CN114522177A - Application of ginsenoside Re in preparation of antidepressant - Google Patents
Application of ginsenoside Re in preparation of antidepressant Download PDFInfo
- Publication number
- CN114522177A CN114522177A CN202111505247.5A CN202111505247A CN114522177A CN 114522177 A CN114522177 A CN 114522177A CN 202111505247 A CN202111505247 A CN 202111505247A CN 114522177 A CN114522177 A CN 114522177A
- Authority
- CN
- China
- Prior art keywords
- ginsenoside
- reserpine
- group
- depression
- mouse
- 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.)
- Pending
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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Botany (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to application of ginsenoside Re in preparing antidepressant drugs, namely application of ginsenoside Re in treating depression, which is explained from two aspects of dosage and administration time of ginsenoside Re to depression-like behaviors induced by reserpine, repeated administration of ginsenoside Re for 7 days or 14 days can reduce immobility time prolonged by reserpine in forced swimming and tail suspension experiments, is caused by activating TrkB signal channels, and can improve learning and memory ability of mice. The mechanism of the anti-depression effect of the ginsenoside Re is elucidated for the first time, a basis is provided for the ginsenoside Re as an anti-depression medicament, and the anti-depression medicament has important economic and social values for the development of the anti-depression medicament.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of ginsenoside Re in preparation of antidepressant drugs.
Background
Depression is a common affective disorder disease with depression as a main characteristic caused by various reasons, which is mainly characterized by persistent and significant mood drop and is clinically manifested by a wide range of mental, emotional or physical disorders and pains, such as mood drop, depressed mood, insomnia and hypodynamia, autonomy, thought retardation, fatigue and weakness, independent residence with closed doors, social contact avoidance, hypomnesis and other symptoms. As shown by the recent health organization data, the number of people suffering from depression is second to the diseases such as heart disease, AIDS and the like, and the depression becomes one of the most serious diseases in the world by 2030.
At present, the majority of drug therapy is based on chemically synthesized western medicines, such as serotonin reuptake inhibitors, dual serotonin and norepinephrine reuptake inhibitors and the like. The main effects of these drugs are closely related to increasing synaptic cleft neurotransmitter content. However, these chemically synthesized antidepressants generally have the disadvantages of slow effect, long period and great side effect, and the traditional Chinese medicine has the advantages of small side effect, rich source, wide target spot and the like, so that the application of the traditional Chinese medicine in the aspect of depression treatment is increasingly wide, and therefore, more traditional Chinese medicines capable of treating depression need to be developed.
In addition to monoamine neurotransmitters, the down-regulation of Brain Derived Neuropathic Factor (BDNF) function is closely related to the onset of depression. Studies report atrophy of the prefrontal cortex and hippocampus in patients with clinical depression, a phenomenon that correlates with down-regulation of BDNF expression. The use of antidepressant drugs can up-regulate the expression reduction of BDNF caused by depression and produce antidepressant-like effects. Tyrosine Kinase B (TrkB), a functional receptor for BDNF, is highly distributed in the brain by binding to BDNF and initiates the second messenger pathway through a series of reactions. And K252a, as a selective TrkB receptor blocking agent, is widely used in pharmacological research. The down-regulation of TrkB expression in the prefrontal cortex and hippocampus was found in postmortem brain studies in depressed patients. BDNF undergoes conformational changes upon activation by the TrkB receptor and phosphorylates tyrosine residues autonomously, further causing a downstream signaling pathway signaling cascade. Mainly affects Mitogen-activated Protein kinases (MAPK)/Extracellular regulated Protein kinases (ERK) and Phosphatidylinositol 3-kinase (PI 3K)/Protein kinase B (AKT) pathways that ultimately regulate transcription and expression of various genes by activating nuclear transcription factor cyclic adenosine monophosphate response element binding Protein (CREB). The reserpine-induced depression model has short modeling period and definite pathological mechanism, such as reduction of monoamine neurotransmitters and reduction of BDNF, TrkB and CREB, and is used as an animal model for screening the drug effect of traditional Chinese medicines or western medicines.
Ginseng is abundant in northeast China, is a perennial root herbaceous plant of Panax of Araliaceae, is an important treasure in China, is called the king of Baicao, has the effects of tonifying spleen and lung, invigorating primordial qi, calming nerves and improving intelligence, and is the first choice of natural medicinal materials. Ginsenoside is the main bioactive substance of ginseng. To date, over 60 ginsenoside monomers have been isolated and identified, of which 5 major saponins (ginsenosides Rb1, Rb2, Rc, Re and Rg1) account for over 80% of the total saponins. The ginsenoside Re has rich content, mature extraction, separation and purification process, easily obtained monomers and better druggability. Ginsenoside Re is tetracyclic triterpene derivative, and is colorless needle crystal. Ginsenoside Re is mainly distributed in the root, stem and leaf of ginseng, especially in the lateral root of ginseng. A large number of researches prove that the ginsenoside Re has pharmacological activity in multiple aspects of resisting oxidative stress damage, resisting inflammation, resisting allergy, resisting cancer, resisting aging, improving immunity and the like. Meanwhile, researches show that the ginsenoside Re has some effects on neuroinflammation and neurodegenerative diseases. In particular, ginsenoside Re can improve brain function in central nervous system through antioxidation and anti-inflammatory effects. This further suggests the medicinal value of ginsenoside Re. However, the research and report on the antidepressant action and the action mechanism of the ginsenoside Re in a reserpine-induced depression model are not found.
Disclosure of Invention
The invention aims to solve the problem of how to take effect quickly and perform anti-depression treatment with lasting curative effect, and research the anti-depression effect of ginsenoside Re and the anti-depression effect mechanism mediated by TrkB signal channel.
In order to solve the problems, the invention firstly provides the application of the ginsenoside Re in the preparation of the antidepressant drugs for animals.
The depression of the invention is due to depression-like behavior of the animal after the expression of t-TrkB is inhibited in the hippocampus of the brain.
The immobility time of the depressive-like behavior is prolonged or the learning and memory ability is reduced.
The depressive-like behavior according to the invention occurs after the use of reserpine.
The animal of the invention is a mammal.
The mammal is human or mouse.
The dosage of the ginsenoside Re used for a mouse depression model is 30 mg/day/kg, and the administration time is 7-14 days.
The mouse depression model is obtained by inducing reserpine.
The depression-like behavior of the mouse depression model is one or more of reduction of immobility time, decline of learning and memory ability, mouse eyelid ptosis or body temperature decline.
