CN104825499B

CN104825499B - Application of maitake mushroom extract in preparation of anti-depression drug

Info

Publication number: CN104825499B
Application number: CN201410588545.9A
Authority: CN
Inventors: 杜静; 肖春杰; 保红坤; 朱明�
Original assignee: Yunnan University YNU
Current assignee: Yunnan University YNU
Priority date: 2014-10-28
Filing date: 2014-10-28
Publication date: 2020-04-03
Anticipated expiration: 2034-10-28
Also published as: CN104825499A

Abstract

The invention relates to application of a maitake extract in preparing an anti-depression medicament, which belongs to the field of pharmacy and is characterized in that bioactive components of the maitake extract are used for preparing the anti-depression medicament, and the medicament can be used for treating or preventing depression, has obvious anti-depression effect, strong effect and no toxic or side effect of conventional anti-depression medicaments, such as epilepsy induction, ataxia and the like, and can be used as an excellent anti-depression candidate medicament.

Description

Application of maitake mushroom extract in preparation of anti-depression drug

Technical Field

The invention relates to the field of pharmacy, in particular to application of a maitake mushroom extract in resisting depression.

Background

Depression has become a common and frequently encountered disease in modern society, and the incidence rate is increasing. The symptoms are characterized by depressed mood, decreased interest, retarded thinking, and decreased speech and movement, and severe depression has a thought of boredom or suicide. The pain of the patients and their families and the loss of the society caused by the diseases are incomparable with those caused by other diseases. According to the report published by the World Health Organization (WHO), affective disorders have now become the fourth disease in the world, and the number of patients with global depression has reached 3.4 million. The current incidence of depression in china is approximately 4%. At least 2600 million people in China suffer from depression, and the total economic burden of depression in China reaches 622 billion yuan. An estimated 1700 million people in the united states suffer from depression, 300 million people suffer from bipolar depression, and the cost of treating affective disorders is up to $ 440 million per year (us $ 430 million coronary heart disease). Of particular interest during the past 40 years of affective disorder research has been the high incidence and mortality rates reported to be above 10% with 25 million suicide in china annually.

At present, the main used medicines are serotonin reuptake inhibitors and the like, and the medicines have slow effect, narrow action spectrum and large side effect and are easy to relapse after stopping taking the medicines. At present, a more effective therapeutic drug with quick response, small side effect and high efficiency is urgently needed in the field of antidepressant therapy.

Current antidepressants and their weaknesses: current antidepressants can be broadly divided into three categories: namely monoamine oxidase inhibitors, tricyclic antidepressants and heterocyclic antidepressants. The existing antidepressant drugs can not meet the requirements of patients, and the defects are mainly focused on slow effect taking, narrow antidepressant spectrum, large side effect, easy relapse and the like. The development of new drugs with quick response, wide antidepressant spectrum and small toxic and side effects is a very urgent need in the field and brings huge economic return.

The preparation of the antidepressant drug relates to a maitake extract, which is prepared from a fungus maitake (maitake) which is also called grifola frondosa: also called as Bayesian fungus, cloud mushroom, Qianfo fungus, chestnut mushroom and lotus mushroom. Latin is known as gridlola frontosa (dick.fr.) s.f.gray). Grifola frondosa belongs to the kingdom fungi, Basidiomycotina (Basidiomycotina), Hymenomycetes (Hgmenomycetes), Basidiomycotina (Holobasidiomyceeidae), Aphyllophorales (Aphyllophrales), Polyporaceae (Polyporaceae), and Grifola (Grigola), is a large-scale fungus for both food and medicine, is originally produced in North America, and is also found in northeast of Japan. Grifola frondosa (Maitake) was first discovered by Italian as a fungal species, and thus, Maitake is named by Italian.

At present, the extract of the maitake mushroom is prepared into a medicament, which comprises the maitake D-fraction (or maitake mushroom D-fraction) which is a protein polysaccharide extracted from the maitake mushroom, and the extract can effectively improve the immunity of human bodies, effectively control the growth of tumor cells, prevent the metastasis and the relapse of tumors and relieve the side effect of chemotherapy. Clinical trials have been passed in various countries for the treatment of cancer.

The Grifola frondosa extract comprises Grifola frondosa polysaccharide and active glucan, wherein the Grifola frondosa extract comprises glucan which is combined with β - (1-6) into a main chain β - (1-3) and is combined with a side chain, and the active glucan which is combined with β - (1-3) into a main chain β - (1-6) and is combined with a side chain is proved by experiments to be capable of remarkably inhibiting the growth of tumors by activating immune functions.

The japanese scholars have first conducted studies on extracts of maitake mushroom. Grifolan (GRN) which is a polysaccharide having antitumor activity and extracted from fruiting bodies of Maitake Mushroom by Ohno et al was confirmed to have a structure of C with every 3 sugar groups₆β -1, 3-glucan having one chain thereon, having a molecular weight of about 500000, as shown in FIG. 1, then Ohno investigated the conformations of this polysaccharide and found that it exhibited two conformations in the solid state, i.e., native and helicalThe polysaccharide is in a spiral type under severe conditions, and the polysaccharides in two conformations have obvious antitumor activity.

The research on the Grifola frondosa extract is also carried out in China, and fruiting body polysaccharide F-D and mycelium polysaccharide M-D are respectively extracted from Grifola frondosa fruiting bodies and mycelium; F-D and M-D are protein-containing proteoglycans, both have Ri-1, 3 and p-1,6 glycosyl bonds, F-D is composed of fucose, arabinose, xylose, mannose, galactose and glucose, and M-D is composed of rhamnose, fucose, arabinose, xylose, mannose, galactose and glucose.

China is the country which uses fungi for treating diseases at first, the fungi have high medicinal value, wild Maitake mushroom (Grifola frondosa) is light gray and grows around the roots of persimmon trees, chestnut trees and elms in the north of China, so the wild Maitake mushroom (Grifola frondosa) is also called chestnut mushroom in the north of China, scientists in China also discover a substance Maitake extract which can effectively resist cancers from the Maitake mushroom, and researches show that the anticancer activity of the extract is 35 percent higher than that of chemotherapeutic drug mitomycin and is 16.5 times of that of lucid ganoderma!

The American national cancer institute, as early as 1992, demonstrated that extracts of Maitake Mushroom have efficacy against AIDS virus. Japanese doctor of Duobo Hongzhong finds that Maitake has curative effect on breast cancer, lung cancer and liver cancer in experiments; can also improve various adverse reactions caused by tumor chemotherapy, such as anorexia, emesis, nausea, hair loss, leukopenia, etc.; in addition, the research also proves that the extract of the maitake mushroom, the maitake mushroom and the sanguinea root have the effects of controlling blood sugar, inhibiting fat cell accumulation, reducing blood pressure and enhancing immunity. In 1986, professor shibo hong of university of drugstore of japan published a research report on Maitake extract-D (Maitake-D) in japan journal of pharmacy. The report states that: there are A, B, C, D four kinds of Maitake Mushroom polysaccharide, all of which have anticancer effect, but the D component has the best effect. The tumor inhibition rate of the single application of the maitake mushroom polysaccharide is 86.6 percent (1.0mg/kg body weight), and compared with the drug effect of the international chemotherapy drug mitomycin, the maitake mushroom extract is singly administered, the tumor inhibition rate is 80 percent, the mitomycin is singly administered, the tumor inhibition rate is 45 percent, and the two are administered together, the tumor inhibition rate is 98 percent. This method, which has been the first choice for clinical anticancer in the united states, canada japanese, is called "the fourth cancer treatment".

Through the immune characteristic research of polysaccharide in America and Japan, including a plurality of clinical experimental researches, the Grifola frondosa extract can effectively activate the human immune system, activate immune cells, such as NK cells, antitoxic T cells, phagocytes and the like, activate immune cells, such as phagocytes, natural killer cells and the like, induce the secretion of cytokines, such as interleukin, interferon-gamma, tumor necrosis factor- α and the like, and an immunotherapy medicament (interference with the interferon-gamma, the tumor necrosis factor- α and the like)

2) Has synergistic effect, and can inhibit tumor cell growth and induce cancer cell apoptosis.

Today, over 3000 oncologists in more than twenty countries, such as the united states, japan, canada, and china, have been applied and validated for clinical efficacy against grifola frondosa, which is also used as the first line clinical medicine for tumor treatment in western countries, such as europe and america. However, through extensive literature inquiry, no literature report is found on the application of the maitake mushroom extract to treat the depression.

Disclosure of Invention

The invention provides a maitake extract as an anti-depression medicament and an anti-depression medicament prepared by the maitake extract. The medicine has the advantages of remarkable antidepressant effect, small side effect and the like, and the technical scheme is as follows:

the application of the maitake mushroom extract in preparing the anti-depression drug is characterized in that the pharmacodynamic active ingredient of the anti-depression drug is the maitake mushroom extract.

The application of the maitake extract in preparing the anti-depression drug is characterized in that the pharmacodynamic active ingredient of the anti-depression drug comprises the maitake extract.

The anti-depression drug is a drug for preventing or treating depression.

The dosage form of the anti-depression drug is tablets, capsules, solution, suspension, injection or drip fluid.

An anti-depression medicament characterized by: the active ingredients include Maitake Mushroom extract.

The anti-depression refers to the prevention or treatment of depression.

The dosage form is tablet, capsule, solution, suspension, injection or infusion solution.

The medicine also comprises pharmaceutically acceptable auxiliary components.

The medicine also comprises a medicinal component which has positive effect on treating depression when being matched with the maitake mushroom extract or the derivative thereof, or a component for improving the stability of the maitake mushroom extract.

An anti-depression method characterized by: providing a therapeutically effective amount of a medicament comprising Maitake Mushroom extract to a subject on schedule.

In the method, the medicament for providing the treatment effective dose on time is 0.5-1000 mg of maitake mushroom extract/kg of body weight per day, and the administration mode is oral administration, instillation or injection; the subject to be administered is a mammal, including a human.

The administration dosage is low dosage (5mg/kg), medium dosage (8mg/kg) and high dosage (12.5mg/kg) of the Grifola frondosa extract injected every day, and the inventors of the invention find that the Grifola frondosa extract has a remarkable antidepressant effect on mammals. Experimental research shows that in a mammal mouse experiment, the maitake mushroom extract has an obvious and strong anti-depression effect, and the anti-depression effect can be generated continuously. Patients with depression generally complain of inflammatory pain symptoms such as headache, stomach pain, back pain, and the like. The Maitake Mushroom extract has antidepressant effect and also can improve inflammatory symptoms of patients. Many tumor patients are treated by chemotherapy and radiotherapy and develop depression, and the Maitake Mushroom extract has anti-tumor and anti-depression effects. Therefore, the Grifola frondosa extract can comprehensively improve various symptoms of depression patients, including mental depression symptoms, pain, inflammation and the like. Its antidepressant effect is significant, rapid and durable in animal models. The antidepressant drugs currently used are very slow acting, generally requiring several weeks. The development of fast acting antidepressant drugs is urgently needed.

The Maitake extract adopted by the invention is commercially available, comprises Maitake d-fraction (maitake d-fraction), has an average molecular weight of 100 ten thousand, has a structure diagram shown in figure 1, is one of polysaccharide compounds separated from polyporaceae, Grifola and Grifola frondosa, can be taken by human beings for a long time, has no toxic or side effect reported so far, and has no defects of tranquilization, epilepsy induction, ataxia and the like of the conventional antidepressant medicaments in the test process. Has the potential of becoming a quick, high-efficiency and anti-depression new drug without toxic and side effects, and has strong industrial practicability and huge commercial value.

The drug screening test adopted by the invention is as follows: the forced swimming and tail suspension tests of the mouse are two common animal behavior despair depression model tests, and can better ensure the reliability of a screening result.

The forced swimming test of mice has been used for screening tests of many antidepressant drugs. Moreover, most clinically therapeutic antidepressants have been shown to be effective in reducing immobility time in forced swim tests. By immobile, it is meant that "the animal stops struggling in water, or is in a floating state, only exposing nostrils to keep breathing, and only having small limb movements to keep the head floating on the water". Drugs to be screened were given prior to testing. Animals cannot escape from the harsh environment due to downstream swimming in a forced state, resulting in despair behavior of the animals. The model method is simple, convenient and reliable, and is widely used for screening and evaluating the antidepressant.

The tail suspension test of the mouse is that the mouse does not struggle under the tail suspension state and presents a special quiet immobility state, and the antidepressant can obviously shorten the duration time of the immobility state. During testing, the tail of the mouse is fixed and suspended by a clamp. The tail of the mouse is not twisted and folded. And recording the immobility time. The immobility indexes are as follows: "animals are immobile in all limbs except for respiration". The tail suspension test is sensitive to various antidepressants, and avoids the interference of temperature and animal movement dysfunction in the swimming test, so that the results of the forced swimming test can be effectively verified and supplemented when some mice are used for screening the antidepressants.

The application of the Grifola frondosa extract as an anti-depression medicament is not limited to the application of the Grifola frondosa extract with the structural formula shown in figure 1 in the preparation of anti-depression medicaments, the preparation of the Grifola frondosa extract into salts, esters or glycosides of the Grifola frondosa extract is routine experimental skill of a person skilled in the art, and the salt, the ester or the glycosides of the Grifola frondosa extract have similar drug effect which can be reasonably expected by the person skilled in the art, so the invention also requests to protect the application of the salts, the esters or the glycosides of the Grifola frondosa extract in the preparation of anti-depression medicaments.

The application of the Grifola frondosa extract in preparing the anti-depression drug can be used for adding auxiliary components which do not influence the drug effect of the drug, such as a carrier, an excipient and the like, based on the common knowledge of technical personnel in the pharmaceutical field. The medicament can take effect by oral administration, injection, subcutaneous embedding and the like, so the preparation forms can be various.

The anti-depression drug provided by the invention can also be mixed with other drug components which have positive effects on treating depression when being matched with the maitake extract or the derivatives thereof.

Because the stability of the Grifola frondosa extract is not strong, a person skilled in the art can add a stabilizer, and the obtained anti-depression drug is within the protection scope of the invention as long as the exertion of the drug effect of the Grifola frondosa extract is not influenced.

The invention provides an anti-depression drug, which comprises two stages of prevention and treatment.

The invention also claims the application of the Grifola frondosa extract in the anti-depression treatment within the allowable range of patent law, and the dosage range for stably achieving the anti-depression treatment effect in animal model tests is 8mg/kg of the Grifola frondosa extract and 12.5mg/kg of the Grifola frondosa extract which are injected daily.

Because the shortening of the animal immobility time in the classical depression animal model is probably caused by the central excitability of the medicine, in order to identify whether the action of the maitake mushroom extract can increase the animal activity, the invention also carries out a mouse Open field test (Open field test) at the same time to check the autonomous activity of the mouse and avoid the interference of the central excitant. The experimental results show that each dose of the maitake mushroom extract has no obvious influence on the autonomous activity of mice, so that the possibility of false positive results can be eliminated, and the antidepressant effect of the medicine is proved to be reliable.

Drawings

FIG. 1 shows the chemical structure of Maitake Mushroom;

figure 2. results 60 min after three days of treatment in the mouse tail suspension experiment:

vertical coordinates are: tail suspension experiment mice immobility time (% control),

the abscissa: from left to right are: maitake Mushroom extract control (0.9% physiological saline), Maitake Mushroom extract low (5mg/kg), Maitake Mushroom extract medium (8mg/kg), Maitake Mushroom extract high (12.5mg/kg), imipramine control group (15 mg/kg);

FIG. 3 shows the results of the forced swimming test of mice 60 minutes after three days,

vertical coordinates are: forced swimming test mouse immobility time (% control);

FIG. 4. results of total distance from open field experiments-four days after 1 hour of treatment,

vertical coordinates are: total distance (meters);

FIG. 5. results of intermediate distances in open field experiments-after 1 hour of treatment four days,

vertical coordinates are: intermediate distance (meters);

the abscissa: from left to right are: maitake Mushroom extract control (0.9% physiological saline), Maitake Mushroom extract low (5mg/kg), Maitake Mushroom extract medium (8mg/kg), Maitake Mushroom extract high (12.5mg/kg), and imipramine control group (15 mg/kg).

Detailed description of the preferred embodiments

The following embodiments are only intended to illustrate and demonstrate the novel use of the grifola frondosa extract in anti-depression found in the present invention, but not to limit the present invention.

Examples

Test materials and methods

Detailed information of experimental animals

1. Animal breed strains: mouse, CD-1(ICR)

2. Grade: SPF stage

3. Animal specification: purchase initial week old and body weight (5 week old: 20-22g)

Formal experiment week old and body weight (7 weeks old: 30-39g)

4. Sex: male sex

5. The unit of mass detection: beijing Wittiulihua laboratory animal technology Co Ltd

6. The application is as follows: scientific research

7. Selling units: beijing Wittiulihua laboratory animal technology Co Ltd

8. License number: SCXK (Jing) 2012-0001

Second, experimental animal feeding conditions

1. Experimental animals took an airline early flight (8: 10 takeoff) from the beijing capital airport on 7 months and 15 days in 2014, 13 pm: 30 to Kunming long water plant cargo flow center. The chartered plane connects experimental animals from Yunnan university to Kunming long water plant goods flow center to Toho 301 animal feeding room of Yunnan university biological center, and allows mice to be fed in cages after resting for 2 hours in original boxes.

2. 4 mice were housed per cage, with free access to water and food.

3. The mice were fed with distilled water (self-made by laboratory equipment) and the feed for mice was obtained from the department of animal experiments at Kunming medical university.

4. Light/dark cycle 12 hours per day, morning 9: 00 light on, 21 night: 00 turning off the lamp.

5. Feeding at room temperature of 23 deg.C.

6. The padding is replaced for the mouse every two days, so that the mouse has a comfortable living environment.

7. The mice began the official experiment after one week of acclimation in the new feeding environment.

Detailed information of Maitake Mushroom extract drop

Maitake essence drops: purchased from Hangzhou Zhengshu health food Co Ltd, general agency of China, and having the following specific parameters

Preparing materials: vegetable glycerin, water, Maitake Mushroom extract (30% Maitake Mushroom D-fraction);

the production date is as follows: 31/5/2013;

shelf life: three years;

plant address: new jersey, usa;

production enterprises: health food company, mike usa.

Fourthly, precipitating the maitake mushroom extract by an alcohol method:

1. sequentially marking 10 centrifugal tubes with 1.5 ml by Arabic numerals, and then weighing and recording the centrifugal tubes in an empty tube;

2. 200ul of Maitake mushroom essence drops are added into 600ul of 95% ethanol in each 1.5 ml centrifuge tube, and then the mixture is placed at room temperature for 2 hours, so that the sediment at the bottom of the 1.5 ml centrifuge tube can be clearly observed.

3. The precipitate at the bottom of the centrifuge tube was clearly observed after centrifugation at 12000 rpm for 1 hour at 4 ℃, and the supernatant was transferred to another tube after 1.5 ml of the centrifuge tube was removed from the centrifuge.

4. The 1.5 ml centrifuge tube and the remaining sediment at the bottom were placed in a 37 ℃ incubator for one hour.

5. The 1.5 ml centrifuge tube was air dried at room temperature and weighed. And obtaining the content of the Grifola frondosa extract by a weight reduction method.

6. About 10mg of Grifola frondosa extract was added to each 1.5 ml centrifuge tube.

The method comprises the following steps: precipitating with 95% ethanol 3 times the volume of the extract, washing with acetone and diethyl ether, and lyophilizing with vacuum freeze dryer to obtain Maitake Mushroom extract sample.

Fifthly, a preparation method of the concentration required by the Grifola frondosa extracts with different concentrations for mouse injection comprises the following steps:

1. the weight reduction method was carried out to obtain 108.4mg of Grifola frondosa extract in 10 1.5 ml centrifuge tubes, and 200. mu.l of 0.9% physiological saline (0.9% physiological saline purchased from hospitals for injection) was added to each 1.5 ml centrifuge tube to dissolve the precipitate air-dried at the bottom of the centrifuge tube, and then the completely dissolved solution was transferred from 10 1.5 ml centrifuge tubes to a sterile 7ml centrifuge tube using 200. mu.l pipette gun, and 2ml of 0.9% physiological saline was added to dilute the solution (4 ml of 0.9% physiological saline was added in total). The concentration of the final Maitake Mushroom extract solution is 108.4mg/4 ml-27.1 mg/ml.

2. The different dosage dilution times of the Grifola frondosa extract are as follows:

the maitake extract is respectively filled in a centrifugal tube of 1.5 ml according to the dilution times, the whole centrifugal tube of 1.5 ml is wrapped by tin foil paper, a tube opening is sealed by a sealing film and then the centrifugal tube is placed in a refrigerator of minus 80 ℃ for freezing storage, the maitake extract is taken out and unfrozen according to the requirement before injection every day, then 0.9 percent of normal saline is added according to the calculated dilution ratio to dilute the maitake extract into the required injection dosage, and the maitake extract can be injected for use after shaking and mixing the maitake extract uniformly.

4. The required dose dilution of imipramine is as follows:

weighing 30mg of powdered imipramine, placing the powdered imipramine into a sterile 7ml centrifuge tube, adding 2ml of 0.9% physiological saline to dissolve the imipramine (the concentration of the final imipramine solution is 30mg/2ml ═ 15mg/ml), shaking and uniformly mixing, then subpackaging the mixture into 1.5 ml centrifuge tubes according to the dilution times, wrapping the whole 1.5 ml centrifuge tube with tinfoil paper, sealing the tube opening with a sealing film, placing the tube opening in a refrigerator at minus 80 ℃ for freezing storage, taking out the solution for thawing as required before injection every day, then adding 0.9% physiological saline according to the calculated dilution ratio to dilute the solution into the required injection dosage, shaking and uniformly mixing, and then injecting for use.

Fifthly, behavioristic experiment operation:

1. mice were allowed to acclimate to our new breeding environment for one week before starting the experiment (i purchased this batch of mice that were 5 weeks old at the time, so the official experiment was started 2 weeks after breeding in our new breeding environment);

2. the experiment was started from 30 days 7 months 2014, and the drugs were prepared and the equipment needed for the experiment was prepared before 10 am, each day at 10 am: mice weighing and injection started at 00 hours;

3. experimental arrangements

4. Forced swimming conditions: room temperature: 23 ℃ and water temperature: 24 ℃ and humidity: 62-67%, and changing water once every two groups.

5. The experimental results are as follows:

results of behavioral experiments on CD-1 mice treated with various doses of Grifola frondosa extract:

1) the results of the tail overhang experiment after 60 minutes after three days of treatment with Maitake Mushroom extract (8 replicates) are shown in FIG. 2.

2) The results of forced swimming test 60 minutes after three days of treatment with Maitake Mushroom extract (8 replicates) are shown in FIG. 3.

And (3) analyzing an experimental result:

from the bar graph (fig. 2) of the results of the tail suspension experiment after 60 minutes after three days of treatment with the grifola frondosa extract (8 replicates), it can be seen that the low dose (5mg/kg) of the grifola frondosa extract showed significant antidepressant-like effects compared to 0.9% saline (P ═ 0.0267, P <0.05), the dose (8mg/kg) of the grifola frondosa extract showed significant antidepressant-like effects compared to 0.9% saline (P ═ 0.0355, P <0.05), and the high dose (12.5mg/kg) of the grifola frondosa extract showed significant antidepressant-like effects compared to 0.9% saline (P ═ 0.0246, P < 0.05). (as shown in FIG. 2)

From the bar graph of the results of the forced swimming test 60 minutes after the treatment of the grifola frondosa extract (8 replicates) for three days (fig. 3), it can be seen that the dose (8mg/kg) in the grifola frondosa extract shows a very significant antidepressant-like effect compared to 0.9% physiological saline (P ═ 0.0065, P < 0.01); high doses of maitake extract (12.5mg/kg) also showed significant antidepressant-like effects compared to 0.9% saline (P ═ 0.0115, P < 0.05). (as shown in FIG. 3 above)

3) The total box distance results of the field experiment after 60 minutes after four days of treatment with Maitake Mushroom extract (8 replicates) are shown in FIG. 4.

4) The results of the distance between the middle boxes in the field experiment after 60 minutes after four days of treatment with Maitake Mushroom extract (8 replicates) are shown in FIG. 5.

And (3) analyzing an experimental result:

from the histogram of the results of the total distance between the open field experiments after 60 minutes after four days of treatment with the Maitake Mushroom extract (8 replicates) (FIG. 4), it can be seen that the low dose (5mg/kg) of the Maitake Mushroom extract, the medium dose (8mg/kg) of the Maitake Mushroom extract, and the high dose (12.5mg/kg) of the Maitake Mushroom extract were not significantly poor (P >0.05) compared to 0.9% physiological saline, and the results indicate that the immobility time of the mice was not shortened due to the central excitatory action of the drug (Maitake Mushroom extract). (as shown in FIG. 4 above)

From the bar graph (fig. 5) of the results of the intermediate distance between the field experiments after 60 minutes after four days of treatment with the grifola frondosa extract (8 replicates), it can be seen that the low dose (5mg/kg) of the grifola frondosa extract, the medium dose (8mg/kg) of the grifola frondosa extract, and the high dose (12.5mg/kg) of the grifola frondosa extract are not significantly inferior (P >0.05) compared to 0.9% physiological saline, and the results further indicate that the immobility time of the mice is not shortened due to the central excitability of the drug (grifola frondosa extract). (as shown in FIG. 5 above)

In other embodiments of the invention, a directly extracted maitake extract is used: the fine powder of Maitake Mushroom fruiting body is extracted with purified hot water at a ratio of 1: 30. The optimal process conditions are as follows: the pH value is 6.5-7.0, and the extract is obtained by leaching for 3 hours at the temperature of 98 ℃ and then concentrating. In the mouse experiment, almost identical results were obtained as shown in FIGS. 2-4.

Claims

1. The application of the maitake mushroom extract in preparing the anti-depression drug is characterized in that: the extract of the maitake mushroom is a product obtained by adding 3 times volume of 95% ethanol into a maitake mushroom essence drop for alcohol precipitation, then washing with acetone and diethyl ether respectively, and freeze-drying with a vacuum freeze dryer.

2. The use according to claim 1, wherein the medicament is in the form of a tablet, capsule, solution, suspension, injection or infusion solution.

3. The use according to claim 1 or 2, the medicament further comprising pharmaceutically acceptable auxiliary ingredients.

4. The use according to claim 1 or 2, the medicament further comprising a pharmaceutical ingredient having a positive effect on the treatment of depression after simultaneous administration with the Maitake Mushroom extract, or comprising an ingredient that increases the stability of the Maitake Mushroom extract.