CN104546824A - Application of isoflavonoids in preparation of medicine for treating multiple sclerosis diseases - Google Patents

Application of isoflavonoids in preparation of medicine for treating multiple sclerosis diseases Download PDF

Info

Publication number
CN104546824A
CN104546824A CN201410818123.6A CN201410818123A CN104546824A CN 104546824 A CN104546824 A CN 104546824A CN 201410818123 A CN201410818123 A CN 201410818123A CN 104546824 A CN104546824 A CN 104546824A
Authority
CN
China
Prior art keywords
tectorigenin
multiple sclerosis
iridin
medicine
cpz
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201410818123.6A
Other languages
Chinese (zh)
Other versions
CN104546824B (en
Inventor
倪鑫
陈海生
张琰敏
金丽
郑幽
金永生
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Second Military Medical University SMMU
Original Assignee
Second Military Medical University SMMU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Second Military Medical University SMMU filed Critical Second Military Medical University SMMU
Priority to CN201410818123.6A priority Critical patent/CN104546824B/en
Publication of CN104546824A publication Critical patent/CN104546824A/en
Application granted granted Critical
Publication of CN104546824B publication Critical patent/CN104546824B/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to the technical field of natural pharmaceutical chemistry and medicine, in particular to application of isoflavonoids, namely tectorigenin and tectoridin, in belamcanda chinensis for treating multiple sclerosis diseases. The scheme adopted by the invention is as follows: a model experiment is conducted that 2% of cuprizone is used to induce demyelination of a mouse, and the experimental result shows that tectorigenin and tectoridin can significantly improve the pathological alteration and ultrastructural changes of demyelination at the callosum part of the mouse in the cuprizone-induced demyelination model; both of tectorigenin and tectoridin can significantly reverse the performance of a decreased myelin-associated protein expression level of the demyelinated mouse induced by cuprizone; both of tectorigenin and tectoridin can significantly alleviate the depression-like behaviors and the spatial learning and memory impairments of the mouse in the demyelination model, and show a remarkable protective function. Therefore, the two isoflavonoids namely tectorigenin and tectoridin can be used to prepare medicine for treating multiple sclerosis related diseases.