The dosage of the ginsenoside Re is 30 mg/day/kg, and the administration time is 7-14 days.
The dosage form of the medicine provided by the invention is one of tablets, capsules, granules, oral liquid or injection.
The invention also provides an antidepressant drug composition, wherein the ginsenoside Re in the drug composition is used as a single active ingredient of the drug composition or other compounds for activating TrkB signal channels are used as common active ingredients.
The medicament for treating the depression of the animal is a regulator for activating a TrkB signal channel. The monomer ginsenoside Re can play a therapeutic role in reserpine-induced depression by activating TrkB signal channels, and the monomer ginsenoside Re administration obviously increases the expression of TrkB protein.
The invention discovers the therapeutic action of the monomer ginsenoside Re on reserpine-induced depression for the first time, explains the action of the monomer ginsenoside Re on reserpine depression-like behaviors from two aspects of the administration dosage and the administration time of the ginsenoside Re, and proves that the monomer ginsenoside Re can play a role in shortening the immobility time in forced swimming and tail suspension tests, recovering the learning and memory ability of mice, reducing the eyelid closure degree of the mice and improving the body temperature of the mice induced by reserpine.
The monomer ginsenoside Re is a natural traditional Chinese medicine monomer extracted from traditional Chinese medicine ginseng, has lower toxic and side effects on human bodies, higher biological safety, obvious curative effect and obvious curative effect, is suitable for long-term administration, can better understand the action mechanism of the traditional Chinese medicine for the research of the traditional Chinese medicine monomer with definite chemical structure, lays a foundation for the wide application of the traditional Chinese medicine or the optimization of the compatibility proportion of the traditional Chinese medicine and other traditional Chinese medicines, and has great significance.
The ginsenoside Re has obvious relieving effect on the decline of learning and memory abilities and the like of the secondary depression.
Detailed Description
The present invention will be further described with reference to examples, but the scope of application of the present invention is not limited to the following embodiments. It will be evident to those skilled in the art that the invention is not limited to the details of the following illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Ginsenoside Re used in the present invention was purchased from Jilin university chemical institute and its purity was 99%. Ginsenoside Re belongs to a tetracyclic triterpene derivative, is colorless needle crystal, and has a molecular formula of C48H82O18Molecular weight of 947.14, and its chemical formula is as follows:
example 1 effect of ginsenoside Re administration for 7 days on reserpine-induced depressive-like behavior in a mouse model of depression.
Main drugs and reagents: ginsenoside Re (Ginsenoside Re, GS-Re), Fluoxetine Hydrochloride (sigma), Reserpine crystallized (sigma).
Experimental animals: male SPF grade ICR mice, weighing 21-23g, were housed in a single cage in the animal experiment center of the basic medical college of Jilin university, maintaining the circadian rhythm for 12h, controlling the indoor temperature at 22 + -1 deg.C, and were fed with sufficient water and feed for free access to water. All animal experiments were performed in compliance with the relevant provisions of the animal ethics committee of the university of gilin.
The main experimental apparatus: the mouse open field behavior tester (homemade, diameter 48.8cm, diameter 16cm, bottom 19 equal parts), the mouse forced swimming behavior tester (homemade, height 25cm, diameter 11cm, water depth 12cm, water temperature 25 +/-1 ℃), electronic balance (CNSHP Shanghai balance instrument and meter factory).
Grouping and administration: randomly dividing mice into 7 groups, wherein each group comprises 7 mice, namely a Control group (Control), a Reserpine model group (Reserpine, i.p, 2mg/kg), a Reserpine + ginsenoside Re low dose group (10mg/kg), a Reserpine + ginsenoside Re medium dose group (30mg/kg), a Reserpine + ginsenoside Re high dose group (90 mg/kg), a Reserpine + Fluoxetine (Fluoxetine)10mg/kg group and a Reserpine + Fluoxetine 20mg/kg group; ginsenoside Re, fluoxetine and 0.3% sodium carboxymethylcellulose (CMC, solvent) are fasted for two hours before intragastric administration, and physiological saline or reserpine is injected into abdominal cavity after intragastric administration for 1 hour. Ginsenoside Re is dissolved in 0.3 percent sodium carboxymethylcellulose, fluoxetine is dissolved in double distilled water, and reserpine is dissolved in normal saline, and detection is carried out after 7 days of continuous administration.
One, open field experiment
Mice after 7 days of continuous administration were placed in the center of an open field laboratory box (made of polypropylene material, diameter 48.8cm, height 16cm) and the bottom of the experimental device was divided into 19 equal areas, after each mouse experiment, the experimental device was wiped clean and sterilized with alcohol to remove residual smell of the mice and prevent the influence on the movement of the next mouse. The experimental time was 6 minutes, and the number of horizontal movements (crosses) and vertical movements (lifts of the forelimbs) of the mice were recorded with a video camera during the experiment. Results are expressed as mean ± SE.
Second, forced swimming experiment
A transparent cylindrical organic glass container (height 25cm, diameter 11cm) is prepared, and is filled with warm water (water depth 12cm, water temperature 25 + -1 deg.C). A single mouse was placed in a glass container and forced to swim, with a swimming time of 6 minutes per mouse. During the experiment, the whole course was recorded with a video camera and the immobility time of the mouse was counted from the third minute, which means that the mouse stopped struggling or kept the head floating on the water surface only by a slight limb movement. After the swimming experiment was completed, the body of the mouse was wiped dry with a clean towel and returned to the original mouse cage. Clean water is replaced once per mouse tested, and the influence caused by excrement and odor left by the previous mouse is reduced.
Three, tail suspension experiment
The tail (about 1cm from the tail tip) of the mouse is stuck on a bracket, the mouse is hung upside down on an experiment table, the head of the mouse is about 15cm from the experiment platform, two sides of each mouse are separated by wood boards to prevent the mice from directly watching each other to interfere the experiment, the mouse is hung for 6 minutes and recorded by a camera, and the immobility time of the mouse in the next 4 minutes is counted.
The test of the influence of repeated administration of ginsenoside Re for 7 days on the spontaneous motility of the mice in the open field test is shown in tables 1A and 1B, the ginsenoside Re (10, 30 and 90mg/kg) and fluoxetine (10, 20mg/kg) are continuously administered to the mice for 7 days, and the spontaneous motility of the mice in the open field test has no obvious change compared with a reserpine control group, which indicates that the administration of the ginsenoside Re does not change the spontaneous motility of the mice, and the antidepressant effect of the ginsenoside Re has specificity.
