CN105770357A - Use of alliin in preparation of antidepressants - Google Patents
Use of alliin in preparation of antidepressants Download PDFInfo
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- CN105770357A CN105770357A CN201610158023.4A CN201610158023A CN105770357A CN 105770357 A CN105770357 A CN 105770357A CN 201610158023 A CN201610158023 A CN 201610158023A CN 105770357 A CN105770357 A CN 105770357A
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- Prior art keywords
- alliin
- depression
- bulbus allii
- medicine
- salt
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- XUHLIQGRKRUKPH-DYEAUMGKSA-N alliin Chemical compound OC(=O)[C@@H](N)C[S@@](=O)CC=C XUHLIQGRKRUKPH-DYEAUMGKSA-N 0.000 title claims abstract description 119
- XUHLIQGRKRUKPH-GCXOYZPQSA-N Alliin Natural products N[C@H](C[S@@](=O)CC=C)C(O)=O XUHLIQGRKRUKPH-GCXOYZPQSA-N 0.000 title claims abstract description 117
- XUHLIQGRKRUKPH-UHFFFAOYSA-N S-allyl-L-cysteine sulfoxide Natural products OC(=O)C(N)CS(=O)CC=C XUHLIQGRKRUKPH-UHFFFAOYSA-N 0.000 title claims abstract description 117
- 235000015295 alliin Nutrition 0.000 title claims abstract description 117
- 239000000935 antidepressant agent Substances 0.000 title claims abstract description 39
- 229940005513 antidepressants Drugs 0.000 title abstract description 13
- 230000001430 anti-depressive effect Effects 0.000 claims abstract description 18
- 240000002234 Allium sativum Species 0.000 claims abstract description 16
- 235000004611 garlic Nutrition 0.000 claims abstract description 16
- 239000003814 drug Substances 0.000 claims description 26
- 239000000284 extract Substances 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- 239000007924 injection Substances 0.000 claims description 15
- 238000002347 injection Methods 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 14
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- 238000012360 testing method Methods 0.000 description 19
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
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- XZZXIYZZBJDEEP-UHFFFAOYSA-N imipramine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2N(CCC[NH+](C)C)C2=CC=CC=C21 XZZXIYZZBJDEEP-UHFFFAOYSA-N 0.000 description 4
- 229960002102 imipramine hydrochloride Drugs 0.000 description 4
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- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
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- 229910052717 sulfur Inorganic materials 0.000 description 2
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
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- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
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- 230000002000 scavenging effect Effects 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/404—Indoles, e.g. pindolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/896—Liliaceae (Lily family), e.g. daylily, plantain lily, Hyacinth or narcissus
- A61K36/8962—Allium, e.g. garden onion, leek, garlic or chives
-
- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention relates to use of alliin in the preparation of antidepressants and belongs to pharmacy. The invention is characterized in that alliin is used as an effective component, or raw garlic, garlic extract and/or an alliin salt equivalent to the alliin is used as the effective component. The invention the advantages such as significant antidepressant effect, high acting speed, and no toxic and side effect.
Description
Technical field
The present invention relates to pharmaceutical technology, particularly to alliin purposes in preparing anti-depression drug.
Background technology
Depression is also known as depressive disorder, low for main clinical characteristics with notable and lasting mental state.Clinical visible mental state is low unbecoming with its situation, and the downhearted of emotion can from depressed to extremely grieved, and depression of feeling oneself inferior is even pessimistic and worldweary, can have suicidal attempt or behavior.Some cases has obvious anxiety and mobility intense, and severe patient may occur in which the psychotic symptoms such as hallucination, vain hope.Outbreak continues at least two weeks more than every time, up to the several years.Majority of cases has the tendency of recurrent exerbation, and outbreak great majority can be alleviated every time, and part can have residual symptoms or transfer to chronic.
Drug therapy is the primary treatment measure of the above paralepsy of moderate.Traditional tricyclic antidepressants, tetracyclic antidepressants and oxidase inhibitor are relatively big due to untoward reaction, and application significantly reduces.The antidepressants of a line mainly include selective serotonin reuptake inhibitor, 5-hydroxy tryptamine and NRI etc. clinically at present, but use this kind of drug effect slow, and action spectrum is narrow, easily recurs after drug withdrawal.At present, whole industry is all at research and development instant effect, side effect medicine little, more efficiently.
