Application of 5-methoxyindole-3-acetic acid in preparation of medicine for treating depression

Abstract

The invention discloses an application of 5-methoxyindole-3-acetic acid or a pharmaceutical salt thereof in preparation of a medicine for preventing and / or treating depression. The invention provides a new application of 5-methoxyindole-3-acetic acid in the treatment of depression. The 5-methoxyindole-3-acetic acid can effectively relieve depression-like behaviors of depressive mice and reduce mouse hippocampus neuron cell damage, and has a certain neuroprotection effect, so that the 5-methoxyindole-3-acetic acid can be used as a medicine for treating depression.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and specifically relates to an application of 5-methoxyindole-3-acetic acid in the preparation of a medicine for treating depression. Background Art

[0002] Depression, as a common disabling mental illness, has received increasing attention from the academic community in recent years. According to the definition of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), if an individual has 5 or more symptoms listed in DSM-5 (such as sadness, despair, decreased activity, insomnia, etc.) for 2 consecutive weeks, accompanied by low mood or anhedonia, he or she can be diagnosed with depression. Monoamine neurotransmitters, neuroendocrine, neurotrophic, immune, oxidative stress, and the gut-brain axis may all be involved in the pathophysiological process of depression.

[0003] As the research continues to deepen, researchers have found that the levels of some active metabolites in tryptophan metabolism are closely related to the occurrence and treatment of depression. Some metabolic enzymes in tryptophan metabolism, such as monoamine oxidase, have become one of the therapeutic targets of antidepressants. More and more scientific research evidence shows that changes in the tryptophan metabolic pathway play an important role in the pathogenesis and treatment of depression. Tryptophan is mainly metabolized through three pathways: "tryptophan-kynurenine", "tryptophan-5-hydroxytryptamine" and "tryptophan-indole". Indole metabolites are usually produced by intestinal microbial metabolism. The metabolites of the intestinal microbiota play an important role in the bidirectional regulatory axis of the gut-brain axis.

[0004] 5-Methoxyindole-3-acetic acid (5-MIAA) is a tryptophan metabolite belonging to the indole class of compounds. Studies have reported that it can be metabolized by Lactobacillus rhamnosus and has antioxidant biological activity. Currently, there are few studies on the role of 5-MIAA in mental illness, and no studies have been reported on 5-MIAA regulating emotions and behaviors. Summary of the invention

[0005] The purpose of the present invention is to provide an application of 5-methoxyindole-3-acetic acid in the preparation of a medicine for treating depression.

[0006] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] The first aspect of the present invention provides a use of 5-methoxyindole-3-acetic acid or a pharmaceutically acceptable salt thereof in the preparation of a medicament for preventing and / or treating depression.

[0008] The CAS number of the 5-methoxyindole-3-acetic acid is 3471-31-6. The 5-methoxyindole-3-acetic acid can alleviate the depressive-like behavior of depressed mice and reduce the damage of neuronal cells in the hippocampus of mice.

[0009] The pharmaceutically acceptable salts refer to the following salts formed by 5-methoxyindole-3-acetic acid and the corresponding base: sodium salt, calcium salt, potassium salt, zinc salt or meglumine salt, etc.

[0010] The pharmaceutically acceptable salt refers to a salt formed by the reaction of 5-methoxyindole-3-acetic acid with a pharmaceutically acceptable inorganic acid or organic acid; wherein the inorganic acid is at least one of hydrochloric acid, hydrobromic acid, phosphoric acid, carbonic acid, nitric acid or sulfuric acid; and the organic acid is at least one of formic acid, acetic acid, propionic acid, succinic acid, 1,5-naphthalenedisulfonic acid, asiatic acid, carbenoxolone acid, glycyrrhetinic acid, oleanolic acid, hawthorn acid, ursolic acid, corosolic acid, betulinic acid, boswellic acid, oxalic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, valeric acid, diethylacetic acid, malonic acid, succinic acid, fumaric acid, pimelic acid, adipic acid, maleic acid, malic acid, aminosulfonic acid, phenylpropionic acid, gluconic acid, ascorbic acid, stearic acid, nicotinic acid, isonicotinic acid, benzenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, citric acid or amino acid.

[0011] In the application, 5-methoxyindole-3-acetic acid or a pharmaceutically acceptable salt thereof is used as the only active ingredient.

