CN115737624B - Application of natural medicine in preparation of anti-Acinetobacter baumannii medicine - Google Patents
Application of natural medicine in preparation of anti-Acinetobacter baumannii medicine Download PDFInfo
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- CN115737624B CN115737624B CN202211164703.9A CN202211164703A CN115737624B CN 115737624 B CN115737624 B CN 115737624B CN 202211164703 A CN202211164703 A CN 202211164703A CN 115737624 B CN115737624 B CN 115737624B
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- acinetobacter baumannii
- medicine
- growth
- meropenem
- harmine
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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Abstract
The invention relates to the technical field of medicines, in particular to application of a natural medicine in preparation of an anti-Acinetobacter baumannii medicine. The invention discovers that various natural medicines can be used for preparing antibacterial medicines; the mangiferin has good inhibition effect on the growth of Acinetobacter baumannii; the caffeic acid methyl ester has good inhibition effect on Acinetobacter baumannii; the invention also discovers that harmine can be used as a synergist of meropenem to enhance the antibacterial effect of the meropenem on klebsiella pneumoniae; either harmine alone or meropenem alone cannot inhibit the growth of klebsiella pneumoniae, but 128 μg/mL harmine in combination with 4 μg/mL meropenem can significantly inhibit the growth of klebsiella pneumoniae and reduce its growth rate to below 5%.
Description
The scheme is as follows: the division of 202111677086.8 cases (application date: 2021, 12, 31, invention creation name: application of natural medicine in preparing antibacterial medicine).
Technical Field
The invention relates to the technical field of medicines, in particular to application of a natural medicine in preparation of an antibacterial medicine.
Background
The disclosure of this background section is only intended to increase the understanding of the general background of the invention and is not necessarily to be construed as an admission or any form of suggestion that this information forms the prior art already known to those of ordinary skill in the art.
Bacterial resistance is also called drug resistance, which means the tolerance of bacteria to the action of antibacterial drugs, and once the drug resistance is generated, the antibacterial action of the drugs is obviously reduced. When antibiotics are used for a long time, most sensitive strains are continuously killed, and drug-resistant strains are propagated in a large quantity to replace the sensitive strains, so that the drug-resistant rate of bacteria to the drug is continuously increased. Among the numerous resistant bacteria, multi-resistant acinetobacter baumannii (MDR-AB) refers to 3 and more classes of drugs resistant to class 5 antimicrobial drugs, and is a multi-resistant strain including cephalosporins (e.g., ceftazidime or cefepime), carbapenems (e.g., imipenem), β -lactamase inhibitors (e.g., cefoperazone/sulbactam), fluoroquinolones (e.g., ciprofloxacin), and aminoglycosides (e.g., amikacin). The inventor finds that some multi-drug resistant acinetobacter baumannii antibacterial preparations in the prior art can produce inhibition effects on the multi-drug resistant acinetobacter baumannii only at a concentration of at least 25 mug/mL, and the inhibition effects are not very different along with the increase of the concentration of the antibacterial preparations.
In addition, klebsiella pneumoniae is an important gram-negative pathogenic bacterium, and can cause various infectious diseases, and in recent years, the drug resistance type of klebsiella pneumoniae to carbapenem antibiotics is rapidly increased. Thus, there is an urgent need to explore means and medicaments capable of overcoming klebsiella pneumoniae.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention aims to provide the application of natural medicines in the preparation of antibacterial medicines, and the invention discovers that both natural medicines mangiferin and caffeic acid methyl ester can be used as antibacterial medicines to inhibit the growth of Acinetobacter baumannii, and natural medicines harmine can be used as sensitizer of the antibiotic meropenem to realize the function of inhibiting klebsiella pneumoniae, thereby providing an effective solution for solving the drug resistance of bacteria.
In a first aspect of the invention, there is provided: the application of natural medicine in preparing antibacterial medicine;
preferably, the natural medicine comprises: mangiferin, methyl caffeate, harmine;
specifically, the invention provides application of mangiferin in preparing a medicine for resisting Acinetobacter baumannii; preferably, the acinetobacter baumannii is multi-drug resistant acinetobacter baumannii;
according to the invention, the study shows for the first time that mangiferin has good in-vitro antibacterial activity on Acinetobacter baumannii, and can inhibit the growth of more than 80% of experimental strains when the concentration of mangiferin is 64 mug/mL; when the concentration of mangiferin is 128 mug/mL, the mangiferin can completely inhibit the growth of experimental strains; however, mangiferin has no inhibiting effect on escherichia coli, klebsiella pneumoniae and staphylococcus aureus.
