CN105193784B - Application of the ginkgetin in preparation treatment streptococcus suis infection drug - Google Patents
Application of the ginkgetin in preparation treatment streptococcus suis infection drug Download PDFInfo
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- CN105193784B CN105193784B CN201510680558.3A CN201510680558A CN105193784B CN 105193784 B CN105193784 B CN 105193784B CN 201510680558 A CN201510680558 A CN 201510680558A CN 105193784 B CN105193784 B CN 105193784B
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- streptococcus suis
- ginkgetin
- suis infection
- infection
- drug
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- SQGLUEWZRKIEGS-UHFFFAOYSA-N Ginkgetin Natural products C1=CC(OC)=CC=C1C1=CC(=O)C2=C(O)C=C(OC)C(C=3C(=CC=C(C=3)C=3OC4=CC(O)=CC(O)=C4C(=O)C=3)O)=C2O1 SQGLUEWZRKIEGS-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229930045534 Me ester-Cyclohexaneundecanoic acid Natural products 0.000 title claims abstract description 28
- AIFCFBUSLAEIBR-UHFFFAOYSA-N ginkgetin Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C(C=1)=CC=C(OC)C=1C1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=C(O)C=C1 AIFCFBUSLAEIBR-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 206010061372 Streptococcal infection Diseases 0.000 title claims abstract description 21
- 239000003814 drug Substances 0.000 title claims abstract description 12
- 229940079593 drug Drugs 0.000 title claims abstract description 8
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 208000015181 infectious disease Diseases 0.000 claims description 4
- 208000035143 Bacterial infection Diseases 0.000 claims 2
- 208000022362 bacterial infectious disease Diseases 0.000 claims 2
- 238000002347 injection Methods 0.000 claims 2
- 239000007924 injection Substances 0.000 claims 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 241000194017 Streptococcus Species 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 230000000813 microbial effect Effects 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 9
- 206010018910 Haemolysis Diseases 0.000 abstract description 7
- 230000008588 hemolysis Effects 0.000 abstract description 7
- 230000001225 therapeutic effect Effects 0.000 abstract description 5
- 210000003743 erythrocyte Anatomy 0.000 abstract description 4
- 235000008100 Ginkgo biloba Nutrition 0.000 abstract description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 abstract description 3
- 241000218628 Ginkgo Species 0.000 abstract description 2
- 235000011201 Ginkgo Nutrition 0.000 abstract description 2
- 230000003115 biocidal effect Effects 0.000 abstract description 2
- 230000006378 damage Effects 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 210000002540 macrophage Anatomy 0.000 abstract description 2
- 206010059866 Drug resistance Diseases 0.000 abstract 1
- 238000009509 drug development Methods 0.000 abstract 1
- 239000003596 drug target Substances 0.000 abstract 1
- 239000002547 new drug Substances 0.000 abstract 1
- 241000194021 Streptococcus suis Species 0.000 description 12
- 108010006464 Hemolysin Proteins Proteins 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000003228 hemolysin Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 3
- 230000005779 cell damage Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 201000009906 Meningitis Diseases 0.000 description 2
- 230000001147 anti-toxic effect Effects 0.000 description 2
- 230000002949 hemolytic effect Effects 0.000 description 2
- 230000007918 pathogenicity Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241001478240 Coccus Species 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 241000218791 Ginkgoaceae Species 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000034486 Multi-organ failure Diseases 0.000 description 1
- 208000010718 Multiple Organ Failure Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 230000001464 adherent effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 206010014665 endocarditis Diseases 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 description 1
- 244000039328 opportunistic pathogen Species 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000007923 virulence factor Effects 0.000 description 1
- 239000000304 virulence factor Substances 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of the ginkgetin in preparation treatment streptococcus suis infection drug.The present invention confirms that ginkgetin has preferable therapeutic effect to streptococcus suis infection by the therapeutic effect test of the test of rabbit erythrocyte hemolysis, the protection test of macrophage (J774) damage and mouse streptococcus suis infection.Present invention ginkgo extract for treating streptococcus suis infection has and has no drug resistance compared with antibiotic treatment, the high advantage of cure rate.Therefore ginkgetin can be used for anti-streptococcus suis infection new drug development, and confirm important in inhibiting to drug targets.
Description
Technical field
The present invention relates to application of the ginkgetin in preparation treatment streptococcus suis infection drug, belong to field of medicaments.
Background technique
Ginkgetin is present in the leaf and exosper of Ginkgoaceae plant Ginkgo biloba.Ginkgetin has various biological activity, also
Have the effects that expand blood vessel and treats angina pectoris.As the novel innate efficacy factor, ginkgetin is in food industry, medical work
Industry etc. plays an important role.But have no the report of ginkgo extract for treating streptococcus suis infection both at home and abroad so far.
Streptococcus suis is a kind of infectious diseases common to human beings and animals opportunistic pathogen of serious world-wide prevalence, can lead to people and moves
Meningitis, septicemia and the endocarditis of object；In addition, the multiple organ failure such as kidney, liver, lungs and heart can also be caused
With dead and hearing permanent loss.Streptococcus suis infection is set to B class disease by OIE, and very big threat is caused to public health.
The pathogenicity of Streptococcus suis and its virulence factor are closely related, and wherein the hemolysin of Streptococcus suis secretion may make pathogen to escape
It host immune system attacks and breaks through blood-brain barrier and causes meningitis, it is even dead.Therefore hemolysin is Streptococcus suis
Infect the potential target of antitoxin power medicament research and development.In recent years due to the abuse of antibiotic and its inevitably easy inducible resistance
Property occurrence and development, therefore there is an urgent need to seek novel, small toxicity and select the small anti-infectives of pressure.The present invention is for the first time
It was found that can directly neutralize pore-forming activity and the inside and outside inhibition Streptococcus suis of Hemolysin without the active ginkgetin of antibacterial
Pathogenicity.
Summary of the invention
The purpose of the present invention is to provide a kind of pair of streptococcus suis infections to have medicative antitoxin power drug.
The molecular structure of ginkgetin is as follows:
The present invention passes through the test of rabbit erythrocyte hemolysis, the protection test of macrophage (J774) damage and mouse pig chain
Coccus infection therapeutic effect test, it was demonstrated that ginkgetin can inhibit Hemolysin pore-forming activity and its to pig hammer
Bacterium infection has therapeutic effect.
Specific embodiment
1. hemolytic test
The Hemolysin of purifying makees continuous doubling dilution in 96 orifice plates, is added 10 in each hole7A rabbit
Red blood cell is centrifuged after being incubated for 30min in 37 DEG C.The highest extension rate for wherein dissolving red blood cell is considered as haemolysis titre
(Hemolysis titre)。
The haemolysis titre such as table 1 of the lower Hemolysin of various concentration ginkgetin processing:
Inhibiting effect of 1. ginkgetin of table to Hemolysin hemolytic activity
| Ginkgetin (μ g/ml) | Haemolysis titre (Hemolysis titre) |
| 0 | 4096 |
| 2 | 512 |
| 4 | 128 |
| 8 | 16 |
| 16 | 2 |
2. ginkgetin mediates the protectiveness of J774 cellular damage effect to test Streptococcus suis
Streptococcus suis is cultivated in THB culture medium to OD600nm=0.8, and the bacterial cultures of 5ml is taken, and is centrifuged and is resuspended
In the DMEM culture medium of 10ml.J774 cell in DMEM culture medium (be added 10% fetal calf serum) in 37 DEG C, 5%CO2Training
After supporting for 24 hours, with 2 × 104A cells/well is laid in 96 porocyte culture plates, every 200 μ l of hole.After cell is adherent, pig hammer is added
Bacterium bacteria suspension (bacterium: cell=5:1), and the ginkgetin of various concentration is added is placed in cell incubator in 37 DEG C, 5%CO2
Co-culture 5h.100 μ l supernatant of centrifuging and taking, and LDH reagent 100 μ l, 37 DEG C of incubation 30min are added, after survey 570nm with microplate reader and inhale
Light value calculates the survival rate (table 2) of various concentration ginkgetin processing group cell.The result shows that ginkgetin can protect Streptococcus suis
To the cellular damage that J774 is mediated, and dose dependent is presented in the effect.
The cellular damage that 2. ginkgetin of table inhibits Streptococcus suis to mediate J774
| Ginkgetin (μ g/ml) | Cell mortality (%) |
| 0 | 56.37±5.07 |
| 2 | 46.02±5.63 |
| 4 | 35.17±4.42 |
| 8 | 20.79±3.76 |
| 16 | 6.43±4.36 |
3. the experimental therapeutic of mouse streptococcus suis infection is studied
3.1 mouse streptococcus suis infection models
BALB/c mouse (male, 18-22g) is through being injected intraperitoneally 200 μ l Streptococcus suis suspensions (1010CFU/ml), establish small
Mouse streptococcus suis infection model.
The test of 3.2 protective rates
The ginkgetin of 100,50 and 25mg/kg (100 μ l) is subcutaneously injected in 2h respectively after mouse inoculation Streptococcus suis, at interval of
6h is administered once.Control group is not administered, 100 μ l physiological saline, every group of 50 mouse are subcutaneously injected between simultaneously.It is given by dosage regimen
After medicine, the death rate after mouse infection streptococcus suis 2 4h, 48h and 72h is recorded respectively.The result shows that (table 3), gives through ginkgetin
After medicine treatment, the death rate (P < 0.05) of mouse streptococcus suis infection is significantly reduced.
3. ginkgetin of table reduces the mouse streptococcus suis infection death rate
Claims (3)
1. application of the ginkgetin in preparation treatment streptococcus suis infection drug.
2. application of the ginkgetin as described in claim 1 in preparation treatment streptococcus suis infection drug, it is characterised in that institute
The streptococcus suis infection stated refers to the bacterial infection as caused by streptococcus bacterium, and wherein bacterial infection refers to by pig hammer
Microbial infection.
3. application of the ginkgetin as described in claim 1 in preparation treatment streptococcus suis infection drug, it is characterised in that institute
The ginkgetin preparation stated be suitble to clinical use anti-streptococcus suis infection pharmaceutical preparation, the pharmaceutical preparation be injection,
Capsule, tablet or powder-injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510680558.3A CN105193784B (en) | 2015-10-20 | 2015-10-20 | Application of the ginkgetin in preparation treatment streptococcus suis infection drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510680558.3A CN105193784B (en) | 2015-10-20 | 2015-10-20 | Application of the ginkgetin in preparation treatment streptococcus suis infection drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105193784A CN105193784A (en) | 2015-12-30 |
| CN105193784B true CN105193784B (en) | 2019-04-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510680558.3A Active CN105193784B (en) | 2015-10-20 | 2015-10-20 | Application of the ginkgetin in preparation treatment streptococcus suis infection drug |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105193784B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106667996B (en) * | 2017-02-27 | 2019-04-09 | 吉林大学 | Morin is preparing the application in anti-streptococcus suis medicine |
| CN111973585B (en) * | 2020-09-08 | 2022-04-08 | 广州中医药大学第一附属医院 | Application of ginkgetin in preparing medicine for resisting myeloid-inhibiting cells |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005092324A1 (en) * | 2004-03-19 | 2005-10-06 | The Trustees Of Columbia University In The City Of New York | Ginkgolide compounds, compositions, extracts, and uses thereof |
| CN104940184A (en) * | 2014-03-25 | 2015-09-30 | 上海医药工业研究院 | Application of ginkgetin compound |
-
2015
- 2015-10-20 CN CN201510680558.3A patent/CN105193784B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005092324A1 (en) * | 2004-03-19 | 2005-10-06 | The Trustees Of Columbia University In The City Of New York | Ginkgolide compounds, compositions, extracts, and uses thereof |
| CN104940184A (en) * | 2014-03-25 | 2015-09-30 | 上海医药工业研究院 | Application of ginkgetin compound |
Non-Patent Citations (3)
| Title |
|---|
| Antimicrobial Effects of Herbal Extracts on Streptococcus mutans and;Sung-Hoon Lee;《Journal of Microbiology》;20130831;第51卷(第4期);第484-489页 * |
| Ouratea genus: chemical and pharmacological aspects;Queli C. Fidelis等;《Rev Bras Farmacogn》;20140131;第24卷(第1期);第1-19页 * |
| 抗猪源链球菌30味中草药的筛选及其活性成分研究;宋晓言;《中国优秀硕士学位论文全文数据库 农业科技辑》;20150115;D050-522 * |
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| Publication number | Publication date |
|---|---|
| CN105193784A (en) | 2015-12-30 |
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| C06 | Publication | ||
| PB01 | Publication | ||
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| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Deng Xuming Inventor after: Wang Jianfeng Inventor after: Li Gen Inventor after: Ma Heran Inventor after: Lu Gejin Inventor after: Zhang Bing Inventor before: Deng Xuming Inventor before: Wang Jianfeng Inventor before: Li Gen Inventor before: Lu Gejin Inventor before: Zhang Bing |
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| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20181025 Address after: 130021 Xinmin Street, Changchun, Changchun, Jilin Applicant after: The First Hospital of Jilin University Address before: 130012 No. 2699 Qianjin Street, Jilin, Changchun Applicant before: Jilin University |
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| GR01 | Patent grant |