Alliin, is a kind of bioactive substance in Bulbus Allii, as non-protein class sulfur-containing amino acid unique in Bulbus Allii, accounts for the 0.6%-2% of Bulbus Allii dry weight.Chinese another name: (S)-3-(pi-allyl sulfenyl)-ALANINE;English name: Alliin;Molecular formula: C6H11NO3S;Molecular weight: 177.2214;Molecular structural formula is Fig. 1 such as.
Modern medicine shows: alliin has the multiple pharmacological effects such as antitumor, collaborative blood pressure lowering, antibacterial sterilization, scavenging free radicals, hepatoprotective and anti-diabetic.Long-term taking alliin effect in blood fat reducing, raising body immunity, sterilization, flu antibacterial, anti-, defying age, blood circulation promoting, cancer-resisting etc. is notable.The multiple pathogen of the harm mankind is had inhibitory or killing effect by it, it it is natural phytocide, as to pathogenic staphylococcus, pyococcus, dysentery bacterium, escherichia coli, Bacillus typhi, tubercule bacillus, diphtheria corynebacterium, anthrax bacillus, bacillus subtilis, Salmonella paratyphi, meningitis and diplococcus, vibrio cholera, streptococcus, Staphylococcus albus, permitted blue achorion etc., there are significantly antibacterial and bactericidal action;To much bacillary, fungoid and anti-protozoal infection, treatment and prevention are all had to be worth.But, application alliin there is not yet as the report of active ingredient preventing/treating depression.
Summary of the invention
The present invention provides alliin purposes in preparing antidepressant drug and the antidepressant drug prepared with alliin, and this medicine has the advantages such as antidepressant effect is notable, rapid-action, have no side effect.The technical scheme that the present invention is claimed is as follows:
The medicine of a kind of depression, it is characterised in that active ingredient is alliin, or the salt of the considerable amount of uncooked garlic of alliin, Bulbus Allii extract and/or alliin.
The medicine of a kind of depression, it is characterised in that active ingredient includes alliin or the salt of the considerable amount of uncooked garlic of alliin, Bulbus Allii extract and/or alliin.
The medicine of a kind of quick-acting depression, it is characterised in that active ingredient is alliin, or the salt of the considerable amount of uncooked garlic of alliin, Bulbus Allii extract and/or alliin, and dosage is
Every kg body weight 0.01-30mg alliin, or
The salt of every considerable amount of uncooked garlic of kg body weight 0.01-30mg alliin, Bulbus Allii extract and/or alliin;
It is administered in latter 90 minutes and can produce antidepressant effect.
Any of the above-described medicine, it is characterised in that: dosage form is powder, tablet, capsule, solution, suspension, injection or drip liquid.
Described medicine, also includes acceptable auxiliary element on pharmacopedics.
Any of the above-described medicine, also include after using with alliin simultaneously to treatment depression have the ingredient of positive role and/or make the stability-enhanced composition of alliin.
Alliin purposes in preparing anti-depression drug, it is characterised in that prepare anti-depression drug for active ingredient with alliin.
A kind of method for the treatment of/prevention of depression, it is characterised in that make experimenter take in alliin or the salt of the considerable amount of uncooked garlic of alliin, Bulbus Allii extract and/or alliin.
Described method, wherein dosage is: provide 0.01-30mg alliin or the salt of the uncooked garlic of 0.01-30mg alliin equivalent, Bulbus Allii extract and/or alliin by every kg body weight every day.
The research of the present invention finds, in mammal mouse experiment, alliin has effect of Fast Anti depression, and more more effective than conventional antidepressant agents imipramine, the advantage also with no dependence and side effect.