Description

The application of isoflavonoid in preparation treatment multiple sclerosis disease medicine
Technical field
The present invention relates to Natural Medicine Chemistry and medical art, be specifically related to the application of isoflavonoid in preparation treatment multiple sclerosis disease medicine.
Background technology
Multiple sclerosis (Multiple Sclerosis, MS) is the flammatory demyelinating disease of a kind of central nervous system, is the disease damaged based on brain and substantia alba medullae spinalis that cellular immunization and humoral immunization participate in causing jointly.Pathological manifestations is the formation etc. of inflammatory reaction, myelinoclasis and glial scar.Wherein the mistake of myelinoclasis and reparation thereof is compensatory is one of pathologic basis of CNS functional.The MS course of disease repeatedly, still lacks the remedy measures fully effective to MS at present.Multiple sclerosis can cause depression, ability of learning and memory weakens (see document: Franco-Pons N, Torrente M, Colomina MT, Vilella E, Behavioral deficits in the cuprizone-induced murine model of demyelination/remyelination, Toxicol Lett.2007,169 (3): 205-213.).
The demyelinated model that bisoxalydihydrazone (cuprizone, CPZ are called for short copper hydrazone) is induced is at present for one of classical model studying MS.By adding 0.2%CPZ and feeding 6-8 week Modling model in normal mice grain.CPZ is chelating copper ions agent, can specific effect in the oligodendrocyte (OL) of CNS.The key pathological of this model is changed to the depigmentation of corpus callosum and cerebellar white matter region myelin.This model manipulation is simple, and repeatable high, and the myelinoclasis caused under not relating to immunomodulating situation.
Iridin (1), tectorigenin (2), iris aglycone-4 '-O-β-D-Glucose glycosides (3), Tectorigenin (4), iridin (5) are that the isoflavone compounds got from Iridaceae Rhizoma Belamcandae platymiscium Rhizoma Belamcandae Belamcanda chinensis (L.) DC. is (see document: Jin Li, Chen Hai-sheng, Jin Yong-Sheng, et al.Chemical constituents from Belamcanda chinensis Journal of Asian Natural Products Research 2008,10 (1): 89-91; Qiu Yingkun etc., the chemical constitution study of Rhizoma Belamcandae, Chinese Pharmaceutical Journal 2006; 41 (15): 1133-1135).Their chemical structure of general formula is as follows:
The structure matching of five compounds is as follows:
1 iridin R 1=R 4=OH, R 2=R 5=R 6=OCH 3, R 3=Oglc
2 tectorigenin R 1=R 3=R 5=OH, R 2=OCH 3, R 4=R 6=H
3 iris aglycone-4 '-O-β-D-Glucose glycosides R 1=R 3=OH, R 2=OCH 3, R 5=Oglc, R 4=R 6=H
4 Tectorigenin R 1=R 4=R 3=OH, R 2=R 5=R 6=OCH 3
5 iridin R 1=R 5=OH, R 2=OCH 3, R 3=Oglc, R 4=R 6=H
The applicant, in early-stage Study, has found that tectorigenin, iridin significantly can improve dermal pathology performance caused by ultra-vioket radiation, if significantly suppress the skin keratinocytes apoptosis caused by ultra-vioket radiation, has shown significant cytoprotection; Significantly can suppress the inflammatory reaction of damaged skin tissue after ultra-vioket radiation; Significantly alleviate the oxidative damage of damaged skin tissue homogenate after ultra-vioket radiation.And applied for Chinese invention patent on March 29th, 2012, and obtain the authorization, the patent No. is ZL201210087404.X, and denomination of invention is " Isoflavones Extracted from Belamcanda Chinensis compound can be used for preparing the medicine that prevention and therapy ultraviolet causes skin injury ", and notification number is CN102631362B.
But so far there are no compounds such as iridin (1), tectorigenin (2), iris aglycone-4 '-O-β-D-Glucose glycosides (3), Tectorigenin (4), iridin (5) are the behavior depression caused by multiple sclerosis disease and the report of ability of learning and memory damage aspect to prevention or treatment.
Summary of the invention
The object of the invention is to the new medical usage of tectorigenin, iridin.
The chemical structural formula of tectorigenin (Tectorigenin) is as shown in formula I:
The chemical structural formula of iridin (English name tectoridin) is as shown in formula II:
The invention provides tectorigenin and/or the application of iridin in preparation prevention or treatment multiple sclerosis disease medicine.
Application of the present invention, specifically refers to the nerve injury that tectorigenin and/or iridin can reduce multiple sclerosis and cause.
Application of the present invention, specifically refers to the depression that tectorigenin and/or iridin can be alleviated or improve multiple sclerosis and cause.
Application of the present invention, specifically refers to that tectorigenin and/or iridin can recover or improve the ability of learning and memory that multiple sclerosis causes and weaken.
Application of the present invention, described medicine is for sole active composition with tectorigenin or iridin.