[0012] The second aspect of the present invention also provides a pharmaceutical preparation, which is made of 5-methoxyindole-3-acetic acid or a pharmaceutically acceptable salt thereof and medically acceptable excipients.

[0013] The dosage form of the pharmaceutical preparation is injection, capsule, tablet, granule, pill, microcapsule preparation, microsphere preparation, nano preparation and the like.

[0014] The third aspect of the present invention provides a use of 5-methoxyindole-3-acetic acid or a pharmaceutically acceptable salt thereof in the preparation of a drug for preventing and / or treating mental illness and / or a drug for a disease associated with chronic stress.

[0015] Due to the adoption of the above technical solution, the present invention has the following advantages and beneficial effects:

[0016] The present invention provides a new use of 5-methoxyindole-3-acetic acid in the treatment of depression. The compound can effectively alleviate the depressive-like behavior of depressed mice and reduce the damage of neuronal cells in the hippocampus of mice, and has a certain neuroprotective effect. Therefore, the 5-methoxyindole-3-acetic acid of the present invention can be used as a drug for the treatment of depression. 5-Methoxyindole-3-acetic acid (5-MIAA) is a tryptophan metabolite. Studies have reported that it can be produced by the metabolism of Lactobacillus rhamnosus and has antioxidant biological activity. As an endogenous substance, it has the characteristics of small toxic and side effects and high tolerance. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is a schematic diagram of the test results of sugar water preference (Mean±SD, n=6) in the sugar water preference experiment of mice in each experimental group.

[0018] Figure 2 It is a schematic diagram of the test results of the central area distance (Mean±SD, n=6) of mice in each experimental group in the open field test.

[0019] Figure 3 It is a schematic diagram of the test results of the immobility time (Mean±SD, n=6) of mice in each experimental group in the tail suspension test.

[0020] Figure 4 It is a schematic diagram of the test results of the floating immobility time (Mean±SD, n=6) of mice in each experimental group in the forced swimming test.

[0021] Figure 5 This is a schematic diagram of the Nissl staining results (×40) of the ipsilateral hippocampal CA1 region of mice.

[0022] Figure 6 It is a schematic diagram of the effects of different concentrations of 5-MIAA on the survival rate of BV2 cells (Mean±SD, n=3).

[0023] Figure 7 It is a schematic diagram of the effects of different concentrations of TBHP on cell viability (Mean±SD, n=3).

[0024] Figure 8 It is a schematic diagram of the effects of different concentrations of 5-MIAA on the survival rate of cells injured by 250 μM TBHP (Mean±SD, n=3). DETAILED DESCRIPTION

[0025] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. It should be understood by those skilled in the art that the following specific description is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0026] Example 1

[0027] 5-Methoxyindole-3-acetic acid can reduce depressive-like behavior in mice:

[0028] 1. Establishment of chronic depression model and animal grouping

[0029] The experimental animals were male C57BL / 6 mice, a total of 18 mice, all weighing 20-22g. After one week of adaptation, the animals were randomly divided into 3 groups, 6 mice in each group, namely the blank control group (Ct), the depression model (CUMS) group, and the 5-methoxyindole-3-acetic acid (5-MIAA) group.

[0030] The internationally recognized CUMS (chronic unpredictable mild stimulation) method was used to establish a chronic depression model (Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain Behav Immun. 2021; 97: 423-439. doi: 10.1016 / j.bbi.2021.07.022). The blank control group did not receive any stimulation except for behavioral evaluation. The depression model group and the 5-methoxyindole-3-acetic acid (5-MIAA) group received chronic stress stimulation for 6 weeks, once a day, and each stimulation was not repeated within two consecutive days. The stress factors used in the experiment included: wet bedding for 20 hours, tilting the cage at 45 degrees for 24 hours, restraint for 4 hours, swimming in 4℃ cold water for 5 minutes, baking at 40℃ for 5 minutes, shaking the cage for 15 minutes, depriving water for 24 hours, and depriving food for 24 hours.

[0031] Blank control group: The mice did not receive CUMS stimulation, and were gavaged with control solvent (CMC-Na solution) daily from 4 weeks after modeling until the end of the experiment.

[0032] Depression model group: The mice received CUMS stimulation and were gavaged with a control solvent (CMC-Na solution) once a day from 4 weeks after modeling until the end of the experiment.

