Use of aloe pulp powder or active ingredients thereof in the preparation of a drug for treating depression

Abstract

The application belongs to the field of traditional Chinese medicines, and discloses application of aloe pulp powder in preparation of a medicine for treating depression, wherein the aloe pulp powder is a dehydrated solid powder obtained by peeling off the whole leaves of aloe. The inventors construct a mouse depression model by using CUMS, and show that the aloe pulp powder can significantly improve the moving distance of the model mice in an open field experiment and the immobile time of the model mice in a tail suspension test and a forced swimming test, and exhibits significant antidepressant activity. The application also discloses application of at least one of aloe polysaccharide, aloe flavone or aloe polyphenol in preparation of a medicine for treating depression. The aloe polysaccharide, the aloe flavone and the aloe polyphenol all have the efficacy of treating depression, and the efficacy of polysaccharide > the efficacy of flavone > the efficacy of polyphenol. The application further discloses a composition for treating depression, which is a composition of aloe polysaccharide, aloe flavone and aloe polyphenol in a mass ratio of 6.945-31.432:1.185-32.146:0.251-14.323.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of traditional Chinese medicine, and relates to application of aloe pulp powder or at least one of active ingredients polysaccharide, flavone and polyphenol derived from aloe pulp powder in preparation of a medicine for treating depression. TECHNICAL BACKGROUND

[0002] Depression is one of mental diseases and has an important influence on human health. About 300 million people in the world are troubled by the disease. As of now, drug treatment is still the mainstream method for treating depression. However, even after sufficient drug treatment, about 1 / 3 of patients cannot achieve clinical recovery, and these drugs often have the disadvantages of slow effect, many adverse reactions, easy recurrence after drug withdrawal and the like. Although drugs such as ketamine for rapid treatment of depression have been confirmed to have fast effect and clear effect in clinical treatment of depression, the problem of addiction cannot be ignored, and new drugs are needed for treatment of depression.

[0003] Aloe is a perennial succulent herb of Aloe Linn of Liliaceae, and is a medicinal plant integrating food, medicine, beauty and health care. Among them, aloe vera is the most widely used aloe variety, about 98.5% to 99.5% of which is water, and the remaining components are very complex, about 200 chemical components, mainly including carbohydrates, amino acids, vitamins, minerals, organic acids, lignin, phenolic compounds, anthraquinones and phytosterols. The rich natural active ingredients have many effects such as improving intestinal absorption, promoting wound healing, regulating body immunity, anticancer, antiviral, antibacterial, anti-inflammatory, antioxidant, whitening and moisturizing.

[0004] At present, there is no report showing that aloe has the effect of treating depression, and there is no related report on the active substance group of aloe for treating depression. SUMMARY

[0005] The inventors constructed a mouse depression model by using CUMS, and judged the influence of the drug on depression of the mouse by comparing the changes of various behavior indexes in the open field test, tail suspension test and forced swimming test before and after administration.

[0006] The model was used to screen the activity of aloe pulp powder in treating depression, and the results showed that the aloe pulp powder can significantly improve the moving distance of the model mouse in the open field test and the immobility time of the model mouse in the tail suspension test and forced swimming test, and shows significant antidepressant activity.

[0007] In order to further clarify the active ingredients of aloe pulp powder in treating depression, high-purity polysaccharides, flavones and polyphenols derived from aloe pulp powder are obtained, and the activity of these components is detected by using a CUMS-induced mouse depression model, and the results show that the polysaccharides, flavones and polyphenols in the aloe pulp powder all have the effect of treating depression, and the effect of treating depression is polysaccharides > flavones > polyphenols.

[0008] The traditional Chinese medicine compatibility theory believes that different medicinal materials can fully play a synergistic effect and improve the efficacy according to the'monarch, minister, assistant and guide' ratio, and the component traditional Chinese medicine theory believes that the components in traditional Chinese medicinal materials can be classified according to the'monarch, minister, assistant and guide' theory to synergistically improve the efficacy. Therefore, the inventors combine the above components, and screen out an active composition with a significant effect of improving depression, and the activity is significantly higher than that of a single component, and has a synergistic effect.

