CN-121987647-A - Application of forsythoside A in treatment of bacterial infectious pneumonia

Abstract

The invention belongs to the technical field of medicines. The invention discloses application of forsythoside A in preparation of a medicament for treating bacterial infectious pneumonia. Firstly, a model of bacterial infectious pneumonia of mice caused by tracheal intubation instilling pseudomonas aeruginosa Pseudomonas aeruginosa is built in vivo, and the infection symptoms of the mice of the model can be obviously relieved by the treatment of forsythoside A, so that the inflammatory reaction of the lungs can be effectively relieved. And secondly, establishing an alveolar macrophage model infected by pseudomonas aeruginosa Pseudomonas aeruginosa, klebsiella pneumoniae Klebsiella quasipneumoniae or acinetobacter baumannii Acinetobacter baumannii in vitro, and adding forsythoside A can effectively reduce macrophage injury and reduce the quantity of bacteria infected in cytoplasm. These experimental results show that forsythoside A can be effectively used for treating bacterial infectious pneumonia.

Inventors

• JIANG JIANDONG
• LIN YUAN
• HAN YANXING
• CHEN YING
• ZHANG YU
• DING JINWEN
• LAN YI

Assignees

• 中国医学科学院药物研究所

Dates

Publication Date

20260508

Application Date

20241105

Claims (13)

1. 1. Application of forsythoside A in preparing medicine for treating bacterial infectious pneumonia is provided. The structural formula of the forsythoside A is as follows:
2. 2. the use according to claim 1, wherein the bacterial infectious pneumonia in vivo evaluation model is a mouse lung infection model caused by pseudomonas aeruginosa Pseudomonas aeruginosa.
3. 3. The use according to claim 1, wherein forsythoside a significantly reduces bacterial infectious pneumonia symptoms in mice, significantly increases weight in mice compared to model groups, and effectively reduces pulmonary inflammatory responses.
4. 4. The use according to claim 3, wherein forsythoside a is capable of significantly improving the pathological damage level of the lungs of mice after infection.
5. 5. The use according to claim 3, wherein forsythoside a is capable of significantly reducing the number of pathogenic PAO1 in lung tissue of mice after infection.
6. 6. The use according to claim 3, wherein forsythoside a reduces the levels of inflammatory factors TNF- α, IL-1β, IL-6 in the lungs of mice after infection.
7. 7. The use according to claim 3, wherein forsythoside a significantly reduces the number of inflammatory cells in the alveolar lavage fluid of a mouse after infection.
8. 8. The use according to claim 3, wherein forsythoside a is capable of treating bacterial infectious pneumonia in mice and alleviating the associated symptoms at a concentration of 25, 100 mg/kg.
9. 9. The use according to claim 1, wherein the bacterial infectious pneumonia in vitro evaluation model is a model of infection of alveolar macrophages by pseudomonas aeruginosa Pseudomonas aeruginosa, klebsiella pneumoniae Klebsiella quasipneumoniae or acinetobacter baumannii Acinetobacter baumannii.
10. 10. The use according to claim 1, wherein forsythoside a reduces alveolar macrophage injury caused by bacterial infection and reduces the number of bacteria infected in the cell.
11. 11. The use according to claim 10, wherein forsythoside a is capable of significantly reducing the level of lactate dehydrogenase in the cell culture supernatant following bacterial infection.
12. 12. The use according to claim 10, wherein forsythoside a is capable of alleviating alveolar macrophage injury caused by bacterial infection at a concentration of 12.5, 50 μm.
13. 13. The use according to any one of claims 1 to 12, wherein forsythoside a is formulated in a pharmaceutical composition with a pharmaceutically acceptable salt or a pharmaceutically acceptable carrier.