TABLE 1A Effect of ginsenoside Re on reserpine induced horizontal locomotion in open field experiments in mice
| Experiment grouping | Dosage (mg/kg) | Number of passes |
| Blank control group | - | 181.0±23.4 |
| Reserpine model group | 1.5 | 74.3±27.6*** |
| Reserpine + Low dose group | 10 | 75.14±19.1 |
| Reserpine + medium dose group | 30 | 110.6±40.3 |
| Reserpine + high dose group | 90 | 92.04±22.4 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 68.0±27.1 |
| Lixuepin + fluoxetine hydrochloride group | 20 | 90.4±35.3 |
Note: data are expressed as Mean values with standard error (Mean + SE), n-10-20, p <0.001 compared to the blank control.
TABLE 1B Effect of ginsenoside Re on reserpine induced vertical movement in open field experiments in mice
| Experiment grouping | Dosage (mg/kg) | Number of passes |
| Blank control group | - | 59.1±10.7 |
| Reserpine model group | 1.5 | 32.8±14.2** |
| Reserpine + Low dose group | 10 | 24.9±12.8 |
| Reserpine + medium dose group | 30 | 38.7±10.9 |
| Reserpine + high dose group | 90 | 32.0±11.6 |
| Reserpine + fluoxetine hydrochlorideGroup of | 10 | 25.7±10.7 |
| Lixuepin + fluoxetine hydrochloride group | 20 | 30.4±14.6 |
Note: data are expressed as Mean values with standard error (Mean + SE), n-10-20, p <0.01 compared to the blank control.
The influence of repeated administration of ginsenoside Re for 7 days on the immobility time of forced swimming of despair model mice is shown in Table 2, compared with a control group, the immobility time of the mice is obviously increased by repeated administration of reserpine for 7 days, and compared with a model group, the immobility time in a tail suspension experiment of the mice can be obviously shortened by continuous administration of a medium dose (30mg/kg) group of ginsenoside Re for 7 days. While the low and high dose groups (10mg/kg, 90mg/kg) had no significant immobility time improvement. The fluoxetine hydrochloride positive control group (10mg/kg) significantly reduced immobility time.
TABLE 2 Effect of ginsenoside Re on reserpine induced immobility time in forced swimming of mice
| Experiment grouping | Dosage (mg/kg) | Dead time(s) |
| Blank control group | - | 67.1±40.6 |
| Reserpine model group | 1.5 | 97.5±58.1* |
| Reserpine + Low dose group | 10 | 82.7±48.3 |
| Reserpine + medium dose group | 30 | 50.6±47.1# |
| Reserpine + high dose group | 90 | 54.9±65.7 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 52.4±45.1# |
| Lixuepin + fluoxetine hydrochloride group | 20 | 101.4±64.8 |
Note: data are expressed as Mean values of standard error (Mean + SE), n-10-20, p <0.05 for the blank control group and p <0.05 for the reserpine model group.
The influence of repeated administration of ginsenoside Re for 7 days on the immobility time of the mouse tail suspension experiment is shown in Table 3, and compared with a control group, the repeated administration of reserpine for 7 days remarkably increases the immobility time of the mouse. Compared with a model group, the mouse immobility time is obviously reduced by repeatedly administering 30mg/kg of ginsenoside Re for 7 days, and the mouse immobility time is also obviously reduced by repeatedly administering 10mg/kg of fluoxetine for 7 days.
TABLE 3 Effect of ginsenoside Re on reserpine induced mice tail suspension experiment immobility time
Note: data are expressed as Mean values with standard error (Mean + SE), n-10-20, compared to the blank control group, # p <0.001, compared to the reserpine model group, # p < 0.05.
Example 1 shows that the ginsenoside Re medium dose group can remarkably shorten the immobility time of mice in a forced swimming experiment by continuously administering to reserpine induced mice for 7 days, and shows a certain antidepressant effect.
Example 2 mechanism of effect of ginsenoside Re repeatedly administered for 7 days on reserpine-induced depressive-like behavior in depression model mice.
Main drugs and reagents: ginsenoside Re (Ginsenoside Re, GS-Re), Fluoxetine Hydrochloride (sigma), Reserpine crystallized, sigma, anti-TrkB antibody was purchased from Cell Signaling Technology, USA, and anti-GAPDH antibody and HRP antibody were purchased from sigma.
Experimental animals: male SPF grade ICR mice, weighing 21-23g, were housed in a single cage in the animal experiment center of the basic medical college of Jilin university, maintaining the circadian rhythm for 12h, controlling the indoor temperature at 22 + -1 deg.C, and were fed with sufficient water and feed for free access to water. All animal experiments were performed in compliance with the relevant provisions of the animal ethics committee of the university of gilin.
The main experimental apparatus: protein electrophoresis apparatus (JY600C/JY-SPCT, Junyi company), protein blotting electrotransfer apparatus (TJY-ZY5, Junyi company)
Grouping and administration: the experimental groups and administration methods were the same as in example 1.
First, immunoblotting experiment
First, a mouse brain tissue sample was collected. Immediately after the behavioral test, the mouse was decapitated, the prefrontal cortex was cut off quickly using a scalpel, and the hippocampus was peeled off with forceps, and the extracted hippocampus and prefrontal cortex were weighed in a centrifuge tube prepared before the experiment, and the centrifuge tube was placed on ice. The sample is quickly frozen in a refrigerator at-80 ℃ for standby. Then cracking the tissue by using the prepared protein lysate, grinding the tissue by using a refiner to fully crack the tissue, centrifuging and taking supernatant to obtain protein, and performing an immunoblotting experiment.
Detecting the expression level of TrkB protein by a Western Blot method:
polyacrylamide gels were prepared with 10% strength separation gel and 5% strength concentration gel, respectively. After the electrophoresis, the membrane was transferred, antibody reaction was performed, and the mixture was incubated at 4 ℃ overnight, washed, and then incubated with a secondary antibody at room temperature for 1 hour and washed with TBST. Imaging was performed using a Tanon-5200 gel imaging system and the band grayscale values were determined using an Image J software analysis system.
Ginsenoside Re 30mg/kg repeatedly administered for 7 days up-regulated the expression level of t-TrkB total protein (t-TrkB) in hippocampus of mice in reserpine-induced depression model as shown in Table 5, and did not affect the expression level of t-TrkB in prefrontal cortex as shown in Table 4.
