Application of APE1 inhibitors in the preparation of drugs for treating allergic rhinitis

Abstract

This invention belongs to the field of compound medicine and relates to the use of APE1 inhibitors in the preparation of medicaments for treating allergic rhinitis. This invention, for the first time, discovers that APE1 inhibitors can effectively alleviate and treat allergic rhinitis, providing new targets and approaches for the prevention and treatment of allergic rhinitis. Specifically, small molecule compounds represented by the APE1 inhibitor C10 compound and its derivatives have demonstrated excellent efficacy in the treatment of allergic rhinitis.

Description

Technical Field

[0001] The present invention belongs to the field of compound medicine and relates to the application of an APE1 inhibitor in the preparation of a medicine for treating allergic rhinitis. Background Art

[0002] The apurinic and apyrimidinic endonuclease / redox factor APE1 is a crucial bifunctional protein. Its C-terminus participates in base excision repair following DNA mismatches, while its N-terminus contains redox activity, which can reduce low-activity oxidized transcription factors to highly active reduced forms. Reduced transcription factors can bind to promoter sequences of a range of genes to initiate their expression. Transcription factors regulated by APE1 include HIF-1α, Egr-1, AP-1, NF-κB, CREB, and p53. Many of these genes are involved in immune responses, and therefore, APE1 has a significant impact on immune homeostasis, inflammation, and the development of immune diseases.

[0003] APE1 is essential for maintaining cellular homeostasis. As a redox-dependent regulator of multiple transcription factors, these functions make APE1 crucial for regulating cell signaling, aging, and inflammatory pathways. First, APE-1 substrates AP-1, NF-kB, STAT3, and HIF-1 regulate the secretion of inflammatory cytokines such as IL-6, IL-8, and VEGF, affecting the occurrence of inflammatory diseases by regulating the microenvironment. In addition, APE1 is also involved in other key processes in the immune response, including the production of reactive oxygen species and class switch recombination. The multiple functions of APE1 make it an important regulator of the pathogenesis of various diseases.

[0004] Allergic rhinitis (AR), a type of rhinitis also known as allergic rhinitis, is a common non-infectious disease in otolaryngology. It is caused by the release of histamine, a major inflammatory mediator, mediated by IgE, in response to external antigenic stimulation. This release leads to a non-infectious inflammatory disease of the nasal mucosa, involving multiple immune-competent cells and cytokines. Clinical symptoms primarily include sudden and recurrent episodes of nasal itching, sneezing, runny nose, and nasal congestion, severely impacting work, study, and daily life. Commonly used antihistamines can alleviate some of these symptoms, but they often carry side effects such as drowsiness and hepatotoxicity, and fail to address the underlying cause. Furthermore, relevant data indicate that allergic rhinitis is widespread and currently occurs worldwide, with varying prevalence rates in different regions, reaching as high as 40% in some areas. Furthermore, developed countries are relatively more industrialized, leading to a higher prevalence of allergic rhinitis, making it a global health concern and garnering widespread attention.

[0005] The main treatments for AR include medication, which uses glucocorticoids, antihistamines, and antileukotrienes for symptomatic treatment, but is incurable. Surgical treatment involves selectively cutting the pterygoid nerve to alleviate rhinitis symptoms, but is associated with numerous complications and uncertain efficacy, such as persistent dry eye. Specific immunotherapy involves allergen desensitization, which has a long course (3 years), poor compliance, and uncertain efficacy. Recent studies have reported that ganciclovir can effectively alleviate AR symptoms, but it is only used as a last-line therapy after conventional antiallergic drugs have failed. Furthermore, it is an oral, systemic medication and cannot be used as a first-line clinical medication, limiting its clinical use. Furthermore, many clinical studies have found that current conventional treatments for AR are often ineffective and can lead to adverse reactions. Therefore, it is imperative to find more effective and safer methods for treating AR.

[0006] Therefore, it is urgent to develop new safe and effective targets and develop targeted anti-allergic rhinitis drugs. Summary of the Invention

[0007] In early large-scale drug screening, the inventors found that C10 compound and its structural analogues have excellent ability to inhibit the redox end of APE1 without affecting the DNA repair function of APE1. They are characteristic inhibitors that selectively inhibit the redox end of APE1.