[0033] 5-Methoxyindole-3-acetic acid group: 4 weeks after model establishment, the rats were gavaged with 5-MIAA CMC-NA suspension at a dose of 50 mg / kg once a day until the end of the experiment.

[0034] Preparation of 5-MIAA CMC-NA suspension: Add sodium carboxymethylcellulose CMC-Na powder to pure water to make the final concentration of CMC-Na 5% (w / v). Add 5-MIAA to the above CMC-Na solution and mix well to prepare a 5-MIAA CMC-NA suspension with a concentration of 6.25 mg / mL.

[0035] 2. Behavioral evaluation methods

[0036] (1) Sugar water preference experiment: Before the experiment, mice were trained with sugar water for a total of 3 days during the one-week adaptive feeding period. The mice were housed in single cages, and 2 bottles of 1% sugar water were placed in each cage for 1 day. Then, 1 bottle of 1% sugar water and another bottle of pure water were placed for 2 days. The left and right positions of 1% sugar water and pure water were changed on the second day. Then, the mice were subjected to sugar water preference experiments on day 0 (week 0) and day 42 (week 6) of modeling. Water was deprived before the experiment. During the experiment, mice were given a bottle of 1% sugar water and a bottle of pure water at the same time. The detection time was 24 hours. The volume of sugar water and pure water before and after the experiment was measured, and the drinking volume and total drinking volume of the two were calculated respectively. The percentage of sugar water drinking volume to total drinking volume was the percentage of sugar water preference.

[0037] (2) Open field test (OFT): Use an open field test box with a size of 50cm×50cm×40cm, adjust the camera to shoot perpendicular to the ground, and the field of view covers the edge of the open field box. Ensure that the light in the open field box is uniform, without obvious light and dark angles. After wiping the bottom of the open field box with 75% ethanol, place a mouse in the center of the box from the same position and direction each time, and start the test. Record the activity of the mouse within 5 minutes. After the end, remove the mouse, clean its excrement, and wipe the open field box with 75% ethanol before the next round of testing. Use behavioral analysis software to evenly divide the open field into 16 grids and divide it into a central area, a peripheral area, and a wall area. The distance the mouse moves in the central area during this period is used as an evaluation indicator to evaluate the spontaneous activity behavior and exploratory behavior of the mouse in an unfamiliar environment.

[0038] (3) Tail suspension test (TST): The tail suspension test was performed on the 43rd day and was conducted from 15:00 to 17:00. Before the start of the experiment, the mice were transferred to the experimental site 1 hour in advance to adapt to the environment. A cotton thread was tied about 2 cm at the end of the mouse's tail, and the mouse was suspended on a stand so that the mouse was about 25 cm from the ground. Every two mice were separated by an opaque baffle to avoid mutual interference. The camera recorded the behavior of the mice for 6 minutes, and the behavioral analysis software Visutrack was used to analyze the immobility time of the mice after 4 minutes. In the tail suspension test, the mouse gave up struggling, the body hung in the air, and only showed necessary movements to maintain balance, which was considered immobile. After the tail suspension test, the mouse was put back into the cage.

[0039] (4) Forced swimming test (FST): FST was conducted from 15:00 to 17:00. Before the experiment began, mice pre-swimmed for 5 minutes 24 hours in advance to adapt to the environment. A cylindrical barrel with a diameter of 20 cm and a height of 50 cm was filled with warm water at a temperature of about 25°C and a water depth of about 35 cm to prevent the mice from escaping or supporting their limbs on the barrel wall and bottom. Every two animals were separated by an opaque baffle. After the mice were placed in the water, the camera recorded the behavior of the mice for 6 minutes, and the behavioral analysis software Visutrack was used to analyze the immobility time of the mice after 4 minutes. The immobility standard was that the mice stopped struggling in the water and were floating, with only slight limb movement to keep their heads above the water. After each mouse finished swimming, it was wiped dry and replaced with new clean water to continue the forced swimming experiment.

[0040] (5) Statistical analysis: GraphPad Prism 8 (GraphPad Software, USA) was used for statistics and graphing.

