CN101966193B - Application of 2,3,5,4-tetrahydroxystilbene-2-O-beta-D-glucoside to preparing medicaments for treating depression - Google Patents
Application of 2,3,5,4-tetrahydroxystilbene-2-O-beta-D-glucoside to preparing medicaments for treating depression Download PDFInfo
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- CN101966193B CN101966193B CN2010105243868A CN201010524386A CN101966193B CN 101966193 B CN101966193 B CN 101966193B CN 2010105243868 A CN2010105243868 A CN 2010105243868A CN 201010524386 A CN201010524386 A CN 201010524386A CN 101966193 B CN101966193 B CN 101966193B
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Abstract
The invention discloses application of 2,3,5,4-tetrahydroxystilbene-2-O-beta-D-glucoside to preparing medicaments for treating depression, in particular to application of 2,3,5,4-tetrahydroxystilbene-2-O-beta-D-glucoside as an active ingredient to preparing medicaments for treating depression. The invention provides the application of the 2,3,5,4-tetrahydroxystilbene-2-O-beta-D-glucoside as the medicaments for treating depression, and the 2,3,5,4-tetrahydroxystilbene-2-O-beta-D-glucoside is hardly innoxious and is applied to preparing medicaments for preventing or treating various depression symptoms including endogenous depression, reactive depression, masked depression, secondary depression caused by medicaments, menopausal or post-natal depression, depression induced by traumatic brain injury or brain death and depressive neurosis and medicaments for treating diabetes and depression complications and related diseases.
Description
Technical field
The invention belongs to medicine, especially from natural plants, extract obtain 2,3,5, the new medicine use of 4 '-tetrahydroxystilbene-2-O-β-D-glucoside is specifically related to their application in preparation treatment depression product.
Background technology
2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside belongs to diphenylethylene compounds, and molecular formula is C
20H
22O
9Stilbene glucoside in the Radix Polygoni Multiflori has become the specificity index of Radix Polygoni Multiflori medical material at present.To in the Radix Polygoni Multiflori 2,3,5, the research of aspects such as the biological activity of 4 '-tetrahydroxystilbene-2-O-β-D-glucoside, extraction process, analyzing detecting method is deep day by day in recent years.Discover, 2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside have many pharmacotoxicological effects as: have strong anti-oxidation and remove the free radical ability; Effect with CKIs kinase c, thus tumor growth suppressed, also have stronger ACA simultaneously, possibly participate in regulating body's immunity; Can reduce the generation of rat model cerebral hippocampal district A-β, reduce serum cholesterol, low-density lipoprotein cholesterol level, improve hemorheology, have T-CHOL effect in the obvious reduction oils and fats rat feeding serum; Can reduce the rat plasma lipid level; Prevent and treat atherosclerosis and hyperlipemia; Liver-protective function; Arteries had the diastole effect; Control senile dementia and raising memory function
.
Depression is the higher major disease of sickness rate.Depression is the common disease of a kind of psychiatric department, and according to World Health Organization's statistics, depression has become the world's the 4th big illness; China's the 2nd big disease burden predicts the year two thousand twenty, possibly become the second largest disease that is only second to coronary heart disease; Account for 15% of global disease burden; The sickness rate of lifelong depression is between 6%-8%, and along with the progressively aging of population, the sickness rate of depression in crowd more than 60 years old will be up to 20%-50%.Depressive patients is the high-risk group who commits suiside, and falls ill to convalescence patient, has the danger of committing suiside all the time.The identifying and diagnosing rate of depression is very low, and effectively cure rate is also very low.Existing antidepressant Western medicine mainly is: tricyclic antidepressants (TCAs); Selectivity 5-HT reuptake inhibitor (SSRIs); Oxidase inhibitor (MAOIs); The toxic and side effects of their equal various degrees, and cost an arm and a leg, thereby the new antidepressants of research and development have important theory and practical significance from Chinese medicine.
Summary of the invention
Above shortcoming in view of prior art; The objective of the invention is to study one and make 2,3,5; 4 '-tetrahydroxystilbene-2-O-β-D-glucoside is the medical usage more widely of the medicine of active component, makes its being applied in preparation treatment depression medicine.
