CN102138926A - Application of ginsenoside Rd to preparing anti-depression medicament - Google Patents
Application of ginsenoside Rd to preparing anti-depression medicament Download PDFInfo
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- CN102138926A CN102138926A CN2011100229407A CN201110022940A CN102138926A CN 102138926 A CN102138926 A CN 102138926A CN 2011100229407 A CN2011100229407 A CN 2011100229407A CN 201110022940 A CN201110022940 A CN 201110022940A CN 102138926 A CN102138926 A CN 102138926A
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- ginsenoside
- mice
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- medicine
- depression
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Abstract
The invention belongs to the field of medical sanitation, in particular relates to application of a natural compound, i.e. ginsenoside Rd to preparing an anti-depression medicament. The ginsenoside Rd can remarkably shorten immobility time in a mouse tail suspension test under a test dosage, remarkably shorten immobility time in a forced mouse swimming test and remarkably reduce the escape failure number of the mouse in an acquired helplessness test. Proved by tests, the ginsenoside Rd has favorable anti-depression effect and can be used for preventing and treating depression.
Description
Technical field
The invention belongs to medicine and hygiene fields, relate to the purposes of native compound in field of medicaments, the more particularly application of ginsenoside Rd in the preparation anti-depression drug.
Background technology
Ginsenoside Rd (Ginsenoside Rd), molecular formula is C
48H
82O
18Molecular weight is 947.12; Belong to protopanoxadiol type saponin.Its chinesization formal name used at school is 20-(s)-protopanoxadiol-3[O-β-D-Glucopyranose. (1 → 2)-β-D-pyranglucoside]-20-O-β-D-pyranglucoside.CAS：52705-93-8。Its structural formula such as Fig. 5.
There are some researches show, the ginsenoside Rd can reduce the contraction in the guinea pig in vitro uterus that acetylcholine causes, rat is had decreased heart rate and two-phase blood pressure (falling after rising) effect, and behavior and the electroencephalogram of cat shown medium inhibition, in addition, the ginsenoside Rd also has antifatigue effect.We can find so far not the antidepressant research relevant for ginsenoside monomer Rd.
Depression (depression) belongs to affective disorders, be a kind of low with remarkable and persistent mental state be the syndrome of principal character.Along with the enhancing of modern society's rapid development of economy and people's stress, the sickness rate of depression improves year by year, becomes " epidemic diseases of 21 century ", and in the rate of increase cumulative year after year with every year 113%.The World Health Organization (WHO) points out that in " calendar year 2001 World Health Report " depression has become the fourth-largest illness in the world, and may become the second filial generation disease that is only second to ischemic heart desease during to the year two thousand twenty.The ill situation of the depression of China also allows of no optimist: have 20% people that depressive symptom is arranged approximately, have 7% people to suffer from major depressive disorder, depression has become second of Chinese disease burden.As can be seen, depression has caused significant damage for patient and society from these numerals.Therefore the research and development of antidepressant drug have crucial meaning.
At present, applied clinically antidepressant drug roughly is divided into following four classes: (1) tricyclic antidepressants and Fourth Ring class antidepressants according to the different mechanism of action.Tricyclic antidepressants mainly contains miboplatin bright (imipramine), desipramine (desipramine) etc., and the Fourth Ring class has maprotiline (maprotiline).If this class drug main works by blocking-up 5-HT and norepinephrine reuptake.(2) monoamine oxidase, MAO (MAO) inhibitor, clinical application mainly contains phenelzine (phenelzine).The MAO inhibitor is by suppressing MAO, improving monoamine content in the nervous system, thereby bring into play its antidepressant effect.(3) selectivity 5-hydroxy tryptamine cell reabsorption inhibitor (SSRI) is antidepressant clinically general medication.Main medicine has fluoxetine (fluoxetine), paroxetine (paroxetine), and this class drug main will play a role by the reuptake of selective exclusion 5-HT.(4) atypia antidepressants, these class antidepressants no matter from chemical constitution still from mechanism of action and effect characteristics, all can not belong among above-mentioned 3 classes.Mainly comprise norepinephrine and dopamine cell reabsorption inhibitor, 5-HT receptor antagonist and 5-HT cell reabsorption inhibitor.