TABLE 4 Effect of ginsenoside Re administration for 7 days on reserpine Induction of t-TrkB expression levels in prefrontal cortex of mice
| Experimental groups | Dosage (mg/kg) | t-TrkB/beta-actin ratio |
| Blank control group | - | 1.8±0.4 |
| Reserpine model group | 1.5 | 1.6±0.2 |
| Reserpine + Low dose group | 10 | 2.3±0.3 |
| Reserpine + medium dose group | 30 | 1.8±0.4 |
| Reserpine + high dose group | 90 | 1.8±0.3 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 1.9±0.3 |
| Lixuepin + fluoxetine hydrochloride group | 20 | 1.9±0.4 |
TABLE 5 Effect of ginsenoside Re administration for 7 days on reserpine-induced t-TrkB expression levels in hippocampus of mice
Note: data are expressed as Mean values with standard error (Mean + SE), n 10-20, p <0.001 compared to the blank control group, p <0.05, # p <0.01 compared to the reserpine model group.
Example 2 shows that repeated administration of a group of ginsenoside medium doses (30mg/kg) for 7 days up-regulates the expression level of t-TrkB total protein (t-TrkB) in the hippocampus of reserpine-induced depression model mice, and shows an antidepressant effect.
Example 3 effect of ginsenoside Re administration for 14 days on depressive behavior, blepharoptosis and body temperature in reserpine-induced mouse depression model.
Main drugs and reagents: ginsenoside Re (Ginsenoside Re, GS-Re), Fluoxetine Hydrochloride (sigma), Reserpine crystallized (sigma)
Experimental animals: male SPF grade ICR mice, weighing 21-23g, were housed in a single cage in the animal experiment center of the basic medical college of Jilin university, maintaining the circadian rhythm for 12h, controlling the indoor temperature at 22 + -1 deg.C, and were fed with sufficient water and feed for free access to water. All animal experiments were performed in compliance with the relevant provisions of the animal ethics committee of the university of gilin.
The main experimental apparatus: the main experimental instruments are as above
Grouping and administration: ICR male mice were randomly divided into 5 groups (10 per group), a Control group (Control), a Reserpine model group (i.p., 2 mg/kg); reserpine plus ginsenoside Re 30mg/kg, reserpine plus ginsenoside Re 60 mg/kg; the dose group of reserpine + Fluoxetine (Fluoxetine)10 mg/kg; ginsenoside Re, fluoxetine and sodium carboxymethylcellulose (CMC, solvent) are taken back after intragastric administration for two hours, and physiological saline or reserpine is injected into the abdominal cavity after intragastric administration for 1 hour. Ginsenoside Re is dissolved in 0.3 percent of sodium carboxymethylcellulose, fluoxetine is dissolved in double distilled water, and reserpine is dissolved in normal saline. The experimental groups were as follows:
one, open field experiment
The experimental procedure was as in example 1.
Second, forced swimming experiment
The experimental procedure was as in example 1.
Three, tail suspension experiment
The experimental procedure was as in example 1.
Fourth, evaluation of degree of eyelid ptosis and degree of body temperature drop
The degree of eyelid ptosis was evaluated for each mouse as follows: 0 min, opening eyes normally; score 1, eyelid droop 1/4; score 2, eyelid droop 1/2; score 3, eyelid droop 3/4; for 4 minutes, the eyelids were completely closed. The infrared non-contact electron thermometer is adopted to measure the temperature of the anus of the mouse, so that the error caused by the fact that the thermometer is inserted into the anus to stimulate the mouse is avoided. The degree of eyelid ptosis was observed 1 hour after the last dose of reserpine (day seven), and the anal temperature was measured two hours later.
The results of the experiment on the effect of repeated administration of ginsenoside Re for 14 days on the spontaneous motility in the open field experiment are shown in tables 6A and 6B. Compared with a reserpine control group and a reserpine model group, the horizontal cross-cell number and the vertical standing times of the mice are not changed in each administration group, so that the administration of the ginsenoside Re and fluoxetine does not change the spontaneous activity of the mice, and the antidepressant effect of the administration has specificity.
TABLE 6A Effect of ginsenoside Re on reserpine induced horizontal locomotion in open field experiments in mice
| Experiment grouping | Dosage (mg/kg) | Number of passes |
| Blank control group | - | 117.3±25.6 |
| Reserpine model group | 1.5 | 59.5±22.7*** |
| Reserpine + medium dose group | 30 | 60.6±21.5 |
| Reserpine + high dose group | 60 | 64.0±29.1 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 56.7±27.7 |
Note: data are expressed as Mean values with standard error (Mean + SE), n-10-20, p <0.001 compared to the blank control.
TABLE 6B Effect of ginsenoside Re on reserpine induced vertical movement in open field experiments in mice
Note: data are expressed as Mean values with standard error (Mean + SE), n-10-20, p <0.001 compared to the blank control.
The influence of the repeated administration of ginsenoside Re for 14 days on the immobility time of the despair model mouse in forced swimming is shown in Table 7, compared with a control group, the immobility time of the mouse is remarkably increased by the model group, and compared with the model group, the immobility time of the mouse is remarkably reduced by the repeated administration of ginsenoside Re for 30mg/kg for 14 days. Repeated administration of fluoxetine 10mg/kg for 14 days significantly reduced the immobility time of mice compared to the model group.
TABLE 7 Effect of ginsenoside Re on reserpine induced immobility time in forced swimming of mice
| Experiment grouping | Dosage (mg/kg) | Dead time(s) |
| Blank control group | - | 105.1±32.6 |
| Reserpine model group | 1.5 | 171.5±21.5*** |
| Reserpine + medium dose group | 30 | 130.4±38.4# |
| Reserpine + high dose group | 60 | 188.3±28.0 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 118.1±37.2## |
Note: data are expressed as Mean values with standard error (Mean + SE), n 10-20, p <0.001 for the placebo control group, p <0.05 for the reserpine model group, p # 0.01.
The influence of repeated administration of ginsenoside Re for 14 days on the immobility time of the mouse tail suspension experiment is shown in Table 16, and compared with a control group, reserpine in a model group remarkably increases the immobility time of the mouse. Compared with reserpine in the model group, the immobility time of the mice is not changed in other administration groups.
