Application of bilobalide in preparation of medicine for treating asthma
By using ginkgolactone to reduce the airway constriction index and inflammatory cell number in asthma mice, the adverse reactions and insufficient effectiveness of existing asthma treatment drugs were solved, demonstrating its potential application value in asthma treatment.
Patent Information
- Application Number
- CN202411664187.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-20
- Publication Date
- 2025-01-17
AI Technical Summary
The existing asthma treatment drugs have limited long-term use due to adverse reactions and lack of effective new treatment methods, making it difficult to effectively reduce airway hyperresponsiveness and inflammatory infiltration.
Ginkgolactone is used as a natural compound to reduce the occurrence of inflammation by reducing the airway constriction index, airway hyperresponsiveness and the number of inflammatory cells in the lungs of asthmatic mice.
Ginkgolactone significantly reduced the airway constriction index and inflammatory cells in asthma mice, reduced inflammatory infiltration of lungs, and showed potential application value in asthma treatment.
Smart Images
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of application of natural compounds, and particularly relates to the application of bilobalide in preparing medicines for treating asthma. Background Art
[0002] Asthma (i.e. bronchial asthma) is a chronic airway inflammatory disease characterized by variable airflow limitation, airway inflammation and airway hyperresponsiveness. Clinically, it is mainly manifested by recurrent wheezing, shortness of breath, chest tightness or coughing, which often occur or worsen at night and early morning. There are about 300 million people suffering from asthma worldwide. The proportion of adults suffering from asthma in my country is about 1.24%. It is more common in people with a family history of asthma, comorbidities (such as allergic rhinitis, allergic conjunctivitis, eczema, respiratory diseases and other allergic and respiratory diseases), obesity, smoking, allergen exposure, etc. The inducing factors include climate factors, exercise factors, respiratory tract infections, mental and psychological factors, trace element deficiency and drug factors. Due to urbanization and changes in biochemical patterns, the prevalence of asthma has shown an increasing trend year by year.
[0003] Asthma is currently incurable, and only some methods and measures can be used to relieve asthma symptoms. According to the 2024 edition of the Global Initiative for Asthma (GINA), the goal of asthma treatment is to achieve the best possible long-term asthma control results, including long-term symptom control and long-term minimization of the risk of disease exacerbation, decreased lung function, and adverse drug reactions. The main therapeutic drugs currently include glucocorticoids, leukotriene inhibitors, beta-receptor agonists, H1 receptor antagonists, theophylline drugs, etc., which can relieve a series of symptoms of asthma such as wheezing, shortness of breath, chest tightness, and shortness of breath. However, the adverse reactions caused by the use of drugs to the cardiovascular system, central nervous system, digestive system, immune system, skeletal system, etc. limit the long-term use of drugs. Therefore, there is an urgent need to find new and effective treatments.
[0004] Bilobalide is a sesquiterpene substance extracted from the Ginkgo biloba plant. Bilobalide has a good therapeutic effect on cardiovascular and cerebrovascular diseases such as angina pectoris, myocardial infarction, coronary heart disease, hypertension and arrhythmia. However, the therapeutic effect of bilobalide in asthma has not been studied. The research results of the present invention found that bilobalide can reduce the airway narrowing index of asthmatic mice, reduce airway hyperresponsiveness, reduce the number of inflammatory cells in the bronchoalveolar lavage fluid of asthmatic mice, reduce inflammatory infiltration of the lungs, and reduce the occurrence of inflammation. Summary of the invention
[0005] In order to solve the above technical problems, the purpose of the present invention is to provide an application of bilobalide in the preparation of a drug for treating asthma, which is a new application of bilobalide in asthma and has good application value and development prospects. The bilobalide includes its pharmaceutically acceptable salts, the molecular formula of bilobalide is: C15H18O8, and the structural formula is as follows:
[0006] Preferably, the bilobalide and its pharmaceutically acceptable salts or other derivatives are natural compounds for treating asthma.
[0007] Preferably, the bilobalide and its pharmaceutically acceptable salts or other derivatives are natural compounds that reduce the occurrence of inflammation in asthma and reduce airway hyperresponsiveness.
[0008] The research results of the present invention show that bilobalide can reduce the airway narrowing index of asthmatic mice, reduce airway hyperresponsiveness, reduce the number of inflammatory cells in the alveolar lavage fluid of asthmatic mice, reduce inflammatory infiltration in the lungs, and reduce the occurrence of inflammation. BRIEF DESCRIPTION OF THE DRAWINGS
[0009] Figure 1 In the mouse asthma model, bilobakide 12.5, 25, and 50 mg / kg can dose-dependently reduce the airway narrowing index of mice, reduce airway hyperresponsiveness, and relieve asthma symptoms. Group settings: control: normal control group, Model: model group, Bilobakide 12.5 mg / kg: bilobakide 12.5 mg / kg, Bilobakide 25 mg / kg: bilobakide 25 mg / kg, Bilobakide 50 mg / kg: bilobakide 50 mg / kg, Dex 1 mg / kg: dexamethasone 1 mg / kg. Compared with the normal control group, ##, p < 0.01; compared with the model group, *, p < 0.05.