The present invention adopts classical model-copper hydrazone (2% bisoxalydihydrazone (cuprizone of research MS, the demyelinated model of CPZ) inducing, bull C57 mice is selected to be that object is tested, matched group gives normal mice grain, the Mus grain of model group and medicine group feeding 0.2%CPZ, and after 6 weeks, medicine group gives lumbar injection tectorigenin or iridin (10mg, 20mg, 50mg), all the other organize injecting normal saline, continuous 2 weeks.Afterwards, carry out Behavior test, comprise the experiment of spacious field and tail-suspention test that measure animal mood reaction; And evaluate Morris water maze laboratory and the inquiry experiment of animal learning memory ability.Finally, collect animal specimen and carry out morphological observation, comprise LFB dyeing (dyeing of specificity myelin protein) and the transmission electron microscope (observing myelin ultrastructure) at each treated animal corpus callosum position; And the tissue getting corpus callosum position carries out the quantitative analysis of Nogo protein (MBP).Behavioristics's result display, model group mice shows obvious behavior depression, and spatiality ability of learning and memory is significantly smaller than matched group and medicine group; Morphological outcomes shows, after the LFB dyeing at model group mice corpus callosum position, scoring is significantly lower than matched group and medicine group, transmission electron microscope results shows, the myelin at model group mice corpus callosum position is loose, thinning, axon diameter reduces, and after giving pharmaceutical intervention, above-mentioned pathological manifestations is all significantly improved; Protein quantification result shows, and the MBP protein content at the corpus callosum position of model group mice is all lower than matched group and medicine group.
In sum; behavioristics, morphology and the display of molecular biological experimental result; CPZ induces demyelinated model modeling success; after giving tectorigenin and iridin intervention; emotional response and the learning and memory function of animal pattern all improve; consistent with Pathological, prompting tectorigenin and iridin have protective effect to the demyelinated model that CPZ induces.
Therefore, the present invention proves through zoopery, and tectorigenin and iridin all have protective effect to the emotional response of copper hydrazone induction demyelinated model mice and ability of learning and memory.Tectorigenin, iridin can be used for the medicine preparing prevention or treatment multiple sclerosis disease.
The present invention is that clinical treatment multiple sclerosis disease provides new means.
Accompanying drawing explanation
Fig. 1 is the behavior depression that iridin (10mg/kg, 20mg/kg and 50mg/kg) significantly can improve CPZ guidance model Mus; Wherein A is spacious field experiment-total activity distance, and B is spacious field experiment-zone line activity distance, and C is tail-suspention test-dead time, * *, p<0.01vs control; #, p<0.05; ##, p<0.01vs CPZ.
Fig. 2 is the behavior depression that tectorigenin (10mg/kg, 20mg/kg and 50mg/kg) significantly can improve CPZ guidance model Mus; Wherein A is spacious field experiment-total activity distance, and B is spacious field experiment-zone line activity distance, and C is tail-suspention test-dead time, * *, p<0.01vs control; #, p<0.05; ##, p<0.01vs CPZ.
Fig. 3 is the ability of learning and memory damage that iridin (10mg/kg and 20mg/kg) significantly can improve CPZ guidance model Mus; Wherein A is the average time of acquired training-find platform, and B is the time of staying of inquiry experiment-target quadrant, wherein * *, p<0.01vs control; #, p<0.05; ##, p<0.01vs CPZ.
Fig. 4 is the ability of learning and memory damage that tectorigenin (10mg/kg and 20mg/kg) significantly can improve CPZ guidance model Mus; Wherein A is the average time of acquired training-find platform, and B is the time of staying of inquiry experiment-target quadrant, * *, p<0.01vs control; ##, p<0.01vs CPZ.
Fig. 5 is the pathological manifestations that iridin (10mg/kg and 20mg/kg) significantly can improve CPZ guidance model Mus corpus callosum region demyelination; Wherein A corpus callosum position LFB dyes (400 ×), and B is myelin staining scoring cartogram, wherein * *, p<0.01vs control; #, p<0.05; ##, p<0.01vs CPZ.
Fig. 6 is the pathological manifestations that tectorigenin (10mg/kg and 20mg/kg) significantly can improve CPZ guidance model Mus corpus callosum region demyelination; Wherein A corpus callosum position LFB dyes (400 ×), and B is myelin staining scoring cartogram, wherein * *, p<0.01vs control; #, p<0.05; ##, p<0.01vs CPZ.
Fig. 7 is the pathological manifestations that iridin (10mg/kg, 20mg/kg and 50mg/kg) significantly can improve CPZ guidance model Mus corpus callosum region demyelination; Wherein A is ratio (G-ratio) cartogram of corpus callosum myelin (sagittal plane) transmission electron microscope picture (1200 ×/3000 ×), B nerve fiber axon diameter and total nerve fiber diameter.
Fig. 8 is the pathological manifestations that tectorigenin (10mg/kg and 20mg/kg) significantly can improve CPZ guidance model Mus corpus callosum region demyelination; Wherein A corpus callosum myelin (sagittal plane) transmission electron microscope picture (1200 ×/3000 ×), B is ratio (G-ratio) cartogram of nerve fiber axon diameter and total nerve fiber diameter.
Fig. 9 is the reduction that iridin (10mg/kg and 20mg/kg) significantly can improve CPZ guidance model Mus corpus callosum MBP protein level; Wherein * *, p<0.01vs control; #, p<0.05; ##, p<0.01vs CPZ.
Figure 10 is the reduction that tectorigenin (10mg/kg, 20mg/kg and 50mg/kg) significantly can improve CPZ guidance model Mus corpus callosum MBP protein level; Wherein *, p<0.05vs control; #, p<0.05; ##, p<0.01vs CPZ.
Detailed description of the invention
Now in conjunction with the accompanying drawings and embodiments, the present invention is described in detail, but enforcement of the present invention is not limited only to this.
The experimental technique of unreceipted actual conditions in the following example, usually conveniently condition, or according to the condition that manufacturer advises.Unless otherwise indicated, otherwise percentage ratio and number calculate by weight.