The results of the effects of reserpine on body temperature and blepharoptosis of mice are shown in tables 8A and 8B, and compared with the control group, the body temperature of the mice in the reserpine group is reduced, and the body temperature is obviously increased after the ginsenoside Re 30mg/kg is repeatedly administered for 14 days, so that the body temperature is restored to the normal level. Compared with a control group, the mouse with the reserpine model group has a remarkably-increased score of the degree of eyelid closure. Compared with the model group, the ginsenoside Re 30mg/kg obviously reduces the eyelid closure degree of the mice.
TABLE 8A Effect of ginsenoside Re on reserpine induced anal temperature in mice
| Experiment grouping | Dosage (mg/kg) | Body temperature difference |
| Blank control group | - | 0.11±0.2 |
| Reserpine model group | 1.5 | 0.01±0.1 |
| Reserpine + medium dose group | 30 | 0.11±0.1 |
| Reserpine + high dose group | 60 | 0.13±0.1 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 0.12±0.2 |
TABLE 8B Effect of ginsenoside Re on reserpine induced drooping of mouse eyelids
| Experiment grouping | Dosage (mg/kg) | Scoring |
| Blank control group | - | - |
| Reserpine model group | 1.5 | 2.2±0.5 |
| Reserpine + medium dose group | 30 | 1.5±0.7# |
| Reserpine + high dose group | 60 | 1.9±0.7 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 1.5±0.5## |
Note: data are expressed as Mean value shima error (Mean + SE), n 10-20, # p <0.05, # p <0.01, compared to reserpine model group.
Example 3 shows that compared with the control group, the degree of eyelid ptosis of the model group mice is remarkably increased after 7 days of repeated administration of reserpine, and the mouse eyelid ptosis is reversed by repeated administration of 30mg/kg of ginsenoside Re and 10mg/kg of fluoxetine for 14 days. In forced swimming experiments, repeated administration of 30mg/kg of ginsenoside Re and 10mg/kg of fluoxetine for 14 days significantly reduced the immobility time prolonged by reserpine. Further shows that the ginsenoside Re 30mg/kg and the fluoxetine 10mg/kg have antidepressant effect after being repeatedly administrated for 14 days. In open field experiments, all test drugs did not affect the spontaneous activity of the mice compared to the model group. Thus, the antidepressant-like effects of ginsenoside Re and fluoxetine are not intended to reduce immobility time by stimulating motor activity centers.
Example 4 effect of ginsenoside Re on reserpine induced learning and memory function in mice.
Main drugs and reagents: ginsenoside Re (Ginsenoside Re, GS-Re), Fluoxetine Hydrochloride (sigma), Reserpine crystallized (sigma)
Experimental animals: male SPF grade ICR mice, weighing 21-23g, were housed in a single cage in the animal experiment center of the basic medical college of Jilin university, maintaining the circadian rhythm for 12h, controlling the indoor temperature at 22 + -1 deg.C, and were fed with sufficient water and feed for free access to water. All animal experiments were performed in compliance with the relevant regulations of the animal ethics committee of the university of ghrelin.
The main experimental apparatus: y-mazey maze spontaneous alternation experimental facility, plastic box (self-made, 40cm X40 cm)
Grouping and administration: the ICR male mice were randomly divided into 5 groups (10 mice per group), a Control group (Control), and a Reserpine model group (Reserpine; i.p., 2 mg/kg); reserpine plus ginsenoside Re 30mg/kg, reserpine plus ginsenoside Re 60 mg/kg; the dose group of reserpine + Fluoxetine (Fluoxetine)10 mg/kg; ginsenoside Re, fluoxetine and sodium carboxymethylcellulose (CMC, solvent) are taken back after intragastric administration for two hours, and physiological saline or reserpine is injected into the abdominal cavity after intragastric administration for 1 hour. Ginsenoside Re is dissolved in 0.3 percent of sodium carboxymethylcellulose, fluoxetine is dissolved in double distilled water, and reserpine is dissolved in normal saline.
First, spontaneous alternation experiment of Y-mazey maze: the spontaneous alternation experimental device of the Y-mazey maze consists of 3 equal-length black arms (30cm multiplied by 8cm multiplied by 15cm), the included angle between every two arms is 120 degrees, a mouse is placed at the tail end of any arm of the Y maze and is allowed to freely explore for 8min, the camera system records the behavior change of the animal for 8min, and the following indexes are recorded: total arm advance times: the number of times the mouse entered the maze arm (four feet of the mouse entered the arm to count as one arm entry); ② take turns (alternate) once: enter the Y maze in sequence and continuously for all three arms once. ③ maximum number of turns: total arm-advance times-2. Spontaneous rotation behavior score-total number of rotations/maximum number of rotations (total number of arm entries-2) × 100%.
II, new object identification experiment: the new object identification experiment is used for detecting the learning and memory functions of animals, and is characterized in that the identification capability is not influenced by the motion functions of the animals, and the novel objects are explored. A plastic box (40cm × 40cm × 40cm) with a closed periphery and A, B, C3 special cubes (5cm × 5cm × 5cm) with the same size and material were prepared, wherein A, B objects had the same color, and C objects had a color different from A, B objects. 5min before the beginning of the formal experiment, the mouse and the A and B objects are placed in the field for 5min identification so as to adapt to the test environment. After 5min, the object B in the field is replaced by the object C, the mouse is placed back to the experimental field, and the time for the mouse to explore the new object C (expansion time for new object Tn) and the old object A (expansion time for the object Tf) within 5min is recorded. And finally, calculating a preference index of the new object, wherein the formula is as follows: the recognition coefficient is Tn/(Tn + Tf), i.e., the ratio of the new object recognition time to the total time.
The results of the influence of repeated administration of ginsenoside Re for 14 days on the spontaneous alternate behavior score of the mice in the Y-maze spontaneous alternation experiment are shown in Table 9, and compared with the control group, the spontaneous alternate behavior score of the mice in the model group is obviously reduced; compared with the model group, the spontaneous alternate behavior score of the mice in the group which is repeatedly dosed with 30mg/kg of ginsenoside Re for 14 days is obviously increased.
TABLE 9 influence of ginsenoside Re on reserpine induced spontaneous rotation behavior of mice in maze experiment Y
| Experiment grouping | Dosage (mg/kg) | Scoring |
| Blank control group | - | 0.57±0.10 |
| Reserpine model group | 1.5 | 0.50±0.12* |
| Reserpine + medium dose group | 30 | 0.54±0.11# |
| Reserpine + high dose group | 60 | 0.47±0.20 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 0.52±0.10# |
Note: data are expressed as Mean values of standard error (Mean + SE), n-10-20, p <0.05 for the blank control group and p <0.05 for the reserpine model group.