[0008] It is known that innate immune cells, such as type II innate lymphoid cells (ILC2) and specialized dendritic cell (DC) populations, are located at the epithelial barrier, where they are exposed to pathogens or allergens, providing molecular cues and alarms for the immune system and inflammatory response. Innate immune cells also acquire antigens at these sites, which they present to T cells to trigger a T helper 2 (TH2) cell response. TH2 cells and ILC2s produce large amounts of type II cytokines IL-4, IL-5, IL-9, and IL-13, promoting pleiotropic type II immune mechanisms, including B cell secretion of immunoglobulin E (IgE), eosinophilia, mastocytosis, goblet cell mucus secretion, and M2 macrophage polarization. IL-13 can also promote the migration of dendritic cells (DC) to the lymph nodes, further stimulating TH2 cell activation.

[0009] Therefore, theoretically, APE1 should play an important role in type II immune response diseases.

[0010] Based on this, the present invention provides a therapeutic drug or pharmaceutical composition for allergic rhinitis with an APE1 inhibitor as an active ingredient, wherein small molecule compounds represented by C10 and its derivatives show excellent effects in the treatment of AR.

[0011] Specifically, the technical solution of the present invention is as follows:

[0012] Use of an APE1 inhibitor in the preparation of a drug for treating allergic rhinitis, wherein the APE1 inhibitor includes a C10 compound or E3330 (APX-3330, CAS No.: 136164-66-4). Further, the APE1 inhibitor is a C10 compound, and the C10 compound has a structure shown in Formula 1 below:

[0013]

[0014] Wherein R is C, N, S or O element; R1, R2, R3, R4, R5 or R6 are hydrogen, or various saturated or unsaturated, cyclic or non-cyclic, substituted or unsubstituted alkyl compounds.

[0015] Furthermore, the C10 compound has a structure as shown in Formula 2 below:

[0016]

[0017] The structure of E3330 is as follows:

[0018]

[0019] Furthermore, pharmaceutical formulations containing the aforementioned APE1 inhibitors as active ingredients, with inhibition of the redox end of APE1 as a specific mechanism of action, such as tablets, gels, capsules, dispersions, injections, sprays, oral solutions, and any pharmaceutically acceptable carriers and / or excipients, fall within the scope of the present invention. Administration of the APE1 inhibitors includes oral, intranasal, injection, or topical administration, with intranasal administration being preferred.

[0020] Furthermore, the drug for treating allergic rhinitis also includes pharmaceutically acceptable excipients or solvents.

[0021] The present invention also provides a pharmaceutical composition for treating allergic rhinitis, comprising the C10 compound or a pharmaceutically acceptable salt, stereoisomer, solvate or prodrug thereof, and a pharmaceutically acceptable excipient and / or adjuvant.

[0022] Optionally, the C10 compound is a pharmaceutically acceptable salt thereof, and the pharmaceutically acceptable salt is a salt commonly used in pharmacy. Further, the salt is selected from one or more of acetate, hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, benzoate, fumarate, maleate, succinic acid, tartaric acid, citrate, oxalic acid, glyoxylic acid, aspartic acid, tartrate, 2,5-dihydroxybenzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, benzoylsulfonate, hydroquinonesulfonate and p-toluenesulfonate.

[0023] The beneficial effects of the present invention are: the C10 compound of the present invention has an excellent therapeutic effect on allergic rhinitis, can effectively alleviate clinical symptoms, and provides a new approach for the prevention and treatment of AR.

[0024] Secondly, the C10 of the present invention has a simple structure, excellent potential, is a small molecule drug, has a simple synthesis method, and has good industrialization prospects.

[0025] The research of the present invention shows that APE1 has the function of regulating the DNA binding activity of a series of transcription factors, inducing ILC2 and Th2 cells to secrete type II inflammatory response cytokines IL-4, IL-5, IL-9 and IL-13, and promoting the pleiotropic type II immune mechanism; it also has the function of inducing APE1 nuclear translocation through oxidative stress response, and promoting the production of type II inflammatory cytokines.