Mouse model tail-suspention test finds, CD1 male mice is through the alliin lumbar injection of various dose, high dose group (10mg/kg) mice is after injection 45 minutes, namely some antidepressant effects are demonstrated, between 45-90 minute, relative blank group, mice remission is more and more obvious, namely activity is more and more frequent, hence it is evident that shortening the dead time.And positive control imipramine group just starts relative blank group after injecting 60-70 minute and shows the shortening dead time.Namely alliin is when dosage is lower than imipramine, earlier demonstrates antidepressant effect than imipramine.
Listing in embodiment 1 and respectively organize mice after injecting 90 minutes in observed 6 minutes, latter 4 minutes interior accumulative dead times, result is as shown in Figure 2.
Further, in forced swim test, alliin has higher antidepressant effect than conventional antidepressant agents imipramine.The dead time of positive controls (15mg/kg) is longer than dead time during alliin dosage 10mg/kg.As shown in Figure 3.
The antidepressant drug that current people use, it is generally required to several weeks could alleviate or eliminate depressive symptom, have been reported that record, adult's every day every 50 kg body weight to take the general consumption of imipramine be 12.5~75mg (0.25~1.5mg/kg), owing to side effect is obvious, such as tachycardia, perspiration, blurred vision, dizziness, abalienation, gastrointestinal reaction, urticaria, tremble, cardiac damage etc., every day, threshold dose was 200-300mg.Within the scope of general dose, onset time is about two weeks;And the anti-depression drug of the present invention, take in by every kg body weight 0.01-30mg every day, the highest 1500mg that can take in for each person every day, have no side effect, within the fastest 1~1.5 hour, depressive symptom can be alleviated.Alliin of the present invention, is non-protein class sulfur-containing amino acid unique in Bulbus Allii, and its chemical structural formula is as shown in Figure 1.Long-term taking alliin has the effects such as raising immunity of organisms, bactericidal, anti-flu, cancer-resisting, and its toxic and side effects is not reported so far.Therefore, alliin can simultaneously work as antidepressant, improves patient's autoimmunity, eliminate the effect infected.Therefore, alliin is expected to become new antidepressant quick, efficient, that have no side effect.
Experimental data based on the present invention; the anti-depression drug that it is active ingredient with alliin that the present invention is claimed, namely any with alliin, for active ingredient and to identify the medicine that its indication comprises depression be all the patent anti-depression drug that the present invention is claimed.In like manner, any with alliin be active ingredient, identify its indication and comprise depression and dosage every day every kg body weight the medicine of 0.01-30mg alliin is provided, be all the quick-acting anti-depression drug of patent that the present invention is claimed.
The medicament screening experiment that the present invention adopts is: forced swim test and Tail suspension test, is two kinds of conventional animal behavior despair depression model experiments, can ensure the reliability of the selection result preferably.
Mouse forced swimming test has been used for the screening of a lot of antidepressant drug.And great majority have the antidepressants of clinical treatment effect to be also proved can effectively reduce the dead time in forced swim test.What is called is motionless refers to " animal stops struggling in water, or in floating state, only exposes nostril and keep breathing, and only tiny limb motion, to keep head to keep afloat ".Give to intend the medicine of screening before the test.Swimming under obsessive state due to animal makes animal can not escape from adverse circumstances, causes that animal behavior is desperate.This kind of model method simplicity, reliably, is widely used in screening and the evaluation of antidepressant medicament.
Tail suspension test is that mice no longer struggles under outstanding shape of tail state, presents the motionless state of distinctive peace and quiet, and antidepressants can substantially shorten the persistent period of motionless state.During test, mouse tail fixed, hang by the feet.Do not make mouse tail distortion folding.The meter record dead time.Stationarity indices is: " animal all limbs except breathing are all motionless ".Tail-suspention test is all very sensitive to various antidepressants, and avoids temperature and the handicapped interference of animal movement in swimming test, thus when screening antidepressant drug by some Mus kinds, it is possible to the result of checking and supplementary forced swim test effectively.
The alliin provided by the invention purposes in preparing anti-depression drug, the prepared and anti-depression drug that obtains, it is possible to add the auxiliary element not affecting medicine effect based on the general knowledge of technical staff of pharmaceutical field, such as carrier, excipient etc..Owing to this medicine all can be taken effect by the mode such as oral, injection, subcutaneous embedding, therefore, dosage form can be various, includes but not limited to powder, tablet, capsule, solution, suspension, injection or drip liquid.