[0009] The purpose of the present application is to provide the application of aloe pulp powder in preparing a medicine for treating depression, wherein the aloe pulp powder is a dehydrated solid powder obtained by peeling the whole aloe leaf.

[0010] The aloe whole leaf powder contains polysaccharides, flavones and polyphenols.

[0011] Another purpose of the present application is to provide the application of at least one of aloe polysaccharides, aloe flavones or aloe polyphenols in preparing a medicine for treating depression.

[0012] The aloe polysaccharides are prepared by the following method: according to the mass-volume ratio of 1:8 kg / L of aloe pulp powder and 80% ethanol, the aloe pulp powder is added into 80% ethanol, and then the mixture is placed at 4 DEG C overnight, centrifuged, and the supernatant is discarded, and the precipitate is vacuum dried to obtain crude polysaccharides I; the crude polysaccharides I are dissolved in distilled water, and 0.1-0.2% of papain is added, and then the mixture is heated to 60 DEG C and stirred for 6 hours, centrifuged, and the supernatant is obtained, which is the crude polysaccharides II after deproteinization; the D101 macroporous adsorption resin is wet-packed, and the crude polysaccharides II are prepared into a sample solution with a mass fraction of 20% by using distilled water, and then the sample solution is added to the D101 macroporous adsorption resin column, and then 50% ethanol with the same volume as the sample solution is used for elution, and then the eluate is recovered to be alcohol-free, and then concentrated in a water bath and vacuum dried to obtain aloe polysaccharides.

[0013] The aloe flavones are prepared by the following method: according to the mass-volume ratio of 1:8 kg / L of aloe pulp powder and 80% ethanol, the aloe pulp powder is added into 80% ethanol, and then the mixture is centrifuged, and the supernatant is obtained, and then the supernatant is added to the D101 macroporous adsorption resin column, and then the sample solution is eluted with 2 times the volume of distilled water to remove impurities, and then 80% ethanol is used for elution until there is no flavone reaction, and then the 80% ethanol eluate is collected, and then the 80% ethanol eluate is recovered to be alcohol-free, and then concentrated in a water bath and vacuum dried to obtain total flavones.

[0014] The aloe polyphenol is prepared by the following method: according to the mass-volume ratio of aloe pulp powder and 80% ethanol 1:20 kg / L, the aloe pulp powder is dissolved in 60% ethanol, ultrasonic treatment for 45 min at 60 DEG C, filtration, to obtain an extract, and the extract is concentrated into a solid powder; according to the mass-volume ratio of the solid powder and 60% ethanol 1:2 kg / L, the solid powder is dissolved in 60% ethanol, and an appropriate amount of CaCl2 solution is added until no precipitate is generated, the precipitate is collected, hydrochloric acid is added until the precipitate is completely dissolved, ethyl acetate is extracted, the organic phase is collected, and concentrated to obtain the aloe polyphenol.

[0015] Another object of the present application is to provide a composition for treating depression, wherein the mass ratio of aloe polysaccharide, aloe flavone and aloe polyphenol is (6.945-31.432):(1.185-32.146):(0.251-14.323).

[0016] Preferably, the mass ratio of aloe polysaccharide, aloe flavone and aloe polyphenol is 6.945:1.185:0.251, 31.432:32.146:14.323.

[0017] Another object of the present application is to provide the use of the composition in the preparation of a medicament for treating depression.

[0018] Another object of the present application is to provide a medicament for treating depression, wherein the medicament comprises the composition as the main active ingredient and a pharmaceutically acceptable carrier.

[0019] The dosage form is tablet or capsule. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 Fig. 1 is the improvement result of aloe pulp powder on the depression-like behavior index of CUMS-induced mice; wherein, Figure 1 A, Figure 1 B is the total moving distance and moving speed of mice in the open field experiment, Figure 1 C, Figure 1 D is the immobility time of mice in the tail suspension test and forced swimming test; #### P<0.0001, compared with the control group; **p<0.01, ***p<0.001, ****p<0.0001, compared with the Model group.

[0021] Figure 2 Fig. 2 is the improvement result of polysaccharide, polyphenol and flavone from aloe pulp powder on the depression-like behavior index of CUMS-induced mice; wherein, Figure 2 A, Figure 2 B is the total moving distance and moving speed of mice in the open field experiment, Figure 2C、 Figure 2 D are the immobile time of mice in tail suspension test, forced swimming immobility test, respectively; #### P<0.0001, compared with the control group; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001, compared with the Model group.

[0022] Figure 3 The left graph is the contour plot of the mathematical model, and the right graph is the 3D response surface of the mathematical model.

[0023] Figure 4 The results of the combination of polysaccharides, polyphenols and flavonoids from aloe pulp powder in improving the depressive-like behavior of CUMS-induced mice are shown; wherein, Figure 4 A、 Figure 4 B are the total distance moved and the moving speed of mice in the open field test, respectively, Figure 4 C、 Figure 4 D are the immobile time of mice in tail suspension test, forced swimming immobility test, respectively; #### P<0.0001, compared with the control group; **p<0.01, ***p<0.001, ****p<0.0001, compared with the Model group. Specific embodiments

[0024] To further illustrate the technical solutions of the present application, a series of examples are listed below. These examples are illustrative and should not be construed as limiting the present application.

[0025] The aloe pulp powder used in the examples is aloe vera gel freeze-dried powder (Hainan Zhongchen Biological Engineering Co., Ltd.), which is a solid powder after dehydration of the whole leaf of aloe vera.

[0026] Example 1

[0027] Aloe pulp powder was administered intragastrically to CUMS-induced depressive mouse models, and the changes in the movement distance, movement speed in the open field test (OFT), and the immobile time in the tail suspension test (TST) and forced swimming test (FST) of the model mice were observed to determine whether the aloe pulp powder had therapeutic activity for depression.

[0028] Experimental design:

[0029] The test animals were subjected to 12 h light-dark cycle (light on at 6:00, light off at 18:00), reared at a temperature of (25±2) °C, humidity of 50%±20%, and water and bedding were regularly changed every 2 d, free to eat and drink water, 5 per cage. After 5 d of adaptive feeding, the mice were divided into a blank control group (10) and a model group (30), and the mice in the model group were subjected to chronic unpredictable stress for 4 weeks according to Table 1 and Table 2, and received one or two kinds of stimulation every day, and the modeling method was not repeated within 3 days.

[0030] Table 1. Chronic unpredictable stress modeling methods

[0031] Stimulus name Modality Inclined cage Inclined cages at 45 degrees for 24 h Wet bedding Bedding in cages wetted with water for 24 h Horizontal shaking Horizontal shaking of cages for 5 min Food deprivation Animals deprived of food for 24 h Water deprivation Animals deprived of water for 24 h Restraint Animals placed in plastic bottles for 2-6 h of restricted activity Cold water swim Animals placed in cold water (4°) for 5-10 min of swimming Tail pinch Mice tails pinched with a clamp for 5 min

[0032] Table 2. Modeling schedule

[0033] After the modeling was completed, the mice in the model group were randomly divided into 3 groups, i.e., a model group (Model, 10), a positive drug group (Flu, 10, fluoxetine 20 mg / kg), and an aloe pulp powder group (10, 20 mg / kg). The positive drug group and the aloe pulp powder group were administered with normal saline solution or dispersion at 10 mL / kg by gavage, and the blank control group and the model group were replaced with an equal amount of normal saline, once a day, for 14 consecutive days. Changes in the moving distance, moving speed of the model mice in the open field test, and the immobile time in the tail suspension test and forced swimming test were observed, and the statistical method of One-Way ANOVA was used to determine whether the aloe pulp powder had the efficacy of treating depression.

[0034] Experimental results:

[0035] In the open field test (OFT), the total distance and moving speed reflect the autonomous activity state of the mice. As shown in Figure 1 A and Figure 1 B, compared with the blank control group of mice, the total moving distance and moving speed of the model group of mice were significantly reduced, indicating that the modeling was successful; compared with the model group of mice, the total moving distance and moving speed of the aloe pulp powder group of mice and the positive drug group of mice were significantly increased, indicating that the aloe pulp powder was effective.

[0036] In the tail suspension test (TST) and forced swimming immobility (FST) test, the immobile time of the mice reflects the depression state. As shown in Figure 1 C and Figure 1 D, compared with the blank control group of mice, the resting time of the model group of mice was significantly increased, indicating that the modeling was successful; compared with the model group of mice, the immobile time of the aloe pulp powder group of mice and the positive drug group of mice was significantly reduced, indicating that the drug was effective, and the effect of the aloe pulp powder was comparable to that of fluoxetine.

[0037] In summary, aloe pulp powder significantly improved the CUMS-induced depressive-like behavior in mice.

[0038] Example 2

[0039] High-purity polysaccharides, flavonoids and polyphenols were extracted from aloe pulp powder. Polysaccharides, flavonoids and polyphenols were applied to CUMS-induced depression mouse models, respectively. The changes in movement distance and speed in the open field test, as well as the immobility time in the tail suspension test and forced swimming test were observed to determine whether polysaccharides, flavonoids and polyphenols in aloe pulp powder have the efficacy of treating depression.

[0040] Preparation of aloe polysaccharide:

[0041] According to the mass-volume ratio of aloe pulp powder and 80% ethanol of 1:8 kg / L, aloe pulp powder was added to 80% ethanol, and the mixture was placed at 4°C overnight. The mixture was centrifuged at 1350 r / min for 10 min, and the supernatant was discarded. The precipitate was vacuum dried to obtain crude polysaccharide I. Crude polysaccharide I was completely dissolved in distilled water, and 0.1% papain was added. The mixture was heated to 60°C and stirred for 6 h. After centrifugation, the supernatant was collected, which was the crude polysaccharide after deproteinization, denoted as crude polysaccharide II. D101 macroporous adsorption resin was wet-packed. Crude polysaccharide II was weighed and dissolved in distilled water to prepare a sample solution with a mass fraction of 20%. The sample solution was added to the D101 macroporous adsorption resin column, and the same volume of 50% ethanol as the sample solution was used for elution. The flow rate was 1 / 2 of the sample solution volume per hour. The eluate was recovered to remove ethanol, and then concentrated in a water bath and vacuum dried to obtain aloe polysaccharide.

[0042] Determination of the content of aloe polysaccharide:

[0043] Accurately weigh 50 mg of glucose (105°C oven dried to constant weight) and place it in a 500 mL volumetric flask. Prepare glucose standard solutions with concentrations of 0.02, 0.04, 0.06, 0.08, and 0.1 mg / mL using distilled water. Take 1 mL of distilled water and 1 mL of each of the different concentrations of glucose standard solution, add 1 mL of 5% phenol solution to each, and then quickly add 5 mL of concentrated sulfuric acid. Let it stand for 10 min, shake well, and then place it at 30°C for 30 min. Measure the OD value at 490 nm. Prepare a standard curve with glucose content as the abscissa and OD value as the ordinate.

[0044] Take aloe polysaccharide and prepare a sample solution with a concentration of 0.1 mg / mL using distilled water. Take 1.0 mL of the sample solution and follow the above procedure to measure the OD 490 nm. Then, substitute the value into the standard curve to calculate the total sugar content of the sample. The content of aloe polysaccharide is measured to be 90.3%.

[0045] Preparation of aloe flavone: according to the mass-volume ratio of aloe pulp powder and 80% ethanol 1:8 kg / L, the aloe pulp powder was added to 80% ethanol, centrifuged at 1350 r / min for 10 min, the supernatant was taken, and the sample was added to the D101 macroporous adsorption resin column, and the sample solution (i.e. the supernatant) was eluted with 2 times the volume of distilled water to remove impurities, and then eluted with 80% ethanol until no flavonoids were reacted. The 80% ethanol eluate was collected, the 80% ethanol eluate was recovered to remove the alcohol taste, concentrated in a water bath, and vacuum dried to obtain total flavones.

[0046] Determination of the content of aloe flavone:

[0047] Precisely take 1.0 g of total flavones (oven dried at 120°C to constant weight), and add methanol to prepare a 1 g / mL test sample stock solution.

[0048] Preparation of color reagent: precisely take 1.34 g of AlCl3, and add methanol to make up to 100 mL to prepare a 0.1 mol / L AlCl3 solution. Precisely take 2.72 g of CH3COONa·3H2O, and dissolve in 100 mL of double distilled water to prepare a 0.2 mol / L sodium acetate solution. Precisely take 1.15 mL of glacial acetic acid, and dilute with double distilled water to 100 mL to prepare a 0.2 mol / L acetic acid solution.

[0049] Precisely take 1 mL of the test sample stock solution, and place it in a 10 mL volumetric flask. Add 2 mL of 0.1 mol / L AlCl3 solution, and make up with methanol. Color fully for 20 min, and record the absorbance value at 270 nm. Prepare a standard solution using rutin as the standard material (standard solution: 0.025 g of rutin dissolved in methanol and made up to 50 mL). Take different amounts of the standard solution, and determine the absorbance value through the optimized experimental procedure. Use the least squares method to perform linear fitting to obtain the relationship between the rutin concentration C and the absorbance value A. The absorbance value shows a good linear relationship in the range of 0.1-0.7 A. The aloe flavone content is measured to be 89.6%.

[0050] Extraction of aloe polyphenols:

[0051] According to the mass-volume ratio of aloe pulp powder and 80% ethanol 1:20 kg / L, the aloe pulp powder was dissolved in 60% ethanol, ultrasonicated at 60°C for 45 min, filtered, and concentrated into a solid powder. According to the mass-volume ratio of the solid powder and 60% ethanol 1:2 kg / L, the solid powder was dissolved in 60% ethanol, and an appropriate amount of CaCl2 solution was added until no precipitate was precipitated. The precipitate was collected, and 1M hydrochloric acid was slowly added until the precipitate was completely dissolved. Ethyl acetate was added for extraction, the organic phase was collected, and concentrated to obtain aloe polyphenols.

[0052] Determination of aloe polyphenol content:

[0053] Accurately weigh 5.00 mg of gallic acid standard, place it in a 50 mL volumetric flask, and dilute to the mark with 60% ethanol, shake well, and obtain a gallic acid standard solution with a concentration of 0.1 mg / mL. Accurately transfer 0 mL, 0.1 mL, 0.2 mL, 0.3 mL, 0.4 mL, 0.5 mL, 0.6 mL, and 0.7 mL of the gallic acid standard solution into a 10 mL volumetric flask, respectively, add 0.5 mL of Folin-phenol reagent, then add 1.5 mL of a 1 M Na2CO3 solution, dilute with distilled water, heat in a 75°C water bath for 10 min, and naturally cool. Perform full-wavelength scanning, and the maximum absorption is at 760 nm. Draw a standard curve with the gallic acid concentration (c) as the abscissa and the absorbance (A) at 760 nm as the ordinate, and fit the linear regression equation: A = 121c - 0.0562, R 2 = 0.9996. The aloe polyphenol content is measured to be 84.2%.

[0054] Experimental design: The test animals are subjected to 12 h light-dark alternating light (lights on at 6:00 and lights off at 18:00), reared at a temperature of (25 ± 2) °C, humidity of 50% ± 20%, and water and bedding changed regularly every 2 d, with free access to food and water, 5 animals per cage. After 5 d of adaptive feeding, the mice are divided into a blank control group (10) and a model group (50), and the mice in the model group are subjected to chronic unpredictable stress for 4 weeks according to Tables 1 and 2, and receive one or two kinds of stimulation per day, with the modeling method not repeated within 3 days.

[0055] After the modeling is completed, the mice in the model group are randomly divided into 5 groups, i.e., a model group (10), a positive drug group (10, fluoxetine 20 mg / kg), an aloe polysaccharide group (10, 20 mg / kg), an aloe flavone group (10, 20 mg / kg), and an aloe polyphenol group (10, 20 mg / kg). The mice in the positive drug group, the aloe polysaccharide group, the aloe flavone group, and the aloe polyphenol group are administered with intragastric administration at 10 mL / kg, and the blank control group and the model group are replaced with an equal amount of normal saline, once a day, for 14 consecutive days. The changes in the moving distance, moving speed in the open field experiment, and the immobility time in the tail suspension test and the forced swimming test of the mice are observed, and the statistical method of One-Way ANOVA is used to determine whether the polysaccharides, flavones, and polyphenols in the aloe pulp powder have the efficacy of treating depression.

[0056] Experimental results:

[0057] In the open field experiment, the total distance and moving speed reflect the autonomous activity state of the mice. For example, Figure 2 A and Figure 2B shows that compared with the blank control group mice, the total moving distance and moving speed of the model group mice are significantly reduced, indicating that the modeling is successful; compared with the model group mice, the total moving distance and moving speed of the aloe polysaccharide group, the aloe flavone group, the aloe polyphenol group and the positive drug group mice are significantly increased, indicating that aloe polysaccharide, aloe flavone and aloe polyphenol are effective.

[0058] In the tail suspension test and forced swimming immobility test, the immobility time of mice reflects their depression state. As shown in Figure 2 C and Figure 2 D shows that compared with the blank control group mice, the resting time of the model group mice is significantly increased, indicating that the modeling is successful; compared with the model group mice, the immobility time of the aloe polysaccharide group, the aloe flavone group, the aloe polyphenol group and the positive drug group mice is significantly reduced, indicating that the drugs are effective.

[0059] In summary, polysaccharide, flavone and polyphenol derived from aloe pulp powder can significantly improve the depression-like behavior of CUMS-induced mice, and the antidepressant efficacy is: aloe polysaccharide > aloe flavone > aloe polyphenol.

[0060] Example 3

[0061] The aloe polysaccharide, aloe flavone and aloe polyphenol obtained in Example 2 were used as the matching unit, and were mixed in the proportions shown in Table 2. The mixture was used to treat CUMS-induced mouse models, and only the moving distance in the open field test was detected. The D-optimal design method was used to construct a 3D model under the premise of keeping the total amount consistent, and the best efficacy matching ratio was obtained.

[0062] Experimental design:

[0063] The test animals were subjected to 12h light-dark alternating illumination (light on at 6:00 and light off at 18:00), the feeding temperature was (25±2)℃, the humidity was 50%±20%, the water and bedding were regularly replaced every 2d, and the animals were allowed to freely eat and drink, 5 animals per cage. After 5d of adaptive feeding, the mice were divided into a blank control group (10 animals) and a model group (130 animals). The mice in the model group were subjected to chronic unpredictable stress for 4 weeks according to Table 1 and Table 2, and received one or two kinds of stimulation every day. The modeling method was not repeated within 3 days.

[0064] After the modeling was completed, the mice in the model group were randomly divided into 13 groups, i.e. a model group (10 animals), a positive drug group (10 animals, fluoxetine 20mg / kg), and drug administration groups 1-11 (10 animals in each group, 20mg / kg). The mice in the positive drug group and the drug administration groups 1-11 were administered with physiological saline or dispersed according to 10mL / kg, and were administered by gavage. The mice in the blank control group and the model group were replaced with an equal amount of physiological saline, once a day, for 14 consecutive days. The moving distance of the model mice in the open field test was observed.

[0065] Table 1. Different mass ratios of aloe polysaccharide, aloe flavone and aloe polyphenol

[0066]

[0067] Experimental results:

[0068] As Figure 3 , the different compatibility ratios showed differences in the moving distance of CUMS-induced mice in the open field experiment. Through the constructed model, it was found that when the mass ratio of aloe polysaccharide: aloe flavone: aloe polyphenol was 6.945-31.432: 1.185-32.146: 0.251-14.323, the three components had a synergistic effect on the efficacy.

[0069] Example 4

[0070] The aloe polysaccharide, aloe flavone and aloe polyphenol obtained in Example 2 were combined according to the mass ratios 6.945: 1.185: 0.251 and 31.432: 32.146: 14.323, and were used on CUMS-induced depression mouse models. The moving distance and speed of the model mice in the open field experiment, and the immobility time of the model mice in the tail suspension experiment and forced swimming experiment were observed. The statistical method of One-Way ANOVA was used to determine whether the aloe polysaccharide, aloe flavone and aloe polyphenol had a synergistic effect on the treatment of depression at this ratio.

[0071] Experimental design:

[0072] The test animals were subjected to 12h light and dark alternation illumination (light on at 6:00 and light off at 18:00), and the feeding temperature was (25±2)℃, the humidity was 50%±20%, the water and bedding were regularly replaced every 2d, and the animals were allowed to freely eat and drink, 5 animals per cage. After 5d of adaptive feeding, the mice were divided into a blank control group (10 animals) and a model group (40 animals). The mice in the model group were subjected to chronic unpredictable stress for 4 weeks according to Table 1 and Table 2, and received one or two kinds of stimulation every day, and the modeling method was not repeated within 3 days.

[0073] After the end of modeling, the model group mice were randomly divided into 4 groups, namely the model group (10), the positive drug group (10, fluoxetine 20mg / kg), the drug administration group I (aloe polysaccharide: aloe flavone: aloe polyphenol mass ratio = 6.945:1.185:0.251, 10, 20mg / kg), the drug administration group II (aloe polysaccharide: aloe flavone: aloe polyphenol mass ratio = 31.432:32.146:14.323, 10, 20mg / kg), the positive drug group, the drug administration group I and the drug administration group II mice were dissolved or dispersed with physiological saline, and were administered with 10mL / kg by gavage, and the blank control group and the model group mice were replaced with the same amount of physiological saline, once a day, for 14 days of continuous administration. The changes in the moving distance and speed of the model mice in the open field experiment, and the immobile time of the model mice in the tail suspension experiment and the forced swimming experiment were observed to determine whether aloe polysaccharide, aloe flavone and aloe polyphenol had the efficacy of treating depression.

[0074] Experimental results:

[0075] In the open field experiment, the total distance and moving speed reflect the autonomous activity state of the mice. As shown in Figure 4 A and Figure 4 B, compared with the blank control mice, the total moving distance and moving speed of the model mice were significantly reduced, indicating that the modeling was successful; compared with the model mice, the total moving distance and moving speed of the drug administration group I, the drug administration group II and the positive drug group mice were significantly increased, indicating that the drug administration group I, the drug administration group II and the positive drug group were effective.

[0076] In the tail suspension experiment and the forced swimming immobility experiment, the immobile time of the mice reflects the depression state. As shown in Figure 4 C and Figure 4 D, compared with the blank control mice, the resting time of the model mice was significantly increased, indicating that the modeling was successful; compared with the model mice, the immobile time of the drug administration group I, the drug administration group II and the positive drug group mice was significantly reduced, indicating that the drugs were effective, and indicating that aloe polysaccharide, aloe flavone and aloe polyphenol had the efficacy of synergistically treating depression when the mass ratio was 6.945-31.432:1.185-32.146:0.251-14.323.

Claims

1. A composition for treating depression, characterized in that: The composition is a combination of aloe polysaccharides, aloe flavonoids and aloe polyphenols in a mass ratio of (6.945–31.432):(1.185–32.146):(0.251–14.323); The aloe polysaccharide is prepared by the following method: Aloe vera pulp powder is added to 80% ethanol at a mass-to-volume ratio of 1:8 kg / L, allowed to stand overnight at 4°C, centrifuged, and the precipitate is dried under vacuum to obtain crude polysaccharide I; crude polysaccharide I is dissolved in distilled water, and 0.1–0.2% (by mass) of papain is added, heated to 60°C and stirred for 6 hours, centrifuged, and the supernatant is collected to obtain crude polysaccharide II; D101 macroporous adsorption resin is wet-packed, and crude polysaccharide II is prepared into a 20% (by mass) sample solution using distilled water, loaded onto the D101 macroporous adsorption resin column, and eluted with an equal volume of 50% ethanol. The eluent is recovered until no alcohol odor remains, concentrated in a water bath, and dried under vacuum to obtain aloe polysaccharide; The aloe polyphenols mentioned above are prepared by the following method: Aloe vera pulp powder is dissolved in 60% ethanol at a mass-to-volume ratio of 1:20 kg / L, ultrasonicated at 60°C for 45 min, filtered, and the extract is concentrated into a solid powder; the solid powder is dissolved in 60% ethanol at a mass-to-volume ratio of 1:2 kg / L, and an appropriate amount of CaCl2 solution is added until no precipitate forms. The precipitate is collected, hydrochloric acid is added until the precipitate is completely dissolved, extracted with ethyl acetate, the organic phase is collected, and concentrated to obtain aloe polyphenols. The aloe vera flavonoids are prepared by the following method: aloe vera pulp powder and 80% ethanol are added to 80% ethanol at a mass-to-volume ratio of 1:8 kg / L, centrifuged, and the supernatant is collected. The supernatant is then loaded onto a D101 macroporous adsorption resin column, and impurities are removed by elution with distilled water at a volume twice the volume of the sample liquid. Then, 80% ethanol is used to elute until no flavonoid reaction occurs. The 80% ethanol eluent is collected, and the ethanol is recovered from the 80% ethanol eluent until no alcohol odor is detected. The eluent is concentrated in a water bath and dried under vacuum to obtain total flavonoids.

2. The composition according to claim 1, characterized in that: The mass ratios of aloe polysaccharides, aloe flavonoids, and aloe polyphenols were 6.945:1.185:0.251 and 31.432:32.146:14.323, respectively.

3. The use of the composition according to claim 1 in the preparation of a medicament for treating depression.

4. A drug for treating depression, characterized in that: The drug is a drug made from the composition of claim 1 as the main active ingredient and a pharmaceutically acceptable carrier.

5. The drug according to claim 4, characterized in that: The drug dosage forms mentioned are tablets and capsules.

6. Application of aloe flavonoids in the preparation of drugs for treating depression; among which, The aloe vera flavonoids are prepared by the following method: aloe vera pulp powder and 80% ethanol are added to 80% ethanol at a mass-to-volume ratio of 1:8 kg / L, centrifuged, and the supernatant is collected. The supernatant is then loaded onto a D101 macroporous adsorption resin column, and impurities are removed by elution with distilled water at a volume twice the volume of the sample liquid. Then, 80% ethanol is used to elute until no flavonoid reaction occurs. The 80% ethanol eluent is collected, and the ethanol is recovered from the 80% ethanol eluent until no alcohol odor is detected. The eluent is concentrated in a water bath and dried under vacuum to obtain total flavonoids.

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