Application of corilagin in preparation of staphylococcus aureus inhibitor

Abstract

The invention relates to application of corilagin in preparation of a staphylococcus aureus inhibitor. Experiments prove that corilagin is directly combined with staphylococcus aureus cell wall hydrolase, so that bacterial proliferation is slowed down, and biofilm formation is reduced; the hemolytic activity of the alpha-hemolysin protein and the bacterial culture supernatant can be reduced through two ways of directly inhibiting the staphylococcus aureus alpha-hemolysin and inhibiting the secretion of the staphylococcus aureus alpha-hemolysin to the culture medium supernatant; corilagin has no cytotoxic effect, and can significantly inhibit human pulmonary epithelial cell-mediated cytotoxicity and adhesion effect of staphylococcus aureus; by constructing a staphylococcus aureus infected mouse pneumonia model, it is found that corilagin remarkably improves the survival rate of infected mice, colonization of staphylococcus aureus in mice lungs is reduced, and edema and inflammatory response of the mice lungs are relieved. The results show that corilagin has a good application prospect in the aspect of resisting staphylococcus aureus infection.

Description

Technical Field

[0001] The invention belongs to the technical field of medical pharmacy, and in particular relates to the use of corilagin in the preparation of Staphylococcus aureus inhibitors. Background Art

[0002] Staphylococcus aureus is a Gram-positive, facultative anaerobic pathogen that is widely present in the natural environment and on the human body. It is one of the main pathogens of hospital-acquired and community-acquired infections. The bacterium can cause a variety of serious diseases, including skin and soft tissue infections, pneumonia, endocarditis, sepsis, and toxic shock syndrome. In particular, the widespread spread of methicillin-resistant Staphylococcus aureus (MRSA) has significantly increased the difficulty of clinical treatment and posed a serious threat to global public health security. Staphylococcus aureus's resistance to multiple antibiotics and its ability to form biofilms on the surface of medical devices have further exacerbated the complexity of infection control and caused huge medical and economic burdens. Cell wall hydrolases are an amidase expressed during the infection of Staphylococcus aureus. They can cut the amide bond between the peptidoglycans connecting the bacterial parent and offspring, resulting in the breakage of peptidoglycans, helping the separation of bacterial parents and offspring to achieve cell division and proliferation. When the function of cell wall hydrolases is inhibited, the bacterial parent and offspring cannot be separated normally, which manifests as excessive bacterial growth and slow proliferation. In addition, cell wall hydrolases also affect the formation of bacterial biofilms and the adhesion of bacteria to host cells. Staphylococcus aureus α-hemolysin is a vital exotoxin secreted during the infection of Staphylococcus aureus. It plays a multi-faceted role in promoting infection during the infection of Staphylococcus aureus. After being secreted into the external environment, α-hemolysin binds to host-specific receptors to form a heptamer, pierces the host cell membrane, triggers the leakage of cell contents, triggers cytotoxicity and inflammatory reactions, and leads to cell dysfunction. Therefore, cell wall hydrolases and α-hemolysin are ideal targets for the development of new inhibitors against Staphylococcus aureus infection. Traditional antibiotics mainly work by inhibiting bacterial growth or directly killing bacteria, but long-term abuse has led to the accelerated evolution of drug-resistant strains (such as MRSA), seriously weakening the effectiveness of existing therapies. In this context, anti-virulence strategies have attracted much attention due to their advantages of specifically inhibiting the pathogenic mechanism of pathogens, reducing host damage and delaying the development of drug resistance. By targeting cell wall hydrolases and α-hemolysins, the bacterial infection process can be blocked, while cooperating with the host immune system to eliminate pathogens, providing a new direction for dealing with drug-resistant bacterial infections. Corilagin is a natural polyphenolic compound widely present in various medicinal plants such as Phyllanthus, and has been applied in the fields of food, health products and traditional medicines. Research shows that corilagin has various biological activities such as antioxidant, anti-tumor and protection of cardiovascular and cerebrovascular systems. It has high safety and is easy to obtain from natural sources. Although there have been studies reporting the inhibitory effect of corilagin on some pathogenic microorganisms, there are currently no relevant published results on its inhibition of Staphylococcus aureus biofilm formation by targeting Staphylococcus aureus cell wall hydrolase and α-hemolysin, alleviating the cytotoxic effect and inflammatory response of Staphylococcus aureus on host cells, and thus reducing the pathogenicity of Staphylococcus aureus. Based on this, exploring the new use of corilagin as an inhibitor of Staphylococcus aureus cell wall hydrolase and α-hemolysin not only provides innovative ideas for the research and development of antivirulence drugs, but also opens up a sustainable strategy for solving the problem of drug-resistant bacterial infections, with important scientific value and application prospects. Summary of the Invention