[0041] 3. Results display

[0042] (1) The results of the sugar water preference experiment are as follows Figure 1 As shown, Figure 1 It is a schematic diagram of the test results of sugar water preference (Mean±SD, n=6) in the sugar water preference experiment of mice in each experimental group. *** P<0.001, compared with the blank control group, ### P<0.001, compared with the model group. After 6 weeks of stimulation in the depression model group and 2 weeks of gavage treatment in the 5-methoxyindole-3-acetic acid group, the percentage of sugar water preference of the mice in the depression model group decreased compared with the blank control group (P<0.001); the percentage of sugar water preference of the mice in the 5-methoxyindole-3-acetic acid group increased compared with the depression model group (P<0.001). This indicates that gavage of 5-MIAA can improve the anhedonia behavior of depression model mice.

[0043] (2) The results of the open field experiment are as follows Figure 2 As shown, Figure 2 It is a schematic diagram of the test results of the central area distance (Mean±SD, n=6) of mice in each experimental group in the open field test. ** P<0.01, compared with the blank control group, #P<0.05, compared with the model group; compared with the blank control group, the 6-week stimulation reduced the central area distance of the depression model group mice (P<0.01); compared with the depression model group, the central area distance of the 5-methoxyindole-3-acetic acid group mice increased (P<0.05). This result shows that 5-MIAA improves the reduction of the central area distance of mice induced by CUMS.

[0044] (3) The results of the tail suspension test are as follows Figure 3 As shown, Figure 3 It is a schematic diagram of the test results of the immobility time (Mean±SD, n=6) of mice in each experimental group in the tail suspension test. ** P<0.01, compared with the blank control group, # P<0.05, compared with the model group. Compared with the blank control group, the 6-week stimulation prolonged the immobility time of the mice in the depression model group (both P<0.01); compared with the depression model group, the immobility time of the mice in the 5-methoxyindole-3-acetic acid group was shortened (P<0.05). The results showed that 5-MIAA improved the prolongation of the immobility time of the mice induced by CUMS.

[0045] (4) The results of the forced swimming test are as follows Figure 4 As shown, Figure 4 It is a schematic diagram of the test results of the floating immobility time (Mean±SD, n=6) of mice in each experimental group in the forced swimming test. *** P<0.001, compared with the blank control group, ## P<0.01, compared with the model group. Compared with the blank control group, the immobility time of mice in the depression model group was significantly prolonged (P<0.001, respectively); compared with the depression model group, the immobility time of mice in the 5-methoxyindole-3-acetic acid group was shortened (P<0.01). This indicates that 5-MIAA can improve the behavior of prolonged forced swimming immobility time in mice induced by CUMS.

[0046] Example 2

[0047] Effects of 5-methoxyindole-3-acetic acid on hippocampal neurons in depressed mice:

[0048] Nissl staining of mouse hippocampal sample slices: after behavioral evaluation, one mouse was taken from each group, anesthetized with 20% urethane (0.4 mL / 100 g) by intraperitoneal injection, the chest was quickly opened and the heart was completely exposed, the needle was inserted into the left ventricle, the right atrial appendage was cut open, the abdominal aortic vein was clamped, and 30 mL PBS was injected to quickly pressurize and perfuse the blood until the fluid outflowing from the right atrial appendage was basically clear, and the perfusion was stopped. At this time, the mouse lungs, eyeballs and claws were observed to be white. Then 30 mL of 4% paraformaldehyde was quickly perfused under pressure. At this time, the mouse upper limb head muscle stiffness was used as a sign, the perfusion was stopped, and the brain was removed by decapitation. After the brain tissue was sampled through the coronal plane, it was fixed in 4% paraformaldehyde for 48 hours as soon as possible. After fixation, the tissue was dehydrated in ethanol from low to high concentrations, 50% ethanol (2h) → 75% ethanol (2h) → 85% ethanol (2h) → 95% ethanol (1h) → 95% ethanol (2h) → anhydrous ethanol (1h) → anhydrous ethanol (1.5h). Then it was transparent in xylene, 1h in the first tank and 1h in the second tank. It was embedded in paraffin with a melting point of 52-60℃, and the transparent brain tissue was transferred to the melted paraffin for wax immersion, the first tank (1h), the second tank (2h). The paraffin around the brain tissue was retained for about 2mm, and the excess paraffin was trimmed with a blade, and the tissue was sliced ​​to a thickness of 5μm. The temperature of the slide was 45℃, and the sliced ​​slides were placed in a 60℃ baking machine for 2h. Paraffin sections were dewaxed in xylene, 5 min each in the first, second and third cylinders, followed by 5 min each in anhydrous ethanol, 95% ethanol, 85% ethanol and 75% ethanol, and rinsed with tap water for 1 min. The sections were placed in a 1% toluidine blue aqueous solution and stained in a 56°C incubator for 20 min, and then washed with distilled water. After differentiation in 70% ethanol for about 1 min, they were differentiated in 95% ethanol and controlled under a microscope, with the Nissl bodies showing clearly. Dehydrated quickly in anhydrous ethanol, made transparent in xylene, and sealed.