The present invention has studied 2,3,5, the application of 4 '-tetrahydroxystilbene-2-O-β-D-glucoside in preparation treatment depression medicine, and with 2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside is effective ingredient manufacturing control depression medicine.
The invention provides and contain 2; 3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside is as the purposes of prevention and treatment depression medicine; It has the little characteristics of toxicity, and degradation under the learning memory of depression secondary is had tangible mitigation.2; 3; 5; 4 '-tetrahydroxystilbene-2-O-β-D-glucoside or be used to prepare with its Pharmaceutical composition of forming as active component etc. depression that prevention or treatment comprise that endogenous depression, reactive depression, masked depression, drug-induced secondary depression, climacteric or postpartum depression, cerebral trauma or apoplexy bring out and depressive neurosis various depressive symptoms medicine application and be used for diabetes and merge depression; And be used to prepare prevention and treat the insecondary learning and memory decline that depression causes, the application in the medicine of symptoms such as anhedonia.
The specific embodiment
Below in conjunction with embodiment the present invention is described further.
Following zoopery is to further explain of the present invention, but and does not mean that any restriction of the present invention.Obviously, since the selected laboratory animal pharmacology feasible popularity that has expressed the present invention use should trace back and the animal realm.
Laboratory animal: male kunming mouse, begin to test body weight 18g-30g, purchase medical experiment animal center in Sichuan Province; SCXK [river] 2008-14, it is dark to accept 12h illumination/12h every day, and periodicity of illumination is 8:00-20:00; 20 ± 2 ℃ of laboratory temperatures; Humidity 60%, animal can absorb standard feed and cleaning water voluntarily, and International Laboratory Animal ethics requirement is observed in zoopery.
Medicine:
2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside (standard substance) is provided along vigorous biotechnology company limited by Shanghai, processes the suspendible medicinal liquid with 0.5% shuttle methylated cellulose aqueous solution, and is subsequent use.
Experimental program:
1, desperate (behavioural despair, BD) depression model of behavior
The BD model comprises forced swimming experiment (Forced Swimming Test; FST) and outstanding tail experiment (Tail Suspension Test; TST), its theoretical basis is: under the stressed condition of forced swimming or outstanding tail, animal via is struggled, and the back appearance is desperate to show; Be motionless state, and antidepressant can shorten the dead time of animal.Dead time after the former is draped with animal with dead time, the latter of animal in water is as the index of estimating depressed degree.Because changing almost, the behavioristics of this type of animal pattern can be reversed by now clinical applied most antidepressants; Have responsive, easy characteristics; So be usually used in the rapid screening of antidepressants, be that animal model is the most widely used in present antidepressant drug screening.But the factor that influences the BD model is more, all possibly have influence on the accuracy of experimental result like the judgement of the motionless state of animal, the quiet degree of environment and the time of experiment etc.
Experimental technique:
100 random packet of KM mice are normal control group, 2,3,5, and the 4 '-tetrahydroxystilbene-2-O-β-high, medium and low dose groups of D-glucoside amounts to 5 groups, every group of 20 animals, and each treated animal dosage regimen is following:
⑴ normal control group: the oral distilled water of giving;
⑵ 2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside high dose group 200mg/kg.d;
⑶ 2,3,5, dose groups 100mg/kg.d in 4 '-tetrahydroxystilbene-2-O-β-D-glucoside;
⑷ 2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside low dose group 50mg/kg.d
(5) prozac group: 5mg/kg.d
Outstanding tail experiment (Tail Suspension Test, TST)
Each treated animal gastric infusion every day 1 time, successive administration 7 days, last day, positive controls was given prozac, behind the administration 30min, mouse tail was fixed with clip apart from the about 2cm of end place, made the mice reversal of the natural order of things in outstanding boot, and its head is about 5cm at the bottom of case.Behind the mice suspension 2min, get started observation, observe lasting 6min, the dead time of mice in this 6min of accumulative total (mice aloft stops to struggle, or tiny limb motion is only arranged).