[0026] Therefore, as an effective APE1 inhibitor, the C10 compound can significantly inhibit the pathological symptoms of chronic sinusitis, including alleviating the symptoms of nasal hypersensitivity in AR mice, specifically alleviating Th2 and Th17 type inflammation, reducing eosinophil infiltration and oxidative damage, improving cell activity, and reducing the level of immunoglobulin E (IgE) in the serum of AR mice, and has an anti-allergic effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The accompanying drawings, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0028] Figure 1 This is a comparison chart of AR symptoms in mice in the C10 treatment group and the AR model group in the examples;

[0029] Figure 2 1 is a comparison chart of the total cell count and inflammatory cell (eosinophil and neutrophil) count in the nasal lavage fluid of mice in the C10 treatment group and the AR mouse model group in the examples;

[0030] Figure 3 This is a comparison of HE staining of the nasal mucosa of mice in the C10 treatment group and the AR model group in the example;

[0031] Figure 4 This is a comparison of PAS staining of the nasal mucosa of mice in the C10 treatment group and the AR model group in the example;

[0032] Figure 5 Comparison of serum IgE and OVA-sIgE in mice of the C10 treatment group and AR model group in the examples;

[0033] Figure 6This is a comparison of Th1, Th2, and Th17 inflammatory factors in the nasal lavage fluid of mice in the C10 treatment group and the AR model group in the example;

[0034] Figure 7 This is a comparison of TUNEL staining of nasal mucosal tissues of mice in the C10 treatment group and the AR model group in the example;

[0035] Figure 8 Comparison of ROS staining in nasal mucosal tissues of mice in the C10 treatment group and AR model group in the examples;

[0036] Figure 9 This is a transmission electron microscopic comparison of the nasal mucosal tissues of mice in the C10 treatment group and the AR model group in the examples;

[0037] Figure 10 This is a comparison of HNEPCs apoptosis detected by flow cytometry between the C10 treatment group and the AR model group in the examples;

[0038] Figure 11 This is a comparison of ROS in HNEPCs in the C10 treatment group and the AR model group in the examples;

[0039] Figure 12 2 is the histopathological test result of nasal concha mucosa in the embodiment. DETAILED DESCRIPTION

[0040] In order to enable those skilled in the art to better understand the present application, the present application will be further elaborated in conjunction with specific implementation methods.

[0041] In some embodiments, the drug for treating allergic rhinitis or the pharmaceutical composition for treating allergic rhinitis can be used to treat mammals suffering from allergic rhinitis diseases, disorders or conditions, including but not limited to any member of the class Mammalia: humans, non-human primates (such as chimpanzees and other apes and monkeys); livestock, such as cattle, horses, sheep, goats, pigs; domestic animals, such as rabbits, dogs and cats; laboratory animals, including rodents, such as rats, mice and guinea pigs, etc.

[0042] In some embodiments, the C10 compound of the present invention will be provided as a pharmaceutical formulation in a single dose at a concentration of 1 mg / ml, 5 mg / ml, 10 mg / ml, 20 mg / ml, 50 mg / ml, depending on the therapeutic effect. In other embodiments, administration will be carried out at a ratio of the mass of the C10 compound to the mass of the individual being treated, such that the dose will be 1 mg / kg, 5 mg / kg, 10 mg / kg, 20 mg / kg, 50 mg / kg, 100 mg / kg, or more, depending on the therapeutic effect. In multiple-dose embodiments, the dosing schedule may be 1 dose / day, 2 doses / day, 3 doses / day, or more, and may be continued for as long as necessary, such that administration may continue for 1 week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 10 weeks, 20 weeks, or permanently for the lifetime of the individual.

[0043] As used herein, "treating" includes alleviating, alleviating, or ameliorating symptoms of a disease or condition, preventing other symptoms, ameliorating or preventing potential metabolic causes of symptoms, inhibiting a disease or condition, such as arresting its progression, relieving a disease or condition, causing amelioration of a disease or condition, relieving symptoms caused by a disease or condition, or suspending symptoms of a disease or condition. Furthermore, the term encompasses preventive purposes. The term also encompasses achieving a therapeutic effect and / or a preventative effect.

[0044] Unless otherwise specified, the raw materials and reagents used in the examples of the present invention are commercially available products.

[0045] Unless otherwise specified, the percentages used in the examples of the present invention are all by mass.

[0046] Example 1

[0047] Clinical study: Inpatients with cerebrospinal fluid rhinorrhea / nasal septum deviation and AR in the Department of Otolaryngology, Qilu Hospital of Shandong University and some healthy volunteers were selected. Following ethical requirements and with informed consent from the patients, a small amount of inferior turbinate mucosal tissue was obtained after anesthesia on the mucosal surface. The tissue was fixed or frozen for further histopathological examination. Analysis of clinical samples revealed that compared with normal nasal mucosal tissue, the expression of APE1 in the nasal mucosal tissue of AR patients was significantly upregulated, and this upregulation was accompanied by pathological changes in the nasal mucosal tissue ( Figure 12 ), which suggests that APE1 is a target for allergic rhinitis.