The results of the effects of repeated administration of ginsenoside Re for 14 days on the mouse new object recognition time are shown in table 10, and compared with the control group, the mouse new object recognition time of the model group is significantly reduced; compared with the model group, the recognition time of the new object of the mice in the group of 14 days after repeated administration of 30mg/kg of ginsenoside Re is obviously increased.
TABLE 10 influence of ginsenoside Re on reserpine-induced mouse neoformant recognition time
| Experiment grouping | Dosage (mg/kg) | Scoring |
| Blank control group | - | 0.52±0.05 |
| Reserpine model group | 1.5 | 0.31±0.11* |
| Reserpine + medium dose group | 30 | 0.53±0.02# |
| Reserpine + high dose group | 60 | 0.55±0.20 |
| Lixuepin + fluoxetine hydrochloride group | 10 | 0.52±0.02# |
Note: data are expressed as Mean values of standard error (Mean + SE), n-10-20, p <0.05 for the blank control group and p <0.05 for the reserpine model group.
Example 4 shows that reserpine can cause damage to learning and memory abilities of mice, and compared with reserpine model group, the ginsenoside Re medium dose group can obviously restore the learning and memory abilities of mice.
Example 5 effect of repeated administration of TrkB inhibitor k252a to ginsenoside Re for 7 days on reserpine-induced depressive-like behavior in mice model depression.
Main drugs and reagents: ginsenoside Re (Ginsenoside Re, GS-Re), Fluoxetine Hydrochloride (sigma), Reserpine crystallized, sigma), k252a (sigma)
Experimental animals: male SPF grade ICR mice, weighing 21-23g, were housed in a single cage in the animal experiment center of the basic medical college of Jilin university, maintaining the circadian rhythm for 12h, controlling the indoor temperature at 22 + -1 deg.C, and were fed with sufficient water and feed for free access to water. All animal experiments were performed in compliance with the relevant provisions of the animal ethics committee of the university of gilin.
The main experimental apparatus: the main experimental instruments are as above
Grouping and administration: ICR male mice were randomly divided into 5 groups (10 per group), a Control group (Control), a Reserpine model group (i.p., 2 mg/kg); reserpine plus ginsenoside Re 30 mg/kg; reserpine + ginsenoside Re 30mg/kg + k252 a; reserpine + k252a group; the food is withdrawn before the administration of ginsenoside Re and sodium carboxymethylcellulose (CMC, solvent) for two hours, the normal saline or k252a inhibitor is injected into the abdominal cavity after the administration for 1 hour, and the normal saline or reserpine is injected into the abdominal cavity after the injection for 1 hour of the k252a inhibitor. Ginsenoside Re was dissolved in 0.3% sodium carboxymethylcellulose, k252a and reserpine in physiological saline.
One, open field experiment
The experimental procedure was as in example 1.
Second, forced swimming experiment
The experimental procedure was as in example 1.
Three, tail suspension experiment
The experimental procedure was as in example 1.
Fourth, evaluation of degree of eyelid ptosis and degree of body temperature drop
The experimental procedure was as in example 3.
The effect of repeated administration of ginsenoside Re for 7 days under the action of TrkB inhibitor k252a on the spontaneous motility in the open field test is shown in tables 11A and 11B. Compared with a reserpine control group and a reserpine model group, the horizontal cross-grid number and the vertical standing times of the mice are not changed in each administration group, so that the spontaneous activity of the mice is not changed by the administration of the ginsenoside Re and the ginsenoside k252a, and the antidepressant effect of the mice is specific.
TABLE 11 influence of ginsenoside Re on reserpine induced horizontal locomotion in open field experiments in mice
| Experimental groups | Dosage (mg/kg) | Number of passes |
| Blank control group | - | 94.3±10.4 |
| Reserpine model group | - | 64.0±13.5 |
| Reserpine and ginsenoside Re group | 30 | 52.8±7.5 |
| Reserpine + ginsenoside Re + k252a group | 30 | 57.8±3.2 |
| Reserpine + k252a group | - | 68.3±11.9 |
Note: data are expressed as Mean value, Mean + SE, with n ranging from 10 to 20.
TABLE 11 influence of ginsenoside Re on reserpine induced vertical movement in open field experiments in mice
Note: data are expressed as Mean value, standard error (Mean + SE), n-10-20.
The experimental results of the influence of repeated administration of ginsenoside Re for 7 days on the spontaneous motility of the open field experiment under the action of TrkB inhibitor k252a are shown in Table 12, compared with a control group, the immobility time of a mouse is remarkably increased by a model group, and compared with the model group, the immobility time of the mouse is remarkably reduced by repeated administration of ginsenoside Re 30mg/kg for 7 days. Compared with the ginsenoside treatment group, reserpine + ginsenoside Re + k252a antagonizes the recovery effect of ginsenoside Re treatment on mice with prolonged immobility time.
TABLE 12 Effect of ginsenoside Re on reserpine induced immobility time in forced swimming of mice
| Experiment grouping | Dosage (mg/kg) | Dead time(s) |
| Blank control group | - | 68.1±26.2 |
| Reserpine model group | - | 193.2±7.3** |
| Reserpine and ginsenoside Re group | 30 | 81.3±12.9#### |
| Reserpine + ginsenoside Re + k252a group | 30 | 148.6±11.3&& |
| Reserpine + k252a group | - | 182.0±13.1** |
Note: data are expressed as Mean value of standard error (Mean + SE), n is 10-20, p <0.01, reserpine model group, # # p <0.0001, and ginsenoside treatment group, & & p < 0.01.
The influence of repeated administration of ginsenoside Re for 7 days on the immobility time of the mouse tail suspension experiment is shown in Table 13, and compared with a control group, reserpine in a model group remarkably increases the immobility time of the mouse. Compared with a model group, the mouse immobility time is obviously reduced by repeatedly administering 30mg/kg of ginsenoside Re for 7 days. The reserpine + ginsenoside treatment + k252a inhibitor group antagonized the recovery effects of ginsenoside treatment on mice with prolonged immobility time compared to the ginsenoside treatment group.
