Application of gentalin in preparation of medicine for preventing and controlling virus or bacteria infection

Abstract

The application discloses application of gentiopicroside in preparation of a medicine for preventing and controlling viral or bacterial infection. At present, the main prevention strategy for infectious diseases is to develop vaccines, and corresponding antibiotic treatment can be considered for bacterial infection treatment, but at present, antibiotics also have the problem of multiple drug resistance, and specific drugs for viral infection are still lacking. The application starts from the angle of improving the body's own anti-infection immunity, finds effective components for preventing and controlling infection from natural compounds, and provides a new candidate medicine for preventing and controlling infection.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medicine, and particularly relates to the application of gentiopicroside in the preparation of a medicine for preventing viral or bacterial infection. BACKGROUND

[0002] Viruses and bacteria have long coexisted with humans, and the development history of human society is closely related to epidemics. Bacterial infection is a disease caused by the invasion of bacteria into the body and causing pathological damage, which can occur in any part, including the skin, respiratory tract, digestive tract, urinary system, etc. Bacterial infection can cause fever, abscess, etc., and severe cases can also cause complications such as sepsis, which can threaten life. At present, bacterial treatment mainly relies on antibiotic drug treatment. Viral infection is caused by the invasion of viruses into the body and replication, which can also occur in various tissues, causing diseases such as upper respiratory tract infection, pneumonia, etc. In response to the modernization of the disease control system, the prevention and treatment strategy for infectious diseases is mainly the development of an antiviral vaccine, but the vaccine has problems such as low protection rate, sometimes effective, long development time, etc., and the development of prophylactic and therapeutic anti-infective drugs as an important part of prevention and treatment should design and find more reasonable lead compounds. However, at the present stage, a large number of experimental studies are focused on drug screening, and there is a lack of research on the effective components and molecular mechanisms of drugs. Strengthening the research on drugs can promote the development of multiple disciplines such as immunology and pharmacology.

[0003] Natural drugs are an important source of drugs for humans to prevent and treat infectious diseases. Traditional Chinese herbal medicines have the characteristics of multi-target, low toxicity and side effects, low price, and abundant natural resources, and are ideal natural drugs. However, there are still problems in the prevention and treatment of traditional Chinese medicine, such as low repeatability of clinical efficacy, uncertainty of effective components, and different judgment standards, etc., so the research on natural small molecule compounds in Chinese herbal medicines that play a major pharmacological role has great development potential. Gentiopicroside (GPS) is a seco-iridoid small molecule compound widely derived from plants of the Gentiana genus, with a chemical formula of C 16 H 20 O9 and a molecular weight of 356.3. The earliest related pharmacological studies have proved that it is an effective hepatoprotective drug, and the pharmacological activity of Chinese herbal medicines such as gentiana and gentiana is mainly due to this. Gentiopicroside is approved by the State Food and Drug Administration for the treatment of acute jaundice and chronic active hepatitis, and has been long regarded as an effective drug for the treatment of hepatitis, cirrhosis and other liver diseases. Subsequent research results show that it has the effects of cholagogue, stomachic, anti-inflammatory and other effects, but its pharmacological mechanism has not been clearly defined, especially the research on the drug in the prevention and treatment of infectious diseases has not been expanded, and further research is needed in the direction of enhancing human natural immunity. Natural compounds have structural diversity, biological activity diversity, clear chemical composition and multi-target properties, and are ideal drug candidate molecules, therefore, the purified compound gentiopicroside has high research depth and potential development value. SUMMARY

[0004] The present application is based on improving the body's own anti-infection immunity, starting from finding effective ingredients in natural compounds to prevent and control infection, and providing new candidate drugs for preventing and controlling infection.

[0005] The application discloses application of gentiopicroside in preparation of a medicine for preventing and controlling bacterial infection.

[0006] The application discloses application of gentiopicroside in preparation of a medicine for preventing and controlling viral infection.

[0007] The application discloses application of gentiopicroside in preparation of a natural immunity enhancer.

[0008] The application discloses application of gentiopicroside in preparation of a medicine for enhancing release of nitric oxide by macrophages.

[0009] The application discloses application of gentiopicroside in preparation of a medicine for activating release of type I interferon by macrophages.

[0010] The present application first uses gentiopicroside as an active ingredient to prepare a medicine for preventing and controlling viral or bacterial infection, and the medicine dosage form is preferably an in vivo medicine, and is further preferably an oral medicine.

[0011] The body mainly relies on its own immune response to respond to various bacterial or viral infections. When a pathogen invades the body, the immune system will produce a series of responses, including innate immunity and adaptive immunity, and the adaptive immunity is mainly mediated by T and B lymphocytes, while the innate immunity as the first line of defense against foreign pathogens can be rapidly activated after infection to play a broad-spectrum anti-infection effect. The innate immune cells such as macrophages recognize pathogen-associated molecular patterns through pattern recognition receptors PRRs, thereby activating downstream signaling pathways to start the anti-infection and anti-viral immune response. Type I interferon and inflammatory cytokines are important signal molecules in the anti-viral immune response, which can activate downstream pathways to promote immune response and inhibit viral infection. At present, the main prevention strategy for infectious diseases is to develop vaccines, and the treatment means for bacterial infection can consider corresponding antibiotic treatment, but currently antibiotics also have the problem of multiple drug resistance, and there is still lack of specific drugs for viral infection. Activating the host immune response to enhance the body's immunity to clear the infectious pathogens is an important research and development angle of drugs, and the existing technology cannot solve the problem of complex multi-target mechanism of the biological immune system when the pathogen invades the body, therefore, it is urgent to develop biologically active molecules with diverse biological activities and clear chemical composition as drugs for preventing and treating infection. The present application is based on improving the body's own anti-infection immunity, starting from finding effective ingredients in natural compounds to prevent and control infection, and providing new candidate drugs for preventing and controlling infection. BRIEF DESCRIPTION OF DRAWINGS

[0012] Figure 1 Gentiamarin GPS inhibits replication of E. coli in mice. E. coli

[0013] Figure 2 Gentiamarin GPS inhibits replication of VSV virus in mice.