[0048] Experimental animals: BALB / C female mice, 6-8 weeks old, weighing 18-20 g, were purchased from Beijing Weitonglihua Experimental Animal Technology Co., Ltd. The mice were housed in an SPF constant temperature animal room (temperature: 23+2°C, relative humidity: 55±10%, light-dark cycle 12 h) and modeling was performed after 1 week of isolation and adaptive feeding.

[0049] Experimental materials: ovalbumin (OVA, A5503, Sigma Aldrich), aluminum hydroxide adjuvant (239186, Sigma Aldrich), phosphate buffered saline (PBS, B310KJ, source culture), C10 compound (Formula 2, synthesized by Biochemical Company), E3330 (49581, Novus Biologicals), bronchial epithelial cell culture medium (3211, ScienCell), IL-13 recombinant protein (HY-P7033, MCE), LPS from Escherichia coli (L4391, Sigma-Aldrich), rat tail collagen (A1142801, Gibco), dimethyl sulfoxide DMSO (D8371, Solarbio), corn oil (C7030, Solarbio).

[0050] Reagent preparation: Sensitization solution: Weigh 1 mg OVA and 112.5 mg Al(OH)3 into 10 ml PBS and shake thoroughly in a 4°C constant temperature oscillator; 1% OVA challenge solution (10 mg / ml OVA): Weigh 100 mg OVA into 10 ml PBS, dissolve thoroughly, and mix. The challenge solution must be freshly prepared.

[0051] Experimental methods:

[0052] 1. Construction of animal model:

[0053] 1.1 Animal Grouping: Animals were randomly divided into 7 groups, with 6 animals in each group. Group A was the blank control group; Group B was the AR model group (intranasal drops control, OVA i.n.); Group C was the C10 intranasal drops group (C10 i.n.); Group D was the E3330 intranasal drops group (E3330 i.n.); Group E was the AR model group (oral gavage control, OVA po); Group F was the C10 oral gavage group (C10 po); and Group G was the E3330 oral gavage group (E3330 po).

[0054] 1.2 Establishment of the Animal Model: An AR mouse model was established using OVA. During the basal sensitization phase, groups B, C, D, E, F, and G were sensitized with 200 μL of the sensitizing drug via intraperitoneal injection on days 1, 8, and 15, respectively. The blank control group was intraperitoneally injected with an equal dose of PBS on days 1, 8, and 15. One week later, starting on day 22, groups B, C, D, E, F, and G were administered nebulized 1% OVA challenge solution for 20 minutes, once daily, for one week. After each nebulization, the mice were observed for 30 minutes for symptoms of nasal scratching, sneezing, and runny nose. The total score was recorded using the cumulative method. The scores are shown in the table below. A score of more than 5 indicates successful AR modeling.

[0055] Table 1 AR symptom scoring table

[0056]

[0057] 1.3 Animal Dosing: After successful model establishment, mice in groups C and D were administered intranasal drops (10 mg / kg) 1 hour before OVA challenge, 20 μl per intranasal drop (10 μl each for the left and right nasal cavities), once daily for 2 weeks. Mice in group B (i.e., AR model intranasal drop control group) were administered an equal volume of PBS + DMSO intranasally once daily for 2 weeks. Mice in groups F and G were administered intragastrically (10 mg / kg for group F and 20 mg / kg for group G) 1 hour before OVA challenge, 200 μl per intragastric drop, once daily for 2 weeks. Mice in group E (i.e., AR model intragastric gavage control group) were administered intragastricly with an equal volume of DMSO + corn oil once daily for 2 weeks. Mice in the blank group were simultaneously administered intranasally and intragastricly with an equal volume of PBS. For the C10 nasal solution, dissolve 28.6 mg of C10 powder in 0.286 ml of DMSO. Once completely dissolved, add 2.574 ml of PBS for dilution, resulting in a drug concentration of 10 mg / ml. For the E3330 nasal solution, dissolve 28.6 mg of E3330 powder in 1.83 ml of DMSO for dilution, adding 1.03 ml of PBS for dilution, resulting in a drug concentration of 10 mg / ml. For the C10 intragastric solution, dissolve 30 mg of C10 powder in 1.2 ml of DMSO for dilution, adding 28.8 ml of corn oil for dilution, resulting in a drug concentration of 1 mg / ml. For the E3330 nasal solution, dissolve 57.2 mg of E3330 powder in 0.572 ml of DMSO for dilution, adding 28.028 ml of corn oil for dilution, resulting in a drug concentration of 2 mg / ml.

