provides theoretical bases for clarifying the action mechanism of SLBZP on BA and AC and promoting its clinical application (Figure 1).

Screening of Common Targets.
e targets related to active compounds, BA, and AC were matched and mapped by using the bioinformatics and evolutionary genomics platform (http://bioinformatics.psb.ugent.be/webtools/ Venn/). At the same time, a Venn diagram was drawn to obtain the common targets of the active compounds of SLBZP for treating BA and AC.

GO and KEGG Enrichment Analysis of Common Targets.
e enrichment analysis and visualization of Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were carried out for the common targets of SLBZP in treating BA and AC with the species set as "Homo sapiens" and the threshold set as P < 0.05 by the "ggplot2", "enrichplot", "clusterprofiler" [30], and "ggpubr" packages of R software (version 3.6.1).

Construction of Active Compound-Key Target Network.
e obtained common targets were imported into Cytoscape software (version 3.8.0; http://www.cytoscape.org) [31], and the "cytoHubba" plug-in was used to screen out the key targets. en, an active compound-key target network was constructed by Cytoscape software, of which the network topology analysis was carried out by "Network Analysis" in the tool. e network showed the connection between the active compounds and key targets, and the molecular mechanism of SLBZP in treating BA and AC was explored on this basis.

Molecular Docking Verification.
According to the above analysis results, the key target proteins and the important active compounds were molecularly docked. e protein structures of the targets were obtained from the RCSB PDB database (https://www.rcsb.org/) [32]. e 2D structures of the active compounds were obtained from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/) [33] and were optimized to save as 3D structures with Chem3D software. AutoDockTools and AutoDockVina software were used for molecular structure processing and molecular docking. PyMOL and Discovery Studio were used to visualize the docking results.

Construction of Key Target-microRNA (miRNA) Network.
e miRTarBase database (https://mirtarbase.cuhk.edu.cn/% 7EmiRTarBase/miRTarBase_2019/php/index.php) is used to predict upstream miRNAs targeting key targets [34]. e collected miRNA-mRNA interactions have been verified by different types of experiments including report analyses in miRTarBase, western blot, qPCR, microarray, and next-generation sequencing experiments. In order to make predictions more reliable and accurate, only miRNAs that may interact with the targets were obtained through reporter gene analyses. After selecting "By Target Gene" and the species as "Human", key targets were entered to predict miRNAs. en, the key targets and their corresponding predicted miRNAs were organized into an Excel file that was imported into Cytoscape software. Finally, the network of the predicted miRNAs and key targets were constructed by Cytoscape software.

Acquirement of Active Compounds of SLBZP.
Preliminarily, a total of 335 active compounds were acquired from the BATMAN-TCM database; a total of 443 active compounds were acquired from the ETCM database; a total  Evidence-Based Complementary and Alternative Medicine

Acquirement of Targets of Active Compounds of SLBZP for
Treating BA and AC. After searching the above-mentioned qualified potential active compounds of SLBZP in the TCMSP database, and removing the repeated targets, 281 targets of active compounds of SLBZP were obtained. e bioinformatics and evolutionary genomics platform was used to match the potential targets of drugs with disease targets, and a Venn diagram was drawn ( Figure 2). 149 common targets were obtained (Table 2).

GO and KEGG Pathway Enrichment
Analysis. GO enrichment analysis revealed 2933 biological functions with remarkable significance, including 2687 for biological processes (BP), 75 for cellular component (CC), and 171 for molecular function (MF). e results of GO enrichment analysis showed that the common targets of SLBZP in treating BA and AC mainly involved response to oxidative stress, response to molecule of bacterial origin, membrane region, membrane microdomain, signaling receptor activator activity, receptor ligand activity, and other biological functions ( Figure 3). 182 significant pathways were obtained by KEGG pathway enrichment analysis, mainly involving PI3K-Akt signaling pathway, proteoglycans in cancer, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, apoptosis, 17 cell differentiation, and other pathways related to inflammation, cancer, apoptosis, and immunity ( Figure 4).

Construction and Analysis of Active Compound-Key Target Network.
e 149 common targets obtained above were screened by "cytoHubba", a plug-in of Cytoscape software, and then the 20 key targets with the highest degree value were obtained ( Figure 5). ese 20 key targets and their corresponding active compounds were imported into Cytoscape software for network construction and visualization ( Figure 6). ere were 131 active compounds related to key targets (Table 3). In the active compound-key target network, the degree of the network topology analysis carried out by "Network Analysis" reflects the connectivity of nodes that respectively represent active compounds and key targets. A higher degree value indicates more associations between nodes, which explains the significances of active compounds and key targets. e results of network topology analysis showed that the 5 active compounds most connected to the key targets were quercetin, luteolin, betacarotene, kaempferol, and naringenin, and the top 6 key targets of connectivity were prostaglandin G/H synthase 2 (PTGS2), caspase-3 (CASP3), RAC-alpha serine/threonineprotein kinase (AKT1), transcription factor AP-1 (JUN) [, cellular tumor antigen p53 (TP53), and vascular endothelial growth factor A (VEGFA), which indicated that the above compounds and targets were critical and had important implications in SLBZP for treating BA and AC.
3.6. Molecular Docking Results. Based on the above analysis results, the 5 important active compounds (quercetin, luteolin, beta-carotene, kaempferol, and naringenin) and the key targets were docked by AutoDockVina software. e docking results are shown in Table 4 and Figure 7. e smaller the binding free energy value, the lower the energy required for binding, which is more conducive to the binding of ligand and protein. Among them, the docking results of MMP9 with luteolin, quercetin, and kaempferol, ALB with luteolin, and PTGS2 with luteolin were the best, as shown in Figure 8. For example, luteolin formed conventional hydrogen bonds with MMP9 protein structure 6ESM amino acid residues A chain TYR245, LEU243, GLN227, LEU188, ALA189, formed π-σ interactions with amino acid residues A chain TYR248 and LEU188, formed π-π stacked interactions with amino acid residue A chain HIS226, and formed π-alkyl interactions with amino acid residues A chain VAL223 and LEU188. ese forces reduced the binding energy and increased the affinity, which played an auxiliary role in the binding of compound ligand molecules to the residues of target protein structures. Target-miRNA Network. 94 miRNAs were predicted from 6 key targets by the miRTarBase database. Cytoscape software was used to  Evidence-Based Complementary and Alternative Medicine Evidence-Based Complementary and Alternative Medicine construct a key target-miRNA network (Figure 9), among which hsa-miR-16-5p, hsa-miR-101-3p, hsa-miR-143-3p, hsa-miR-199a-5p, hsa-miR-30d-5p, hsa-miR-30c-5p, hsa-miR-30e-5p, hsa-miR-302d-3p, hsa-miR-203a-3p, hsa-miR-200b-3p, hsa-miR-125a-5p, hsa-miR-15a-5p, hsa-miR-504-5p, and hsa-miR-150-5p all targeted multiple key targets.

Discussion
e theory of traditional Chinese medicine believes that the spleen is the foundation of acquired life and that the spleen is not harmonious and causes all kinds of diseases. erefore, it has always paid attention to regulating the spleen to protect the five internal organs. e pathogenesis of spleen deficiency is involved in the occurrence and development of BA and AC. SLBZP, one of the classic Earth-cultivating and gold-generating prescriptions, can not only treat BA and AC with simultaneous treatment of different diseases but also protect the spleen to prevent and promote recovery. is study aimed to explore the action mechanism of SLBZP in treating BA and AC with simultaneous treatment of different diseases by using network pharmacology and molecular docking, so as to provide references for more in-depth experimental research and wider clinical applications.
GO annotation results showed that the biological functions involved in common targets were mainly response to oxidative stress, response to molecule of bacterial origin, membrane region, membrane microdomain, signaling receptor activator activity, receptor ligand activity, and so on. In addition, the main enrichment pathways of common targets were PI3K-Akt signaling pathway, proteoglycans in cancer, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, apoptosis, 17 cell differentiation, and other pathways related to inflammation, cancer, apoptosis, and immunity. Studies pointed out that, during the onset of asthma, both PI3K-Akt signaling pathway and MAPK signaling pathway were active [35,36]. Many targets of the PI3K pathway play critical roles in the expression and activation of inflammatory mediators, inflammatory cell recruitment, immune cell function, airway remodeling, and corticosteroid insensitivity in chronic inflammatory airway disease [37]. ere were evidences that selective PI3K inhibitors could reduce inflammation and some characteristics of diseases such as abnormal proliferation of airway smooth muscle cells (ASMC) in experimental animal models, which strongly supported that PI3K/Akt inhibitors might be a useful new therapy for asthma [37,38]. In recent years, many studies confirmed that inhibiting PI3K−Akt signaling pathway and MAPK signaling pathway could effectively inhibit allergic airway inflammation, ASMC proliferation and migration, and phenotypic switching, so as to alleviate    airway remodeling and airway hyperresponsiveness (AHR) in asthma [39][40][41][42]. Additionally, upregulation of dualspecificity phosphatase-1 (DUSP1), a negative regulator in the MAPK signaling pathway, to healthy levels and downregulation of inflammatory MAPKs at the gene and protein levels could reduce the prevalence of childhood asthma [43]. Proteoglycans enhanced deposition in the airway walls of asthmatics playing a role in airway remodeling, and the difference of deposition in the airway smooth muscle layer of moderate and severe asthmatic patients might affect the functional behavior of airway smooth muscle [44,45]. IL-17A in the IL-17 signaling pathway was positively correlated with neutrophil accumulation, mucus secretion, macrophage mobilization, and smooth muscle reactivity in various experimental airway models, as well as with disease severity, suggesting that specifically targeting IL-17A had the potential of clinical utility in patients with moderate and severe asthma and high reversibility [46]. Moreover, the reduction of skin inflammation and airway inflammation in the IL-17induced mouse asthma model was related to the reduction of IL-17-mediated mRNA stability [47]. In TLR ligand-mediated allergic airway inflammation, TLR ligand induced TNF to send signals through airway epithelial cells to promote the development of 2 in lymph nodes, and TNF was also indispensable in the allergen stimulation stage of neutrophilic and eosinophilic airway inflammation and AHR [48]. Activated TNF-TNFR2 signal transduction could inhibit the differentiation of 2 and 17 cells to alleviate allergic airway inflammation [49]. Bronchial cell apoptosis could be observed in some airway biopsies from asthmatic patients, especially those with serious diseases, possibly resulting in airway damage, and dysregulation of leukocyte, eosinophil, and neutrophil apoptosis could lead to asthmatic airway inflammation and was related to the pathogenesis of asthma [50]. 17 cells, a potent and unique subset that modulated primary bronchial epithelial cell function, were related to the development and pathophysiology of asthma [51,52]. A study found that asthma-associated IL4R variants promoted the transformation of regulatory T cells into TH17-like cells, thereby exacerbating airway inflammation [53]. It should be noted that because there have been relatively few studies related to allergic colitis all the time, there is almost no relevant research report on the relationship between the above signaling pathways and allergic colitis. However, it is worth mentioning that if further research is carried out on this basis in the future, it will be very innovative and instructive for clarifying the pathogenesis of allergic colitis and developing new drugs that can effectively target the disease. e above showed that SLBZP treated BA and AC with simultaneous treatment of different diseases by multiple functions and pathways, suggesting that further research in the future could be based on these biological functions and pathways, which had guiding significances. e active compound-key target network of this study showed that the five active compounds of quercetin, luteolin, beta-carotene, kaempferol, and naringenin, and the 6 key targets of PTGS2, CASP3, AKT1, JUN, TP53, and VEGFA were particularly important. Moreover, the results of molecular docking also verified that these five active compounds had good binding characteristics with their corresponding important key targets, indicating that they played vital roles in SLBZP for treating BA and AC with simultaneous treatment of different diseases and had critical potential research values.
Studies suggested that quercetin was known for its antioxidant activity in free radicals scavenging and antiallergic properties [54]. It is characterized by stimulating the immune system and antiviral activity, inhibiting histamine release, reducing proinflammatory cytokines, and producing leukotrienes [55]. It was reported to improve 1/ 2 balance, inhibit the formation of antigen-specific IgE antibodies, and also be effective in inhibiting enzymes such as lipoxygenase, eosinophils, and peroxidase and inflammatory mediators [56]. All the mentioned mechanisms contribute to the anti-inflammatory and immunomodulatory properties of quercetin, which can be effectively used to treat advanced bronchial asthma, allergic rhinitis, and restrictive allergic reactions caused by peanuts [55]. Luteolin, having anti-inflammatory, antiallergic, and immune-enhancing functions, can reduce airway inflammation and allergies in asthma and has antiallergic effects in mouse models of allergic asthma and rhinitis, which has shown therapeutic effects in treating inflammatory diseases, allergies, bronchial asthma, and    [57][58][59]. It was reported to block the activation of MAPK and NF-κB signaling pathways to protect ARPE-19 cells from the proliferation of IL-6, IL-8, sICAM-1, and MCP-1 stimulated by IL-1β, thereby alleviating the inflammatory response [60]. Kaempferol, having antioxidant, anti-inflammatory, anticancer, and antidiabetic effects, could effectively improve allergic and inflammatory airway diseases by interfering with NF-κB signal transduction, which may help alleviate the inflammatory response associated with Cox2 expression [61][62][63]. Naringenin, having immunomodulatory, anticancer, antimutation, anti-inflammatory, antioxidant, antiproliferative, antiarthritis, and anticarcinogenic effects, can be used for treating osteoporosis, cancer, cardiovascular disease, and rheumatoid arthritis, which exhibits lipidlowering and insulin-like properties, can inhibit allergeninduced airway inflammation and airway responsiveness, and inhibit NF-κB activity in a mouse model of asthma [64][65][66]. e above results indicate that SLBZP can fully exert its therapeutic effect by the synergy of multiple compounds, multiple targets, and multiple pathways and provide more new clues for the development of traditional Chinese medicine monomers to treat BA and AC. In addition, the effects of beta-carotene in treating BA and AC are currently seldom studied and reported, which can be used as a direction for in-depth research in the future.

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PTGS2, as the most critical target in the network, is one of the key factors of cell response to inflammation and has long been considered to play a key role in the pathogenesis of respiratory inflammation, including asthma [67,68]. In addition to its anti-inflammatory effect, it can also exert antiinflammatory/bronchial protection functions in the airway and can be expressed quickly and powerfully in response to various proinflammatory cytokines and mediators [68]. Caspase-3 is necessary for the development of various tissues, playing an important role in neurogenesis, synaptic activity, neuron growth cone guidance, and glial development. It was reported to mediate many nonapoptotic functions in cells and cell death in the process of apoptosis, participate in T and B cell homeostasis in a way that did not depend on apoptosis, and protect compressed organs from cell death [69]. AKT1 ablation promoted the polarization of macrophage M1, which could affect the severity of inflammatory diseases, such as inflammatory bowel disease, and was related to the regulation of innate immunity and inflammation [70]. JUN, the activation of which is caused by the imbalance of pulmonary oxidation and antioxidation in asthma, is an important therapeutic target for allergic airway inflammation and a key transcription factor for the antiinflammatory activity of dexamethasone and may be an important molecular mechanism of steroids in asthma and other chronic inflammatory lung diseases [71,72]. As an important mediator of oncogenic β-catenin signaling in the intestine, JUN is not only involved in inflammatory response and tumorigenesis but is also related to the inflammatory response in mice with LPS-induced macrophages and DSS-  [73,74]. TP53, as a tumor suppressor protein, can produce anti-inflammatory reactions in the lungs and has a potential therapeutic effect in pneumonia, whose dysfunction is associated with acute lung injury, acute respiratory distress syndrome, chronic obstructive pulmonary disease, pulmonary fibrosis, bronchial asthma, pulmonary hypertension, pneumonia and tuberculosis, and so on [75]. It often mutates in human cancers. After the mutations, it prolongs the activation of NF-κB and promotes chronic inflammation and inflammation-related colorectal cancer, which is also related to the occurrence and development of inflammatory bowel disease [76][77][78]. VEGFA plays a fundamental role in the physiological and pathophysiological forms of angiogenesis. During airway growth, the balance regulation of angiogenic growth factor and vascular inhibitory protein enables the lung to obtain rich blood supply [79]. However, during chronic inflammation, VEGF stimulates angiogenesis and edema and induces 2 and eosinophilic inflammation, mucous metaplasia, subepithelial fibrosis, myocyte proliferation, and dendritic cell activation, which is a sign of asthma exacerbation and can be used as a target for treating lung diseases and inflammatory bowel diseases [79][80][81][82]. e above studies indicate that these six key targets deserve attention in the study of the molecular mechanism of SLBZP for treating BA and AC with simultaneous treatment of different diseases and can be used as potential research objects.
e key target-miRNA network shows that hsa-miR-16-5p, hsa-miR-101-3p, hsa-miR-143-3p, hsa-miR-199a-5p, hsa-miR-30d-5p, hsa-miR-30c-5p, hsa-miR-30e-5p, hsa-miR-302d-3p, hsa-miR-203a-3p, hsa-miR-200b-3p, hsa-miR-125a-5p, hsa-miR-15a-5p, hsa-miR-504-5p, and hsa-miR-150-5p all target and regulate multiple key targets, which may have important upstream regulatory effects and are of great significance for the occurrence, development, and treatment of BA and AC. Studies suggested that baseline airway secretion signatures of hsa-miR-302d-3p and hsa-miR-612 were detected during rhinovirus (RV) infection that was the most common cause of asthma exacerbation and the most important early risk factor for asthma development after childhood in children, which was helpful to develop novel strategies for treating and monitoring respiratory conditions in all age groups [83]. e low tissue level of hsa-miR-200b-3p is related to the cytopathic inflammation caused by human cytomegalovirus infection [84]. Hsa-miR-15a-5p may play an important role in reducing retinal leukopenia by inhibiting inflammatory cell signals, which can be used as a potential target for the inhibition of inflammatory mediators in diabetic retinopathy [85]. In addition to these miRNAs that could target and regulate multiple key targets, hsa-miR-146a-5p, as one of the predicted miRNAs, was upregulated in asthmatic patients to inhibit the expression level of PDE7A, which might be involved in mediating the pathogenesis of asthma [86]. Upregulation of Hsa_circ_0005519 could inhibit the expression of has-let-7a-5p in CD4 T cells of asthmatic patients and promote the production of IL-13 and IL-6, thereby exacerbating asthma [87]. Combining hsa-miR-155-5p and has-miR-532-5p could predict changes in asthma budesonide (ICS) treatment response over time [88]. In allergic settings, the expressions of hsa-miR-139-5p and hsa-miR-542-3p significantly decreased, resulting in increasing expression of pro-inflammatory and antiviral response genes, which might be important during asthma exacerbations [89]. Hsa-miR-19b-3p decreased in the plasma of BA patients, and the ROC curve showed that it could be used as a biomarker for the diagnosis of BA [90]. Hsa-miR-20a-5p, one of the dysregulated miRNAs in asthmatic patients, targeted and inhibited the expression of HDAC4, suppressed the expressions of TNF-α, IL-1β, and IFN-c, and promoted the production of IL-10, thereby reducing allergic inflammation [91]. Downregulation of hsa-miR-145-5p that increased airway smooth muscle cell proliferation was a risk factor for an early decline (ED) pattern of lung function growth in asthmatic children with chronic obstructive pulmonary disease (COPD) [92]. Once again, it is  particularly noted that, at present, there are basically no relevant research reports on these predicted miRNAs related to AC, and there are also very few research reports on these predicted miRNAs related to BA, which means that this study not only provides new insights for in-depth understanding of the pathogenesis of BA and AC and formulating corresponding new treatment strategies but also provides a practical basis for future validation studies. In general, there are few reports on the above-mentioned miRNAs that have great research potentials.

Conclusions
In conclusion, network pharmacology and molecular docking technology demonstrated that SLBZP in treating BA and AC with simultaneous treatment of different diseases was a complex process involving multiple compounds, multiple targets, and multiple pathways. It may involve important active compounds and key targets represented by quercetin, luteolin, beta-carotene, kaempferol, naringenin, PTGS2, CASP3, AKT1, JUN, TP53, and VEGFA, may be related to inflammation, cancer, apoptosis, and immunerelated pathways, and may involve the targeted regulation of multiple upstream miRNAs. ese can provide references for future clinical and experimental studies.
Data Availability e data used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Conflicts of Interest
e authors declare that they have no conflicts of interest.

Authors' Contributions
Liying Zeng collected and analyzed all the data and is the major writer of the paper. Shaodan Sun, Piwen Chen, and Qina Ye helped in writing the paper and contributed to the analysis of these data. Xiaoling Lin, Hongjun Wan, and Yawen Cai revised the paper. Liying Zeng and Xiaogang Chen designed the study. Xiaogang Chen also revised the paper. All the authors have read and approved the manuscript.