TABLE 13 influence of ginsenoside Re on the immobility time of reserpine induced mouse tail suspension experiment
| Experiment grouping | Dosage (mg/kg) | Dead time(s) |
| Blank control group | - | 29.2±13.6 |
| Reserpine model group | - | 175.2±15.0**** |
| Reserpine and ginsenoside Re group | 30 | 48.5±6.7#### |
| Reserpine + ginsenoside Re + k252a group | 30 | 111.9±12.7&& |
| Reserpine + k252a group | - | 153.9±24.2** |
Note: data are expressed as Mean value standard error (Mean + SE), n is 10-20, compared to the blank control group, # p <0.0001, # p <0.01, reserpine model group, # # p <0.0001, compared to the ginsenoside treated group, # p < 0.01.
The results of the effects of reserpine on body temperature and blepharoptosis of mice are shown in tables 14A and 14B, and compared with the control group, the body temperature of the mice in the reserpine group is reduced, and the body temperature is obviously increased after the ginsenoside Re 30mg/kg is repeatedly administered for 7 days, so that the body temperature is restored to the normal level. The mouse with the reserpine model group has obviously higher score of the closed degree of the eyelid compared with the control group. Compared with a model group, the ginsenoside Re 30mg/kg obviously reduces the degree of eyelid closure of mice, and after the k252a inhibitor is injected into the abdominal cavity, the recovery effect of the ginsenoside Re is influenced, and the k252a inhibitor antagonizes the effect of partial ginsenoside Re.
TABLE 14 influence of ginsenoside Re on reserpine-induced anal temperature in mice
| Experiment grouping | Dosage (mg/kg) | Body temperature |
| Blank control group | - | 38.4±0.4 |
| Reserpine model group | - | 34.2±0.2** |
| Reserpine and ginsenoside Re group | 30 | 35.4±0.3# |
| Reserpine + ginsenoside Re + k252a group | 30 | 34.4±0.3& |
| Reserpine + k252a group | - | 34.3±0.2*** |
TABLE 14B Effect of ginsenoside Re on reserpine induced eyelid ptosis in mice
Note: data are expressed as Mean values of standard error (Mean + SE), n-10-20, compared to the blank control group, # p <0.001, # p <0.01, in the reserpine model group, # p <0.05, compared to the ginsenoside treated group, # p < 0.05.
Example 5 shows that the degree of eyelid ptosis of the model group mice significantly increased after repeated administration of reserpine for 7 days, and that repeated administration of ginsenoside Re 30mg/kg for 7 days reversed the cases of eyelid ptosis and body temperature drop of the mice, compared to the control group, but that the recovery effect of ginsenoside Re on body temperature drop and eyelid ptosis was suppressed when k252a was administered simultaneously. In forced swimming and tail suspension experiments, repeated administration of 30mg/kg of ginsenoside Re for 7 days significantly reduced the immobility time prolonged by reserpine, and this effect was inhibited by administration of k252 a. Further indicates that the action mechanism of the antidepressant-like effect generated by repeated administration of 30mg/kg of ginsenoside Re for 7 days is related to the activation of TrkB receptors.
Example 6 mechanism of effect of ginsenoside Re repeatedly administered for 7 days on reserpine-induced depressive-like behavior in mice as model of depression under the action of TrkB inhibitor k252 a.
Main drugs and reagents: ginsenoside Re (Ginsenoside Re, GS-Re), Fluoxetine Hydrochloride (sigma), Reserpine crystallized, sigma, anti-AKT, pAKT, CREB, pCREB, mTOR, TrkB and BDNF antibodies were purchased from Cell Signaling Technology, USA, and anti-beta-actin antibodies and HRP antibodies from sigma.
Experimental animals: male SPF grade ICR mice, weighing 21-23g, were housed in a single cage in the animal experiment center of the basic medical college of Jilin university, maintaining the circadian rhythm for 12h, controlling the indoor temperature at 22 + -1 deg.C, and were fed with sufficient water and feed for free access to water. All animal experiments were performed in compliance with the relevant regulations of the animal ethics committee of the university of ghrelin.
Main experimental apparatus: protein electrophoresis apparatus (JY600C/JY-SPCT, Junyi company), protein blotting electrotransfer apparatus (TJY-ZY5, Junyi company)
Grouping and administration: the experimental groups and administration methods were the same as in example 6.
First, immunoblotting experiment
The samples were collected and prepared as in example 6.
The expression levels of AKT, pAKT, CREB, pCREB and TrkB proteins are detected by a Western Blot method:
the procedure was as in example 6.
The expression level of total t-TrkB protein (t-TrkB) in hippocampus of reserpine-induced depression model mice is shown in Table 15 when ginsenoside Re 30mg/kg is repeatedly administered for 7 days.
TABLE 15 Effect of ginsenoside Re administration for 7 days on reserpine-induced t-TrkB expression levels in hippocampus in mice with concurrent administration of k252a inhibitor
| Experiment grouping | Dosage (mg/kg) | t-TrkB/beta-actin ratio |
| Blank control group | - | 1.39±0.1 |
| Reserpine model group | - | 0.78±0.1** |
| Reserpine and ginsenoside Re group | 30 | 1.29±0.1# |
| Reserpine + ginsenoside Re + k252a group | 30 | 0.81±0.1& |
| Reserpine + k252a group | - | 0.81±0.1** |
Note: data are expressed as Mean value, Mean + SE, with n ranging from 10 to 20.
Table 16 effect of ginsenoside Re administration for 7 days on reserpine induction of CREB expression levels in hippocampus of mice.
TABLE 17 Effect of ginsenoside Re administration for 7 days on reserpine induced AKT expression levels in mouse hippocampus
| Experiment grouping | Dosage (mg/kg) | pAKT/AKT ratio |
| Blank control group | - | 1.32±0.06 |
| Reserpine model group | - | 0.80±0.03** |
| Reserpine and ginsenoside Re group | 30 | 1.19±0.09# |
| Reserpine + ginsenoside Re + k252a group | 30 | 0.39±0.08&&&& |
| Reserpine + k252a group | - | 0.47±0.1**** |
Note: data are expressed as Mean values of standard errors (Mean + SE), n is 10-20, compared to the blank control group, # p <0.0001, # p <0.01, # p <0.05, compared to the reserpine model group, # p <0.05, compared to the ginsenoside treated group, # p <0.0001, & p < 0.05.
Example 7 shows that repeated administration of a dose (30mg/kg) group of ginsenoside for 7 days up-regulates the expression levels of TrkB, AKT and CREB proteins in the hippocampus of mice in a reseated depression model induced by reserpine, while inhibitor k252a reduces the expression levels of these proteins, indicating that the antidepressant effect of ginsenoside is related to the activation of TrkB signaling pathway.