Describe the present invention below in conjunction with embodiment and accompanying drawing.But the following example should not regard limitation of the scope of the invention as.
Experimental technique in following embodiment, if no special instructions, is conventional method.
The tectorigenin used in embodiment, iridin, extract (see document: Jin Li according to literature method, Chen Hai-sheng, Jin Yong-Sheng, et al.Chemical constituents from Belamcanda chinensis Journal of Asian Natural Products Research 2008,10 (1): 89-91); Other reagent are purchased from Shanghai branch company of traditional Chinese medicines group.
Embodiment 1: tectorigenin and the application of iridin in preparation treatment multiple sclerosis disease medicine
1 Experimental agents and animal
1.1 Experimental agents and preparation: it is initial concentration that tectorigenin and iridin DMSO are dissolved into 0.6g/ml, every day becomes 3mg/ml with normal saline dilution before lumbar injection again, carries out lumbar injection.
1.2 modeling medicine and preparations: bisoxalydihydrazone (CPZ is called for short copper hydrazone), available from Sigma, again suppresses after mixing by 0.2% with normal mice grain, feeding 6-8 week;
1.3 laboratory animals: C57 male mice purchased from The 2nd Army Medical College Experimental Animal Center, body weight 20-25g.
2 test methods
2.1 bisoxalydihydrazones (CPZ) induce demyelination damage model: CPZ suppresses after mixing with normal mice grain by 0.2% again, feeding 6-8 week.
2.2 pharmaceutical intervention methods: 0.2%CPZ Mus grain feeding, after 6 weeks, gives tectorigenin or the iridin of various dose (10mg/kg, 20mg/kg, 50mg/kg body weight) in the mode of lumbar injection.Every day injection before weigh, injected dose 400ul, less than 400ul with normal saline polishing.CPZ group gives physiological saline same dose.Effect of drugs is observed after continuous 2 weeks.
2.3 observation index:
(1) Behavior test:
A () open field test: center district mice being put into dark inspection box, starts timing simultaneously, is mounted with RF transmitter and camera head in case, effectively can record the various crawler behaviors of mice, every mice carries out 5min record continuously simultaneously.The experiment video analytic system that application Ji Liang software scientific & technical corporation provides, can the every behavioral indicator of real time record laboratory animal, movement locus figure and monitoring video in real time, and derives by excel data mode.By the movement locus of computer analysis mice, movable total distance and the zone line time of staying.Thoroughly clean inspection box before putting into mice at every turn.
(b) tail-suspention test: mouse tail is about 1cm place clip apart from end and fixes, it is made to hang upside down on the cross bar of distance ground about 15cm, animal is for overcoming abnormal position and struggle activity, but after movable a period of time, occur that discontinuity is motionless, show disappointed state, the dead time in accumulative each group of 3min.Its principle is that after utilizing mouse tail suspension, attempt is escaped but cannot escape, thus abandons struggling, and enter the motionless state of distinctive depression, recording the animal dead time in experimentation reflects depressive state.
(c) Morris water maze and inquiry experiment: be mainly used in test experiments animal and locus is felt and the ability of learning and memory of direction sensation (space orientation).The swimming pool diameter being applicable to mice is 120cm, platform diameter 8cm.The experiment video analytic system that application Ji Liang software scientific & technical corporation provides, can real time record laboratory animal every behavioral indicator, movement locus figure and monitoring video in real time in swimming pool, and derives by excel data mode.Experimental period is fixed on every morning 9:00 and starts, and water temperature is constant in 22-25 DEG C, and tank water is white with white non-toxic dyes, and the water surface need be about 2cm higher than platform.First carry out acquired training, experiment mice head is put into water towards pool wall, put into position and get one of East, West, South, North four original positions at random.Record animal finds the time of underwater platform.In front training several times, if mice can not find platform in 60s, then guided to platform, and stopped 10s on platform.Then animal removed and dry (under if desired rat being placed on the electric filament lamp of 150W, roasting 5min, puts back in cage).Every animal trains 4 times every day, interval 15 ~ 20min between twice training, continuously training 4 days.5th day, platform is removed, start the inquiry experiment (probe test) of 30s.Mice is put into water by the offside of original platform place quadrant.Record mice at target quadrant (quadrant of original placement platform) institute's time spent and the number of times entering this quadrant, in this, as the Testing index of spatial memory.Total distance of being trained by the every day of computer analysis mice, find time (incubation period) needed for platform, the data such as the time of staying, traversing times in selected quadrant such as swimming average speed can react the learning and memory ability that mice feels to locus.
(2) morphological indexes: after performance testing second day, puts to death mice with excessive 20% urine ester anesthesia, get different parts cerebral tissue capable below analyze:
A () LFB dyes: LFB dyeing and luxol fast blue dye, and are one of myelinic specific stain methods.Take out rapidly Mice brain tissues to put into paraformaldehyde solution be fixed on ice, then embed into paraffin enclosed mass, in coronalplane section to corpus callosum position, slice thickness is about 25um, carries out LFB dyeing.Myelin can be dyed blueness by LFB dyeing, observes the depth of stained positive fiber and how many and carry out marking with the relevant myelin change such as quantitative analysis Demyelination and Remyelination situation accordingly.Scoring is 4 grades, is respectively that 0 point-myelin is lost completely, 1 point of-1/3 myelin retains, 2 point of-2/3 myelin retains and 3 points-normal morphology myelin.
(b) transmission electron microscope: take out Mice brain tissues rapidly on ice, and isolate corpus callosum position, put into paraformaldehyde solution and fix, after 30 minutes, tissue is cut into 1*1*1mm 3piece of tissue, fixing about 24 hours, carry out transmission electron microscope sample process subsequently, and observe the myelin at corpus callosum position at sagittal plane, whether occur that myelin is loose, the situation of loss.Be that index computation analyzes myelin damage situation with G-ratio, this ratio is containing the overall diameter of myelin aixs cylinder and the ratio of aixs cylinder interior diameter, and ratio is more about serious close to 1 representative damage;
(3) molecular Biological Detection: the corpus callosum homogenate of getting mice, detects by Western blot method and analyzes the change of MBP protein level.
3 results
3.1 behavior depressions are observed:
Compared with feeding normal mice grain, feeding carries out having total activity distance to reduce in the experiment of spacious field containing the mice of 0.2%CPZ Mus grain, the performance (Figure 1A B, Fig. 2 AB) that the middle section time of staying reduces; Find after carrying out tail-suspention test, this group mouse tail suspension dead time also obviously increases (Fig. 1 C, Fig. 2 C), and prompting feeding can the behavior depression of inducing mouse containing 0.2%CPZ Mus grain.Various dose tectorigenin and iridin all significantly can improve the behavior depression of feeding containing the mice of 0.2%CPZ Mus grain.
3.2 ability of learning and memory are observed:
The acquired training test result display of Morris water maze, compared with feeding normal mice grain, feeding finds obviously extend the incubation period of platform containing the mice of 0.2%CPZ Mus grain in 60s, points out the Spatial learning ability of this group group mice to be subject to obvious impact (Fig. 3, Fig. 4); Inquiry experiment test result shows, and feeding obviously reduces in the target quadrant time of staying containing the mice of 0.2%CPZ Mus grain, points out the spatial memory capacity of this group mice to decline (Fig. 3, Fig. 4).Various dose tectorigenin and iridin all significantly can improve the damage of feeding containing the spatiality ability of learning and memory of the mice of 0.2%CPZ Mus grain.
3.3 LFB dyeing are observed:
Feeding is obviously weaker than normal group containing the myelin dyeing in the mice corpus callosum region of 0.2%CPZ Mus grain, and the integrity of prompting myelin is impaired, and myelin is lost serious (Fig. 5, Fig. 6), and after LFB dyeing, scoring is lower.Tectorigenin and iridin all significantly can improve the performance of feeding containing the myelin damage at mice corpus callosum position after 0.2%CPZ Mus grain, and myelin scoring obviously improves, and shows significant therapeutic effect.
3.4 transmission electron microscope observings:
Corpus callosum sagittal plane as shown in Figure 7, Figure 8, feeding is loose containing the mice corpus callosum region sheath structure of 0.2%CPZ Mus grain, and disintegrate lacks even completely, and G-ratio is close to 1.Tectorigenin and iridin all significantly can improve the performance of feeding containing the myelin damage at mice corpus callosum position after 0.2%CPZ Mus grain, and G-ratio significantly reduces, and has significant protective effect.
3.5 MBP molecular level changes:
As shown in Figures 9 and 10, compared with the mice of feeding normal mice grain, feeding significantly reduces containing the MBP protein level at the mice corpus callosum position of 0.2%CPZ Mus grain, points out the myelin at this position to lose serious.And tectorigenin and iridin can make the MBP protein level recovery in various degree of reduction, show that myelin damage is significantly repaired.
Experimental result shows, tectorigenin, iridin all significantly can improve feeding containing the demyelination damage caused by 0.2%CPZ quantity; Remarkable behavior depression and the damage of spatiality ability of learning and memory improving CPZ induction; Improve the loose of the corpus callosum position myelin of CPZ induction and lose; The Hippocampus of remarkable promotion CPZ induction and the recovery of corpus callosum region Nogo protein MBP level.Therefore, tectorigenin, iridin can be used for the medicine preparing prevention or treatment multiple sclerosis disease.
Below the preferred embodiment of the invention is illustrated, but the invention is not limited to described embodiment, those of ordinary skill in the art also can make all equivalent modification or replacement under the prerequisite without prejudice to the invention spirit, and these equivalent modification or replacement are all included in the application's claim limited range.