[0058] 2. Nasal symptom assessment: On day 42, 30 minutes after the last OVA challenge, three observers counted the number of sneezes and nasal scratches within 10 minutes to evaluate the improvement of nasal symptoms in AR mice treated with C10.

[0059] 3. Mouse serum collection: 24 hours after drug intervention, mice were anesthetized with an intraperitoneal injection of 2% sodium pentobarbital. Peripheral blood was collected from the eyes into 1.5 ml EP tubes and stored at room temperature for 0.5 h. After stagnation until chromatography was achieved, the blood was centrifuged (3000 rpm / 15-30 min / 4°C) and the supernatant was frozen at -80°C.

[0060] 4. Collection and testing of nasal lavage fluid: Mice were sacrificed by cervical dislocation and disinfected with 75% alcohol. The oral cavity was opened to fully expose the posterior nasopharynx. 1 mL of pre-chilled PBS was used to gently perfuse the nasal cavity through the posterior nares. The nasal lavage fluid was collected and centrifuged (1200 rpm / 5 min / 4°C). The supernatant was frozen at -80°C for ELISA analysis. The cell pellet was resuspended in 100 μl of PBS, counted using a cell counter, and spun at 1000 rpm / 5 min. The cells were fixed with paraformaldehyde for subsequent Diffusion staining to assess the status of nasal inflammation.

[0061] 5. Histopathological examination: Mice were fixed in a clean bench, the nasal dorsum skin was split open, and the entire nasal bone including the maxillary bone of some mice was removed intact. The nasal bones were immediately fixed in 4% neutral paraformaldehyde solution for 24 hours. Subsequently, the nasal bones were decalcified with EDTA decalcifier, dehydrated, paraffin-impregnated, embedded, and sectioned. HE and PAS staining were performed to observe the structural integrity of the mouse nasal mucosa and the inflammatory infiltration.

[0062] 6. Transmission electron microscopy: Remove the mouse nasal mucosa and quickly place it in the transmission electron microscopy fixative.

[0063] The samples were then rinsed with PBS, fixed with 1% osmium hydroxide, and then graded with ethanol, permeabilized, and embedded to form resin blocks. After trimming the resin block surface, ultrathin sections were made at 70 nm and transferred to two aramid grids. The sections were stained with 2% uranyl acetate for 30 minutes, then with lead citrate for 5 minutes, and then rinsed thoroughly. The sections were baked under infrared light for 10 minutes. After drying, the ultrastructure was observed using a transmission electron microscope at 80 kV and photographed at different magnifications.

[0064] 7. ELISA Assay: Remove mouse serum and nasal lavage fluid supernatant samples and thaw on ice. Follow the reagent instructions to add the standard and sample. After enzyme addition, incubation, washing, color development, and termination, measure absorbance on an instrument and calculate sample concentration.

[0065] 8. Cell Culture: Primary human nasal epithelial cells (HNEPCs) were obtained from outpatients or inpatients by scraping the inferior turbinate tissue using a nasal probe. Six-well plates were pre-coated with rat tail collagen. Primary human nasal epithelial cells were transferred to the plates and filled with bronchial epithelial cell culture medium to 2 ml. The cells were cultured in a 37°C, 5% CO2 incubator. When the cells reached 50-60% confluency, they were treated with C10 (20 μM) or E3330 (40 μM) for 1 hour. The cells were then stimulated with 20 ng / mL IL-13 recombinant protein combined with 2 μg / ml LPS for 48 hours.

[0066] 9. Flow cytometry: Carefully dissect the mouse nasal tissue from back to front along the cranial suture. Remove the mouse nasal mucosa and place it in 1640 medium containing collagenase D, DNase I, and DSpase II. Mince the mucosa and incubate it in a 37°C waterbath for 40-50 minutes. Grind the digested nasal mucosa and filter it through a 70μm filter to obtain a single-cell suspension. After 48 hours of treatment, HNEPCs were digested and the cell suspension was obtained. Stain the cells according to the apoptosis kit instructions and analyze the cell suspension.

[0067] 10. TUNEL Assay: After dewaxing, nasal tissue sections were incubated with 20 μg / ml DNase-free proteinase K (#ST532, Beyotime) at 37°C for 30 min. The sections were then incubated with 50 μl of TUNEL assay solution at 37°C for 1 hour. Samples were examined using a fluorescence microscope.

[0068] 11. Statistical Analysis: All experimental data were analyzed using SPSS 25.0 software. Quantitative data are expressed as (x ± S). For comparisons between three or more groups, if the data conformed to a normal distribution and had homogeneous variances, one-way ANOVA was used. If the data did not conform to a normal distribution, the nonparametric Kruskal-Wallis test and Dunnett's pairwise comparisons were used. P < 0.05 indicated statistical significance, P < 0.01 was considered significantly different, P < 0.001 was considered significantly different, and NS indicated no statistically significant difference. All statistical graphs were generated using GraphPad Prism 8.0.

[0069] The experimental results are as follows Figures 1-11 shown.

[0070] pass Figure 1 It can be seen that when the AR mouse model was established using OVA, the number of sneezing and nose scratching in the C10 nasal drops group was significantly lower than that in the AR model group, indicating that the C10 compound can significantly improve the symptoms of sneezing and nose scratching in the AR mouse model, indicating that the C10 compound reduces the severity of AR in mice.

[0071] pass Figure 2 It can be seen that compared with the AR model group, the number of eosinophils and neutrophils in the C10 nasal drops group was significantly reduced. The C10 compound can effectively reduce the total number of exfoliated cells and the number of eosinophils and neutrophils in the nasal lavage fluid, indicating that the inflammatory state of the nasal cavity of AR mice has improved.

[0072] pass Figure 3It can be seen that compared with the AR model group, the C10 compound can effectively improve the structural integrity of the nasal mucosal tissue, relieve nasal mucosal edema, and reduce the local infiltration of eosinophils and neutrophils, indicating that the pathological changes in the nasal mucosa of AR mice are alleviated.

[0073] pass Figure 4 It can be seen that compared with the AR model group, C10 can effectively reduce the number of goblet cells and improve the proliferation and hypertrophy of goblet cells.

[0074] pass Figure 5 It can be seen that compared with the AR model group, C10 can effectively reduce the expression levels of IgE and OVA-sIgE in serum, indicating that C10 can improve the allergic reaction of AR mice.

[0075] pass Figure 6 It can be seen that compared with the AR model group, C10 can upregulate the expression levels of Th1 (IFN-γ) type and downregulate the expression levels of Th2 type (IL-4, IL-5, IL-13) and Th17 type (IL-17A) inflammatory factors, indicating that C10 can regulate the local tissue immune balance.

[0076] pass Figure 7 It can be seen that compared with the AR model group, C10 inhibited the apoptosis of nasal mucosal epithelial cells in AR mice.

[0077] pass Figure 8 It can be seen that compared with the AR model group, C10 effectively reduced the production of ROS in the nasal mucosal tissue of AR mice, indicating that C10 reduced oxidative damage in the nasal mucosal tissue of AR mice.

[0078] pass Figure 9 It can be seen that compared with the AR model group, C10 effectively improved the mitochondrial morphology in the nasal mucosal tissue of AR mice.

[0079] pass Figure 10 It can be seen that in the in vitro model of AR induced by HNEPCs stimulated by IL-13 recombinant protein combined with IL-1β, C10 inhibited epithelial cell apoptosis and improved cell activity.

[0080] pass Figure 11 It can be seen that in the in vitro model of AR induced by HNEPCs stimulated by IL-13 recombinant protein combined with IL-1β, C10 effectively reduced the production of ROS in epithelial cells.

Claims

1. Use of an APE1 inhibitor in the preparation of a drug for treating allergic rhinitis, characterized in that: The APE1 inhibitor is a C10 compound; the C10 compound has a structure shown in Formula 2 below: Formula 2.

2. Use of the APE1 inhibitor according to claim 1 in the preparation of a drug for treating allergic rhinitis, characterized in that: The dosage form of the drug for treating allergic rhinitis is nasal drops, nasal sprays, aerosols or powder sprays.

3. Use of the APE1 inhibitor according to claim 1 in the preparation of a drug for treating allergic rhinitis, characterized in that: The administration method of the drug for treating allergic rhinitis is oral administration, intranasal administration, injection administration or external administration.

4. Use of the APE1 inhibitor according to claim 1 in the preparation of a drug for treating allergic rhinitis, characterized in that: The administration method of the drug for treating allergic rhinitis is intranasal administration.

5. Use of the APE1 inhibitor according to claim 1 in the preparation of a drug for treating allergic rhinitis, characterized in that: The drug for treating allergic rhinitis also includes pharmaceutically acceptable excipients.

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