Anti-depression drug provided by the invention can also be mixed with other with alliin or derivatives thereof with the use of the ingredient that treatment depression has positive role.
Those skilled in the art can add makes the stability-enhanced stabilizer of alliin, as long as not affecting the performance of drug effect, the anti-depression drug of gained is all in the scope of protection of present invention.
Anti-depression drug provided by the present invention, described depression includes prevention and two stages for the treatment of.
The consumption of described anti-depression drug is: every day, every kg body weight provided 0.01-30mg alliin or the Bulbus Allii extract of 0.01-30mg alliin equivalent or uncooked garlic.
The administering mode of described anti-depression drug is oral, instillation or injection;Administration object is mammal, and described mammal includes people.
Owing in classical depressed animal model, the shortening of animal dead time is likely due to caused by the central excitatory effect of medicine, therefore the present invention has also carried out mice Open field activity (Openfieldtest) simultaneously, to check the autonomic activities of mice, it is to avoid the interference of central stimulants.It is shown that compared with saline control group, mice autonomic activities is not made significant difference by high concentration alliin, therefore the probability of false positive results can be got rid of, it was demonstrated that alliin has significant antidepressant effect really.
In the present invention, alliin extracts from Bulbus Allii.Bulbus Allii, also contains alliin in Bulbus Allii extract, it is therefore possible to use the salt of uncooked garlic, Bulbus Allii extract and/or alliin replaces alliin.When replacing, the dosage of alliin in embodiment according to alliin provided by the invention, that those skilled in the art can measure or according to the alliin content that existing document is recorded, converse the salt of required considerable amount of uncooked garlic, Bulbus Allii extract and/or alliin.Such as, it is assumed that alliin effective dose is Xmg/kg, obtain alliin according to general general knowledge or detection and account for the 0.6-2% of Bulbus Allii dry weight, then when adopting Bulbus Allii to substitute, the effective dose of Bulbus Allii is for being { X/ (0.006~0.02) } mg/kg body weight.
Accompanying drawing explanation
Fig. 1. the chemical structural formula of alliin
Fig. 2. the alliin impact on Tail suspension test, the result observed after injecting 90 minutes.Wherein
Vertical coordinate: tail-suspention test mice dead time (s),
Abscissa: be from left to right followed successively by: saline control group, imipramine matched group (15mg/kg), low concentration alliin process group (5mg/kg), high concentration alliin process group (10mg/kg).
Result: CD1 male mice is after the alliin lumbar injection 90 minutes of various dose, and high concentration alliin process group demonstrates antidepressant effect in Tail suspension test.Every treated animal 8-12, * t checks p < 0.05.
Fig. 3. the alliin impact on mouse forced swimming test, wherein
Vertical coordinate: swimming test mice dead time (s),
Abscissa: be from left to right followed successively by: saline control group, imipramine matched group (15mg/kg), low concentration alliin process group (5mg/kg), high concentration alliin process group (10mg/kg).
Result: CD1 male mice, after the alliin lumbar injection five days of various dose, demonstrates antidepressant effect in mouse forced swimming test.This antidepressant effect is compared with tradition antidepressant drug imipramine higher trend.Every treated animal N=8-12, * t checks p < 0.05, * * p < 0.01.
Detailed description of the invention
Below by way of specific embodiment, the present invention is explained and illustrated, it is to be understood that following embodiment is only used as explanation and illustrates, the protection domain not limited the present invention in any way.
The not specified experiment reagent of the present embodiment is this area conventional reagent, it is possible to being purchased or prepared by this area conventional method and obtain, specification is the pure level of laboratory.
The antidepressant experiment of embodiment 1. alliin
1, tail-suspention test
Laboratory animal:
Male CD1 kind mice, weight 25-35 gram, SPF level, Beijing Vital River Experimental Animals Technology Co., Ltd. provide, for scientific research, credit number: SCXK (capital) 2012-0001.By mice sub-cage rearing, light and shade cycle 12h/12h, room temperature 20~22 DEG C, drinking-water takes food freedom, drinking water, and feedstuff is provided by Inst. of Genetics and Development Biology, CAS's Experimental Animal Center.