The forced swimming experiment (Forced Swimming Test, FST)
After each is organized the mice last and gives relative medicine or distilled water 30min, mouse head is put into the swimming cup of diameter 16cm, depth of water 18cm down, 25 ± 2 ℃ of water temperatures are immediately with the dead time in the stopwatch record mice 6min.
Each group of table 1 in the mouse tail suspension experiment with the forced swimming experiment in the dead time influence (
± S)
| Group | n | The outstanding tail dead time (second) | Non-swimming time (second) |
| Matched group | 20 | 141.08±34.89 | 68.15±28.61 |
| The prozac group | 20 | 80.09±28.38 △△ | 34.21±12.28 △△ |
| The high group of ethylene glycosides | 20 | 78.33±23.81 △△ | 33.36±13.96 △△ |
| Organize in the ethylene glycosides | 20 | 80.08±23.84 △△ | 35.92±14.43 △△ |
| The low group of ethylene glycosides | 20 | 93.14±27.59 △ | 55.86±18.24 |
Annotate: compare with matched group
△P<0.05,
△ △P<0.01
2, to the influence of drug-induced depressive state
Chemical compounds such as reserpine mainly comprise through the symptomes complice that monoamine transmitters in the exhaustion brain brings out animal: body temperature decline, blepharoptosis and movable the inhibition.The generation of these symptoms possibly reduce monoamine transmitters in the brain with reserpine. 5-hydroxy tryptamine (5-HT) especially, and the result that supervention 5-HT receptor sensitivity changes.The monoamine transmitters system mainly comprises 5-HT system, NE system and dopamine (DA) system, in the pathogenesis of depression, plays an important role.5-HT in patients with depression brain and the cerebrospinal fluid, 5-HI-AA, the NE equal size is all low than the normal person.5-HT relates to the adjusting of emotion, sleep, vigilance, memory and appetite etc., and the NE deficiency then can cause spirit sluggish.Monoamine oxidase, MAO (MAO) is that (important inactivator DA) if this enzyme is suppressed, will make monoamine transmitters content increase in the brain to monoamine transmitters for 5-HT, NE, and this has positive effect to improving depression.In 1950's, people are when observing the curative effect of antihypertensive reserpine, and discovery has the patient of 10-15% to take this medicine for a long time approximately can produce depressive symptom.Pharmaceutical research afterwards shows; The basic pharmacological action of reserpine is the monoamine neurotransmitter of exhausting in the teleneuron vesicle; The monoamine hypothesis of depression has been proposed thus. think that it is the depressed mechanism that takes place that the synaptic space monoamine neurotransmitter reduces; And antidepressants reduce and the performance antidepressant effect mediator metabolism through blocking-up monoamine-reuptake or inhibition monoamine oxidase, MAO (MAO).
Experimental technique:
120 random packet of KM mice are normal control group, model group, fluoxetine group, 2,3,5, and the 4 '-tetrahydroxystilbene-2-O-β-high, medium and low dose groups of D-glucoside amounts to 6 groups, every group of 20 animals, and each treated animal dosage regimen is following:
⑴ normal control group: the oral distilled water of giving;
⑵ 2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside high dose group 200mg/kg.d;
⑶ 2,3,5, dose groups 100mg/kg.d in 4 '-tetrahydroxystilbene-2-O-β-D-glucoside;
⑷ 2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside low dose group 50mg/kg.d
(5) prozac group: 5mg/kg.d
(6) model group: reserpine 1mg/kg.d
Each organized mice continuous irrigation stomach distilled water or relative medicine 6 days, and each group is given reserpine 1mg/kg except that normal group, blepharoptosis behind the 60min, behind the 180min body temperature descend, the movable inhibition.30min puts into mice prologue experimental box after mice last administration next day, adapts to 2min, observes level, the vertical movable number of times of the interior mice of 4min subsequently, promptly creep the grid number and the number of times of standing.