The invention also provides application of the caffeic acid methyl ester in preparing the anti-Acinetobacter baumannii medicament; preferably, the acinetobacter baumannii is multi-drug resistant acinetobacter baumannii;
according to the research of the invention, the caffeic acid methyl ester has a good in-vitro inhibition effect on the Acinetobacter baumannii strain, the caffeic acid methyl ester can obviously inhibit the growth of the experimental strain at the concentration of more than 32 mug/mL, and the antibacterial rate of the experimental strain at the concentration of 128 mug/mL is more than 99%.
The invention also provides an application of the harmine as an antibiotic sensitizer; preferably, the antibiotic is meropenem;
further, an application of harmine and meropenem in preparing medicine for resisting klebsiella pneumoniae is provided;
according to the research, the harmine can be used as a synergist of meropenem, so that the antimicrobial effect of the harmine on klebsiella pneumoniae can be enhanced, and the harmine has a remarkable inhibiting effect on klebsiella pneumoniae KP 37; either harmine alone or meropenem alone cannot inhibit the growth of klebsiella pneumoniae KP 37; when 128 mu g/mL of harmine is combined with 4 mu g/mL of meropenem, the growth of KP37 can be obviously inhibited, and the growth rate can be reduced to below 5%, namely, the combination of 128 mu g/mL of harmine and 4 mu g/mL of meropenem has obvious inhibition effect on KP 37.
In a second aspect of the present invention, an antibacterial agent comprising mangiferin, methyl caffeate, or a combination of harmine and meropenem.
In a third aspect of the invention, a pharmaceutical formulation comprises the above antibacterial agent and a pharmaceutically acceptable carrier or adjuvant.
The specific embodiment of the invention has the following beneficial effects:
the invention discovers that various natural medicines can be used for preparing antibacterial medicines; the mangiferin has good inhibition effect on the growth of Acinetobacter baumannii, and can inhibit the growth of more than 80% of experimental strains when the concentration of the mangiferin is 64 mug/mL; when the concentration of mangiferin is 128 mug/mL, the mangiferin can completely inhibit the growth of experimental strains;
the invention also discovers that the caffeic acid methyl ester has good inhibition effect on Acinetobacter baumannii; the caffeic acid methyl ester can obviously inhibit the growth of the experimental strain at the concentration of more than 32 mug/mL, and the antibacterial rate of the experimental strain at the concentration of 128 mug/mL is more than 99 percent;
the invention also discovers that harmine can be used as a synergist of meropenem to enhance the antibacterial effect of the meropenem on klebsiella pneumoniae; either harmine alone or meropenem alone cannot inhibit the growth of klebsiella pneumoniae, but 128 μg/mL harmine in combination with 4 μg/mL meropenem can significantly inhibit the growth of klebsiella pneumoniae and reduce its growth rate to below 5%.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the invention.
FIG. 1 shows the effect of mangiferin at different concentrations on the growth rate of different strains in example 1;
wherein, graph A is the effect on the growth rate of Acinetobacter baumannii AB11 strain;
panel B shows the effect on E.coli E1 strain growth rate;
panel C shows the effect on the growth rate of Klebsiella pneumoniae KP50 strain;
panel D shows the effect on the growth rate of Staphylococcus aureus M11 strain;
FIG. 2 is a graph showing the effect of different concentrations of amygdalin on the growth rate of different strains in example 1;
wherein, graph A is the effect on the growth rate of Acinetobacter baumannii AB11 strain;
panel B shows the effect on E.coli E1 strain growth rate;
panel C shows the effect on the growth rate of Klebsiella pneumoniae KP50 strain;
panel D shows the effect on the growth rate of Staphylococcus aureus M11 strain.
Detailed Description
It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the present application. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
It is noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments in accordance with the present application. As used herein, the singular is also intended to include the plural unless the context clearly indicates otherwise, and furthermore, it is to be understood that the terms "comprises" and/or "comprising" when used in this specification are taken to specify the presence of stated features, steps, operations, devices, components, and/or combinations thereof.
In one or more embodiments of the present invention, there is provided a method of: the application of natural medicine in preparing antibacterial medicine;
preferably, the natural medicine comprises: mangiferin, methyl caffeate, harmine;
specifically, the invention provides application of mangiferin in preparing a medicine for resisting Acinetobacter baumannii; preferably, the acinetobacter baumannii is multi-drug resistant acinetobacter baumannii;
preferably, the effective concentration of mangiferin for inhibiting Acinetobacter baumannii in vitro is more than or equal to 64 mug/mL or more than or equal to 128 mug/mL.