Experimental drug:
Alliin, purchased from Beijing flourishing age Kang Pu Chemical Engineering Technology academy, article No. S-053-150620.
Imipramine hydrochloride (Imipraminehydrochloride) is Sigma Products, article No. I7379, lot number O56K1380.
Experiment equipment:
Cross bar;Adhesive plaster;SumsungIntelli-200m DV (Samsung of Korea S);JUNSO Multifunctional time-meter.
Experimental procedure:
Male CD1 mice is raised one week through adaptability, is randomly divided into 4 groups, often group 24.Respectively
Saline control group,
Tradition antidepressant drug imipramine positive controls (15mg/kg imipramine, be dissolved in normal saline),
Low concentration alliin process group (5mg/kg is dissolved in normal saline),
High concentration alliin process group (10mg/kg is dissolved in normal saline).
0.3ml/30g body weight is pressed to mouse peritoneal drug administration by injection during the morning 10.
After injecting 45 minutes, random 12 in each group of mice being started tail-suspention test, mouse tail be bonded on a horizontal cross bar from tail point 2 centimeters with adhesive plaster, making animal is reversal of the natural order of things state, about 15 centimetres away from desktop be of its head.
Observe: injecting latter 45 minutes mice depressive symptoms and start to alleviate, namely activity is more and more frequent relative to blank group, hence it is evident that shortening the dead time.And positive control imipramine group is after injection between 45 minutes to 60 minutes, activity and blank group indifference, until after 60 minutes, it is relatively frequently movable to begin with.
After injecting 90 minutes, the residue 12 in each group of mice only starting tail-suspention test, operation is ibid.
Record 6 minutes, observe latter 4 minutes interior accumulative dead times.Stationarity indices is: animal all limbs except breathing are all motionless.
Statistical method:
Experimental result mean value ± SE represents, two sample mean compare to be checked with t.
As a result, alliin process group, compared with saline control group, begins to display after injecting 45 minutes and shortens the mouse tail suspension dead time.
Imipramine positive controls starts after 90 minutes to shorten the outstanding tail dead time.
Observed result after injecting 90 minutes, as shown in Figure 2, alliin dosage is dead time during 10mg/kg be reduced to 58.92 ± 8.20s (P < 0.05) by 93.46 ± 12.36s compared with saline control group, shortens 36.96%.Low concentration alliin process group demonstrates the trend reduced, but not yet substantially lower, it is shown that a dose response.
It is indicated above that the alliin process group (concentration is lower than imipramine positive controls) of high concentration gets final product onset in a short period of time, it is possible to the depressive symptom of rapid recovery/anti-mouse is caused because forcing outstanding tail.
2, forced swim test
Laboratory animal:
Male CD1 kind mice, weight 25-35 gram, SPF level, Beijing Vital River Experimental Animals Technology Co., Ltd. provide, credit number: SCXK (capital) 2012-0001.Mice sub-cage rearing, light and shade cycle 12h/12h, room temperature 20~22 DEG C are drunk water and are taken food freedom the last week by experiment, and feedstuff is provided by Inst. of Genetics and Development Biology, CAS's Experimental Animal Center.
Experimental agents:
Alliin, purchased from Beijing flourishing age Kang Pu Chemical Engineering Technology academy, article No. S-053-150620.Imipramine hydrochloride (Imipraminehydrochloride) is Sigma Products, article No. I7379, lot number O56K1380.
Experimental apparatus:
Glass cylinder (high 40cm, diameter 14cm);The open case of mice (long and width respectively 50cm, high 40cm, bottom 16 decile);Thermometer;JUNSO Multifunctional time-meter.
Medicine prepares same tail-suspention test.
