CN109010346A - A kind of new opplication of oleanolic acid - Google Patents
A kind of new opplication of oleanolic acid Download PDFInfo
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- CN109010346A CN109010346A CN201811249525.3A CN201811249525A CN109010346A CN 109010346 A CN109010346 A CN 109010346A CN 201811249525 A CN201811249525 A CN 201811249525A CN 109010346 A CN109010346 A CN 109010346A
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- oleanolic acid
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Dermatology (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract
The present invention relates to field of medicaments, the in particular to new opplication of oleanolic acid, especially inhibit the application in scytitis in preparation.The present invention, which is experimentally confirmed oleanolic acid, effectively to inhibit the release of inflammatory factor, to achieve the purpose that anti-inflammatory.The above result shows that oleanolic acid can be used for preparing scytitis inhibitor.
Description
Technical field
The present invention relates to field of medicaments, in particular to a kind of application of oleanolic acid.
Technical background
Inflammation (inflammation) refer to the living tissue with vascular system to destructive stimulus (such as destructive stimulus,
Germ or physical damnification) caused by a kind of complexity self-defense reaction.The generation of inflammation and many Chronic Progressives are scorching
Property disease disease hair (such as arthritis, ulcerative colitis, pyemia, atherosclerosis) it is closely related, it there are tight
Human health is threatened again.The problems such as with China human mortality increase and aging of population, highlights, the disease incidence of such inflammatory disease
Also it increases year by year, has become and cannot be neglected one of public health problem.And it is situated between since inflammatory reaction is related to numerous inflammation
The participation of matter and the activation of unlike signal access are still at present a very stubborn problem for the treatment of such disease.
Though having many anti-inflammatory drugs to emerge, and curative effect is good, the presence of adverse reaction and side effect is to limit these drugs
The main reason for extensive use.Therefore, how to alleviate or eliminate side effect, and inhibited anti-for unlike signal access
Scorching drug research is the research hotspot in anti-inflammatory drug field in recent years.
Summary of the invention
In view of this, the present invention provides the new opplications of oleanolic acid, i.e., in the drug of preparation treatment scytitis
Using.
In order to achieve the above-mentioned object of the invention, the present invention the following technical schemes are provided:
The present invention provides application of the oleanolic acid in the drug of preparation treatment scytitis.
The present invention provides a kind of application of oleanolic acid in the drug that preparation reduces mice auricle swelling degree.
The present invention measures the swelling journey of Mice Auricle by phorbol exters (TPA) inducing mouse auricle edema animal model test
Degree, experimental result show that TPA can effectively cause inflammation, cause ear that oedema occurs, and the TPA model that smearing gives oleanolic acid is small
The swelling degree of mouse auricle tissue is effectively suppressed.Show that oleanolic acid can be effectively reduced mice auricle swelling degree.
The present invention proved by immunohistochemical test, and oleanolic acid can obviously reduce the excessive of inflammatory cell in auricle
Expression.Therefore, the present invention also provides oleanolic acids reduces answering in the drug of inflammatory cell quantity in auricle tissue in preparation
With and oleanolic acid preparation reduce ear tissue in iNOS or COX-2 protein level drug in application.
The present invention smears on the animal model established in single TPA, real by Westernblot experiment and immunohistochemistry
It tests, discovery oleanolic acid can be effectively reduced the secretion level of inflammatory factor iNOS and COX-2 in brain tissue, inhibit auricle tissue
Swelling degree, and then achieve the purpose that anti-inflammatory, the above results show that, scytitis correlation can be treated or be alleviated to oleanolic acid
Disease, can be used for preparing the drug for inhibiting the relevant a variety of diseases of inflammation.Therefore, the present invention provides oleanolic acids to prepare
Treat the application in the drug of scytitis.
Preferably, the inflammatory skin conditions are the relevant skin disease of inflammation.
Preferably, the relevant disease of the inflammation includes dermatitis.