The invention also provides application of the caffeic acid methyl ester in preparing the anti-Acinetobacter baumannii medicament; preferably, the acinetobacter baumannii is multi-drug resistant acinetobacter baumannii;
preferably, the effective concentration of the caffeic acid methyl ester for inhibiting Acinetobacter baumannii in vitro is more than or equal to 32 mug/mL or more than or equal to 128 mug/mL.
Mangiferin (English name: mangiferin; CAS number: 4773-96-0; molecular formula: C) 19 H 18 O 11 The method comprises the steps of carrying out a first treatment on the surface of the Molecular weight: 422.35 Is a biological active ingredient from different parts of higher plants and mango fruits, has strong antioxidant activity and multi-factor pharmacological actions, and comprises the functions of resisting diabetes, resisting tumor, regulating fat metabolism, protecting heart, resisting hyperuricemia, neuroprotection, resisting oxidation, resisting inflammation, relieving fever, easing pain, resisting bacteria, resisting viruses and regulating immunity; the caffeic acid methyl ester is an ester derivative which is extracted from plants and then oxidized, and researches show that the caffeic acid methyl ester has various pharmacological effects. However, mangiferin or methyl caffeate has no effect of resisting Acinetobacter baumannii in the prior art.
According to the invention, the study shows for the first time that mangiferin has good in-vitro antibacterial activity on Acinetobacter baumannii, and can inhibit the growth of more than 80% of experimental strains when the concentration of mangiferin is 64 mug/mL; when the concentration of mangiferin is 128 mug/mL, the mangiferin can completely inhibit the growth of experimental strains; however, mangiferin has no inhibiting effect on escherichia coli, klebsiella pneumoniae and staphylococcus aureus.
The invention also discovers that the methyl caffeate has good in-vitro inhibition effect on the Acinetobacter baumannii strain, the methyl caffeate can obviously inhibit the growth of the experimental strain at the concentration of more than 32 mug/mL, and the antibacterial rate of the experimental strain at the concentration of 128 mug/mL is more than 99%.
The invention also provides an application of the harmine as an antibiotic sensitizer; preferably, the antibiotic is meropenem;
further, an application of harmine and meropenem in preparing medicine for resisting klebsiella pneumoniae is provided;
preferably, the concentration ratio of the harmine to the meropenem for in vitro inhibition of klebsiella pneumoniae is 32:1, a step of;
preferably, when the harmine and the meropenem are combined for in vitro inhibition of klebsiella pneumoniae, the minimum effective concentration of the harmine is 128 mug/mL, and the minimum effective concentration of the meropenem is 4 mug/mL;
the harmine is a beta-carboline alkaloid extracted from the perennial herb peganum harmala, and has various pharmacological effects of resisting bacteria, inflammation, tumor and the like; however, the prior art does not disclose that harmine can be used as a sensitizer for antibiotics to inhibit the growth of Klebsiella pneumoniae.
The research of the invention shows that the harmine can be used as the synergist of meropenem to enhance the antibacterial effect of the harmony to klebsiella pneumoniae and has obvious inhibition effect to klebsiella pneumoniae KP 37; either harmine alone or meropenem alone cannot inhibit the growth of klebsiella pneumoniae KP 37; when 128 mu g/mL of harmine is combined with 4 mu g/mL of meropenem, the growth of KP37 can be obviously inhibited, and the growth rate can be reduced to below 5%, namely, the combination of 128 mu g/mL of harmine and 4 mu g/mL of meropenem has obvious inhibition effect on KP 37.
In one or more embodiments of the present invention, an antibacterial agent is provided, which comprises mangiferin, methyl caffeate, or a combination of harmine and meropenem.
In one or more embodiments of the present invention, a pharmaceutical formulation is provided, comprising the above antibacterial agent and a pharmaceutically acceptable carrier or adjuvant.
The pharmaceutically acceptable carrier or auxiliary material is selected from one or more of diluents, disintegrants, precipitation inhibitors, glidants, binders, dispersants, suspending agents, isotonic agents, thickening agents, emulsifying agents, preservatives, stabilizers, hydration agents, ion exchangers, flavoring agents or antioxidants.
In one or more embodiments, the dosage form of the pharmaceutical formulation includes a powder, a tablet, a granule, a capsule, a solution, an emulsion, or a suspension; injection, transdermal preparation, or spray.
The invention is further illustrated and described below in connection with specific examples.
