CN109925306A - Syringaresinol is preparing the purposes in resisting rheumatoid arthritis drug - Google Patents
Syringaresinol is preparing the purposes in resisting rheumatoid arthritis drug Download PDFInfo
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- CN109925306A CN109925306A CN201910329372.1A CN201910329372A CN109925306A CN 109925306 A CN109925306 A CN 109925306A CN 201910329372 A CN201910329372 A CN 201910329372A CN 109925306 A CN109925306 A CN 109925306A
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- rheumatoid arthritis
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Abstract
The invention discloses syringaresinols to prepare the purposes in resisting rheumatoid arthritis drug.Syringaresinol is a kind of double tetrahydrofuran lignans, present invention firstly discovers that syringaresinol can obviously inhibit the proliferation of synoviocytes in rheumatoid arthritis, induces the apoptosis of synoviocytes in rheumatoid arthritis.Therefore, which can be used for preparing prevention and/or treats the drug of rheumatoid arthritis, clinical value with higher and development prospect.
Description
Technical field:
The present invention relates to pharmaceutical technology field, in particular to a kind of syringaresinol is preparing resisting rheumatoid arthritis drug
In purposes.
Background technique:
Rheumatoid arthritis (rheumatoid arthritis, RA) is a kind of chronic systemic based on arthropathy
Property autoimmune disease, its pathogenesis remains unknown at present, clinic think RA morbidity mainly due to patient itself
Immune dysfunction leads to allergic reaction, makes the rotten denaturation of anti-inflammatory cells, be deposited on joint part and make joint tissue deformity,
Disable.According to investigations, the disease incidence of RA is about 1-2% in world wide, and China RA patient populations fall ill more than 4,000,000
Rate is still in rising trend.
Currently, mainly using non-steroidal anti-inflammatory drugs (diclofenac sodium, aspirin etc.) for rheumatoid arthritis and being immunized
Inhibitor (Ismipur etc.) is treated, but these drugs have apparent adverse reaction, as the former damages gastrointestinal tract
Mucous membrane leads to peptic ulcer, and the latter's selective action is poor, is easy to induce infection etc..Therefore, safe and effective control is researched and developed
Treating rheumatoid arthritis drug is a current urgent task.
In recent years, domestic and foreign scholars have made extensive and intensive studies in terms of botanical medicine treats RA, find many days
Right drug such as tripterygium glycosides, total glucoside, malicious rattan alkali etc. has preferable RA therapeutic effect.Therefore, it is developed from botanical medicine
Safe and efficient RA therapeutic agent has broad prospects out.
Summary of the invention:
In view of this, it is necessary to provide a kind of syringaresinols to prepare the purposes in resisting rheumatoid arthritis drug.
The purpose of the present invention is to provide a kind of compound syringaresinols to inhibit synoviocytes in rheumatoid arthritis proliferation
And the application in prevention and/or treatment rheumatoid arthritis.
Compound syringaresinol structural formula according to the present invention is shown in formula I:
Syringaresinol is a kind of double tetrahydrofuran type lignanoid, has the effects that anti-oxidant, anti-inflammatory, anti-gastric-ulcer.But mesh
Before have no syringaresinol for preventing and treating the report of rheumatoid arthritis related disease.
The application of syringaresinol provided by the present invention includes two aspects: 1) being it in preparation prevention and/or treatment class wind
Application in wet arthritic product；It 2) is its answering in the product that preparation inhibits synoviocytes in rheumatoid arthritis proliferation
With.
It is in particular in that syringaresinol can obviously inhibit the proliferation of synoviocytes in rheumatoid arthritis, induction rheumatoid is closed
The apoptosis for saving scorching synovial cell can be used for preparing prevention and/or treat the drug of rheumatoid arthritis.
In addition, the following products prepared using syringaresinol as effective component: 1) preventing and/or treat rheumatoid arthritis
Product；2) product for inhibiting synoviocytes in rheumatoid arthritis proliferation, also belongs to protection scope of the present invention.
Prevent and/or treat the drug of rheumatoid arthritis in the present invention and synoviocytes in rheumatoid arthritis is inhibited to increase
The drug grown can by injection, injection, infiltration, absorption, physically or chemically the method that mediates import body for example muscle, it is intradermal,
Subcutaneously, vein, mucosal tissue；Or body is imported after other material mixings or package.
When needs, one or more pharmaceutically acceptable carriers can also be added in said medicine.The load
Body includes diluent, excipient, filler, adhesive, wetting agent, disintegrating agent, the sorbefacient, surface of pharmaceutical field routine
Activating agent, absorption carrier, lubricant etc..
A variety of shapes such as injection, tablet, pulvis, granule, capsule, oral solution, paste, creme can be made in said medicine
Formula.The drug of the above various dosage forms can be prepared according to the conventional method of pharmaceutical field.
