CN108703962A - Purposes of the linalool compound in preparing antirheumatic - Google Patents
Purposes of the linalool compound in preparing antirheumatic Download PDFInfo
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
The invention belongs to medical-use invention fields, specifically disclose purposes of the linalool compound in preparing treating rheumatoid arthritis drug, linalool is disclosed as crude drug extract, 50% pain threshold ED of AA rats can be reduced by the foot swelling of mitigation AA rats50, mitigate AA rat ankle joints pathological change and its immune internal organs pathological change, inhibit IL-1 β in AA rat blood serums, IL-6 and IL-10 pro-inflammatory cytokines expression and/or the multiple action mechanism for inhibiting the expression of NF- κ B/p65 albumen in AA rat ankle joints, the efficient notable therapeutic effect of multiaction target spot, low toxicity is played to rheumatoid arthritis, the possibility for increasing patient with rheumatoid arthritis cure rate, reducing types of medicines and dosage, it uses it for preparing and be used in treatment medicine for treating rheumatoid arthritis, there is prominent marked improvement meaning.
Description
Technical field
The present invention relates to medicinal usage invention fields, and in particular to linalool compound is preparing treatment rheumatoid arthritis
Purposes in drug.
Background technology
Rheumatoid arthritis (rheumatoid arthritis, RA) is a kind of slow characterized by arthrosynovitis
Property, systemic autoimmune disease, and clinical common rheumatic disease is mainly shown as symmetry, chronic, progressive
Panarthritis, main pathological characters are that synovial tissue's hyperplasia, inflammatory cell infiltration and pannus are formed, and cartilage and bone occur
Destruction, can finally cause joint deformity and function to lose.Illness rate is 0.32%~0.36%, and women is more than male.RA at present
Treatment joint symptoms are mainly alleviated using drug, it includes non-steroid to delay the state of an illness, Saving cortilage function etc., primary treatment drug
Body anti-inflammatory agent (NSAIDs), improves state of an illness antirheumatic drug (DMARDs), biological agent TNF-α inhibitor and IL- at glucocorticoid
1 antagonist etc., but said medicine is largely chemical industry synthesis drug, and toxic side effect is larger, influences the compliance of patient.
China's Traditional Chinese Medicine thinks that RA belongs to " rheumatism " scope, treats mainly using heat-clearing, dehumidifying, wind-dispelling, analgesia as method.Mesh
It is preceding that clinically there are no the drugs that can control disease development completely.And it is existing research shows that many inflammatory cells in RA patient's synovial membrane
The expressions such as the factor such as IL-1 β, IL-6, IL-10 increase, and NF- κ B/p65 albumen is activated in RA patient peripheral's blood lymphocytes
Expression increases the pathogenesis that may participate in RA, and is proportionate with RA the severity of disease.
Linalool compound (Linalool, molecular formula C10H18O it is) a kind of acyclic monoterpene alcoholic compound, is slightly soluble in water, easily
It is dissolved in organic solvent, it is volatile.Existing pharmacological research finds, linalool has analgesia, antianxiety, tranquilizing soporific, antitumor, anti-
Bacterium pharmacological activity can be widely applied for preparing deodorant, insecticide, antiseptic, catalyst and sedative.
But so far, there are no documents and materials refers to related linalool to rheumatoid arthritis, especially adjuvanticity
(effective treatment of (adjuvant arthritis, AA) acts on and its research of mechanism of action for arthritis.
Invention content
It is an object of the invention to overcome medication toxic side effect existing for existing treating rheumatoid arthritis drug big, medication
The strong disadvantage of compliance, less toxic efficient, the multiaction target spot of rheumatoid arthritis disease treatment generation can be directed to by providing one kind
Compound linalool prepare treat rheumatoid arthritis agents in purposes.
To achieve the above object, following technical solution provided by the invention：
Purposes of the linalool compound in preparing antirheumatic, wherein the linalool compound
Structural formula such as formula (I) shown in.
Further, the linalool compound can be immune by anti-inflammatory, analgesia, mitigation ankle-joint pathological change, mitigation
Internal organs pathological change inhibits the table of pro-inflammatory cytokine expression and/or inhibition ankle-joint NF- κ B/p65 albumen in serum
It reaches, to reach treatment rheumatoid arthritis effect.Further, in the serum pro-inflammatory cytokine include IL-1 β,
IL-6 and/or IL-10 cell factors.
Further, the linalool compound can pass through anti-inflammatory, analgesia, mitigation ankle-joint pathological change, mitigation simultaneously
Immune internal organs pathological change inhibits the pro-inflammatory cytokines expression such as IL-1 β, IL-6 and IL-10 in serum and inhibits ankle
The expression of joint NF- κ B/p65 albumen, to play the obvious therapeutic action of multiaction target spot to rheumatoid arthritis.
Further, the linalool compound is extracted from crude drug obtains.Wherein, the crude drug be containing
All kinds of medicinal materials for having linalool compound preferably comprise one or more natural in honeysuckle, anisetree bark and rhizoma homalonemae
Medicinal material, more preferably rhizoma homalonemae crude drug.It is shown through chemical constitution study, a large amount of linalools is contained in Essential Oil from Homalomena Occulta Schott by GC-MS
Close object.It is preferable to use the linalool compounds extracted from above-mentioned crude drug, are used to prepare rheumatoid arthritis treatment medicine
Object, relative to artificial synthesized linalool compound, the more standby efficient advantage of low toxicity.
Further, the drug further includes the auxiliary material and/or excipient of pharmaceutical acceptable.
Further, the dosage form of the drug is capsule, tablet, microcapsule formulation or injection.
It shows that linalool can mitigate the foot swelling of AA rats through 1 experimental result of patent Example of the present invention, reduces AA rats
50% pain threshold ED50；2 experimental result of patent Example of the present invention shows that linalool in addition to above-mentioned anti-inflammatory analgesic action, is also equipped with
Mitigate AA rat ankle joints pathological change and its immune internal organs pathological change, inhibits IL-1 β, IL-6 and IL- in AA rat blood serums
10 Cytokine Expression Levels and the expressional function for inhibiting NF- κ B/p65 albumen in AA rat ankle joints.In summary experiment is ground
Study carefully and shows：Linalool can be immunized internal organs pathological change by anti-inflammation detumescence, reduction ankle-joint pathological change, reduction, inhibit energy
The expression of the NF- κ B/p65 albumen of synovial tissue of joint's lesion and/or attenuating is enough caused to cause the IL- of synovium of joint inflammation swelling
The multiple drug action mechanism of the pro-inflammatory cytokines expression such as 1 β, IL-6, IL-10, to rheumatoid arthritis disease
Play the efficient prevention and treatment effect of multiaction target spot, multiaction effect, low toxicity.
Also, linalool compound of the present invention can be extracted from a variety of crude drugs and be obtained, and medication is safer, knot
The cure mechanism for closing its multiaction target spot increases patient with rheumatoid arthritis cure rate, reduces types of medicines and dosage
Possibility, significantly reduce medication toxic side effect.
In addition, the multidigit point collective effect mechanism and pharmacodynamic profile of above-mentioned linalool compound are also current Clinical practice
Not available for most of antirheumatic, using it for preparing makes in treatment medicine for treating rheumatoid arthritis
With for existing antirheumatic, with prominent marked improvement meaning.
Description of the drawings：
Fig. 1 is that various dose linalool dyes adjuvant arthritis rats ankle-joint histopathology H.E in embodiment 2
Scheme (× 4 times of object lens)；
Fig. 2 is that various dose linalool contaminates Adjuvant Arthritis Model in Rats spleen tissue pathology H.E in embodiment 2
Chromatic graph (× 4 times of object lens)；
Fig. 3 is that various dose linalool contaminates Adjuvant Arthritis Model in Rats thymic tissue pathology H.E in embodiment 2
Chromatic graph (× 4 times of object lens)；
In Fig. 1-3：(a) blank control group；(b) model control group；(c) Tripterygium wilfordii Polyglycosidium Tablets group；(d) linalool high dose
Group (e) linalool middle dose group；(f) linalool low dose group.
Fig. 4 A are the expression gray-scale map of NF- κ B/P65 albumen in each group rat ankle joint in embodiment 3.
Fig. 4 B are NF- κ B/P65 protein expression grayscale value histograms in each group rat ankle joint in embodiment 3.
Specific implementation mode
With reference to test example and specific implementation mode, the present invention is described in further detail.But this should not be understood
It is only limitted to embodiment below for the range of the above-mentioned theme of the present invention, it is all that this is belonged to based on the technology that the content of present invention is realized
The range of invention.
Linalool used, which is specifically extracted from the natural traditional Chinese medicines such as honeysuckle, anisetree bark and/or rhizoma homalonemae, in embodiment obtains
.
Embodiment 1
Anti-inflammatory analgesic drug effect Effect study of the linalool to rheumatoid arthritis
Applicant is using complete Freund's adjuvant Induced Arthritis rat animal model as research object in the present embodiment, into
The following animal imitating experiment of row, therapeutic effect of the research linalool to foot swelling caused by rheumatoid arthritis and chronic foot pain.
Specific experiment operation is as follows：
S1, modeling and grouping
The SPF grade SD male rats 60 of weight (170 ± 10) g, random number is taken to choose 10 according to table of random number
Rat carries out AA rat model modelings as blank control group, remaining 50 rat injection CFA.Modeling method is referring specifically to Qiao Wei
Flat, Jin He, Xu Lin vomiting nuts treat the animal experiment study of rheumatoid arthritis;J]Jilin traditional Chinese medicine, 2009,29 (2):
It is operated disclosed in 168-169.：After rat is fixed, CFA, every 0.1mL is subcutaneously injected with left hind foot pad position, causes scorching, sky
White control group is then in the isometric physiological saline of same injection location.
Successful 50 rats of modeling are randomly divided into 5 groups again, every group 10, i.e. model control group (N=10), tripterygium wilfordii
More glycosides groups (N=10), linalool high dose group (N=10), linalool middle dose group (N=10), linalool low dose group (N=
10).Start gavage and give corresponding drug, successive administration 7 days within the 19th day after modeling.Model control group distilled water gavage, it is other
Each group carries out gavage after being prepared by each group drug concentration.
The influence of S2, linalool to the foot swelling of AA rats
Experiment before the left and right toes portion of rat respectively make one label, and before experiment (the 0th day) and test the 2nd day, the 7th day,
Rat left foot and right sufficient is measured with vernier caliper within 10th day, the 14th day, the 18th day, the 21st day, the 23rd day and the 25th day respectively
Mark toes thickness records the situation of change of rat toes thickness in experimentation.
The each group rat equal indifference opposite sex (P> of (the 0th day) left and right toes before immune;0.05).Before drug treatment (the 18th day)
AA rats are apparent relative to blank control group rat left foot swelling, and difference has statistical significance (P<0.01), AA rats phase
For blank control group Rat Right foot without obvious tumefaction (P>0.05).
(1) left foot primary swelling
Left foot starts swelling after modeling rat immunity, and effect left foot swelling reaches peak within 18 hours, and subsequent left foot swelling is opened
Begin to reduce, rear foot swelling in 14th day is immunized up to second of peak, starts to be administered within 19th day after immune, successive administration is treated 7 days.Respectively
Treatment group's drug treatment rear left foot swelling has reduction trend, the 5th day (23rd day immune) linalool high dose group of administration and mould
Type control group mitigates compared to left foot swelling has otherness (* * P<0.01) (25th day immune) high agent of linalool in the 7th day, is administered
The left foot swelling compared with model control group of amount group, which mitigates, has otherness (* P<0.05), linalool middle dose group and low dose group
The trend of reduction, but no difference of science of statistics (P> are all had compared with model control group;0.05).Specific experiment data statistics result
Refer to table 1.
1 each group rat left foot toe thickness situation of change (x ± s, n=10, mm) of table
Compared with model control group*P<0.05,**P<0.01。
(2) the secondary side swelling of right foot
Start within 7th day right foot after model group rats are immune and swelling occur, swelling in the 14th day reaches peak, and drug treatment 7 days is right
Foot swelling reduces.Each therapeutic administratp group drug treatment rear right foot swelling has reduction trend, the 3rd day (21st day immune) virtue of administration
The right foot swelling compared with model control group of camphor tree alcohol high dose group, which reduces, has otherness (* P<0.05) it, is administered the 7th day (immune the
25 days) the right foot swelling compared with model control group of linalool high dose group reduces has otherness (* P<0.05 or * * P<0.01),
Linalool low dose group all has the trend of reduction, but no difference of science of statistics (P> compared with model control group after drug treatment;
0.05), specific experiment data statistics is the results detailed in Table 2.
2 each group Rat Right toes thickness situation of change of table (N=10, mm)
Compared with model control group*P<0.05,**P<0.01。
According to known to specific statistical data result in Tables 1 and 2：Relative to the existing positive drug control group thunder having verified that
For the public more glycosides piece groups of rattan, the treatment that linalool can equally play AA rat model foot swelling symptoms notable anti-inflammation detumescence is made
With.
S2, linalool are to the podalgia threshold value ED of AA rats50Influence
(administration the 7th day) is evaluated fiber (VonFrey ciliums) with the pain sensation using up-down methods and is measured 25th day after immune
50% pain reaction threshold value ED of Rat Right foot50。
Rat is placed in the transparent plastic container that a bottom is woven wire eye pad, adapts it to 30min.It then begins to
Pain sensation testing experiment selects the fiber (0.6g, 1.0g, 1.4g, 2g, 4g, 6g, 8g, 10g, 15g) of different pressures vertically to stimulate big
The skin of the right foot the 3rd of mouse, 4 interdigits, it is for 6 seconds or more, if rat occur metapedes lift, quickly get rid of foot, carry leg, spring,
It the behaviors such as licks foot, shout and being considered as positive reaction, being otherwise considered as negative reaction.Positive reaction is denoted as O, and negative reaction is denoted as X, with
4g is stimulated as starting, when positive reaction, low level-one fiber is selected to stimulate, and when negative reaction, high level-one fiber is selected to pierce
Swash, when occurring reflecting change of properties, hereafter as first actual data measures 5 data as initial data, look into phase again
Tables of data is answered, 50% amount of causing a positive reaction (ED is calculated50).Wherein,
ED50=10loga+k×b
In formula：a：Cilium respective value used in last actual data；b：The mean value of the difference of adjacent cilium respective value logarithm；k：
Parameter is corresponded in table.
Protection phenomenon, the blank control groups such as in experiment, the appearance of AA rat hindlegs is hanging, licks foot do not have above-mentioned protection phenomenon.
The 7th day (25th day immune) is administered, 50% pain threshold ED of rat is measured using VonFrey ciliums50.Compared with model control group, give
The 7th day linalool high dose group ED of medicine50Significantly increase, and there is significant difference (P<0.05), linalool middle dose group and low
Dosage group ED50Have the tendency that increasing compared with model control group, but does not have statistical significance (P>0.05) 3, are shown in Table.
3 linalool various dose of table is to 50% pain threshold ED of adjuvant arthritis rats50Influence
Compared with model control group*P<0.05,**P<0.01。
According to known to 3 experiment statistics result of table：Relative to the existing positive drug control group Tripterygium wilfordii Polyglycosidium Tablets having verified that
For group, the linalool of linalool, especially high dose group equally can play notable town to adjuvant-induced arthritis (AA) rat
Pain acts on.
Known to the above-mentioned all experimental studies results of comprehensive the present embodiment：Linalool compound can significantly mitigate the foot of AA rats
Swelling simultaneously reduces by 50% pain threshold ED50 of AA rats；Further verification illustrates that linalool compound can be made by anti-inflammatory, analgesia
With playing therapeutic effect to rheumatoid arthritis.
Embodiment 2
After embodiment 1 is tested, anesthetized rat, abdominal aorta acquires rat blood, stripping thymus gland, spleen, left side
With right side ankle-joint, it is respectively placed in corresponding requirements solution, it is spare.
Influence of 2.1 linalool of embodiment to AA rat ankle joint pathological changes
Above-mentioned spare AA rats with left and right side ankle-joint is taken to carry out H.E dyeing tests, H.E dyes test result as schemed
Shown in 1：
Blank control group：Synovial membrane is thin and complete, is made of 1~2 layer of synovial cell, has no tissue edema, cell infiltration
And blood vessel hyperplasia, cartilage surface is smooth, has no osteoclasia, and joint structure is complete, and articular cavity gap ratio is normal (see Fig. 1 (a)).
Model control group：Synovial membrane epithelial cell has mild hyperplasia, it is seen that 3~5 layers of synovial cell, arrangement is slightly disorderly, companion or
Not with a small amount of cell infiltration, partial joint gaps visible narrows, and articular cartilage surface is smooth, structural integrity, has no that sclerotin is broken
Bad, intracavitary has no that inflammatory oozes out (see Fig. 1 (b)).
Positive controls (Tripterygium wilfordii Polyglycosidium Tablets group)：It can be seen that 7 are consistent with the performance of model control group pathological characteristic, it is synovial membrane
Mild hyperplasia, companion or does not narrow with cell infiltration and joint space, remaining 1 no abnormality seen changes (see Fig. 1 (c)).
Linalool high dose group：It can be seen that 4 synovial membrane mild hyperplasias, companion or not companion's cell infiltration, remaining 4 no abnormality seen
Change (see Fig. 1 (d)).
Linalool middle dose group：It can be seen that 6 cell infiltrations and 4 synovial cell's mild hyperplasias, have 2 no abnormality seens to change
Become (see Fig. 1 (e)).
Linalool low dose group：It can be seen that 6 synovial membrane mild hyperplasias, companion or not companion's cell infiltration, remaining 2 no abnormality seen
Change (see Fig. 1 (f)).Each group ankle-joint lesion score, which summarizes, is shown in Table 4.
4 rat ankle joint pathological change grade form of table (N=8, point)
Compared with blank control group,**P<0.01,*p<0.05；Compared with model control group,##P<0.01,#p<0.05。
According to above-mentioned test result：For model control group, linalool compound of the present invention can also
Play the drug action for substantially reducing AA rat ankle joint pathological changes；And linalool compound of the present invention reduces ankle and closes
Section pathological change effect is significantly better than positive controls drug.
Influence of 2.2 linalool of embodiment to AA rat immunity internal organs pathological changes
(1) linalool influences AA Rats Spleen pathological changes
Above-mentioned spare AA Rats Spleens are taken to carry out H.E dyeing tests, test results are shown in figure 2：
Blank control group：Splenic structure is clear, and red pulp, white pulp and marginal zone ratio are normal, acini lienalis B cell and artery week
It is normal (see Fig. 2 (a)) to enclose lymph sheath T cell quantity.
Model control group：Splenic structure is clear, and B cell area and the expansion of marginal belt T cell area, lymphocyte quantity increase
(see Fig. 2 (b)).
Positive controls (Tripterygium wilfordii Polyglycosidium Tablets group)：See 3 splenic B cells areas and the expansion of T cell area, lymphocyte quantity
Increase (see Fig. 2 (c)).
Linalool high dose group：See that 4 splenic B cells areas and the expansion of T cell area, lymphocyte quantity increase (see Fig. 2
(d))。
Linalool middle dose group：See that 1 splenic B cells area and the expansion of T cell area, lymphocyte quantity increase (see Fig. 2
(e))。
Linalool low dose group：See that 2 splenic B cells areas and the expansion of T cell area, lymphocyte quantity increase (see Fig. 2
(f))。
(2) linalool influences AA rat chest gland pathological changes
Above-mentioned spare AA rat chest glands are taken to carry out H.E dyeing tests, test results are shown in figure 3：
Blank control group：Thymus structure is clear, and cortex and medullary substance ratio are normal, it is seen that (T is thin for a large amount of thymocytes in cortical area
Born of the same parents), a small amount of macrophage etc., coloring is relatively deep (see Fig. 3 (a)).
Model control group：Thymus structure is clear, and cortex and medullary substance ratio are normal (see Fig. 3 (b)).
Positive controls (Tripterygium wilfordii Polyglycosidium Tablets group)：1 atrophy of thymus gland, cortilymph cell quantity are reduced, lighter,
Skin medullary substance demarcates unclear (see Fig. 3 (c)).
Linalool high dose group：1 atrophy of thymus gland, cortilymph cell quantity are reduced, lighter (see Fig. 3 (d)).
Linalool middle dose group：Thymus structure is clear, and cortex and medullary substance ratio are normal (see Fig. 3 (e)).
Linalool low dose group：Thymus structure is clear, and cortex and medullary substance ratio are normal (see Fig. 3 (f)).
According to above-mentioned experimental results：For model control group, the linalool of high, medium and low dosage group
The immune organs such as AA Rats Spleens and thymus gland are played with the drug action for reducing pathological change；Also, in of the present invention, it is low
The linalool linalool compound of dosage group is significantly better than positive controls drug to reducing the effect of immune organ pathological change.
Influence of 2.3 linalool of embodiment to pro-inflammatory cytokine in AA rat blood serums
Above-mentioned spare AA rat bloods are taken, are shown through ELISA testing results：
IL-1 β significantly increase (P< compared with blank control group in model control group rat blood serum;0.01), each treatment group is big
IL-1 β contents in mouse serum, compared to there is decline, decline no significant difference (P> in model control group;0.05)；
IL-6 significantly increases (P< compared with blank control group in model control group rat blood serum;0.01), each treatment group rat
IL-6 contents in serum are compared in model control group has decline, the decline in linalool various dose group to have statistics poor
Different (P<0.01 or P<0.05)；
IL-10 significantly increases (P< compared with blank control group in model control group rat blood serum;0.05), each treatment group is big
IL-10 contents in mouse serum are compared in model control group decline, and the decline of linalool middle dose group has statistics poor
Different (P<0.05), specific experiment statistical result refers to table 5.
Influence (x ± s, pg/mL) of the 5 linalool various dose of table to adjuvant arthritis rats serum cytokines
Compared with blank control group*P<0.05,**P<0.01；Compared with model control group#P<0.05,##P<0.01。
It can be seen that：Compared with model control group, the linalool of high, medium and low dosage group can be to IL- in AA rat blood serums
The expression of 1 β, IL-6 and IL-10 pro-inflammatory cytokine is played the role of significantly inhibiting, and the linalool of high dose group has been tested with existing
The positive drug control group Tripterygium wilfordii Polyglycosidium Tablets group function and effect of card are suitable.
Influence of 3 linalool of embodiment to NF- κ B/p65 protein expressions in AA rat ankle joints
Shadow of the linalool to NF- κ B/p65 protein expressions in AA rat ankle joints is detected using Wester Blot experimental methods
It rings, specific experiment step generally comprises as follows：
After dosage period, by rat in cutting left back foot and ankle-joint on ice, cleaned up with PBS buffer solution, point
It from skin and muscle, is immediately placed in the special EP pipes of liquid nitrogen container, label, which is better than in nitrogen tank, temporarily to be preserved, and ﹣ is then transferred quickly to
It is stored in 80 DEG C of low temperature refrigerators, in case being used when experiment.
The preparation of sample albumen
When experiment, spare tissue is taken out, is put into homogenate tube, shredded tissue with clean scissors, 10 times of tissues are added
Volume RIPA lysates are placed in (using protease inhibitors is added in first several minutes) in refiner, are homogenized, 10s is placed on ice
On, it is homogenized again after a while, is placed on ice, repeats homogenate several times, tissue is made to pulverize as possible.After the completion of homogenate, by sample
Pipe takes out, ice bath 30min, once ensures that tissue cracks completely every 5min concussions.Centrifuge is pre-chilled, and lysate centrifuges 10min
(12000rpm) collects supernatant to get total protein solution.Protein quantification.By protein solution according to 4:5* eggs are added in 1 ratio
White sample-loading buffer, after shaking mixing, boiling water bath is denaturalized 15min, is subsequently placed into 20 DEG C of refrigerators of ﹣ and saves backup.
SDS-PAGE electrophoresis
Using preceding cleaning glass plate, then match glue encapsulating, get out electrophoresis liquid, will (1) in ready sample electrophoresis is added
Kong Zhong, with concentrate glue voltage 75V, separation gel 120V electrophoresis.Bromophenol blue band can be terminated close to glass plate lower edge, be turned
Mould.
Revolving die (wet turn)
Wet turn：Tris 3.0g, Gly 14.4g, M-OH 200ml, add deionized water to 1,000ml.300mA constant current revolving dies
NF- κ B/p65 protein samples are transferred on pvdf membrane by 0.5h.Pay attention to：Pvdf membrane needs to be activated with methanol before use.Revolving die mistake
The trough of revolving die need to be placed in ice water and cool down in journey.
Immune response
It will be closed with the TBST containing 5% skim milk (0.5%TBST matches) on the film to take a turn for the better at room temperature decolorization swinging table
Liquid closes pvdf membrane 1h at room temperature, and 4 DEG C of overnight incubations of primary antibody then wash film three times, each 5min.Then secondary antibody is incubated at room temperature
30min, then wash film three times, each 5min.
Chemiluminescence and image analysis
By two kinds of reagents of ECLA and ECLB in the medium volume mixture of centrifuge tube, the double-deck hand of patch on exposure casket in darkroom
The albumen of pvdf membrane is placed between exposure casket double-layer films, the ECL solution mixed is added and fully reacts by set up, 1~
After 2min, most raffinate, the thin film covered above is gone to start to expose.Film development, fixing reagent after exposure are shown
Shadow and fixing.Film is scanned, Alpha softwares processing analysis object tape gray value reacts NF- κ B/p65 protein expression water with this
It is flat.
Laboratory test results are as can be seen from figures 4a-b：NF- κ B/p65 protein expressions in AA model control group rat ankle joints
Amount dramatically increases, and has significant difference (P< with the content of NF- κ B/p65 protein expressions in other five groups of rat ankle joints;0.01 or
P<0.05)；Research finds that NF- κ B/p65 albumen is inflammation height expression albumen, shows modeling success.It is positive after drug treatment 7 days
Control group NF- κ B/p65 albumen is significantly lowered, and the high, medium and low dosage of linalool has lowered the table of NF- κ B/p65 albumen in various degree
It reaches, and the downward of the high, medium and low concentration group of linalool has significant difference (P< compared with blank control group;0.01).
It can be seen that：Linalool of the present invention can play NF- κ B/p65 protein expressions in AA rat ankle joints aobvious
Write inhibiting effect.
In summary all experimental studies show linalool can by anti-inflammation detumescence, reduce ankle-joint pathological change, subtract
Internal organs pathological change is immunized less, inhibits the expression and/or attenuating that can cause the NF- κ B/p65 albumen of synovial tissue of joint's lesion
Cause the multiple drug action of the pro-inflammatory cytokines expressions such as IL-1 β, IL-6, IL-10 of synovium of joint inflammation swelling
Mechanism plays the efficient prevention and treatment effect of multiaction target spot, multiaction effect, low toxicity to rheumatoid arthritis disease.
Claims (8)
1. purposes of the linalool compound in preparing antirheumatic, wherein the linalool compound
Shown in structural formula such as formula (I).
2. purposes according to claim 1, which is characterized in that the linalool compound can by anti-inflammatory, ease pain, subtract
Light ankle-joint pathological change mitigates immune internal organs pathological change, inhibits pro-inflammatory cytokine expression and/or suppression in serum
The expression of ankle-joint NF- κ B/p65 albumen processed, to reach treatment rheumatoid arthritis effect.
3. purposes according to claim 2, which is characterized in that in the serum pro-inflammatory cytokine include IL-1 β,
IL-6 and/or IL-10 cell factors.
4. purposes according to claim 1, which is characterized in that the linalool compound is extracted from crude drug to be obtained
.
5. purposes according to claim 4, which is characterized in that the crude drug includes honeysuckle, anisetree bark and thousand
It is one or more in strong.
6. purposes according to claim 5, which is characterized in that the crude drug is rhizoma homalonemae.
7. purposes according to claim 1, which is characterized in that the drug further include pharmaceutical acceptable auxiliary material and/
Or excipient.
8. purposes according to claim 7, which is characterized in that the dosage form of the drug is capsule, tablet, microcapsule formulation
Or injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810975502.4A CN108703962A (en) | 2018-08-24 | 2018-08-24 | Purposes of the linalool compound in preparing antirheumatic |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810975502.4A CN108703962A (en) | 2018-08-24 | 2018-08-24 | Purposes of the linalool compound in preparing antirheumatic |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108703962A true CN108703962A (en) | 2018-10-26 |
Family
ID=63873418
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810975502.4A Pending CN108703962A (en) | 2018-08-24 | 2018-08-24 | Purposes of the linalool compound in preparing antirheumatic |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108703962A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114569585A (en) * | 2022-04-07 | 2022-06-03 | 四川省医学科学院·四川省人民医院 | Application of patchouli alcohol in preparation of medicine for treating rheumatoid arthritis |
-
2018
- 2018-08-24 CN CN201810975502.4A patent/CN108703962A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114569585A (en) * | 2022-04-07 | 2022-06-03 | 四川省医学科学院·四川省人民医院 | Application of patchouli alcohol in preparation of medicine for treating rheumatoid arthritis |
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Application publication date: 20181026 |