In order to obtain better therapeutic effect, preferably, 5 μm of ol/100 μ L~20 μ of the dosage of oleanolic acid
Mol/100 μ L, i.e. the oleanolic acid of 5 μm of ol~20 μm ol is dissolved in 100 μ L solvents, and can effectively to treat or alleviate inflammation related
Disease, can effectively reduce mice auricle swelling degree, reduce in ear tissue in inflammatory cell quantity and auricle tissue iNOS or
COX-2 protein level, effectively eliminates scytitis.
In above-mentioned application provided by the invention, preferably, the drug includes oleanolic acid and pharmaceutically acceptable
Auxiliary material.
Preferably, the dosage form of drug is oral preparation or injection, wherein the dosage form of the drug is oral preparation,
The oral agents are oral solution, granule, pill, tablet, capsule, microcapsules and dispersion powders.
The present invention has found that oleanolic acid can effectively inhibit the mistake of inflammatory cell proliferation and inflammatory factor by zoopery
Degree expression, reduces its damage to skin, can be used for preparing the medicine for inhibiting the relevant a variety of neurodegenerative diseases of neuroinflamation
Object.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described.
Fig. 1 shows the HE colored graph of Mice Auricle tissue paraffin section de；
Fig. 2 shows the immunohistochemical staining figure of iNOS and COX-2 in Mice Auricle tissue；
Fig. 3 shows the westernblot data of iNOS and COX-2 in Mice Auricle tissue.
Specific embodiment
The present invention provides the new opplication of oleanolic acid, those skilled in the art can use for reference present disclosure, be suitably modified
Realization of process parameters.In particular, it should be pointed out that all similar substitutions and modifications be for a person skilled in the art it is aobvious and
It is clear to, they are considered as being included in the present invention.Method and application of the invention is retouched by preferred embodiment
It states, related personnel can obviously not depart from the content of present invention, change in spirit and scope to method described herein and application
Dynamic or appropriate changes and combinations, carry out implementation and application the technology of the present invention.
In the present invention, raw materials used and reagent is available on the market.
Wherein, for experimental animal using female, the 6 week old BALB/C mice of SPF grade of weight 20-25g is big purchased from southern medical courses in general
Learn Experimental Animal Center, credit number SCXK (Guangdong) 2016-0041.Mouse feed is purchased from Nanfang Medical Univ experimental animal
The heart.Experimental animal is raised in cleaning grade laminar-flow rack, and environment temperature airconditioning control is 25 ± 1 DEG C, and relative humidity is 75 ± 10%.
INOS and COX-2 antibody is purchased from Beijing Bo Aosen Biotechnology Co., Ltd, and hematoxylin eosin staining agent is purchased from upper
The skies Hai Bi Bioisystech Co., Ltd, DAB color developing agent are purchased from DAKO company.
Below with reference to embodiment, the present invention is further explained:
Influence of 1 oleanolic acid of embodiment to the TPA mice auricle swelling induced.
Experimental animal be randomly divided into normal group, it is TPA group, positive drug group (TPA+ prednisolone, 5 μm of ol/100 μ L), neat
Pier tartaric acid low dose group (LPS+ oleanolic acid, OA5,5 μm of ol/100 μ L), oleanolic acid middle dose group (LPS+ oleanolic acid,
OA10,10 μm of ol/100 μ L) and oleanolic acid high dose group (LPS+ oleanolic acid, OA20,20 μm of ol/100 μ L), every group 3.
The administration before TPA is smeared of each experimental group.Except for the normal group, the 15min of remaining each group upon administration starts to smear TPA.It is different
After time, mouse is put to death with cervical dislocation, then cuts mouse ears in time, and existed respectively with the punch of diameter 6mm
Round auricle is laid at same position；Weighing is feminine gender with blank group, by the difference of experimental group auricle weight and blank group auricle weight
As swelling thickness.Experimental data indicates that all experimental datas are all made of 19.0 software of SPSS and are counted with Mean ± SD
It analyzes, parameter is tested with ANOVA between the group of each group mouse, and P < 0.05 is considered statistically significant.Inhibiting rate is by following
Formula calculates: (feminine gender organizes the swollen counterpoise of the swollen each experimental group ear of counterpoise-of ear)/negative swollen counterpoise × 100% of group ear.Experimental result such as table
Shown in 1.