Example 1
Static action determination of mangiferin anti-multiple drug-resistant Acinetobacter baumannii
1. Material
1.1 Experimental strains
During this experiment, the strains (Acinetobacter baumannii AB11, E1E, klebsiella pneumoniae KP50, and Staphylococcus aureus M11) were all obtained from clinical laboratory at hospital, and have been identified as multi-drug resistant strains and their susceptibility to clinically common antibiotics was determined (as in Table 1). The test strains were all stored in-80℃refrigerator and subcultured on MHA solid medium prior to use, with a minimum of two subcultures.
TABLE 1 determination of the sensitivity of test strains to clinically usual antibiotics
1.2 drugs and Primary Agents
Mangiferin, dalian Mei Lun biotechnology Co., ltd (Liaoning Dalian); amygdalin, dalian Mei Lun biotechnology Co., ltd (Liaoning Dalian); calmodulin MH broth (CAMHB broth), qingdao high-tech Industrial garden Haibo biotechnology Co., ltd (Shandong Qingdao); MHA agar medium, qingdao high technology industrial park, seabo biotechnology limited (Qingdao, shandong); normal saline, shanghai Ala Biochemical technologies Co., ltd. (Shanghai);
2. method of
2.1 preparation of bacterial liquid
Thawing Acinetobacter baumannii preserved at-20deg.C at room temperature, inoculating onto MHA agar medium, culturing at 35deg.C for 18-20 hr, inoculating single colony with good development, culturing at 35deg.C for 18-20 hr to ensure strainIn the logarithmic growth phase. Selecting a plurality of bacterial colonies, preparing into bacterial suspension by using physiological saline, adjusting the turbidity of a sample tube to be consistent with that of a 0.5 Meisshiza turbidimetric tube, and at the moment, the concentration of bacterial liquid is about 1.5 multiplied by 10 8 Diluting CFU/mL with CAMHB broth to give final working concentration of 5×10 5 CFU/mL, concentration verification was finally performed with viable counts.
2.2 preparation of mother liquor of medicine
Appropriate drug solvents were selected according to the guidelines of the American clinical and laboratory standards institute (CLSI M100-S30) and the instructions of the reagent manufacturer. Mangiferin and amygdalin are respectively dissolved in dimethyl sulfoxide to prepare a solution with the concentration of 40960 mug/mL, and the solution is stored in a refrigerator with the temperature of minus 20 ℃ for use. Before each use, the medicine is naturally thawed and thawed in a refrigerator at 4 ℃.
2.3 determination of the action of mangiferin against Acinetobacter baumannii
According to the micro-broth dilution method of CLSIM100-S30 scheme, the liquid medicine is diluted by CAMHB broth to 2 times of working concentration, and the concentration range of mangiferin application is 0-512 mug/mL. 100 mu L of mangiferin is sucked from low to high concentration, 96-well plates are added, and 100 mu L of bacterial liquid (5 multiplied by 10) is added into each well 5 CFU/mL), wherein positive growth control wells contained only bacterial fluid without drug and blank control wells contained only camdb broth. The dosed 96-well plates were incubated in a 35℃incubator for 18h according to the requirements of the CLSIM100-S30 protocol, the results were observed and the bacterial growth rate was recorded.
3. Results
TABLE 2 influence of mangiferin on the growth rate of multiple resistant Acinetobacter baumannii AB11
As can be seen from Table 2 and FIG. 1A, mangiferin can inhibit the growth of experimental strain AB11 by more than 80% at a concentration of 64 μg/mL; the mangiferin can completely inhibit the growth of the experimental strain AB11 at the concentration of 128 mug/mL. As can be seen from FIGS. 1B-D, mangiferin has no inhibitory effect on three strains of E1, klebsiella pneumoniae KP50 and Staphylococcus aureus M11. As can be seen from FIGS. 2A-D, amygdalin had no inhibitory effect on all four strains of this example.
Example 2
Action of caffeic acid methyl ester on multiple drug resistant Acinetobacter baumannii
Experimental strains
The clinically isolated Acinetobacter baumannii (AB 2, AB11, AB 12) were collected, the strains were all correctly identified and their susceptibility to clinically usual antibiotics was determined.