[0003] Technical problems to be solved: The purpose of the present invention is to study the use of corilagin in the preparation of Staphylococcus aureus inhibitors. Targeting Staphylococcus aureus cell wall hydrolase and α-hemolysin, a cell wall hydrolase and α-hemolysin inhibitor screened from natural compounds is corilagin. This inhibitor resists Staphylococcus aureus infection by inhibiting the biological functions of cell wall hydrolase and α-hemolysin.

[0004] Technical solution: The use of corilagin in the preparation of Staphylococcus aureus inhibitors. Further, the inhibitory effect of corilagin on the activity of Staphylococcus aureus cell wall hydrolase. Further, the inhibitory effect of corilagin on the activity of Staphylococcus aureus α-hemolysin. Further, the corilagin is purchased from Chengdu Refines Biological Technology Co., Ltd., with a purity ≥ 98%. Further, the structural formula of the corilagin is as follows: The use of the above corilagin or the Staphylococcus aureus inhibitor prepared therefrom in the preparation of drugs for Staphylococcus aureus infection. Beneficial effects: 1. The present invention discovers through research that corilagin monomer (with a purity reaching 98%) can bind to the active centers of Staphylococcus aureus cell wall hydrolase and α-hemolysin, form a stable complex, inhibit the biological functions of cell wall hydrolase and α-hemolysin, and thus reduce the proliferation, biofilm formation and hemolytic activity of Staphylococcus aureus. 2. Through experiments such as molecular docking, molecular simulation, and site-directed mutagenesis of residues, the present invention discovers that corilagin and Staphylococcus aureus cell wall hydrolase interact mainly through van der Waals forces, hydrogen bonding, and electrostatic interactions. During the molecular simulation process, the configurations of corilagin, cell wall hydrolase, and α-hemolysin all remain stable. Moreover, during the simulation, corilagin always maintains in the initial binding pocket of cell wall hydrolase and α-hemolysin. The results of residue energy decomposition show that the residues Glu324, Ala288, Asp384, and His370 in cell wall hydrolase have relatively strong interactions with corilagin, contributing relatively large energy to their binding; the residues Arg200, Trp179, Tyr182, Gln194, Asn176, and Lys198 in α-hemolysin are the key residues promoting its binding with corilagin. The clarification of the interaction mechanism between corilagin and cell wall hydrolase and α-hemolysin lays an important theoretical foundation for the subsequent optimization, modification, and application of compound structures. 3. The present invention constructs a mouse pneumonia model infected with Staphylococcus aureus. By examining indicators such as the survival rate of mice in the corilagin treatment group and the infection group, the number of bacterial colony colonizations in the lung tissues of mice, the wet-to-dry weight ratio of the lung tissues of infected mice, and the inflammation level, it is found that corilagin inhibits the colonization of Staphylococcus aureus in the lung tissues of mice, reduces the edema and inflammatory response in the lung tissues of mice, delays the death time of infected mice, and improves the survival rate of infected mice. In short, corilagin shows an all-round and systematic protective effect on the mouse pneumonia model infected with Staphylococcus aureus. Description of the Drawings Figure 1 It is a diagram showing the effect of corilagin on the function of Staphylococcus aureus cell wall hydrolase. Among them, a is the molecular structural formula of corilagin; b is the binding mode of corilagin and Staphylococcus aureus cell wall hydrolase; c is the quantitative data diagram of corilagin inhibiting the proliferation of Staphylococcus aureus; d is the visualization picture of corilagin inhibiting the proliferation of Staphylococcus aureus. Figure 2 It is a diagram showing the effect of corilagin on the formation of Staphylococcus aureus biofilm and the number of bacteria in the biofilm. Among them, a is the root mean square deviation of the configurations of corilagin and cell wall hydrolase during the molecular simulation process; b is the distance between corilagin and cell wall hydrolase during the simulation; c is corilagin inhibiting the formation of Staphylococcus aureus biofilm; d is corilagin inhibiting the number of viable