The antidepressant types of medicines is various and the mechanism of action is complicated clinically, but still has 1/3 patients with depression not good enough to the antidepressants effect of clinical use, and slow such as taking effect, relapse rate is high.The more important thing is that toxic and side effects is obvious behind some antidepressants life-time service.Therefore, research and development antidepressant drug novel, effective, low toxicity is very necessary.Chinese medicine is pure natural medical, and Clinical Experience in several thousand is arranged, the relative few and low price of toxic and side effects, and various advantages makes it become the first-selection of research and development antidepressant drug.
Use Radix Notoginseng in recent years, Radix Ginseng, the depressed research of Radix Panacis Quinquefolii prevention and treatment gets more and more, as among the CN200710123530.5 " one group of pharmaceutical composition and method for making that is used for the treatment of depression " with Radix Ginseng, the Radix Paeoniae Alba is that raw material is made pharmaceutical composition and is used for antidepressant, be used for antidepressant as making up with Radix Notoginseng total arasaponins and Herba Epimedii total flavones among the CN200810120395.3 " purposes of Herba Epimedii total flavones and notoginseng total saponin compounds ", but present treatment by Chinese herbs depression, the overwhelming majority all is to add panax species in composition of medicine, perhaps adds its total saponins and comes antidepressant.Panax species has antidepressant effect preferably really, and its main antidepressant composition is its saponin component, as described in CN200310107285.0 " a kind of Chinese medicine composition of Cure for insomnia ", Folium Notoginseng total arasaponins has sedation, Folium Notoginseng total arasaponins can obviously suppress the spontaneous activity of mice, central depressant thing chlorpromazine, pentobarbital sodium, penthiobarbital there is synergism, excitement to the mice due to central stimulants amfetamine, the caffeine has antagonism, Folium Notoginseng total arasaponins can be used for Cure for insomnia and depression etc., and curative effect is preferably arranged.But in the total saponins, performance central nervous excitation and inhibiting component exist simultaneously, and the concrete component of performance antidepressant effect can't be described.So in the progressive clear and definite total saponins specifically is which component plays antidepressant effect, have very important significance for the exploitation anti-depression drug and the mechanism of action of understanding Zong Suds glycosides.
Yet, it is also fewer to carry out antidepressant research from single level at present, some monomers of at present having studied have: 20 (s)-protopanoxadiols described in the described ginsenoside Rg2 of CN200410086457.5, the CN200610027507.1, described in the CN200610116353.3 20 (s)-protopanoxadiol derivative, the described ginsenoside Rb3 of 20 described in the CN200810043537.0 (S)-ginsenoside Rh2 and CN201010193222.1.
Although described those protopanoxadiol derivatives of CN200610116353.3, contain specific deriveding group, help promoting antidepressant effect, but the significant degree of those protopanoxadiol derivative curative effects reaches whether bring his its counter productive simultaneously, is still a unknown.Though and the ginsenoside Rd also belongs to protopanoxadiol type saponin, 20 (s)-protopanoxadiol derivatives that itself and CN200610116353.3 limited belong to two kinds of diverse chemical compounds.20 (s)-protopanoxadiol derivative class formation formula such as Fig. 6 defined in the CN200610116353.3 " application of 20 (s)-protopanoxadiol derivative classes in the preparation antidepressant drug ".
By the comparison of formula (I) and formula (II), though as can be known the ginsenoside Rd at R and R
1Be hydrogen on the position, this is consistent with 20 (s)-protopanoxadiol derivative classes that CN200610116353.3 is limited, but the ginsenoside Rd is a glycosyl on the Y position, rather than hydroxyl and hydrogen, 20 (s)-protopanoxadiol derivative classes that this and CN200610116353.3 limited are inconsistent, more inconsistent be with chain hydrocarbon that five carbocyclic rings link to each other on group, 20 (s)-protopanoxadiol derivative classes that CN200610116353.3 limited are hydroxyls, and a macoradical that connects on ginsenoside Rd's the oxygen atom is not a hydrogen.Comprehensively described, the ginsenoside Rd is a kind of native compound, and they are different with 20 (s)-protopanoxadiol derivatives that CN200610116353.3 is limited, and its effect on antidepressant is still a unknown number.