Preparation of bacterial suspension
3 to 5 colonies were picked from MHA plates that had been isolated and cultured overnight and inoculated into sterile 0.9% sodium chloride solution. The bacterial liquid was adjusted to 0.5 Maillard turbidity (about 1X 10) by using a Maillard turbidimeter tube 8 CFU/mL) was diluted 100-fold (approximately 1X 10) with calcd MH broth 6 CFU/mL)。
Preparation of methyl caffeate solution
The concentration of the methyl caffeate stock solution was prepared according to the requirements of the standards of the American clinical laboratory standardization institute and was 40960 mug/mL.
Trace broth dilution method
Methyl caffeate was diluted in calcium-conditioned MH broth to 3 dilution concentrations (32. Mu.g/mL, 64. Mu.g/mL, 128. Mu.g/mL). To the wells of the sterile 96-well plate were added 100. Mu.L of each concentration of methyl caffeate solution, and 100. Mu.L of diluted bacterial solution was added to each well, and negative control and medium control were performed. Culturing at 37 ℃ for 16-18 h, observing the result and recording the corresponding antibacterial rate of each caffeic acid methyl ester solution.
Experimental results
Drug sensitivity results of the experimental strains
The experimental strains used were resistant to the following antibiotics: amikacin, gentamicin, imipenem, meropenem, cefazolin, ceftazidime, cefotaxime, cefepime, aztreonam, ampicillin, piperacillin, amoxicillin/clavulanic acid, ampicillin/sulbactam, piperacillin/tazobactam, sulfamethoxazole/trimethoprim, chloramphenicol, ciprofloxacin, levofloxacin, tetracycline. Therefore, the experimental strains are multi-drug resistant Acinetobacter baumannii.
Bacteriostasis rate of methyl caffeate with different concentrations on multi-drug-resistant acinetobacter baumannii
TABLE 3 antibacterial Rate of methyl caffeate against multiple resistant Acinetobacter baumannii
And (3) table notes: the growth rate (%) in the table is expressed as the mean ± standard deviation of the three experiments. The statistical control group for each methyl caffeate concentration was a drug-free group (methyl caffeate concentration was 0. Mu.g/mL). Statistical analysis p <0.05 was considered statistically different using the Dunnett method in one-way ANOVA analysis.
As can be seen from Table 3, the methyl caffeate significantly inhibited the growth of the experimental strain (p < 0.05) at a concentration of 32. Mu.g/mL or more, compared to the control group to which no methyl caffeate was added. Compared with the control group without the caffeic acid methyl ester, the bacteriostatic rate of the caffeic acid methyl ester on AB2, AB11 and AB12 reaches more than 99 percent (p < 0.05) at the concentration of 128 mug/mL.
Example 3
Determination of antibacterial action of harmine-enhanced meropenem on klebsiella pneumoniae
Experimental strains: klebsiella pneumoniae
In the experimental process, the strains are obtained and identified from clinical laboratory in a hospital, the strains for the experiment are stored in a refrigerator at the temperature of minus 80 ℃, and are subjected to subculture on MHA solid medium before use, and the subculture is carried out twice at least.
Medicaments and primary agents
Harmine, dalian Mei Lun biotechnology Co., ltd (Liaoning Dalian); meropenem, daltemeilan biotechnology limited (liaoning daltesection); calmodulin MH broth (CAMHB broth), qingdao high-tech Industrial garden Haibo biotechnology Co., ltd (Shandong Qingdao); MHA agar medium, qingdao high technology industrial park, seabo biotechnology limited (Qingdao, shandong); phosphate buffer (phosphate buffered saline, PBS), daltemei biotechnology limited (liaoning dalteh).
Method
Preparation of culture medium and medicinal storage liquid
Preparation of camdb broth: weighing 8.80g of CAMHB powder, placing into 500mL glass bottle, adding distilled water, stirring to dissolve, sterilizing at 121deg.C under high pressure for 30min, cooling, and storing in 4 deg.C refrigerator for use.
Preparation of MHA agar medium: weighing 16.80g of MHA powder, placing into 500mL conical flask, adding distilled water, stirring to dissolve, autoclaving at 121deg.C for 30min, cooling, and storing in a refrigerator at 4deg.C for use.
Preparation of a drug storage solution: appropriate drug solvents were selected according to the guidelines of the American clinical and laboratory standards institute (CLSI M100-S30) and the instructions of the reagent manufacturer. Dissolving harmine in dimethyl sulfoxide to obtain 20480 μg/mL solution; meropenem was dissolved in sterile distilled water to prepare a solution with a concentration of 5120. Mu.g/mL. All the drug stock was kept in a refrigerator at-20 ℃ for use. Before each use, the medicine is naturally thawed and thawed in a refrigerator at 4 ℃.