bacteria in the Staphylococcus aureus biofilm. Figure 3It is a confirmation diagram of the mechanism of action of corilagin and Staphylococcus aureus cell wall hydrolase. Among them, a is the binding free energy generated during the binding process of corilagin and cell wall hydrolase; b is the residues with greater energy contribution during the binding process of cell wall hydrolase and corilagin; c is the number and distribution of hydrogen bonds generated in the last 10 ns of trajectory equilibrium during the binding process of corilagin and cell wall hydrolase; d is the occupancy of hydrogen bonds generated in the last 10 ns of trajectory equilibrium. Figure 4 It is an inhibition effect diagram of corilagin on the hemolytic activity of Staphylococcus aureus culture supernatant and its secreted toxin α-hemolysin. Among them, a is the inhibition of the hemolytic activity of Staphylococcus aureus culture supernatant by corilagin; b is the inhibition of the secretion of Staphylococcus aureus α-hemolysin into the culture medium by corilagin; c is the quantitative result of the inhibition of the hemolytic activity of Staphylococcus aureus α-hemolysin protein by corilagin; d is the visualization picture of the inhibition of the hemolytic activity of Staphylococcus aureus α-hemolysin protein by corilagin; e is the binding mode diagram of corilagin and Staphylococcus aureus α-hemolysin. Figure 5 It is a confirmation diagram of the mechanism of action of corilagin and Staphylococcus aureus α-hemolysin. Among them, a is the root mean square deviation of corilagin and Staphylococcus aureus α-hemolysin during the simulation process; b is the analysis of the interaction sites between corilagin and Staphylococcus aureus α-hemolysin; c is the analysis of the energy contribution of residues during the interaction process of corilagin inhibiting Staphylococcus aureus α-hemolysin; d is the binding energy of corilagin and each mutant protein of Staphylococcus aureus α-hemolysin. Figure 6 It is a diagram of corilagin inhibiting the cytotoxicity and adhesion mediated by Staphylococcus aureus to human lung epithelial cells. Among them, a is the cytotoxicity of corilagin at different concentrations; b is the alleviating effect of corilagin on the cytotoxicity mediated by Staphylococcus aureus; c is the inhibitory effect of corilagin on the adhesion of Staphylococcus aureus to human lung epithelial cells. Figure 7 It is a protection effect diagram of corilagin on a mouse pneumonia model infected with Staphylococcus aureus. Among them, a is the survival rate of infected mice in different treatment groups; b is the colonization data of Staphylococcus aureus in the lungs of mice in different treatment groups; c is the wet-to-dry weight ratio of the lung tissues of mice in different treatment groups; d is the lung inflammation level of mice in different treatment groups. Detailed implementation mode The present invention will be further described below in conjunction with the accompanying drawings and embodiments. The following embodiments are explanations of the present invention and the present invention is not limited to the following embodiments: Corilagin was purchased from Chengdu Refine Biological Technology Co., Ltd., with a purity of ≥98%. Example 1 Corilagin binds to the active center of Staphylococcus aureus cell wall hydrolase and then inhibits the normal proliferation of bacteria The cell wall hydrolase of Staphylococcus aureus was set as the receptor, and corilagin was set as the ligand. Before docking, the cell wall hydrolase and corilagin were respectively subjected to hydrogenation and charge addition treatments. By establishing a docking box, the AutoDock Vina program was applied to conduct the docking experiment, and the affinity between corilagin and the cell wall hydrolase was determined by the program scoring. Staphylococcus aureus was co-cultured with corilagin at different concentrations (37 °C, 200 rpm). An appropriate amount of samples was taken every 1 hour to detect the absorbance at 600 nm, and the effect of corilagin on the proliferation of Staphylococcus aureus was analyzed. This study found that corilagin ( Figure 1 a) could directly bind to the active center of the cell wall hydrolase of Staphylococcus aureus, and its affinity was -10.4 kcal / mol ( Figure 1 b); when there was no corilagin in the culture system, Staphylococcus aureus showed a normal growth trend. When Staphylococcus