[0010] Figure 2 In a mouse asthma model, bilobalide 12.5, 25, and 50 mg / kg can reduce the white blood cell count of mice.
[0011] Figure 3 In a mouse asthma model, bilobalide 12.5, 25, and 50 mg / kg can reduce the number of eosinophils in mice.
[0012] Figure 4 In a mouse asthma model, bilobalide 12.5, 25, and 50 mg / kg can reduce the number of lymphocytes in mice.
[0013] Figure 5 In a mouse asthma model, bilobalide 12.5, 25, and 50 mg / kg can reduce the number of monocytes in mice.
[0014] Figure 6The results of histopathological examination showed that obvious infiltration of inflammatory cells around the bronchus was observed in the model control group, and the degree of infiltration of inflammatory cells around the bronchus decreased after the treatment with 12.5, 25, and 50 mg / kg of bilobalide.
[0015] Figure 7 For the statistics of histopathological examination results, obvious infiltration of inflammatory cells around the bronchus was observed in the model control group, and the degree of infiltration of inflammatory cells around the bronchus decreased after the treatment with 12.5, 25, and 50 mg / kg of bilobalide. DETAILED DESCRIPTION
[0016] The technical solution of the present invention will be clearly and completely described below in conjunction with the accompanying drawings and embodiments. The embodiments of the present invention include but are not limited to the following conditions and can be modified within the acceptable range in the art. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without making any creative work shall fall within the scope of protection of the present invention.
[0017] Example 1: Effect of bilobalide on airway resistance in asthmatic mice
[0018] Female mice were divided into 8 groups, namely blank control group, model group, bilobalide (12.5, 25, 50 mg / kg) group, Fritillaria extract (50, 100 mg / kg) group and dexamethasone 1 mg / kg group. There were 8 mice in each group. The mice in each group were gavaged on Day 21, once a day, for 7 consecutive days. On Day 0, mice in each group were injected subcutaneously and intraperitoneally with 2 mg / ml ovalbumin solution (prepared with 4% aluminum hydroxide). The injection sites and the amount of ovalbumin solution for each mouse were as follows: 25 μl (sc) for each hind paw; 25 μl (sc) for each groin on both sides; 50 μl (sc) for each of the two backs; 100 μl (sc) for the neck; 200 μl (ip) for the peritoneal cavity. On Day 14, mice in each group were injected intraperitoneally with 2 mg / ml ovalbumin solution (prepared with 4% aluminum hydroxide) to enhance sensitization. From Day 21 to Day 27, mice in each group inhaled 10 mg / ml ovalbumin solution (0.9% sodium chloride injection) by nebulization for 30 minutes, once a day, for 7 consecutive days. On Day 28, awake mice were placed in the WBP whole body plethysmography system, and 0.9% sodium chloride injection and methacholine chloride 6.25, 12.5, 25, and 50 mg / ml were sprayed in sequence for 1 minute each. The Penh values of mice after spraying methacholine chloride at each concentration were recorded, and the percentage increase of Penh of mice was calculated. Figure 1 .
[0019] Example 2: Effect of bilobalide on inflammatory cells in bronchoalveolar lavage fluid of asthmatic mice
[0020] In the above animal model, mice were killed by cervical dislocation, the airway was isolated and tubed, and the left lung was ligated. The unligated part of the lung tissue was lavaged with 0.5 ml of alveolar lavage fluid, repeated 3 times, and the lavage fluid of 3 times was combined. The total number of white blood cells, eosinophils, lymphocytes and monocytes in the lavage fluid were counted using an automatic blood analyzer. Figure 2-Figure 5 .
[0021] Example 3: Effect of bilobalide on lung histopathology in asthmatic mice
[0022] In the above animal models, formalin-fixed lung tissues were dehydrated, paraffin-embedded, sectioned, stained with H&E, and scored under a microscope. 0: no inflammatory cell infiltration around the bronchi, 1: a small amount of inflammatory cell infiltration around the bronchi, 2: 1 layer of inflammatory cell infiltration around the bronchi, 3: 2 to 4 layers of inflammatory cell infiltration around the bronchi, 4: > 4 layers of inflammatory cell infiltration around the bronchi. See Figure 6-Figure 7 .
[0023] In summary, the present invention provides a novel natural active ingredient for treating asthma. Bilobalide can reduce the airway narrowing index of asthmatic mice, reduce airway hyperresponsiveness, reduce the number of inflammatory cells in the bronchoalveolar lavage fluid of asthmatic mice, reduce inflammatory infiltration in the lungs, and reduce the occurrence of inflammation. Bilobalide shows good application value and development prospects in the treatment of asthma and is a potential drug for the treatment of asthma.
Claims
1. An application of bilobalide in preparing a medicament for treating asthma, characterized in that: The bilobalide includes its pharmaceutically acceptable salts. The molecular formula of bilobalide is: C15H18O8, and the structural formula is as follows:
2. The use according to claim 1, characterized in that: The bilobalide reduces the airway narrowing index of asthmatic mice, reduces airway hyperresponsiveness, reduces the number of inflammatory cells in the alveolar lavage fluid of asthmatic mice, reduces inflammatory infiltration in the lungs, and reduces the occurrence of inflammation.