Summary of the invention
The objective of the invention is to shortcoming, provide a kind of native compound that can significantly prevent and treat depression from the ginsenoside monomer level at existing anti-depression drug.
Invention provides following scheme: the ginsenoside Rd is applied to prepare in the anti-depression drug.
This anti-depression drug can be the ginsenoside Rd of single component, also can be the compound medicine of ginsenoside Rd and other chemical compound or Chinese medicine composition.Wherein the ginsenoside Rd is as main component or non-main component.
Can also contain in disintegrating agent, wetting agent, binding agent, filler, absorption enhancer, solvent, lubricant, surfactant, flavouring agent, sweeting agent, antioxidant, antiseptic and the pigment one or more in the medicine.
Medicine can be prepared as different dosage forms, as oral formulations, sublingual administration tablet pill or injection; Oral formulations can be tablet, capsule, granule, pill, drop, fruit juice agent or syrup; Injection can be injection, injectable powder, lyophilized injectable powder.
When the ginsenoside Rd was applied to prepare anti-depression drug, the application dose of medicine calculated with ginsenoside Rd's weight and can be each 5 ~ 11 mg/kg body weight; Also can be mg/kg body weight every days 5～11.
The ginsenoside Rd is got by Radix Ginseng, Radix Notoginseng or Radix Panacis Quinquefolii extraction separation, perhaps chemosynthesis and getting.From plant during extraction separation, can be by the leaf of Radix Ginseng, Radix Notoginseng or Radix Panacis Quinquefolii, stem, root extraction separation and get.
Compared with prior art, the present invention has following beneficial effect.
(1) the ginsenoside Rb3 described in CN201010193222.1 is in middle dosage (75mg/kg(mice body weight)) the single successive administration can distinguish after 3 days and 4 days and significantly reduce mice forced swimming dead time and mouse tail suspension dead time, at 20 described in the CN200610027507.1 (s)-protopanoxadiol in high dose (15mg/kg(mice body weight)) the single successive administration can significantly reduce the mice dead time after 10 days.And ginsenoside Rd provided by the invention low dosage (50mg/kg(mice body weight) no matter) still high dose (100mg/kg(mice body weight)) just can significantly reduce mouse tail suspension dead time and forced swimming dead time and the escape frequency of failure after 2 days at single-dose.Compare with these monomers, ginsenoside Rd's antidepressant effect is also fine very stable as can be known.And in forced swimming and acquired helpless experiment, the Rd under the proof load can reach the antidepressant effect near paroxetine, these two kinds of positive drugs of maprotiline.This shows the ginsenoside Rd more as a kind of antidepressants, and its prospect is very big.
(2) as said among the CN200810096148.4, the content of ginsenoside Rd in Radix Notoginseng is 10mg/g, in Radix Panacis Quinquefolii 5.88mg/g, in Radix Ginseng 1.35mg/g, ginsenoside Rd's content in panax ginseng plant or other kind of Radix Ginseng section is higher comparatively speaking, especially its content in Radix Notoginseng, so just guaranteed that the ginsenoside Rd can extract from Radix Notoginseng, and need not from the Radix Ginseng of costliness, extract, in addition, ginsenoside Rd's extraction process also develops very ripely, provides a kind of efficient high yield of microbial transformation of utilizing to prepare ginsenoside Rd's method as CN 200810200086.7.Therefore, the ginsenoside Rd has competent source, has guaranteed the antidepressant drug supply of raw material.
(3) as CN 200410086457.5 described ginsenoside Rg2s, belong to protopanaxatriol ginsenoside, though it also has certain antidepressant effect, but it has the effect of remarkable stimulating central nervous system system, and depression is a kind of long-term chronic disease, and its treatment also will be a long process, if take for a long time, make the central nervous system be in excitatory state for a long time, this consequence will be very serious.And ginsenoside Rd provided by the invention (panoxadiol's type saponin) does not have appreciable impact central nervous system's irritability under high dose, thus its good effect not only, and also safety is also high.