aureus was co-cultured with corilagin at different concentrations, it was found that the growth trend of Staphylococcus aureus slowed down to varying degrees, and the higher the concentration of corilagin, the more obvious the growth slowdown trend of Staphylococcus aureus ( Figure 1 c-1d), indicating that the binding of corilagin to the cell wall hydrolase affected its biological function, resulting in the inability of the parent and offspring of Staphylococcus aureus to separate normally, manifested as slowed bacterial proliferation. Example 2 Corilagin reduces the formation of Staphylococcus aureus biofilm and the number of bacteria in the biofilm To verify the reliability of the binding of corilagin to the cell wall hydrolase, a molecular dynamics simulation experiment was carried out using GROMACS 2020.6 software. The simulation time was 100 ns, the force field parameter was Amber14SB, and the water model was TIP3P. After the simulation, the root mean square deviation (RMSD) of corilagin and the cell wall hydrolase was analyzed to evaluate whether they maintained stable configurations during the simulation process. The distance between corilagin and the cell wall hydrolase was analyzed to determine whether corilagin was stably bound to the active center of the cell wall hydrolase. After Staphylococcus aureus was statically co-cultured with corilagin at different concentrations at 37 °C for 24 hours, the supernatant was discarded. The samples were washed 3 times with sterile phosphate buffer and dried at room temperature. 0.1% crystal violet solution was added for staining for 20 minutes. The excess staining solution was discarded. The samples were washed 3 times with sterile phosphate buffer and dried at room temperature. After treatment with 33% glacial acetic acid for 30 minutes, the absorbance of the samples at 570 nm was detected, and the effect of corilagin on the biofilm of Staphylococcus aureus was analyzed. After Staphylococcus aureus was statically co-cultured with corilagin at different concentrations at 37 °C for 24 hours, the supernatant was discarded. The samples were washed 3 times with sterile phosphate buffer, and then the biofilms were collected and diluted. An appropriate amount of samples was spread on LB agar medium and cultured overnight. The next day, the number of colonies was counted, and the effect of corilagin on the number of colonies in the biofilm of Staphylococcus aureus was analyzed. This study found that the root mean square deviations of corilagin and Staphylococcus aureus cell wall hydrolase were stable at around 0.15 nm and 0.10 nm respectively in a 100-ns molecular dynamics simulation experiment ( Figure 2 a), indicating that corilagin and cell wall hydrolase maintained a stable configuration during the simulation; at the same time, the distance between corilagin and cell wall hydrolase was maintained at around 0.33 nm during the simulation ( Figure 2 b), indicating that corilagin was always located in the active pocket of cell wall hydrolase. The amount of unit biofilm formed by Staphylococcus aureus without treatment with corilagin was defined as 100%, and when Staphylococcus aureus was treated with different concentrations of corilagin, the amount of unit biofilm formed gradually decreased ( Figure 2 c), indicating that corilagin could significantly reduce the formation of Staphylococcus aureus biofilm. After counting the viable bacteria in the biofilm, it was found that the number of Staphylococcus aureus in the biofilm formed by the corilagin treatment group was significantly less than that of the untreated group ( Figure 2 d). The above results indicate that after corilagin binds to the active center of cell wall hydrolase, the hydrolysis of amide bonds is inhibited, making the bacteria unable to divide normally, resulting in a decrease in Staphylococcus aureus in the biofilm. It should be noted that the decrease in the formation of Staphylococcus aureus biofilm is not due to the slowdown of bacterial proliferation, because the amount of unit biofilm formation of each sample is presented here. Example 3 Corilagin inhibits the biological function of Staphylococcus aureus cell wall hydrolase by direct steric hindrance After the molecular simulation experiment, it was found by analyzing the simulation trajectory that corilagin and cell wall hydrolase maintained a stable binding mode during the simulation. In order to confirm the residues