Influence of 1 oleanolic acid of table to the TPA mice auricle swelling induced
Compared with negative control group, *: P < 0.05.
As seen from the results in Table 1, cause inflammation effect of the TPA in 6h reaches maximum value, and with the extension of time, causes scorching effect
Fruit gradually decreases.In addition, growth of the mice auricle swelling that induces to TPA of oleanolic acid with the time, inhibitory effect gradually add
By force.By the result of table 1 and 2 it is found that the inhibitory effect of oleanolic acid is in concentration dependent.The inhibition of oleanolic acid high dose group is imitated
Best when fruit, inhibiting rate reaches 81.25%.
Inhibiting rate of 2 oleanolic acid of table to the TPA mice auricle swelling induced
Compared with negative control group, *: P < 0.05.
The influence for the inflammatory cell in Mice Auricle that 2 oleanolic acid of embodiment induces TPA
Experimental group, dosage regimen are the same as embodiment 1.After 6h is administered in mouse, cervical dislocation puts to death mouse, then in time
Cut mouse ears.It is fixed for 24 hours in 4% paraformaldehyde, tap water is rinsed well, with the alcohol serial dehydration of various concentration.It is de-
Water, which is soaked in dimethylbenzene after this, to carry out transparent, and transparent sample is soaked 4h in the paraffin of molten state, is embedded, slice,
HE dyeing is carried out after the rehydration that dewaxes, optical microphotograph is under the microscope.As a result as shown in Figure 1.
The tissue that can be seen that blank group (acetone treatment group) by the result of Fig. 1 is shown there is no significantly changing
There is no change for the appearance of normal tissue, auricle thickness and cuticula.Proinflammatory agent TPA inducing mouse auricle edema is used alone
When, the inflammatory reaction of Mice Auricle is clearly.It is mainly manifested in epidermal hyperkeratosis, cuticula obviously thickens and inflammatory cell
Infiltration increases.Before being generated with TPA stimulation inflammation, the oleanolic acid of various dose is applied to mouse ear in advance respectively
When, the infiltration degree of the inflammatory cell in Mice Auricle can be reduced significantly.By comparison, it was found that oleanolic acid high dose group pair
The mice auricle swelling of TPA induction has apparent morphologic change.
The influence of iNOS and COX-2 content in the Mice Auricle tissue that 3 oleanolic acid of embodiment induces TPA
Experimental group, dosage regimen are the same as embodiment 1.Cervical dislocation puts to death mouse, then cuts mouse ears in time.
It is fixed for 24 hours in 4% paraformaldehyde, tap water is rinsed well, with the alcohol serial dehydration of various concentration.Using immunohistochemical experiment
The content of iNOS and COX-2 in Mice Auricle is measured, experimental data is indicated with Mean ± SD, is counted using SPSS19.0 software
According to processing, is examined using ANOVA and carry out statistical analysis, P < 0.05 shows that, with statistical difference, the results are shown in Table 2.
Immunohistochemical assay: taking out complete auricle tissue, after being placed in the fixation of 4% paraformaldehyde, starts stone after PBS washing
Wax microsection manufacture: key step includes graded ethanol dehydration transparent (50% He of (70%, 95% and 100%) → gradient dimethylbenzene
100%) → waxdip (brain tissue is soaked in 40-50min in the paraffin of thawing) → embedding (paraffin for pouring into embedding extremely solidifies)
→ slice (being sliced with 5 μm of thickness) → roasting piece (paraffin section cut is put in after baking piece 1h in 62-65 DEG C of pre-temperature of baking oven,
Dewax aquation in dimethylbenzene ethanol solution) (histotomy is placed in fills with repairing for citric acid pH6.0 antigen retrieval buffers to → antigen retrieval
In multiple box, in carrying out antigen retrieval in micro-wave oven) → blocking endogenous peroxydase: 3% hydrogenperoxide steam generator, room temperature are protected from light
It is incubated for 25min, then PBS washing → serum closing (is added dropwise BSA and is incubated for 30min) incubation of → primary antibody and (PBS is added dropwise on slice to press
INOS the or COX-2 primary antibody of certain proportion configuration, slice lie against 4 DEG C of overnight incubations in wet box) → secondary antibody incubation (shaking table washing
After primary antibody, the secondary antibody that kind corresponding to primary antibody is added dropwise covers tissue, is incubated at room temperature 50min) → DAB colour developing: shaking table washs secondary antibody
Afterwards, DAB developing solution is added dropwise in slice slightly drying, and developing time is controlled under microscope, and the positive is brown color, and tap water rinses slice eventually
Only colour developing → haematoxylin redye nucleus (shaking table wash secondary antibody after, be added dropwise haematoxylin dye liquor, redye 2min) → mounting (wash by shaking table
After washing 3 times, drying, neutral gum mounting) → microscopy takes pictures (slice in microscopically observation and acquire image), as a result such as Fig. 2
It is shown.