Each group of table 2 to mice prologue experiment creep the grid number and the number of times of standing influence (
± S)
| Group | n | The grid number of creeping | The number of times of standing |
| Matched group | 20 | 55.77 ± 13.66 | 18.54 ± 4.70 |
| Model group | 20 | 13.50 ± 4.56 △△ | 2.50 ± 0.65 △△ |
| The fluoxetine group | 20 | 29.17 ± 10.19 ﹡ | 5.42 ± 0.30 ﹡ |
| The high group of ethylene glycosides | 20 | 14.86 ± 3.90 | 1.14 ± 0.04 |
| Organize in the ethylene glycosides | 20 | 11.00 ± 3.82 | 5.33 ± 1.73 ﹡ |
| The low group of ethylene glycosides | 20 | 44.67 ± 13.17 ﹡﹡ | 14.56 ± 3.21 ﹡﹡ |
Annotate: compare with matched group
△ P<0.05,
△ △ P<0.01; With model group Bi Jiao ﹡ P<0.05 ， ﹡ ﹡ P<0.01.
Can know from above experimental result, 2,3,5, the middle dose groups and the low dose group of 4 '-tetrahydroxystilbene-2-O-β-D-glucoside have tangible antidepressant effect to reserpine induced mice depression model.
3, mice autonomic activities
Experimental technique is the same.
Each organized mice continuous irrigation stomach distilled water or relative medicine 6 days, and each group is given reserpine 1mg/kg except that normal group, blepharoptosis behind the 60min, behind the 180min body temperature descend, the movable inhibition.30min puts into mice autonomic activities appearance after mice last administration next day, the movable number of times in the record 5min.
Each group of table 3 to the influence of mice autonomic activities number of times (
± S)
| Group | n | The autonomic activities number of times |
| Matched group | 20 | 92.77 ± 20.15 |
| Model group | 20 | 59.08 ± 14.79 △ |
| The fluoxetine group | 20 | 78.11 ± 24.02 |
| The high group of ethylene glycosides | 20 | 83.83 ± 19.73 |
| Organize in the ethylene glycosides | 20 | 61.67 ± 18.34 |
| The low group of ethylene glycosides | 20 | 103.90 ± 22.42 ﹡ |
Annotate: compare with matched group
△ P<0.05; Compare with model group
﹡P<0.05.
Can know from above experimental result, 2,3,5, the low dose group of 4 '-tetrahydroxystilbene-2-O-β-D-glucoside can significantly improve mice autonomic activities number of times.
Claims (3)
1.2,3,5, the application of 4 '-tetrahydroxystilbene-2-O-β-D-glucoside in preparation treatment depression medicine, with 2,3,5,4 '-tetrahydroxystilbene-2-O-β-D-glucoside is active component manufacturing control depression medicine.
2. the application according to claim 1; It is characterized in that, the medicine of described control depression at preparation prevention and treatment endogenous depression or/and reactive depression or/and masked depression or/and drug-induced secondary depression or/and climacteric or postpartum depression or/and the depression that cerebral trauma or apoplexy bring out or/and the purposes in the medicine of depressive neurosis.
3. according to claim 1 or 2 said application, it is characterized in that the medicine of described control depression descends or/and the purposes in the anhedonia disease drug at the insecondary learning and memory that preparation prevention and treatment depression cause.
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| KR20100009415A (en) * | 2008-07-18 | 2010-01-27 | 경북대학교 산학협력단 | Composition of treatment for alzheimer disease comprising mesenchymal stem cells |
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| KR20100009415A (en) * | 2008-07-18 | 2010-01-27 | 경북대학교 산학협력단 | Composition of treatment for alzheimer disease comprising mesenchymal stem cells |
Non-Patent Citations (3)
| Title |
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| 徐杰 等.何首乌活性成分——二苯乙烯苷的研究进展.《泰山医学院学报》.2008,第29卷(第1期),78-80. * |
| 黄忠仕 等.二苯乙烯苷对Aβ25-35致NG108-15损伤的保护作用.《右江医学》.2008,第36卷(第5期),517-519. * |
| 黄忠仕 等.二苯乙烯苷对D-半乳糖致拟痴呆小鼠学习记忆和海马APP、Aβ表达的影响.《右江民族医学院学报》.2008,第30卷(第5期),713-716. * |
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