The present inventor's first passage pharmacological evaluation proves that syringaresinol has significant inhibition rheumatoid arthritis
The activity of synovial cell proliferation and induction synoviocytes in rheumatoid arthritis apoptosis can be used for preparing prevention and/or treatment class wind
Wet arthritic drug, therefore its clinical value with higher and development prospect.
Detailed description of the invention:
Fig. 1 is the syringaresinol of various concentration in the embodiment of the present invention 1 to synoviocytes in rheumatoid arthritis Proliferation Ability
The statistical results chart of effect.
Fig. 2 is that the syringaresinol of various concentration in the embodiment of the present invention 2 promotes synoviocytes in rheumatoid arthritis apoptosis
The statistical results chart of effect.
In figure: " * " indicates the significance of difference in statistics.
Specific embodiment:
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to embodiments, to the present invention
It is further elaborated.It should be appreciated that the specific embodiments described herein are merely illustrative of the present invention, it is not used to
Limit the present invention.
Embodiment 1: the inhibiting effect that syringaresinol is proliferated synoviocytes in rheumatoid arthritis
Cell: human rheumatoid arthritis synovial cell (RA-FLS)；
Drug: syringaresinol；
Method: the recovery of 1.RA-FLS
RA-FLS cryopreservation tube is taken out rapidly from liquid nitrogen filling, puts the thermostat water bath that temperature is 37 DEG C into, it is continual to shake
It shakes, accelerates cell and thaw.After thawing completely, the RA-FLS suspension in cryopreservation tube is moved to pipettor in super-clean bench
In 10mL sterile centrifugation tube, it is centrifuged 5min, revolving speed 1000r/min.Supernatant is outwelled, 5mL complete culture solution is added, uses pipettor
It is lasting to blow and beat to uniform cell suspension, RA-FLS is inoculated in 25mL Tissue Culture Flask, is put into cell incubator and cultivates,
Incubator condition setting is 37 DEG C of temperature, CO2Concentration 5%.The growing state for observing RA-FLS after for 24 hours under the microscope, works as hair
Existing cell is adherent, triangular in shape and irregular shuttle shape when, show that cell growth status is good.
The passage of 2.RA-FLS
It observes under the microscope, when RA-FLS adherent growth is to account for entire Tissue Culture Flask bottom 80% or so, i.e.,
It can carry out cell passage.The original fluid in culture bottle is outwelled, is rinsed 2 times with PBS, it is therefore an objective to original fluid be cleaned, avoided
Influence cell dissociation；0.25% tryptic digestive juice is added to be digested, and digests situation in microscopically observation RA-FLS,
Suitable fetal calf serum (FBS) is added when seeing that most cells are rounded under mirror and terminates digestion, is then added a certain amount of complete
Full nutrient solution blows and beats culture bottle inner wall with aseptic straw in culture bottle repeatedly, is in uniform cell suspension；Use cell counting board
Cell is counted, after counting, RA-FLS is inoculated in 2 new culture bottles, and suitable complete culture is added
Liquid is put into cell incubator and cultivates, and incubator condition setting is 37 DEG C of temperature, CO2 concentration 5%, i.e., one mode for passing two passes
It is commissioned to train feeding.
3.MTT method measures cell inhibitory rate
Suitable syringaresinol is taken to be made into 0.01,0.1,1,5,10 μM of culture solution respectively with DMEM.It takes raw in logarithm
Long-term RA-FLS outwells the original fluid in culture bottle, is rinsed 2 times with PBS, and 0.25% tryptic digestive juice is added and carries out
Digestion, and situation is digested in microscopically observation RA-FLS, it is added when seeing that cell is largely rounded under mirror suitable
FBS terminates digestion, and a certain amount of culture solution is then added in culture bottle, culture is ceaselessly blown and beaten with aseptic straw
Bottle inner wall, is in uniform cell suspension, is counted with cell counting board, and adjusting cell concentration with culture solution is 1 × 105A/
RA-FLS is inoculated in 96 hole steril cell culture plates by mL, and every 100 μ L of hole is put into cell incubator and cultivates, incubator item
Part is set as 37 DEG C of temperature, CO2Concentration 5%.Be incubated for for 24 hours after, by 96 orifice plates be divided into 6 groups (i.e. blank control group, 0.01,0.1,
1,5,10 μM of medicine groups, every group of 6 multiple holes), the original fluid in hole is sopped up, the DMEM and various concentration of equivalent are separately added into
Pastille culture medium is put into cell incubator and intervenes.Intervene for 24 hours and after 48h, 20 μ L MTS, 37 DEG C of incubations are added in each hole
1.5h measures absorbance of each hole at 540nm wavelength with enzyme-linked immunosorbent assay instrument, calculates the inhibiting rate of group of cells.