(4) 20 (s)-protopanoxadiol derivatives described in CN200610027507.1, though it also has curative effect preferably, but, said as CN02820659.2, protopanoxadiol derivative is the aglycon of saponin, it is natural panax ginseng plant or other kind of Radix Ginseng section of being present in unlike the ginsenoside Rd, and it can only obtain by being modified by the cracking of dammarane's saponins and/or semisynthetic chemical constitution.Under the saponins acid condition during cracking, protopanoxadiol character less stable easily become the R type by the S type, and semisynthetic its is compared with native compound in addition, and its safety remains progressive research.And ginsenoside Rd provided by the invention is a kind of saponin monomer, can naturally be present in panax ginseng plant or other kind of Radix Ginseng section, and content is also higher relatively, and present preparation technology is also very ripe, so the source is sufficient, the problem that does not have poor stability, being suitable for preparation becomes medicine.
(5) as 20 (s)-protopanoxadiol derivatives that CN200610116353.3 limited, although these protopanoxadiol derivatives are compared with protopanoxadiol, contain specific deriveding group, help promoting antidepressant effect, but the significant degree of the curative effect of those protopanoxadiol derivatives reaches whether bring his its counter productive simultaneously, is still a unknown.But the invention provides the ginsenoside Rd, is a kind of native compound, and it is safe, few side effects.
(6) on the total saponins level, Hu Jing, Fu Baozhong has explanation stem and leaf of Radix Ginseng saponin and Radix Ginseng saponin all in low dosage (50mg/kg(mice body weight) in " research of tricyclic antidepressants medicine and ginsenoside's antidepressant effect "), high dose (200mg/kg(mice body weight)) can significantly reduce the mice forced swimming dead time behind the multiple dosing.And among the present invention, the ginsenoside Rd is low dosage (50mg/kg(mice body weight) no matter) still high dose (100mg/kg(mice body weight)) just can significantly reduce the mouse tail suspension dead time at single-dose after 2 days, forced swimming dead time and escape the frequency of failure, and to the effect of the forced swimming dead time and the escape frequency of failure near two kinds of positive drugs.As seen total saponins and ginsenoside Rd provided by the invention have antidepressant effect preferably, but performance central nervous excitation and inhibitory action component exist simultaneously in the total saponins, concrete antidepressant component is indeterminate, and ginsenoside Rd provided by the invention is as a kind of monomer, its curative effect is not only good, and more definite.
(7) as described 20 (the S)-ginsenoside Rh2s of CN200810043537.0, also belonging to panoxadiol's class, is that fresh ginseng is when being processed into Radix Ginseng Rubra, by a kind of secondary glycosides that generates after some glycol saponins degradation, its natural content is low, the extraction process complexity.And the natural content that the invention provides the ginsenoside Rd is higher relatively, and extraction and preparation technique is also ripe.
Generally speaking, the ginsenoside can pass through multisystem, multi-level, many target spots performance antidepressant effect, good effect, few side effects, and its antidepressant curative effect of ginsenoside monomer Rd provided by the invention is more definite, higher, toxic and side effects is little, and preparation technology is also ripe, is fit to suitability for industrialized production.The present invention also provides foundation for concrete antidepressant composition in the further clear and definite total saponins in addition.
Description of drawings:
Fig. 1 is the ginsenoside Rd to the mouse tail suspension influence of experiment dead time, and * represents P＜0.05, has promptly compared significant difference with the blank group;
Fig. 2 is the influence of ginsenoside Rd to mice prologue experimental activity distance, and * represents P＜0.05, has promptly compared significant difference with the blank group;
Fig. 3 is the ginsenoside Rd to the influence of experiment dead time of mice forced swimming, and * represents P＜0.05, has promptly compared significant difference with the blank group;
Fig. 4 is the influence of ginsenoside Rd to the escape frequency of failure in the acquired helpless experiment of mice, and * represents P＜0.05, has promptly compared significant difference with the blank group;
Fig. 5 is ginsenoside Rd's a structural formula;
Fig. 6 is 20 (s)-protopanoxadiol derivative class formation formulas;
Fig. 7 is the influence result of ginsenoside Rd to the mouse tail suspension experiment dead time;
Fig. 8 is the influence result of ginsenoside Rd to mice prologue experimental activity distance;
Fig. 9 is the influence result of ginsenoside Rd to the mice forced swimming experiment dead time;
Figure 10 ginsenoside Rd escapes the result that influences of the frequency of failure to mice.