interacting between corilagin and cell wall hydrolase, the energy during the binding process was analyzed, and it was found that the binding free energy between corilagin and cell wall hydrolase was -47.65 kJ / moL, including an electrostatic interaction energy of -43.28 kJ / moL, a van der Waals interaction of -114.31 kJ / moL, and a solvation energy of 83.06 kJ / moL ( Figure 3 a). Previous studies have shown that His370, Asp384, and His265 are the key active sites of cell wall hydrolase, and Glu324 and Ala288 are also crucial for the biological activity of cell wall hydrolase. The results of the residue energy decomposition experiment in this study showed that Glu324, Ala288, Asp384, and His370 all contributed relatively large energies to the binding of corilagin and cell wall hydrolase ( Figure 3 b). Further analysis found that more than 20 pairs of hydrogen bonds were formed between corilagin and cell wall hydrolase in the last 10 ns when the simulation reached the equilibrium stage ( Figure 3 c), and 3 pairs of hydrogen bonds had a relatively long existence period ( Figure 3d), The residues involved in these three pairs of hydrogen bonds are Asn284, Asn287, and His382 respectively. The -NH groups in these residues form hydrogen bond interactions with O atoms at different positions in corilagin. Example 4 Inhibitory effect of corilagin on the hemolytic activity of Staphylococcus aureus culture supernatant and its secreted toxin α-hemolysin The inhibitory effect of corilagin on the hemolytic activity of Staphylococcus aureus culture supernatant and its secreted toxin α-hemolysin was evaluated by a hemolytic activity inhibition experiment. The specific process was as follows: After Staphylococcus aureus was co-cultured with different concentrations of corilagin (37 °C, 200 rpm) for 8 hours, it was centrifuged (12,000 rpm, 4 °C, 5 min), the supernatant was collected and filtered through a 0.22 μm filter. An equal volume of the supernatant was added to sterile PBS buffer, and then sterile defibrinated sheep blood (final concentration 2.5%) was added. After incubation at 37 °C for 10 min, it was centrifuged again (12,000 rpm, 4 °C, 2 min). An equal volume of the supernatant was taken to detect the absorbance at 543 nm, and the inhibitory effect of corilagin on the hemolytic activity of Staphylococcus aureus culture supernatant was analyzed. After the supernatant of the co-culture of Staphylococcus aureus and corilagin was harvested by centrifugation, an appropriate amount was added to pre-cooled acetone and precipitated overnight at -20 °C. After centrifugation the next day (12,000 rpm, 10 min), the acetone was discarded. SDS-PAGE loading buffer was added to the precipitated protein, and it was treated at 100 °C for 5 min. After the sample was separated by a 10% SDS-PAGE gel, the effect of corilagin on the secretion of Staphylococcus aureus α-hemolysin into the supernatant was analyzed by Coomassie brilliant blue staining. The binding mode of corilagin and Staphylococcus aureus α-hemolysin was analyzed by molecular docking experiment. The hemolytic activity in the Staphylococcus aureus culture system without corilagin was defined as 100%. When different concentrations of corilagin were added, the hemolytic activity of the culture supernatant showed a significant decreasing trend ( Figure 4 a), Corilagin may reduce the secretion amount of α-hemolysin in the supernatant or may directly bind to α-hemolysin. To further confirm this, protein secretion and α-hemolysin hemolytic activity experiments were respectively carried out. The results showed that corilagin inhibited both the secretion of α-hemolysin into the supernatant ( Figure 4 b), and significantly reduced the hemolytic activity of the purified α-hemolysin protein ( Figure 4 c - 4d), The molecular docking results showed that corilagin bound to the binding pocket in the rim region of α-hemolysin ( Figure 4 e). The above results indicate that corilagin inhibits the hemolytic activity of Staphylococcus aureus culture supernatant through two pathways: directly binding to α-hemolysin and inhibiting its secretion into the supernatant. Example 5 Confirmation of the action mechanism of corilagin and Staphylococcus aureus α-hemolysin To verify the reliability of the binding of corilagin to α-hemolysin, molecular dynamics simulation experiments were carried out using GROMACS 2020.6 software. The simulation time was 100 ns, the force field parameters