Calculation formula is as follows:
Cell inhibitory rate/%=(1- blank control group OD value/each acute drug group OD value) × 100%
As a result: please refer to Fig. 1, the syringaresinol that concentration is 0.1~10 μM can obviously inhibit the proliferation of RA-FLS,
And inhibiting effect enhances with the increase of drug concentration.
Embodiment 2: facilitation of the syringaresinol to synoviocytes in rheumatoid arthritis apoptosis
Cell: human rheumatoid arthritis synovial cell (RA-FLS)；
Drug: syringaresinol；
Method: the recovery of 1.RA-FLS
It is same as Example 1.
The passage of 2.RA-FLS
It is same as Example 1.
3.TUNEL method measures Apoptosis
The fracture of chromosomal DNA is a progressive process stage by stage in Apoptosis, and chromosomal DNA is first in endogenous
Hydrolase nucleic acid under the action of be degraded to the large fragment of 50-300kb.Then about 30% chromosomal DNA is in Ca2+And Mg2+
It under the endonuclease enzyme effect of dependence, is cut off at random between nucleosomal units, forms 180~200bp nucleosome DNA poly
Body.As long as a series of 3 ' ends-OH for the DNA for notch occur on DNA double chain fracture or a chain and generating can be in deoxyribose
Under the action of nucleotide terminal enzyme (DNA) (TdT), by deoxyribonucleotide and fluorescein, peroxidase, alkaline phosphatase
The derivative that enzyme or biotin are formed is tagged to the 3 '-ends of DNA, so as to carry out the detection of apoptotic cell, such methods one
As be known as deoxyribonucleotide terminal enzyme (DNA) mediate Nick End mark (TUNEL).
Suitable syringaresinol is taken to be made into 0.1 and 1 μM of culture solution respectively with DMEM, RA-FLS cell is in blank and drug containing
48h is incubated in culture solution, at room temperature using the fixed 30min of 4% paraformaldehyde.It is rinsed 3 times, is added with phosphate buffer (PBS)
Enter cell membrane penetration liquid (0.1% sodium citrate, 0.1%Triton X-100) effect 2min.Deoxyribose core is used at 37 DEG C
Reaction 1h is marked in thuja acid terminal enzyme (DNA) (TdT) and biotin -11- deoxyuridine triphosphate (biotin-11-dUTP).
Using fluorescence microscope cellular morphology and calculate apoptotic index.
Calculation formula is as follows:
Apoptotic index/%=(apoptosis cell/1000 in 1000 cells) × 100%.
As a result: please refer to Fig. 2, it is sliding that the syringaresinol that concentration is 0.1~1 μM can be obviously promoted rheumatoid arthritis
The apoptosis of theca cell.
The foregoing is merely illustrative of the preferred embodiments of the present invention, is not intended to limit the invention, all in essence of the invention
Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within mind and principle.
Claims (4)
1. application of the syringaresinol in the product of preparation prevention and/or treatment rheumatoid arthritis.
2. application of the syringaresinol in the product that preparation inhibits synoviocytes in rheumatoid arthritis proliferation.
3. application of the syringaresinol as described in claim 1 in the product of preparation prevention and/or treatment rheumatoid arthritis,
It is characterized by: the product of prevention and/or treatment rheumatoid arthritis is drug or health care product.
4. syringaresinol as claimed in claim 2 answering in the product that preparation inhibits synoviocytes in rheumatoid arthritis proliferation
With, it is characterised in that: the product for inhibiting synoviocytes in rheumatoid arthritis proliferation is drug or health care product.
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| CN201910329372.1A CN109925306A (en) | 2019-04-23 | 2019-04-23 | Syringaresinol is preparing the purposes in resisting rheumatoid arthritis drug |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140371307A1 (en) * | 2011-10-18 | 2014-12-18 | Amorepacific Corporation | Sirt 1 activator including syringaresinol |
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2019
- 2019-04-23 CN CN201910329372.1A patent/CN109925306A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140371307A1 (en) * | 2011-10-18 | 2014-12-18 | Amorepacific Corporation | Sirt 1 activator including syringaresinol |
Non-Patent Citations (4)
| Title |
|---|
| GEUM JIN KIM 等: "Cinnamomulactone, a new butyrolactone from the twigs of Cinnamomum cassia and its inhibitory activity of matrix metalloproteinases", 《ARCH. PHARM. RES.》 * |
| JINGHUI WANG 等: "Systems Pharmacology Dissection of Multiscale Mechanisms of Action for Herbal Medicines in Treating Rheumatoid Arthritis", 《MOLECULAR PHARMACEUTICS》 * |
| 姜成帅: "红柳抗类风湿关节炎化学成分研究", 《宁夏医科大学-万方数据》 * |
| 贾月梅: "刺叶锦鸡儿抗类风湿性关节炎活性及化学成分的研究", 《新疆大学硕士论文-万方数据》 * |
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Application publication date: 20190625 |