The specific embodiment
For a better understanding of the present invention, below ginsenoside Rd's antidepressant effect will be described from pharmacodynamic study.At present, to the evaluating drug effect of antidepressants, means are set up whole animal behavior pharmacological model exactly the most intuitively, and follow the principle of multi-model, many indexs.The present invention has just chosen 3 kinds of behavior models, comprises the acquired helpless model of mouse tail suspension model, mice forced swimming model and mice, overall merit ginsenoside Rd's antidepressant effect.
The experiment of embodiment 1 mouse tail suspension
1 materials and methods
1.1 laboratory animal
SPF level kunming mice, male, body weight 18-22g, available from Zhongshan University's medical college Experimental Animal Center, credit number: SCXK(Guangdong) 2009-0011.
Standard feed and bedding and padding are all available from Zhongshan University's medical college Experimental Animal Center.
1.2 medicine and instrument
Medicine: the ginsenoside Rd, available from Yunnan Plant Pharmaceutical Industry Co., Ltd.; The positive drug paroxetine is available from strong people pharmacy, Guangzhou.
Mouse tail suspension experiment automatic photographic analysis system, laboratory mice is irritated stomach syringe needle etc., available from Huaibei Zhenghua Biological Instrument Co., Ltd..
1.3 medicinal liquid preparation
Get the ginsenoside Rd and be dissolved in distilled water, be configured to the solution of low, high two kinds of concentration (5mg/ml, 10mg/ml) respectively.Paroxetine (Paroxetine) medicinal tablet is pulverized, and gets institute's expense in the ratio of effective ingredient.The adding distilled water is mixed with the suspension of 0.6mg/ml, shakes up before the filling stomach.
1.4 experimental technique
40 of mices, be divided into 4 groups, every group 10, be respectively blank group (normal saline), Rd-low dose group (Rd 50mg/kg(mice body weight)), Rd-high dose group (Rd 100mg/kg(mice body weight)), paroxetine group (6mg/kg(mice body weight)).By mice body weight 0.1 ml/10 g gastric infusion, once a day, gastric infusion 1 day hangs the tail test behind second day administration 1h.
With the mice reversal of the natural order of things, be fixed in the tail end of outstanding tailstock with insulating cement apart from the about 1 cm place of tail end, forelimb is apart from about 10 cm in bottom surface.Outstanding tail test process is 6 min, the incipient stage mice all can struggle, can abandon after a period of time struggling, keeps motionless, the dead time of 4 min mices after the analytic record is as the index of judging the behavior of mice depression sample.
1.5 statistical method
Experimental result uses software Origin7.5 to add up mapping, and data are expressed as " meansigma methods ± standard deviation ", and p＜0.05 expression has significant difference.
2, experimental result
In the mouse tail suspension experiment, the ginsenoside Rd can reduce the outstanding tail dead time of mice significantly: compare with the blank group, Rd can reduce by 17% with the dead time when low dosage, the dead time can be reduced by 18% when high dose.The positive drug paroxetine has significant more antidepressant effect, and its dead time with mouse tail suspension is reduced to 25.2%.Total result explanation ginsenoside Rd under test dose to mouse tail suspension the depressed sample behavior effect that is significantly improved, result such as Fig. 7 and shown in Figure 1.
See shown in Figure 1ly, be the ginsenoside Rd to the sketch map that influences of mouse tail suspension experiment dead time, wherein, X-axis is represented each administration group, and Y-axis is represented the outstanding tail dead time (unit " second ") of mice; * represent P＜0.05, promptly compared significant difference with the blank group.