By the result of Fig. 2 it is found that the content of iNOS and COX-2 are significant when TPA stimulation mice auricle swelling is used alone
Increase on ground.After being pre-processed using the oleanolic acid of various dose to Mice Auricle, the swelling degree of Mice Auricle is obvious
Inhibit, and iNOS the and COX-2 content in auricle significantly reduces.
The above results show that oleanolic acid can effectively inhibit inflammatory cell proliferation and point of inflammatory factor iNOS and COX-
It secretes, control inflammation reaction, can be used for the relevant a variety of skin diseases of inflammation.
The above is only a preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (9)
1. application of the oleanolic acid in the drug that preparation reduces mice auricle swelling degree.
2. oleanolic acid reduces the application in ear tissue in the horizontal drug of inflammatory cell in preparation.
3. oleanolic acid reduces the application in ear tissue in iNOS or COX-2 protein level drug in preparation.
4. oleanolic acid is in preparation prevention or the application of the drug for the treatment of inflammation.
5. application according to claim 4, which is characterized in that the inflammation is the relevant disease of scytitis.
6. application according to claim 5, which is characterized in that the relevant disease of the inflammation includes dermatitis and psoriasis.
7. according to the described in any item applications of claim 4 to 6, which is characterized in that the dosage of the oleanolic acid is 5 μ
L~20 μm mol/100 μ ol/100 μ L.
8. application according to claim 4, which is characterized in that the drug includes oleanolic acid and pharmaceutically acceptable
Auxiliary material.
9. application according to claim 9, which is characterized in that the dosage form of the drug is oral preparation, the oral agents
For oral solution, granule, pill, tablet, capsule, microcapsules and dispersion powders.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811249525.3A CN109010346A (en) | 2018-10-25 | 2018-10-25 | A kind of new opplication of oleanolic acid |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811249525.3A CN109010346A (en) | 2018-10-25 | 2018-10-25 | A kind of new opplication of oleanolic acid |
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| Publication Number | Publication Date |
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| CN109010346A true CN109010346A (en) | 2018-12-18 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201811249525.3A Withdrawn CN109010346A (en) | 2018-10-25 | 2018-10-25 | A kind of new opplication of oleanolic acid |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113855807A (en) * | 2021-10-25 | 2021-12-31 | 孙良丹 | Application of reagent in preparation of medicine for treating/inhibiting psoriasis |
| CN117379446A (en) * | 2023-12-12 | 2024-01-12 | 吉林大学 | Application of oleanolic acid-28-O-beta-D-glucopyranoside in preparation of anti-colitis drugs |
-
2018
- 2018-10-25 CN CN201811249525.3A patent/CN109010346A/en not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113855807A (en) * | 2021-10-25 | 2021-12-31 | 孙良丹 | Application of reagent in preparation of medicine for treating/inhibiting psoriasis |
| CN117379446A (en) * | 2023-12-12 | 2024-01-12 | 吉林大学 | Application of oleanolic acid-28-O-beta-D-glucopyranoside in preparation of anti-colitis drugs |
| CN117379446B (en) * | 2023-12-12 | 2024-03-15 | 吉林大学 | Application of oleanolic acid-28-O-beta-D-glucopyranoside in preparation of anti-colitis drugs |
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Application publication date: 20181218 |
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