Claims (5)

1. the application of isoflavonoid in preparation prevention or treatment multiple sclerosis disease medicine, it is characterized in that, described isoflavonoid is tectorigenin or iridin.
2. the application of isoflavonoid according to claim 1 in preparation prevention or treatment multiple sclerosis disease medicine, is characterized in that, described application refers to the nerve injury that tectorigenin or iridin reduction multiple sclerosis cause.
3. the application of isoflavonoid according to claim 1 in preparation prevention or treatment multiple sclerosis disease medicine, is characterized in that, described application refers to the depression that tectorigenin or iridin are alleviated or improved multiple sclerosis and cause.
4. the application of isoflavonoid according to claim 1 in preparation prevention or treatment multiple sclerosis disease medicine, it is characterized in that, described application refers to that tectorigenin or iridin recover or improve the ability of learning and memory that multiple sclerosis causes and weaken.
5. according to the application of the arbitrary described isoflavonoid of claim 1 to 5 in preparation prevention or treatment multiple sclerosis disease medicine, it is characterized in that, described medicine is for sole active composition with tectorigenin or iridin.
CN201410818123.6A 2014-12-19 2014-12-19 Application of isoflavonoids in preparation of medicine for treating multiple sclerosis diseases Expired - Fee Related CN104546824B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410818123.6A CN104546824B (en) 2014-12-19 2014-12-19 Application of isoflavonoids in preparation of medicine for treating multiple sclerosis diseases

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410818123.6A CN104546824B (en) 2014-12-19 2014-12-19 Application of isoflavonoids in preparation of medicine for treating multiple sclerosis diseases

Publications (2)