Description

Application of forsythoside A in treatment of bacterial infectious pneumonia Technical Field The invention relates to application of forsythoside A in treating bacterial infectious pneumonia, belonging to the technical field of medical biology. Background Bacterial infectious pneumonia is a respiratory disease caused by bacteria, and its main symptoms are fever, cough, expectoration, etc. Common pathogens include Streptococcus pneumoniae, staphylococcus aureus, haemophilus influenzae, pseudomonas aeruginosa, klebsiella pneumoniae, acinetobacter baumannii, and the like [1]. Wherein the gram negative bacteria (Pseudomonas aeruginosa, klebsiella pneumoniae and Acinetobacter baumannii) infection has higher and higher proportion in pneumonia, and the transmission speed is increased [2]. The current medicines for treating bacterial infectious pneumonia mainly comprise broad-spectrum antibiotics, including [3] such as cephalosporins, penicillins and the like. Because of overuse or misuse of the antibacterial drugs, the drug resistance speed is continuously accelerated, and the spreading and death risks of infectious diseases are greatly increased. The research and development cycle of novel antibacterial drugs targeting bacteria is long, the investment is high, the return is low, and the research and development speed is far from the bacterial drug resistance speed, so that the research and development enthusiasm of many biological companies is low [4]. In recent years, research on antibacterial drugs (host-acting antibacterial compounds, HACs) targeting hosts provides a new idea for treating infectious diseases. HACs are mostly not directly targeted to bacteria, which solve the problem of multi-drug resistance during infection by enhancing host defenses or increasing the sensitivity of bacteria to body immunity. Potential targets for HACs include, among others, prevention of pathogen adhesion and invasion, inhibition of cytoplasmic pathogen survival and proliferation, inhibition of pathogen spread, and inhibition of excessive inflammation [5]. Macrophages are derived from embryo or bone marrow, are widely present in normal tissues, have the functions of body defense, tissue homeostasis maintenance, repair, inflammation regulation and the like, and are important components [6] of body innate immunity. Alveolar macrophages can directly recognize and phagocytose and clear the invading pathogens while maintaining normal lung function [7] through interactions with alveolar surfactants. Thus, in bacterial infectious pneumonia, enhancement of alveolar macrophage function is one of the important mechanisms in the HACs strategy. Fructus forsythiae is a dry fruit of fructus forsythiae of Oleaceae, is one of the commonly used medicines for clearing heat and detoxicating, and is mainly used for treating common cold, cough, respiratory tract infection and other diseases [8]. Common Chinese patent medicines containing fructus forsythiae comprise Shuanghuanglian oral liquid, lianhua qingwen granule, yinqiao Jiedu tablet and the like. In the 2020 edition of Chinese pharmacopoeia, new national formulary and Chinese Ministry of health and Chinese patent preparation, 183 Chinese patent prescriptions containing Chinese medicinal fructus forsythiae are mainly used for treating lung diseases [9] most commonly. Fructus forsythiae contains phenethyl alcohol glycoside, lignan, terpenoid, volatile oil, flavonoid, etc. Wherein forsythoside A (Forsythiaside A, C 29H36O15,MW 624.59) is one of the main active ingredients of fructus forsythiae, belongs to phenylethanoid glycosides compounds, and has anti-inflammatory, antioxidant, antiviral, antibacterial, neuroprotective and other pharmacological effects [10]. In the in vitro antibacterial activity research, forsythoside A has a certain antibacterial effect [11] on staphylococcus aureus, escherichia coli, streptococcus pneumoniae and the like, but no report on the antibacterial activity of forsythoside A is found in vivo. The forsythoside A has no obvious antibacterial activity on pseudomonas aeruginosa, klebsiella pneumoniae and acinetobacter baumannii in vitro, and plays a role in resisting bacterial infectious pneumonia in mice in the research. Therefore, forsythoside A can achieve the effect of treating bacterial infectious pneumonia of mice by targeting a host and enhancing the host immunity. The study firstly establishes an in-vivo mouse bacterial infectious pneumonia model, and evaluates the treatment effect of forsythoside A on the mouse bacterial infectious pneumonia in aspects of mouse weight, lung homogenate viable count, lung tissue inflammatory factor measurement, lung pathological change and the like. Then, by establishing an in vitro bacterial infection alveolar macrophage model, the protection effect of forsythoside A on alveolar macrophages is further evaluated in terms of the release amount of lactic dehydrogenase in cell supernatant and the counting of intracellular viable