were Amber14SB, and the water model was TIP3P. After the simulation, the root mean square deviation (RMSD) of corilagin and α-hemolysin was analyzed to evaluate whether they maintained stable conformations during the simulation. The distance between corilagin and α-hemolysin was analyzed to determine whether corilagin maintained stable binding to α-hemolysin, and the key residues of their interaction were confirmed by site-directed mutagenesis experiments. Staphylococcus aureus α-hemolysin maintained stable RMSD fluctuations during the simulation, indicating that it maintained a stable conformation during the simulation. The RMSD value of corilagin stabilized near 0.1 nm after the simulation time reached 50 ns, indicating that it also maintained a stable conformation ( Figure 5 a); Through the binding site analysis experiment, it was found that the residues Arg200, Gln177, Trp179, and Tyr182 in α-hemolysin interacted with corilagin, and Gln194, Asn176, and Lys198 formed hydrogen bond interactions with corilagin ( Figure 5 b). During the simulation, the distance between corilagin and α-hemolysin was maintained at 0.32 nm, indicating that they maintained stable binding during the simulation ( Figure 5 c); To further confirm, site-directed mutagenesis experiments were carried out. It was found that after the above residues were mutated to alanine, except for Gln177, the binding energy of other mutant proteins to corilagin was significantly different from that of the non-mutated proteins ( Figure 5 d), indicating that these residues are the key residues for the interaction between corilagin and α-hemolysin. Example 6 Corilagin significantly reduces the cytotoxicity and adhesion effect of Staphylococcus aureus on human lung epithelial cells Human lung epithelial cells A549 cultured overnight in a 96-well plate were co-cultured with corilagin at different concentrations for 6 hours. After centrifugation of the samples (1000 rpm, 10 min), an appropriate amount was taken and an equal volume of lactate dehydrogenase (LDH) reagent was added. After incubation in the dark for 30 min, the absorbance value of the samples at 490 nm was measured to analyze the cytotoxic effect of corilagin. Treatment with 0.1% Triton X-100 was used as a positive control (denoted as Tri), and the group with a corilagin concentration of 0 μg was used as a negative control. The alleviating effect of corilagin on the cytotoxicity mediated by Staphylococcus aureus was also evaluated using the lactate dehydrogenase activity assay. For the adhesion experiment, Staphylococcus aureus in the logarithmic growth phase was added to A549 cells cultured in a 24-well plate, and different concentrations of corilagin were added and co-cultured for 1.5 hours. After discarding the culture medium, the samples were washed 3 times with sterile PBS, the cells were transferred to a sterile centrifuge tube, appropriately diluted, and plated on LB agar medium, and cultured overnight at 37°C. The next day, the number of colonies of different samples was counted to analyze the effect of corilagin on the adhesion of Staphylococcus aureus to A549 cells. A large amount of LDH content was detected in the positive control group, indicating that all the cells were dead, which was defined as 100%. After co-culturing A549 cells with corilagin at different concentrations, the LDH content in the culture medium was almost the same as that in the negative control group (the group with a corilagin concentration of 0 μg), about 5% of the positive control group ( Figure 6 a)( Figure 6 In a, ns is the abbreviation of no significant, representing no significant difference), indicating that corilagin itself has no cytotoxicity. When A549 cells were treated with Staphylococcus aureus, a large amount of LDH was detected in the culture medium, indicating that Staphylococcus aureus caused a strong cytotoxic effect on A549 cells. When different concentrations of corilagin were added for treatment, the LDH in the culture medium gradually decreased ( Figure 6 b), indicating that corilagin significantly alleviated the cytotoxic effect of Staphylococcus aureus on A549 cells. After co-incubation of Staphylococcus aureus and A549 cells, a large number of bacterial colonies were detected after cell lysis and plating, indicating that Staphylococcus aureus successfully colonized on the surface of A549 cells. When different concentrations of corilagin were added for treatment, the