Experimental procedure:
Animal pharmaceuticals is injected:
CD1 mice, at 7 weeks ages, weight 25-35 gram, adapts to environment and starts experiment after one week.It is randomly divided into 4 groups, often 12 mices of group.Every morning 10 starts lumbar injection, and injection volume is 0.3 milliliter/30 grams body weight.Blank group intraperitoneal injection of saline every day, alliin group gives different amounts of alliin, low dosage alliin (5mg/kg is dissolved in normal saline) and high dose alliin (10mg/kg is dissolved in normal saline).Tradition antidepressants imipramine (15mg/kg is dissolved in normal saline) is as positive control.Every day lumbar injection once, continuously injection started forced swim test after five days.
Forced swim test:
It is placed vertically in plexiglass cylinder (40cm height × 14cm diameter) by single for each group of CD1 Mus, depth of water 25cm, water temperature 21-23 DEG C.Each administration group and matched group are recorded a video 6 minutes, and respectively group mice was latter 4 minutes interior accumulative dead times.Dead time judges: mice swims in the water surface, does not make great efforts to climb out of cylinder, only does some and its head must be kept in the action of the water surface.
Statistical analysis technique:
Experimental result mean value ± SE represents, two sample mean compare to be checked with t.
Result (Fig. 3) shows that alliin has stronger antidepressant effect.Compare with blank group, 4 minutes interior dead times of alliin high dose group mouse forced swimming test significantly shorten, and there is certain dose dependent, alliin dosage is that dead time during 5mg/kg and 10mg/kg is compared with blank group, it is reduced to 60.10 ± 12.71s (p < 0.05) and 41.16 ± 9.21s (p < 0.01) by 89.00 ± 11.50s respectively, is respectively shortened 32.47% and 53.75%.Comparing with tradition antidepressants imipramine, the antidepressant effect of high dose alliin is higher.
3, mice Open field activity
Cause owing to the shortening of the dead time in classical depressed animal model is likely due to the central excitatory effect of medicine, so We conducted mice Open field activity to check the central excitatory of alliin.
Experimental result shows, in 1 hour inherent open case of mice after the process of high concentration alliin, total distance of motion is 100.42+4.81m, without significant change (Anova compared with saline control group (95.76 ± 6.95m), p > 0.05, N=8-12), thus can get rid of its cause manic state probability.Therefore, the shortening of mice dead time is not caused by the central excitatory effect of alliin, and alliin has significant antidepressant effect really.
Claims (9)
1. the medicine of a depression, it is characterised in that active ingredient is alliin, or the salt of the considerable amount of uncooked garlic of alliin, Bulbus Allii extract and/or alliin.
2. the medicine of a depression, it is characterised in that active ingredient includes alliin or the salt of the considerable amount of uncooked garlic of alliin, Bulbus Allii extract and/or alliin.
3. the medicine of quick-acting depressions, it is characterised in that active ingredient is alliin, or the salt of the considerable amount of uncooked garlic of alliin, Bulbus Allii extract and/or alliin, and quick-acting dosage is
Every kg body weight 0.01-30mg alliin, or
The salt of every considerable amount of uncooked garlic of kg body weight 0.01-30mg alliin, Bulbus Allii extract and/or alliin;
It is administered in latter 90 minutes and can produce antidepressant effect.
4. according to the arbitrary described medicine of claim 1-3, it is characterised in that: dosage form is powder, tablet, capsule, solution, suspension, injection or drip liquid.
5. medicine according to claim 4, also includes acceptable auxiliary element on pharmacopedics.
6., according to the arbitrary described medicine of claim 1-3, also include after using with alliin simultaneously, treatment depression being had the ingredient of positive role and/or makes the stability-enhanced composition of alliin.
7. alliin purposes in preparing anti-depression drug, it is characterised in that prepare anti-depression drug for active ingredient with alliin.
8. the method for a treatment/prevention of depression, it is characterised in that make experimenter take in alliin or the salt of the considerable amount of uncooked garlic of alliin, Bulbus Allii extract and/or alliin.
9. method according to claim 8, dosage is: provide 0.01-30mg alliin or the salt of the uncooked garlic of 0.01-30mg alliin equivalent, Bulbus Allii extract and/or alliin by every kg body weight every day.
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