The experiment of embodiment 2 mice forced swimmings
1 materials and methods
1.1 laboratory animal
SPF level kunming mice, male, body weight 18-22g, available from Zhongshan University's medical college Experimental Animal Center, credit number: SCXK(Guangdong) 2009-0011.
Standard feed and bedding and padding are all available from Zhongshan University's medical college Experimental Animal Center.
1.2 instrument and medicine
Medicine: the ginsenoside Rd, available from Yunnan Plant Pharmaceutical Industry Co., Ltd.; Positive drug paroxetine, maprotiline are all available from strong people pharmacy, Guangzhou.
Instrument: ZH-QPT forced swimming device and analytical system, ZH-QPT prologue experimental provision and analytical system, laboratory mice is irritated the stomach syringe needle, all available from Huaibei Zhenghua Biological Instrument Co., Ltd.; Thermometer.
1.3 medicinal liquid preparation
Get the ginsenoside Rd and be dissolved in distilled water, be configured to the monomer solution of low, high two kinds of concentration (5mg/ml, 10mg/ ml) respectively.Paroxetine (Paroxetine), maprotiline (Maprotiline) medicinal tablet are pulverized, and get institute's expense in the ratio of effective ingredient.The adding distilled water is mixed with the suspension of 0.6mg/ml and 1.8mg/ml respectively, shakes up before the filling stomach.
1.4 experimental technique
When carrying out the experiment of depressed animal forced swimming behavior model, must check the influence of medicine simultaneously to laboratory animal autonomic activities level.Have only when medicine does not strengthen mice autonomic activities intensity, can think that just the minimizing of dead time in the desperate behavioral experiment is that change by depressive symptom is caused.
60 of mices, be divided into 5 groups, be respectively blank group (normal saline), Rd-low dose group (Rd 50mg/kg(mice body weight)), Rd-high dose group (Rd 100mg/kg(mice body weight)), paroxetine group (6mg/kg(mice body weight)), maprotiline group (18mg/kg(mice body weight)).By mice body weight 0.1ml/10g gastric infusion, once a day, gastric infusion 1 day, experiment and the forced swimming test of beginning behind second day administration 1h.
The prologue experiment is the common method that is used to detect independent activity of animals intensity.The long 30cm of prologue proof box, wide 30cm, high 20cm.After irritating stomach 1h, animal is positioned in the prologue proof box, writes down its activity distance in 5min.
The forced swimming experiment is that mice is placed in the columniform water tank, and initial mice can move about rapidly, struggles, and this environment is fled from attempt.When finding that this environment is inevitable, will abandon struggling, swim on the water surface with a kind of motionless state.Generally with the motionless state simulation mankind's of mice depressed behavior.After the prologue experiment finished, it was that 19cm is high in the cylindrical transparent water tank of 25cm that mice is placed on diameter, depth of water 18cm, and water temperature remains on 23-25 ℃.The swimming state of record mice 6min, the dead time of 4min mice after analyzing.
1.5 statistical method
Experimental result uses software Origin7.5 to add up mapping, and data are expressed as " meansigma methods ± standard deviation ".P＜0.05 expression has significant difference.
2, experimental result
2.1 prologue experiment
In the prologue experiment, the ginsenoside Rd can increase the spontaneous activity of mice when low dosage, consistent with existing document result, promptly has bibliographical information Rd can significantly increase the autonomic activities that mice is forced to walk, and its mechanism remains further to be analyzed.But the ginsenoside Rd to influence of the autonomic activities of mice and blank group zero difference, still can illustrate in following forced swimming experiment when high dose, and Rd makes the dead time of mice swimming reduce that nerve centre is excited no thanks to causes.Satisfy the requirement of desperate experiment behavior.Result such as Fig. 8 and shown in Figure 2.
See shown in Figure 2ly, be the influence sketch map of ginsenoside Rd, wherein mice prologue experimental activity distance
X-axis is represented each administration group, and Y-axis is represented the prologue activity distance (unit " centimetre ") of mice; * represent P＜0.05, promptly compared significant difference with the blank group.