[0014] Figure 3 Gentiamarin GPS promotes macrophage killing of bacteria.

[0015] Figure 4 Gentiamarin GPS enhances NO release from infected macrophages.

[0016] Figure 5 Gentiamarin GPS treatment significantly increases the level of interferon beta expressed by macrophages stimulated with VSV.

[0017] Figure 6 Gentiamarin GPS inhibits replication of VSV virus in mice. DETAILED DESCRIPTION

[0018] The raw materials and reagents of the present application are conventional products, and the specific experiments and tests are conventional techniques.

[0019] Example 1 Gentiamarin significantly inhibits replication of E. coli

[0020] 8-week-old female C57BL / 6 mice were infected intraperitoneally with E. coli (1 x 10 7 / mouse), and 24 hours after infection, 50 μm gentiamarin GPS was administered by gavage. The mice were sacrificed 24 hours later, and the peritoneal lavage fluid was collected and subjected to colony counting. The results showed that GPS treatment before or after infection significantly inhibited the number of bacteria in the peritoneal cavity of the mice, indicating that GPS can control bacterial infection. Figure 1

[0021] Example 2 Gentiamarin significantly prevents and controls VSV infection

[0022] 8-week-old male C57BL / 6 mice were infected intranasally with VSV, and 12 hours before infection or 24 hours after infection, 50 μm gentiamarin GPS was administered by gavage. The mice were sacrificed 24 hours later, and lung tissue was removed for extraction of RNA to detect viral nucleic acid and HE staining to assess lung inflammation caused by viral replication. The results showed that GPS treatment before or after infection significantly inhibited the viral load in the lungs of the mice Figure 2 and alleviated lung inflammation, indicating that GPS can prevent or control VSV virus infection.

[0023] Example 3 Gentiamarin enhances the release of nitric oxide by macrophages

[0024] ​​Mouse primary peritoneal macrophages were isolated and infected with E. coli. Two hours post-infection, cells were washed twice with PBS buffer and treated with GPS (50 mM) or control reagent PBS. Cells were lysed 24 hours later and the lysate was cultured for bacteria counting. The results showed that GPS treatment significantly reduced the number of viable bacteria in macrophages compared with the control ( Figure 3 ). The NO content in the cell culture supernatant was also determined. The results showed that the addition of GPS significantly enhanced the release of NO by macrophages ( Figure 4 ).

[0025] Example 4: Gentiopicroside can activate the release of type I interferon by macrophages

[0026] Mouse primary peritoneal macrophages were isolated and infected with VSV. Two hours post-infection, cells were washed twice with PBS buffer and treated with GPS (50 mM) or control reagent PBS. Cells were collected 24 hours later and the RNA was extracted for RT-PCR detection. The results showed that GPS significantly increased the expression of type I interferon IFN-beta caused by VSV infection ( Figure 5 ) and inhibited the replication of VSV virus ( Figure 6 ).

[0027] The application belongs to the field of biological medicine, and particularly relates to the application of a natural compound Gentiopicroside from a Gentianaceae plant in preventing and treating viral infection. The main prevention strategy for infectious diseases at present is to develop vaccines, and the treatment means for bacterial infection can consider corresponding antibiotic treatment, but at present, antibiotics also have the problem of multiple drug resistance, and there is still a lack of specific drugs for viral infection. Activating host immune response to enhance the body's immunity to clear infectious pathogens is an important research and development angle of drugs, and the existing technology cannot comprehensively solve the problem of the complex multi-target mechanism of the biological immune system when the pathogen invades the body. Therefore, it is urgent to develop biologically active diversity and chemically well-defined molecular compounds as drugs for preventing and treating infection. Macrophages are important cells in the body's natural immune system, which can phagocytize bacteria in the early stage of infection and kill and clear bacteria through oxygen-dependent or oxygen-independent bactericidal mechanisms, and can present antigens to T cells by processing bacteria to activate adaptive immune response. In addition, macrophages can also activate the immune regulation function of adjacent cells by releasing various cytokines and antiviral factors such as type I interferon, and enhance the body's natural immunity against infection. Plasmacytoid dendritic cells pDC are DC cells derived from the lymphoid lineage, which are different from the antigen presentation function of traditional myeloid dendritic cells mDC, and the main feature of pDC is to produce a large amount of type I interferon in response to pathogen infection, which is the main manufacturer of type I and III interferon in the immune system, and pDC produces 95% of IFN-alpha in the body with 0.2% of cell number, and is called type I interferon producing cell, so pDC is also the most efficient responder of pathogen-associated molecular patterns PAMPs. At the same time, pDC interacts with natural immunity and adaptive immunity through cell contact and cytokine action, and widely participates in the body's immune response, activates NK cells to further participate in natural immunity, promotes the maturation of mDC, etc. The application takes the natural compound Gentiopicroside from the Gentianaceae plant as the research object, and discloses the role of Gentiopicroside in activating anti-infection natural immunity. The results show that Gentiopicroside enhances the innate immune response to prevent and control bacterial and viral infection.

Claims

1. Use of gentiopicroside for the preparation of a medicament for the prevention and control of vesicular stomatitis virus infection, characterized in that, The drug is an in vivo drug.

2. Use according to claim 1, characterized in that, The drug is an oral drug.

3. Use according to claim 1, characterized in that, The drug uses gentiopicroside as an active ingredient.

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