Determination of antibacterial action
Preparation of bacterial liquid
Taking out the preserved strain from the refrigerator at-80 ℃, naturally dissolving the strain in a constant temperature oven at 37 ℃, picking a proper amount of bacterial liquid by a bacterial taking ring, inoculating the bacterial liquid to MHA solid culture medium, and culturing the bacterial liquid in the constant temperature incubator at 37 ℃ for 24 hours. Then picking single colony with better growth, inoculating on MHA solid culture medium again, subculturing, and culturing at 37 ℃ for 24 hours. At least three times of subculture, the method can be used for experimental study. Selecting proper amount of colony with good growth from MHA solid culture medium, dissolving in sterile test tube containing sterile PBS solution, shaking and mixing uniformly on vortex mixer, comparing with Chinese bacteria turbidity standard tube, and adjusting the concentration of experimental bacterial solution to 0.5 McSt (1.5X10) 8 CFU/mL), and then sterile camdb brothDiluting to make final working concentration of bacterial liquid 10 6 CFU/mL。
Dilution of liquid medicine
The dilution method of each medicine is the same, and a double micro dilution method is adopted. 10 sterile glass test tubes were placed on a test tube rack, numbered 1-10, and an appropriate amount of sterile camdb broth was used for culture in a sterile small beaker. Taking a proper amount of medicine storage liquid and CAMHB culture, and fully shaking the medicine storage liquid and the CAMHB culture in a test tube to ensure that the concentration in the tube is 2 or 4 times of the working concentration in a 96-well plate.
Determination of antibacterial action
The experiments were divided into 3 groups, specifically as follows:
single harmine group: 100. Mu.L of the bacterial suspension+100. Mu.L of 256. Mu.g/mL harmel solution;
meropenem alone group: 100. Mu.L of bacterial suspension+100. Mu.L of 8. Mu.g/mL meropenem solution;
drug combination group: 10. Mu.L of the bacterial suspension+50. Mu.L of 512. Mu.g/mL of harmel solution of dehydropeganum harmala+50. Mu.L of 16. Mu.g/mL of meropenem solution.
The test was run with a growth control group (200. Mu.L of bacterial suspension) as control. After the liquid medicine and the bacterial liquid are added, the 96-well plate is placed in a constant temperature incubator at 37 ℃ for culturing for 18 hours, experimental results are observed, and each experiment is repeated three times.
Results
Harmine enhances the inhibition of meropenem on klebsiella pneumoniae KP37 growth rate
TABLE 4 Effect of harmine and meropenem combination on strain growth Rate
And (3) table notes: the growth rate (%) in the table is expressed as the average value.+ -. Standard deviation of the growth rate in three experiments. The statistical control group of each experimental group was a drug-free group (growth control group). Statistical analysis p <0.001 was considered statistically different using the Dunnett method in the one-way ANOVA analysis.
As can be seen from Table 4, either harmine alone or meropenem alone did not inhibit the growth of Klebsiella pneumoniae KP37 (p > 0.001) compared to the non-drug loaded growth control group; compared with a growth control group without adding a drug, 128 mu g/mL of harmine can obviously inhibit the growth of KP37 when being combined with 4 mu g/mL of meropenem, and the growth rate can be reduced to below 5%, namely, 128 mu g/mL of harmine and 4 mu g/mL of meropenem are combined to obviously inhibit KP37 (p < 0.001).
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (2)
1. The application of the natural medicine in preparing the antibacterial medicine is characterized in that the natural medicine is mangiferin or caffeic acid methyl ester, and the application is the application in preparing the medicine for resisting multi-drug-resistant acinetobacter baumannii;
the effective concentration of mangiferin for inhibiting multi-drug resistant Acinetobacter baumannii in vitro is more than or equal to 64 mug/mL;
the effective concentration of the caffeic acid methyl ester for inhibiting the multi-drug-resistant Acinetobacter baumannii in vitro is more than or equal to 32 mug/mL.
2. The use of a natural drug as claimed in claim 1 for the preparation of an antibacterial drug,
the effective concentration of mangiferin for inhibiting multi-drug resistant Acinetobacter baumannii in vitro is more than or equal to 128 mug/mL;
the effective concentration of the caffeic acid methyl ester for inhibiting the multi-drug-resistant Acinetobacter baumannii in vitro is more than or equal to 128 mug/mL.
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| CN115414350B (en) * | 2022-09-22 | 2023-08-04 | 湖北省农业科学院畜牧兽医研究所 | Application of mangiferin in preparing medicine for inhibiting haemophilus parasuis |
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