2.2 forced swimming experimental result
In the forced swimming experiment, but all the dead time with mice swimming of significance reduces the ginsenoside Rd when low dosage and high dose.The dead time of low dosage and high dose all is reduced to the value of paroxetine, maprotiline group approaching.Presentation of results, the ginsenoside Rd can significantly improve the depressed sample behavior of mice forced swimming under test dose.And effect can be near paroxetine, maprotiline.Result such as Fig. 9 and shown in Figure 3.
See shown in Figure 3ly, be the influence sketch map of ginsenoside Rd the mice forced swimming dead time.Wherein X-axis is represented each administration group, and Y-axis is represented the forced swimming dead time (unit " second ") of mice; * represent P＜0.05, promptly compared significant difference with the blank group.
Embodiment 3 acquired helpless experiments
1 materials and methods
1.1 laboratory animal
SPF level kunming mice, male, body weight 18-22g, available from Zhongshan University's medical college Experimental Animal Center, credit number: SCXK(Guangdong) 2009-0011.
Standard feed and bedding and padding are all available from Zhongshan University's medical college Experimental Animal Center.
1.2 instrument and medicine
Medicine: the ginsenoside Rd, available from Yunnan Plant Pharmaceutical Industry Co., Ltd.; The positive drug paroxetine is available from strong people pharmacy, Guangzhou.
Instrument: the BA-200 mice is kept away dark instrument, available from Chengdu TME Technology Co., Ltd.; Laboratory mice is irritated the stomach syringe needle, available from Huaibei Zhenghua Biological Instrument Co., Ltd..
1.3 medicinal liquid preparation
Get the ginsenoside Rd and be dissolved in distilled water, be configured to the solution of low, high two kinds of concentration (5mg/ml, 10mg/ml) respectively.Paroxetine (Paroxetine) medicinal tablet is pulverized, and gets institute's expense in the ratio of effective ingredient.The adding distilled water is mixed with the suspension of 0.6mg/ml respectively, shakes up before the filling stomach.
1.4 experimental technique
40 of mices, be divided into 4 groups, every group 10, be respectively blank group (normal saline), Rd-low dose group (Rd 50mg/kg(mice body weight)), Rd-high dose group (Rd 100mg/kg(mice body weight)), paroxetine group (6mg/kg(mice body weight)).By mice body weight 0.1ml/10g gastric infusion, once a day.
Experiment divides to be carried out in two days.Be the modeling phase in first day: mice is placed on to keep away shocks by electricity in the camera bellows, voltage transfers to 36V, and the 15s that at every turn shocks by electricity, midfeather 20-60s do not wait.Shock by electricity so repeatedly mice 60 times.Second day is the testing period.Put in the darkroom behind the mice administration 1h, give the photostimulation of 3s earlier, give the electricity irritation of 3s again,, then be designated as and once escape failure if mice can not flee from out from camera bellows.Giving 30 times stimulates, and statistical analysis blank group mice and administration group mice escape the number of times of failure.
1.5 statistical method
Experimental result uses software Origin7.5 to add up mapping, and data are expressed as " meansigma methods ± standard deviation ".P＜0.05 expression has significant difference.
2, experimental result
In acquired helpless experiment, compare with the blank group, the ginsenoside Rd all can significantly reduce the escape frequency of failure of mice when low dosage and high dose.Wherein, the Rd low dosage can reach the antidepressant effect identical with the positive drug paroxetine.Result such as Figure 10 and shown in Figure 4.
See shown in Figure 4ly, be that the ginsenoside Rd is to escaping the sketch map that influences of the frequency of failure in the acquired helpless experiment of mice.Wherein, X-axis is represented each administration group, and Y-axis is represented the escape frequency of failure (unit " inferior ") of mice; * represent P＜0.05, promptly compared significant difference with the blank group.
This experiment has drawn following conclusion:
1, in the mouse tail suspension experiment, compare with the blank group, the ginsenoside Rd can reduce the dead time of mice significantly.