Publication Number Publication Date
CN104546824A true CN104546824A (en) 2015-04-29
CN104546824B CN104546824B (en) 2017-05-24

Family

ID=53064607

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410818123.6A Expired - Fee Related CN104546824B (en) 2014-12-19 2014-12-19 Application of isoflavonoids in preparation of medicine for treating multiple sclerosis diseases

Country Status (1)

Country Link
CN (1) CN104546824B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112401079A (en) * 2020-11-25 2021-02-26 常州鼠一鼠二生物科技有限公司 Mouse myelin sheath loss model feed and preparation method and application thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09176011A (en) * 1995-12-27 1997-07-08 Kureha Chem Ind Co Ltd Flavonoid-containing agent for suppressing synthesis of protein of hsp27 family

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09176011A (en) * 1995-12-27 1997-07-08 Kureha Chem Ind Co Ltd Flavonoid-containing agent for suppressing synthesis of protein of hsp27 family

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112401079A (en) * 2020-11-25 2021-02-26 常州鼠一鼠二生物科技有限公司 Mouse myelin sheath loss model feed and preparation method and application thereof

Also Published As

Publication number Publication date
CN104546824B (en) 2017-05-24

Similar Documents

Publication Publication Date Title
Nelwan Schistosomiasis: life cycle, diagnosis, and control
McGrath et al. Zebrafish: a predictive model for assessing drug-induced toxicity
Spiller et al. Selective motor neuron resistance and recovery in a new inducible mouse model of TDP-43 proteinopathy
Zhang et al. Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer's disease–like pathology
Ma et al. The effects of unilateral 6-OHDA lesion in medial forebrain bundle on the motor, cognitive dysfunctions and vulnerability of different striatal interneuron types in rats
Giovanoli et al. Single and combined effects of prenatal immune activation and peripubertal stress on parvalbumin and reelin expression in the hippocampal formation
CN102497873B (en) For increasing compositions and the method for the survive time limit and the healthy time limit
Keifer Jr et al. A comparative analysis of mouse and human medial geniculate nucleus connectivity: a DTI and anterograde tracing study
Li et al. Malignant transformation of nasal chondromesenchymal hamartoma in adult: a case report and review of the literature
Cheng et al. Effects of lincomycin hydrochloride on the neurotoxicity of zebrafish
Roberts et al. Preservation of striatal tissue and behavioral function after neural stem cell transplantation in a rat model of Huntington’s disease
Zhao et al. Chronic spinal cord injury repair by NT3-chitosan only occurs after clearance of the lesion scar
Suero-Abreu et al. In vivo Mn-enhanced MRI for early tumor detection and growth rate analysis in a mouse medulloblastoma model
Han et al. Novel derivative of Paeonol, Paeononlsilatie sodium, alleviates behavioral damage and hippocampal dendritic injury in Alzheimer's disease concurrent with cofilin1/phosphorylated-cofilin1 and RAC1/CDC42 alterations in rats
Marmion et al. Viral-based rodent and nonhuman primate models of multiple system atrophy: Fidelity to the human disease
Lin et al. Long‐term and in vivo assessment of Aβ protein‐induced brain atrophy in a zebrafish model by optical coherence tomography
Scherfler et al. Complex motor disturbances in a sequential double lesion rat model of striatonigral degeneration (multiple system atrophy)
Goc et al. A spatiotemporal study of gliosis in relation to depth electrode tracks in drug‐resistant epilepsy
Valenzuela et al. Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial
Lin et al. Neurogranin as an important regulator in swimming training to improve the spatial memory dysfunction of mice with chronic cerebral hypoperfusion
Melloni et al. Changes of white matter microstructure after successful treatment of bipolar depression
Korzh et al. Origin and development of circumventricular organs in living vertebrate
Cordeiro et al. Graft-mediated functional recovery on a skilled forelimb use paradigm in a rodent model of Parkinson's disease is dependent on reward contingency
Xiu et al. Ultrastructural abnormalities and loss of myelinated fibers in the corpus callosum of demyelinated mice induced by cuprizone
Sharma et al. Zebrafish (Danio rerio): A potential model for nephroprotective drug screening

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20170524

Termination date: 20171219