number of colonies colonized on the cell surface gradually decreased ( Figure 6 c), indicating that corilagin significantly inhibited the colonization of Staphylococcus aureus on human lung epithelial cells. Example 7 Corilagin showed an all-round protective effect on a mouse pneumonia model infected with Staphylococcus aureus A mouse pneumonia model was constructed by intranasal instillation of Staphylococcus aureus in the logarithmic growth phase (5×10 8(CFUs / mouse), and then the model mice were randomly divided into 3 groups, namely the infection group (treated only with Staphylococcus aureus), the treatment group (treated with corilagin), and the control group (treated with an equal volume of solvent). After 2 hours of infection, the treatment group was given corilagin (100 mg / kg), once every 12 hours. The treatment group and the control group were given an equal volume of solvent. The survival of the mice was monitored at the designated time points to analyze the effect of corilagin on improving the survival rate of the Staphylococcus aureus-induced murine pneumonia model. The sub-lethal model (3×10 8 CFUs / mouse) was constructed using the same method, and the same treatment protocol was adopted. After 48 hours of infection, the mice were euthanized to obtain bronchoalveolar lavage fluid and lung tissues of the mice. The effect of corilagin on alleviating the symptoms of the Staphylococcus aureus-infected murine pneumonia model was evaluated by indicators such as bacterial colonization, wet / dry weight ratio of lung tissues, and levels of inflammatory factors in bronchoalveolar lavage fluid. The mice in the infection group started to die at 24 hours. After the infection lasted for 72 hours, the survival rate of the mice in the infection group was 3.33%. The mice in the corilagin treatment group started to die at 36 hours, and the final survival rate of this group of mice was 46.67%, which was 43.34% higher than that of the infection group ( Figure 7 a). The bacterial colonization in the lung tissues of the mice in the corilagin treatment group was significantly lower than that in the infection group ( Figure 7 b), the wet / dry weight ratio of the lung tissues of the mice in the corilagin treatment group was significantly lower than that in the infection group ( Figure 7 c), and the levels of inflammatory factors IL-1β and TNF-α in the bronchoalveolar lavage fluid of the tissues of the mice in the corilagin treatment group were both significantly lower than those in the infection group ( Figure 7 d). The above results indicate that corilagin significantly alleviated the edema and inflammatory response of the lung tissues of the mice by inhibiting the colonization of Staphylococcus aureus in the lung tissues of the mice, thereby delaying the death time of the infected mice and significantly improving the survival rate of the infected mice. The above is only a preferred embodiment of the present invention and does not impose any form of limitation on the present invention. Any person skilled in the art can make many possible changes and modifications to the technical solution of the present invention, or modify it into an equivalent embodiment with equivalent changes, without departing from the spirit and technical solution of the present invention. Therefore, any simple modification, equivalent replacement, equivalent change, and modification made to the above embodiments based on the technical essence of the present invention without departing from the technical solution of the present invention still fall within the scope of protection of the technical solution of the present invention.

Claims

1. Use of corilagin in the preparation of Staphylococcus aureus inhibitors.

2. The use according to claim 1, characterized in that: The inhibitory effect of corilagin on the activity of cell wall hydrolases of Staphylococcus aureus.

3. The use according to claim 1, characterized in that: The inhibitory effect of corilagin on the activity of α-hemolysin of Staphylococcus aureus.

4. The use according to claim 1, characterized in that: The purity of the corilagin is ≥98%.

5. The use according to claim 1, characterized in that: The structural formula of the corilagin is as follows:

6. The use according to claim 1, characterized in that: Use of the corilagin or the Staphylococcus aureus inhibitor prepared therefrom in preparing drugs for Staphylococcus aureus infection.

Images