2, in the experiment of mice forced swimming, but ginsenoside Rd's significance reduces the dead time of mice, and in the prologue experiment, the ginsenoside Rd of high dose has no significant effect the mice autonomic activities, illustrates that it not is because due to the raising of level of activation that Rd makes in the mice forced swimming experiment dead time reduce.The credible result of swimming test.
3, find that by acquired helpless experiment the ginsenoside Rd can significantly reduce the escape frequency of failure of mice.
Analysis-by-synthesis by above-mentioned 3 kinds of Animal Behavior Science experiment as can be known, the ginsenoside Rd has antidepressant effect preferably.The positive drug paroxetine that adopts in this experiment, maprotiline mainly work by blocking-up 5-HT and norepinephrine reuptake.These two kinds of medicines are to use clinically more at present, but still have patients with depression not good enough to the antidepressants effect of its clinical use, as it is slow to take effect, and relapse rate is high, the more important thing is life-time service after toxic and side effects obvious.And ginsenoside Rd provided by the invention, as a kind of Chinese medicine, it is safe, and toxic and side effects is few, and the Rd under the experimental concentration can reach antidepressant effect near these two kinds of positive drugs in forced swimming and acquired helpless experiment.So the ginsenoside Rd is made preparation, be used for suitability for industrialized production, have good antidepressant effect and clinical prospect.
Claims (9)
1. the application of ginsenoside Rd in the preparation anti-depression drug.
2. application according to claim 1 is characterized in that described anti-depression drug is the ginsenoside Rd of single component, perhaps is the compound medicine that ginsenoside Rd and other chemical compound or Chinese medicine are formed.
3. application according to claim 2 is characterized in that the ginsenoside Rd is as main component or non-main component in the described compound medicine.
4. application according to claim 2, it is characterized in that described medicine also can contain disintegrating agent, wetting agent, binding agent, filler, absorption enhancer, solvent, lubricant, surfactant, flavouring agent, sweeting agent, antioxidant, antiseptic and pigment etc. any or several.
5. application according to claim 2 is characterized in that described medicine is oral formulations, sublingual administration tablet pill or injection; Described oral formulations is tablet, capsule, granule, pill, drop, fruit juice agent or syrup; Described injection is injection, injectable powder or lyophilized injectable powder.
6. according to the described application of above-mentioned arbitrary claim, it is characterized in that the application dose of described medicine is calculated as each 5 ~ 11 mg/kg body weight with ginsenoside Rd's weight.
7. according to the described application of above-mentioned arbitrary claim, it is characterized in that the application dose of described medicine is calculated as mg/kg body weight every days 5～11 with ginsenoside Rd's weight.
8. application according to claim 6 is characterized in that described ginsenoside Rd is got by Radix Ginseng, Radix Notoginseng or Radix Panacis Quinquefolii extraction separation, perhaps chemosynthesis and getting.
9. application according to claim 8 is characterized in that described ginsenoside Rd is by the leaf of Radix Ginseng, Radix Notoginseng or Radix Panacis Quinquefolii, stem, root extraction separation and get.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109498638A (en) * | 2018-12-21 | 2019-03-22 | 岭南师范学院 | Ginsenoside Rk1 is preparing the application in anti-depression drug |
| CN110934908A (en) * | 2018-09-21 | 2020-03-31 | 邢雅婷 | Compound nutritional health product capable of increasing body temperature to prevent diseases |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152196A (en) * | 2006-09-25 | 2008-04-02 | 中国农业科学院作物科学研究所 | Application of notoginsen triterpenes and its monomer in preparing medicament for treating melancholia |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152196A (en) * | 2006-09-25 | 2008-04-02 | 中国农业科学院作物科学研究所 | Application of notoginsen triterpenes and its monomer in preparing medicament for treating melancholia |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110934908A (en) * | 2018-09-21 | 2020-03-31 | 邢雅婷 | Compound nutritional health product capable of increasing body temperature to prevent diseases |
| CN109498638A (en) * | 2018-12-21 | 2019-03-22 | 岭南师范学院 | Ginsenoside Rk1 is preparing the application in anti-depression drug |
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Application publication date: 20110803 |