The group of the ginsenoside Re medium dose can obviously shorten the immobility time of a mouse in a forced swimming experiment after being continuously administrated to the mouse for 7 days or 14 days, shows a certain anti-depression effect, and blocks the anti-depression effect of the ginsenoside Re under the condition of simultaneously administrating a TrkB inhibitor k252a, which indicates that the anti-depression effect mechanism of the ginsenoside Re is due to the activation of a TrkB signal path.
The embodiment of the invention illustrates the effect of the ginsenoside Re on reserpine-induced depression-like behaviors from two aspects of the administration dose and the administration time of the ginsenoside Re, and the test result shows that the ginsenoside Re 30mg/kg (i.g) with medium dose can reverse eyelid ptosis caused by reserpine, reduce the immobility time prolonged by reserpine in forced swimming and tail suspension experiments, is caused by activating TrkB (BDNF high affinity receptor) channels, and can improve the learning and memory ability of mice. Seven days after the administration of TrkB inhibitor k252a, the therapeutic effect of ginsenoside on depression decreased, further demonstrating that the effect of ginsenoside on depression is produced by activating TrkB pathway.
The medicament containing the ginsenoside Re can be one of tablets, capsules, granules, oral liquid or injection, and has important significance in clinically treating depression.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (10)
1. Application of ginsenoside Re in preparing antidepressant is provided.
2. Use according to claim 1, characterized in that: the depression is due to a depressive-like behavior after the inhibition of t-TrkB expression in the hippocampus of the brain of the animal.
3. Use according to claim 2, characterized in that: the depressive-like behavior is prolonged immobility time or decreased learning and memory ability.
4. Use according to claim 3, characterized in that: the depressive-like behavior occurs after use of reserpine.
5. The use of claim 4, wherein: the animal is a mammal, and the mammal is a human or a mouse.
6. Use according to claim 5, characterized in that: the dosage of the ginsenoside Re applied to a mouse depression model is 30 mg/day/kg, and the administration time is 7-14 days.
7. The use of claim 6, wherein: the mouse depression model is induced by reserpine.
8. The use of claim 7, wherein: the depression-like behavior of the mouse depression model is one or more of reduction of immobility time, reduction of learning and memory ability, mouse eyelid ptosis or reduction of body temperature.
9. An antidepressant pharmaceutical composition characterized by: ginsenoside Re is used as a single active ingredient of the pharmaceutical composition or other compounds for activating TrkB signal channels are used as common active ingredients.
10. The pharmaceutical composition of claim 9, wherein: the dosage form of the medicine is one of tablets, capsules, granules, oral liquid or injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111505247.5A CN114522177A (en) | 2021-12-10 | 2021-12-10 | Application of ginsenoside Re in preparation of antidepressant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111505247.5A CN114522177A (en) | 2021-12-10 | 2021-12-10 | Application of ginsenoside Re in preparation of antidepressant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114522177A true CN114522177A (en) | 2022-05-24 |
Family
ID=81620061
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111505247.5A Pending CN114522177A (en) | 2021-12-10 | 2021-12-10 | Application of ginsenoside Re in preparation of antidepressant |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114522177A (en) |
-
2021
- 2021-12-10 CN CN202111505247.5A patent/CN114522177A/en active Pending
Non-Patent Citations (1)
| Title |
|---|
| 徐乐等: "人参皂苷Re对吗啡依赖戒断后小鼠抑郁样行为的影响", 《延边大学医学学报》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Ansari et al. | Nigella sativa: A non-conventional herbal option for the management of seasonal allergic rhinitis | |
| Wu et al. | Study on the behavioral changes of a post‑stroke depression rat model | |
| CN104225167B (en) | Purposes of the LIUWEI DIHUANG TANG extract in treatment dementia or cognition dysfunction | |
| Sun et al. | Deep brain stimulation improved depressive-like behaviors and hippocampal synapse deficits by activating the BDNF/mTOR signaling pathway | |
| Hu et al. | Effect of kai xin san on learning and memory in a rat model of paradoxical sleep deprivation | |
| Yuan et al. | Xiaoyaosan inhibits neuronal apoptosis by regulating the miR-200/NR3C1 signaling in the prefrontal cortex of chronically stressed rats | |
| Li et al. | Coeloglossum viride var. bracteatum extract attenuates Aβ-induced toxicity by inhibiting RIP1–driven inflammation and necroptosis | |
| Zhang et al. | SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy | |
| WO2020143746A1 (en) | Use of chlorogenic acid in preparing medicine or pharmaceutical composition for preventing or treating pain | |
| CN114522177A (en) | Application of ginsenoside Re in preparation of antidepressant | |
| CN103251635B (en) | Application of 2-[(2-O-glucosyl-5-hydroxybenzoyl) amino]-5-hydroxybenzoic acid methyl ester | |
| CN102861117A (en) | Composition containing Chinese medicine active ingredients and application thereof | |
| CN109718236B (en) | Application of bulleyaconitine A in preparing medicine for treating irritable bowel syndrome | |
| Liu et al. | Aucubin improves chronic unpredictable mild stress-induced depressive behavior in mice via the GR/NF-κB/NLRP3 axis | |
| CN102895602B (en) | Chinese medicinal preparation for preventing and treating depression | |
| CN107854620B (en) | Traditional Chinese medicine composition for improving cognitive dysfunction after brain injury and application thereof | |
| CN101548981A (en) | Application of ginsenosides Rg1, Rh1 and Ppt to resistance of cognitive competence and study memory function disorders | |
| CN115837029B (en) | Application of codonopsis pilosula acetylenic glycoside in preparation of medicines for treating allergic rhinitis | |
| AU2018386145A1 (en) | New medical use of persimmon leaf extract and of preparation of persimmon leaf extract | |
| CN104491226B (en) | A kind of new medical usage of pharmaceutical composition | |
| Qiao et al. | The neuroprotective effect of Cassia o btusifolial extract in rats following TBI. | |
| CN108272917A (en) | A kind of Uygur medicine composition and preparation method thereof for treating failure of memory | |
| CN103520362B (en) | Heart and brain capsule improves application in medicine preparing learning memory disorder | |
| KR102226052B1 (en) | A anti-stress, anxiolytic and anti-depressant formula comprising L-theanine and bee pollen | |
| Zhang et al. | The antinociceptive effect and mechanism of action of SY0916 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |