Application of aloin in prevention and treatment of allergic rhinitis asthma syndrome

Abstract

The present application relates to the compound medicine technical field, specifically to the application of aloin in preventing and treating allergic rhinitis asthma syndrome, including the allergic rhinitis asthma syndrome including the clinical or subclinical respiratory tract allergy and lower respiratory tract allergic symptom, allergic rhinitis and asthma disease type I allergy, the use amount of the aloin is 10000-30000U / ml / d, the present application can bring positive anti-inflammatory activity, inhibiting tumor progression, anti-osteoporosis, anti-pathogenic organism, metabolic regulation and organ protection effect for patients in the course of treatment.

Description

Technical Field

[0001] This invention relates to the field of compound drug technology, specifically to the application of aloin in the prevention and treatment of allergic rhinitis and asthma syndrome. Background Technology

[0002] Allergic rhinitis and asthma are chronic inflammations of the upper and lower respiratory tracts in allergic individuals. They share significant similarities in etiology, immunity, and pathogenesis. Allergic rhinitis often coexists with asthma, influencing each other's disease progression and severity. Therefore, based on the concept of "one airway, one disease," the new medical diagnostic term "allergic rhinitis-asthma syndrome" has been proposed in recent years, referring to the simultaneous occurrence of clinical or subclinical upper respiratory tract allergies (allergic rhinitis) and lower respiratory tract allergic symptoms (asthma). It is characterized by a type 2 immune response with eosinophil infiltration and the production of cytokines such as IL-4, IL-5, and IL-13. For example, IL-5 plays a crucial role in airway eosinophilia, while IL-4 and IL-13 are essential for IgE production. IL-13 promotes hyperresponsiveness, mucus production, and airway fibrosis through tissue remodeling. These cytokines are responsible for the production of allergy-specific IgE, eosinophilia, mast cell activation, and the release of histamine, prostaglandins, and leukotrienes, promoting bronchoconstriction, increased vascular permeability, edema, vasodilation, and airway hyperresponsiveness. The resulting clinical symptoms severely impact patients' quality of life and impose a heavy economic and social burden.

[0003] Currently, treatment primarily employs non-specific therapies such as allergen avoidance and immune modulation. Commonly used medications include antihistamines, topical corticosteroids, mast cell stabilizers, and leukotriene receptor antagonists. However, clinical efficacy remains unsatisfactory, with frequent relapses, poor long-term outcomes, and even serious adverse consequences. Therefore, finding effective treatment measures is of paramount importance. Summary of the Invention

[0004] Technical problems to be solved

[0005] In view of the above-mentioned shortcomings of the prior art, the present invention provides the application of aloin in the prevention and treatment of allergic rhinitis and asthma syndrome, thus solving the technical problems mentioned in the background.

[0006] Technical solution

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] The application of aloin in the prevention and treatment of allergic rhinitis-asthma syndrome, including allergic rhinitis-asthma syndrome including simultaneous clinical or subclinical upper respiratory tract allergic symptoms and lower respiratory tract allergic symptoms, type I hypersensitivity reaction of allergic rhinitis and asthma, wherein the dosage of aloin is 10,000 to 30,000 U / ml / d.

[0009] Furthermore, the aloin was screened for gene targets of aloin through multiple databases, and key targets of allergic rhinitis and asthma were collected. The intersection of aloin and targets of allergic rhinitis and asthma was obtained using the Venny platform.

[0010] Furthermore, the String database was used to construct a target-protein interaction network for common targets, the R software 4.2.1 database was used to perform molecular docking of targets, key gene targets were obtained through Cytoscape 3.9.0 software, and AutoDock Tools software was used to perform molecular docking of key targets with corresponding active ingredients.

[0011] Among them, R software 4.2.1 refers to Bioconductor and Cluster Profiler.

[0012] Furthermore, the aloe-ointense glycoside comprises aloe-ointense glycoside and pharmaceutically acceptable excipients.

[0013] Furthermore, the aloe-emodin is in powder form.

[0014] Furthermore, the volumetric molar concentration of aloe-emodin used in the preparation is:

[0015] 30 mmol / L to 1200 mmol / L.

[0016] Furthermore, the molecular structure of aloin was obtained from the PubChem database, and the compound was then imported into the Swiss Target Prediction database for screening with a probability > 0.

[0017] In the Pharm Mapper database, the target proteins were set to "Human Protein Targets Only," and the top 100 matching proteins were selected as important target proteins. The corresponding protein IDs were found based on the UniProt database identifiers, and the gene names corresponding to these targets were also obtained. The Similarity ensemble approach database search identified the target genes of aloin, and screening was performed with MaxTC > 0.4 as the criterion. The results were merged, deduplicated, and imported into a Venn diagram. The results were recorded as potential targets of aloin.

[0018] Furthermore, the target analysis for allergic rhinitis and asthma used Allergic rhinitis and Asthma as keywords, respectively, to search and screen for disease-related genes in Gene Cards, OMIM, TTD, Drug Bank, and Pharm Gkb databases, and obtained the disease targets of AR and asthma, respectively; further, the intersection of these targets with the potential targets of aloe-emodin was obtained to obtain the intersection targets of aloe-emodin for the treatment of AR and asthma.

[0019] Furthermore, the aloe vera glycoside is mixed in a drug for preventing and treating allergic rhinitis and asthma syndrome, which also contains antibacterial and / or anti-inflammatory active ingredients.

[0020] Furthermore, the aloe-emodin was tested using aloe-emodin with a purity greater than 98%, ovalbumin, aluminum hydroxide, budesonide, an enzyme-linked immunosorbent assay (ELISA) kit, and an ELISA reader.

[0021] Beneficial effects

[0022] Compared with known public technologies, the technical solution provided by this invention has the following beneficial effects:

[0023] 1. This invention provides an application of aloin in the prevention and treatment of allergic rhinitis and asthma syndrome, which can bring positive anti-inflammatory activity, tumor progression inhibition, anti-osteoporosis, anti-pathogen, metabolic regulation and organ protection effects to patients during the treatment process.

[0024] 2. During the experimental phase of this invention, a large amount of data from the Prophet database was used as a verification reference, ensuring the safety and reliability of this aloin application technology. Attached Figure Description

[0025] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are merely some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without any creative effort.

[0026] Figure 1 This is a schematic diagram illustrating the mechanism of action of aloin on CARAS in this invention;

[0027] Figure 2 This is a schematic diagram of the PPI network and topology analysis of aloin and AR in this invention;

[0028] Figure 3 This is a schematic diagram of the PPI network and topology analysis of aloin and asthma in this invention;

[0029] Figure 4 This is a schematic diagram of the molecular docking model in this invention;

[0030] Figure 5 This is a schematic diagram of the CARAS model scheme and symptom assessment in this invention;

[0031] Figure 6 This is a schematic diagram illustrating the effects of aloin treatment on the nasal cavity and lung tissue of CARAS mice in this invention.

[0032] Figure 7 This is a schematic diagram illustrating the effect of aloe-emodin treatment on cytokine production in CARAS mice in this invention. Detailed Implementation

[0033] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0034] The present invention will be further described below with reference to embodiments.

[0035] Example 1

[0036] The application of aloin in the prevention and treatment of allergic rhinitis-asthma syndrome in this embodiment includes the application of aloin in the prevention and treatment of allergic rhinitis-asthma syndrome, which includes simultaneous clinical or subclinical upper respiratory tract allergic symptoms and lower respiratory tract allergic symptoms, type I hypersensitivity reaction of allergic rhinitis and asthma. The dosage of aloin used is 10,000 to 30,000 U / ml / d.

[0037] The application of aloin involves screening gene targets of aloin through multiple databases, collecting key targets of allergic rhinitis and asthma, and using the Venny platform to obtain the intersection of aloin and targets of allergic rhinitis and asthma.

[0038] The String database was used to construct a target-protein interaction network for common targets. The R software 4.2.1 database was used to perform molecular docking of the targets. The Cytoscape 3.9.0 software was used to obtain key gene targets. The Auto Dock Tools software was used to perform molecular docking of key targets with corresponding active ingredients.

[0039] Among them, R software 4.2.1 includes Bioconductor and Cluster Profiler;

[0040] The application of aloin includes aloin and pharmaceutically acceptable excipients;

[0041] The dosage form of the aloe-emodin application is powder;

[0042] The volumetric molar concentration of aloin used in the aforementioned application is:

[0043] 30 mmol / L~1200 mmol / L;

[0044] The molecular structure of aloin was obtained from the PubChem database, and then the compound was imported into the Swiss TargetPrediction database for screening with probability > 0.

[0045] In the Pharm Mapper database, the target sites were set to "Human Protein Targets Only," and the top 100 matching values ​​were selected as important target proteins. The corresponding protein IDs were found based on the UniProt database identifiers, and the gene names corresponding to these targets were also obtained. The Similarity ensemble approach database search identified the target genes of aloin, and screening was performed with MaxTC > 0.4 as the criterion. The results were merged, deduplicated, and imported into a Venn diagram. The results were recorded as potential targets of aloin.

[0046] The application of allergic rhinitis and asthma target analysis used Allergic rhinitis and Asthma as keywords, respectively. Disease-related genes were searched and screened in Gene Cards, OMIM, TTD, Drug Bank and Pharm Gkb databases to obtain disease targets for AR and asthma. Furthermore, the intersection of these targets with the potential targets of aloin was obtained to obtain the intersection targets of aloin for the treatment of AR and asthma.

[0047] The application of aloin mixed in the drug for preventing and treating allergic rhinitis and asthma syndrome, the drug for preventing and treating allergic rhinitis and asthma syndrome also contains antibacterial and / or anti-inflammatory active ingredients;

[0048] The application of aloin, with a purity greater than 98%, along with ovalbumin, aluminum hydroxide, budesonide, an enzyme-linked immunosorbent assay (ELISA) kit, and an ELISA reader, was used in the experiment.

[0049] Example 2

[0050] The application of aloin in the prevention and treatment of allergic rhinitis and asthma syndrome includes the application of aloin in the prevention and treatment of allergic rhinitis and asthma syndrome, which includes simultaneous clinical or subclinical upper respiratory tract allergic symptoms and lower respiratory tract allergic symptoms, type I hypersensitivity reaction of allergic rhinitis and asthma. The dosage of aloin used is 10,000 to 30,000 U / ml / d.

[0051] The application of aloin involves screening gene targets of aloin through multiple databases, collecting key targets of allergic rhinitis and asthma, and using the Venny platform to obtain the intersection of aloin and targets of allergic rhinitis and asthma.

[0052] The String database was used to construct a target-protein interaction network for common targets. The R software 4.2.1 database was used to perform molecular docking of the targets. The Cytoscape 3.9.0 software was used to obtain key gene targets. The Auto Dock Tools software was used to perform molecular docking of key targets with corresponding active ingredients.

[0053] Among them, R software 4.2.1 includes Bioconductor and Cluster Profiler;

[0054] The application of aloin includes aloin and pharmaceutically acceptable excipients;

[0055] The dosage form of the aloe-emodin application is powder;

[0056] The volumetric molar concentration of aloin used in the aforementioned application is:

[0057] 40 mmol / L~1200 mmol / L;

[0058] The molecular structure of aloin was obtained from the PubChem database, and then the compound was imported into the Swiss TargetPrediction database for screening with probability > 0.

[0059] In the Pharm Mapper database, the target sites were set to "Human Protein Targets Only," and the top 100 matching values ​​were selected as important target proteins. The corresponding protein IDs were found based on the UniProt database identifiers, and the gene names corresponding to these targets were also obtained. The Similarity ensemble approach database search identified the target genes of aloin, and screening was performed with MaxTC > 0.4 as the criterion. The results were merged, deduplicated, and imported into a Venn diagram. The results were recorded as potential targets of aloin.

[0060] The application of allergic rhinitis and asthma target analysis used Allergic rhinitis and Asthma as keywords, respectively. Disease-related genes were searched and screened in Gene Cards, OMIM, TTD, Drug Bank and Pharm Gkb databases to obtain disease targets for AR and asthma. Furthermore, the intersection of these targets with the potential targets of aloin was obtained to obtain the intersection targets of aloin for the treatment of AR and asthma.

[0061] The application of aloin mixed in the drug for preventing and treating allergic rhinitis and asthma syndrome, the drug for preventing and treating allergic rhinitis and asthma syndrome also contains antibacterial and / or anti-inflammatory active ingredients;

[0062] The application of aloin, with a purity greater than 98%, along with ovalbumin, aluminum hydroxide, budesonide, an enzyme-linked immunosorbent assay (ELISA) kit, and an ELISA reader, was used in the experiment.

[0063] Example 3

[0064] The application of aloin in the prevention and treatment of allergic rhinitis and asthma syndrome includes the application of aloin in the prevention and treatment of allergic rhinitis and asthma syndrome, which includes simultaneous clinical or subclinical upper respiratory tract allergic symptoms and lower respiratory tract allergic symptoms, type I hypersensitivity reaction of allergic rhinitis and asthma. The dosage of aloin used is 10,000 to 30,000 U / ml / d.

[0065] The application of aloin involves screening gene targets of aloin through multiple databases, collecting key targets of allergic rhinitis and asthma, and using the Venny platform to obtain the intersection of aloin and targets of allergic rhinitis and asthma.

[0066] The String database was used to construct a target-protein interaction network for common targets. The R software 4.2.1 database was used to perform molecular docking of the targets. The Cytoscape 3.9.0 software was used to obtain key gene targets. The Auto Dock Tools software was used to perform molecular docking of key targets with corresponding active ingredients.

[0067] Among them, R software 4.2.1 includes Bioconductor and Cluster Profiler;

[0068] The application of aloin includes aloin and pharmaceutically acceptable excipients;

[0069] The dosage form of the aloe-emodin application is powder;

[0070] The volumetric molar concentration of aloin used in the aforementioned application is:

[0071] 30 mmol / L to 1000 mmol / L;

[0072] Obtain the molecular structural formula of aloin from the PubChem database, then import the compound into the Swiss TargetPrediction database, and screen with the condition of probability > 0;

[0073] In the Pharm Mapper database, set the target as "Human Protein Targets Only", and take the top 100 targets by matching value as important target proteins. Find the corresponding protein numbers according to UniProt database identifiers, and obtain the corresponding gene names of these targets at the same time; the Similarity ensemble approach database retrieves and identifies the target genes of aloin, screens with the condition of MaxTC > 0.4, combines and removes duplicates before importing into a Venn diagram, and the obtained result is recorded as the potential action targets of aloin;

[0074] For the target analysis of allergic rhinitis and asthma in said application, use "Allergic rhinitis" and "Asthma" as keywords respectively to retrieve and screen disease-related genes in Gene Cards, OMIM, TTD, Drug Bank and Pharm Gkb databases, and obtain disease targets of AR and asthma respectively; further intersect them with the potential action targets of aloin respectively to obtain intersection targets of aloin for treating AR and asthma;

[0075] In said application, aloin is mixed into a medicament for preventing and treating combined allergic rhinitis and asthma syndrome, and the medicament for preventing and treating combined allergic rhinitis and asthma syndrome in said application further contains antibacterial and / or anti-inflammatory active ingredients;

[0076] In said application, the test is carried out with aloin having a purity greater than 98%, ovalbumin, aluminum hydroxide, budesonide, an enzyme-linked immunosorbent assay detection kit, and a microplate reader.

[0077] Animal experiment

[0078] Female BALB / c mice aged 6-8 weeks, SPF grade, with a body weight of 20±2.5 g, were used in the experiment. The mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (license number SCXK (Jing) 2021-0006) and raised in the animal room of Qingdao University (license number SYXK (Lu) 20200018). Throughout the experiment, the mice were housed in an environment with a temperature of 23-25°C and a 12 h light-dark cycle, with free access to water and food. The mice used in this study were housed in accordance with the protocol approved by the Animal Committee of Qingdao University. Main reagents and instruments;

[0079] Animal grouping and treatment

[0080] Experimental animals were randomly divided into 6 groups (n=9): normal group, CARAS group (OVA sensitization and challenge), low-dose aloin group (10 mg / kg), medium-dose aloin group (20 mg / kg), high-dose aloin group (40 mg / kg), and budesonide group (0.9 mg / kg, BUD group). The CARAS experimental model was established as follows: On days 0 and 7, mice were sensitized by intraperitoneal injection of 50 μg / ml ovalbumin and 0.2 ml of 10 mg / ml Al(OH)3 suspension. From day 21 to day 37, for three consecutive weeks, all drugs were instilled into the nasal cavity of mice bilaterally at a dose of 20 μl (5 mg / ml, 20 μl / animal) via nasal drops, and the mice were kept in a supine position for several minutes. On day 38, mice were nebulized with OVA (5%) for 30 minutes for five consecutive days. One hour before each OVA challenge, mice were treated with aloin or budesonide, and the normal group mice were treated with PBS in the same way. Mice were sacrificed on day 43 and biological material was collected for analysis.

[0081] Symptoms of scratching the nose and sneezing

[0082] Within 10 minutes of the last OVA stimulation (day 42), observe each animal for symptoms such as scratching its nose and sneezing.

[0083] Histopathological examination

[0084] Tissues fixed in paraformaldehyde were dehydrated with ethanol and embedded in paraffin. Nasal and lung sections were cut into 3–5 μm thin slices using a microtome, then stained with hematoxylin and eosin (H&E) and observed under an optical microscope for histopathological examination to assess the degree of damage to the mouse nasal mucosa and lung tissue.

[0085] Enzyme-linked immunosorbent assay (ELISA)

[0086] After collecting blood and bronchoalveolar lavage fluid (BALF) and allowing them to stand for 2 hours, centrifuge at 4°C for 10 minutes, collect the supernatant, and store at -80°C for later use. ELISA kits were used to determine the serum levels of total IgE, IL-4, IL-5, IL-13, and IFN-γ in mice, as well as the contents of IL-4, IL-5, IL-13, and IFN-γ in BALF. All procedures were strictly performed according to the kit's protocol.

[0087] Statistical analysis

[0088] Data were statistically analyzed using GraphPadPrism 9 software. Quantitative data were expressed as mean ± standard deviation (x ± s), and one-way ANOVA was used for comparisons among multiple groups. A p-value < 0.05 was considered statistically significant.

[0089] result

[0090] Aloe-glycoside target prediction

[0091] Data was sequentially retrieved from databases such as Swiss Target Prediction, Pharm Mapper, and Similarity ensemble approach, exported, and deduplicated to ultimately obtain 131 drug targets.

[0092] Predictive results for targets in allergic rhinitis and asthma

[0093] Using the Gene Cards, OMIM, TTD, Pharm GKB, and Drug Bank databases, a search was conducted using "Allergic rhinitis" as the keyword, resulting in 2047 targets for Allergic rhinitis. Drug targets and disease targets were then merged using the keyword "Vene," ultimately identifying 42 potential targets related to aloe-emodin treatment of AR.

[0094] Similarly, 1613 asthma targets were retrieved from public databases using "asthma" as the keyword, and these were combined with drug targets to obtain 58 potential targets that may be related to the treatment of asthma with urolithiasis A.

[0095] Construction and analysis of PPI (protein-protein interaction) networks

[0096] Forty-two intersecting target sites of aloin for treating allergic rhinitis were imported into the String database to obtain a PPI network graph with 41 nodes and 138 edges. The obtained PPI network graph was imported into Cytoscape 3.9.0 software, and network topology analysis was performed using the Cyto NCA plugin. Important target genes were located in the central region of the network. The selection criteria based on the corresponding medians were set as follows: BC>6, CC>0.247, DC>5, EC>0.078, NC>3, LAC>2. Gene targets meeting all median criteria were retained and labeled, and a new PPI network consisting of 13 nodes and 72 edges was subsequently extracted. Subsequently, in the new PPI network, only targets that meet the selection criteria BC>1.202, CC>0.8, DC>9, EC>0.290, NC>8.304, and LAC>7.111 are retained, resulting in a new PPI network consisting of 5 nodes and 10 edges. Ultimately, the core targets of allergic rhinitis are found to be EGFR, SRC, ESR1, ALB, and MAPK8.

[0097] Simultaneously, a PPI network graph was constructed from 58 intersecting targets of aloin in asthma treatment, resulting in 55 nodes and 205 edges. The obtained PPI network graph was imported into Cytoscape 3.9.0 software, and the selection criteria based on the corresponding medians were set as follows: BC>8.833, CC>0.244, DC>5, EC>0.085, NC>3.333, LAC>2.333. Gene targets meeting all median criteria were retained and labeled, and a new PPI network consisting of 17 nodes and 78 edges was subsequently extracted. Subsequently, in the new PPI network, only targets that meet the selection criteria of BC>3.252, CC>0.696, DC>9, EC>0.234, NC>7.592, and LAC>6.182 are retained, resulting in a new PPI network consisting of 6 nodes and 14 edges. The core targets for asthma that were finally obtained are EGFR, SRC, ESR1, ALB, MAPK8, and KDR.

[0098] GO and KEGG pathway enrichment analysis

[0099] Forty-two overlapping targets of aloin in the treatment of allergic rhinitis were enriched using GO and KEGG analyses. GO results showed that 1049 enriched targets were related to biological processes (BP), 107 to molecular functions (MF), and 25 to cellular composition (CC). Biological processes mainly involved the positive regulation of the MAPK cascade, responses to steroid hormones, and responses to lipopolysaccharides; molecular functions mainly involved serine endopeptidase activity and serine peptidase activity; and cellular composition mainly involved vesicle lumen. KEGG enrichment analysis revealed that the most enriched metabolic pathways in allergic rhinitis included the MAPK signaling pathway.

[0100] Similarly, GO and KEGG enrichment analyses were performed on 58 overlapping targets of aloin in the treatment of asthma. Of the targets identified in asthma, 753 were related to biological processes (BP), 94 to molecular functions (MF), and 19 to cellular composition (CC). Biological processes mainly involved reactive oxygen species metabolism and peptidyl-serine phosphorylation; molecular functions mainly involved endopeptidase activity and serine endopeptidase activity; and cellular composition mainly involved ficolin-1-rich granules and vesicle lumen. KEGG results showed significant enrichment of the MAPK signaling pathway in asthma.

[0101] Molecular docking verification

[0102] To further validate the predictive power of bioinformatics, molecular docking was used to explore the potential of aloin in treating allergic rhinitis (AR) and asthma. After Cyto NCA analysis, molecular docking was performed between aloin and the most important targets of AR (ESR1, EGFR, ALB, SRC, MAPK8). The binding free energies of ESR1, EGFR, ALB, SRC, and MAPK8 with aloin were -7.0, -9.8, -8.6, -8.4, and -7.4, respectively. Simultaneously, molecular docking was performed between aloin and the most important targets of asthma (ESR1, EGFR, ALB, SRC, MAPK8, KDR). The binding free energies of ESR1, EGFR, ALB, SRC, MAPK8, and KDR were -7.0, -9.8, -8.6, -8.4, -7.4, and -7.9, respectively. All the above molecular docking binding free energies were ≤-7, indicating that aloin has a good binding affinity to the core targets of allergic rhinitis and asthma.

[0103] Effects of aloin on symptoms in CARAS mice

[0104] Mice in the normal group moved freely, responded readily to external stimuli, and had normal eating and drinking habits. Mice in the CARAS group exhibited rapid breathing, restlessness, and significant nose rubbing and sneezing. In the low-dose aloe-emodin group, symptoms were not alleviated; in the medium-dose group, symptoms were slightly alleviated; and in the high-dose group, symptoms were significantly reduced, and activity remained largely normal. Mice in the budesonide group had normal eating and drinking habits and were more active. As shown in the figure, compared to the control group, the CARAS group showed a significantly increased frequency of sneezing and nose rubbing every 10 minutes.

[0105] Effects of aloin on the pathology of nasal mucosa and lung tissue in CARAS mice

[0106] like Figure 6 As shown, in the normal group mice, the airway structure of the nasal mucosa and lung tissue pathological sections was regular, with no stenosis of the lumen and only a small number of inflammatory cells occasionally. In the CARAS group mice, a large number of inflammatory cells (especially obvious eosinophil infiltration) were observed in the nasal mucosa and lung tissue. Mucus plugs were visible in the lumen of the nasal mucosal glands, the tissue structure was disordered, and there was obvious vasodilation and alveolar edema in the lung tissue. The airway epithelium was irregular. In the high-dose aloe-emodin group, the inflammatory cell infiltration and alveolar congestion and edema were reduced compared with the CARAS group, and the airway epithelial structure was more intact. In the BUD group, the inflammatory cell infiltration was significantly reduced compared with the CARAS group, and the airway epithelial structure and alveolar structure were intact.

[0107] Effects of aloin on serum and BALF levels in CARAS mice

[0108] Compared with the control group, the CARAS group showed a significant increase in serum total IgE levels, while both treatments (aloe veraside or BUD) reduced the production of this immunoglobulin. Furthermore, the CARAS model mice produced large amounts of type 2 cytokines, such as IL-4, IL-5, and IL-13, while the level of type 1 cytokine IFN-γ was significantly reduced. The low- and medium-dose aloe veraside groups showed no significant decrease in IL-4, IL-5, IL-13, and total IgE levels, while the high-dose aloe veraside group and the BUD group showed significantly reduced serum total IgE, IL-4, IL-5, and IL-13 levels and increased IFN-γ levels in serum and BALF.

[0109] Further such as Figure 2 As shown, (A) the chemical structure of aloin; (B) the Venn diagram of the target intersection of aloin and allergic rhinitis; (C) the PPI network diagram of the target intersection genes; (D) the PPI network topology analysis diagram; (E) the GO enrichment analysis diagram of the target intersection genes; (G) the KEGG pathway analysis diagram of the target intersection genes; and (F) the KEGG pathway and its target analysis diagram.

[0110] Further such as Figure 3As shown, (A) Venn diagram of the intersection of aloe-emodin and asthma targets; (B) PPI network diagram of the target intersection genes; (C) PPI network topology analysis diagram; (D) GO enrichment analysis diagram of the target intersection genes; (E) KEGG pathway analysis diagram of the target intersection genes; (F) KEGG pathway and target analysis diagram.

[0111] Further such as Figure 4 The image shows a molecular model of the binding of aloin to (A) ESR1 (B) EGFR (C) ALB (D) SRC (E) MAPK8 (F) KDR.

[0112] Further such as Figure 5 As shown, (A) the CARAS modeling process and (B) the number of times mice in each group rubbed their noses and sneezed. *p<0.05, **p<0.001, ***p<0.0001.

[0113] Further such as Figure 6 The images show representative micrographs of H&E-stained nasal tissue, with inflammatory parameters indicating strong cellular infiltration. The images also show representative micrographs of H&E-stained lung tissue, with inflammatory parameters indicating strong cellular infiltration and loss of epithelial integrity. (×400x magnification).

[0114] Further such as Figure 7 As shown, ELISA was used to detect the levels of (A) IL-4, (B) IL-5, (C) IL-13, and (D) IFN-γ in BALF, and (E) ELISA was used to detect the levels of (F) IgE, (G) IL-4, (H) IL-5, and (I) IL-13 in serum. Data are expressed as mean ± SEM. Compared with other groups, the CARAS group showed ***P < 0.001, **p < 0.01, and *P < 0.05.

[0115] In summary, the application of aloin in the prevention and treatment of allergic rhinitis and asthma syndrome provided in the above embodiments can bring positive anti-inflammatory activity, inhibit tumor progression, resist osteoporosis, resist pathogens, regulate metabolism and protect organs during the treatment process. In addition, the use of a large amount of data from the Prophet database as a verification reference during the experimental stage ensures the safety and reliability of this aloin application technology.

[0116] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions will not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. The application of aloin in the prevention and treatment of allergic rhinitis-asthma syndrome, characterized in that, The allergic rhinitis-asthma syndrome includes simultaneous clinical or subclinical upper and lower respiratory tract allergic symptoms, type I hypersensitivity reactions of allergic rhinitis and asthma, and the dosage of aloe-emodin is 10,000 to 30,000 U / ml / d. The target analysis for allergic rhinitis and asthma used Allergic rhinitis and Asthma as keywords, respectively. Disease-related genes were searched and screened in Gene Cards, OMIM, TTD, Drug Bank and PharmGkb databases to obtain the disease targets of AR and asthma. Furthermore, the intersection of these targets with the potential targets of aloe-emodin was obtained to obtain the intersection targets of aloe-emodin for the treatment of AR and asthma. The aloe verain is mixed in a drug for preventing and treating allergic rhinitis and asthma syndrome, and the drug for preventing and treating allergic rhinitis and asthma syndrome also contains antibacterial and / or anti-inflammatory active ingredients. The aloe-emodin was tested using aloe-emodin with a purity greater than 98%, ovalbumin, aluminum hydroxide, budesonide, an enzyme-linked immunosorbent assay (ELISA) kit, and an ELISA reader.

2. The application according to claim 1, characterized in that, The aloin was screened for gene targets in multiple databases, and key targets for allergic rhinitis and asthma were collected. The intersection of aloin and targets for allergic rhinitis and asthma was obtained using the Venny platform.

3. The application according to claim 1, characterized in that, Use the String database to target proteins for common targets. Interaction network construction, target point analysis using R software 4.2.1 database, and key information acquisition using Cytoscape 3.9.0 software. Key gene targets were identified, and Auto Dock Tools software was used to perform molecular docking between key targets and corresponding active ingredients. Among them, R software 4.2.1 refers to Bioconductor and Cluster Profiler.

4. The application according to claim 1, characterized in that, The aloe-glycosides include aloe-glycosides and pharmaceutically acceptable excipients.

5. The application according to claim 4, characterized in that, The aloe-glycoside is in powder form.

6. The application according to claim 1, characterized in that, The volumetric molar concentration of aloin used in the preparation is 30 mmol / L to 1200 mmol / L.

7. The application according to claim 1, characterized in that, The molecular structure of aloin was obtained from the PubChem database, and then the compound was imported into the Swiss Target Prediction database for screening based on a probability > 0. In the Pharm Mapper database, the target was set to "Human Protein Targets Only", and the top 100 matching values ​​were selected as important target proteins. The corresponding protein numbers were found based on the UniProt database identifiers, and the corresponding gene names of these targets were also obtained. The Similarity ensemble approach database was used to search and identify the target genes of aloin, and screening was performed based on a MaxTC > 0.

4. The results were merged, deduplicated, and imported into a Venn diagram. The results were recorded as potential targets of aloin.

Images