[0049] The results are as follows Figure 5 As shown, Figure 5 Figure 1 is a schematic diagram of the Nissau staining results (×40) in the ipsilateral hippocampal CA1 region of mice. A is a schematic diagram of the results of the Ct group; B is a schematic diagram of the results of the CUMS group; and C is a schematic diagram of the results of the 5-MIAA group. Compared with the blank control group, the pyramidal cells in the hippocampal CA1 region of the depression model group were disordered, the intercellular space was enlarged, the Nissau bodies in the cell bodies were reduced or completely disappeared, and the cells were pyknotic; compared with the depression model group, the pyramidal cells in the hippocampal CA1 region of the 5-methoxyindole-3-acetic acid group were neatly arranged, and the Nissau bodies in the cell bodies were clearly visible, which was close to the blank control group. This suggests that 5-MIAA has antidepressant activity against CUMS-induced depressed mice.

[0050] Example 3

[0051] Effects of 5-methoxyindole-3-acetic acid on the viability of mouse microglia (BV2 cells) induced by tert-butyl hydroperoxide (TBHP)

[0052] 1. Cell Culture

[0053] DMEM medium was supplemented with 10% fetal bovine serum and 1% double antibody for culturing BV2 cells. The cells were placed in a constant temperature incubator at 37°C and containing 5% carbon dioxide.

[0054] 2. CCK8 assay to determine cell viability

[0055] CCK-8 was used to detect the cytotoxicity of 5-MIAA and the protective effect of 5-MIAA on TBHP-induced oxidative stress injury in BV2 cells. 4 Cells were inoculated at a density of 100 μL / mL in a 96-well plate, 100 μL of cell suspension was added to each well, and the plate was cultured in a constant temperature incubator for 24 h, and the culture medium was discarded for subsequent operations.

[0056] (1) Evaluation of 5-MIAA cytotoxicity

[0057] 100 μL of culture medium containing 5-MIAA or methanol was added, with the concentrations being normal culture medium, 0 μM (the culture medium only contained the solvent methanol), 50 μM, 500 μM, 2.5 mM, 5 mM, 7.5 mM, and 10 mM, respectively. Three replicate wells were prepared for each concentration, and the cells were cultured in a constant temperature incubator for 24 h.

[0058] (2) TBHP-induced cell damage

[0059] Tert-butyl hydroperoxide (TBHP) is an oxidant that is often used to induce oxidative stress damage in cells. Add 100 μL of culture medium containing TBHP at concentrations of normal culture medium, 10 μM, 50 μM, 100 μM, 200 μM, 300 μM, 400 μM, 500 μM, and 600 μM. Each concentration is replicated in 3 wells and cultured in a constant temperature incubator for 12 hours.

[0060] (3) Protective effect of 5-MIAA on TBHP-induced cellular oxidative stress damage

[0061] First, 100 μL of complete medium containing different concentrations of 5-MIAA was added for stimulation for 6 h, with 3 replicates for each concentration. After discarding the medium containing 5-MIAA, 100 μL of complete medium containing TBHP was added, with a TBHP concentration of 250 μM, for stimulation for 12 h.

[0062] Remove the culture medium from the wells, add 100 μL of culture medium containing 10% CCK-8, incubate in a constant temperature incubator for 1 to 4 hours, and measure the OD value at a wavelength of 450 nm. The wells without cells and culture medium containing only 10% CCK-8 are used as negative control wells, and the wells without any stimulation of cells are used as positive control wells to calculate the cell survival rate.

[0063] Cell survival rate = (OD drug-containing well-OD negative control well) / (OD positive control well-OD negative control well)

[0064] Statistical analysis: GraphPad Prism 8 (GraphPad Software, USA) was used for statistics and graphing.

[0065] 3. Experimental results

[0066] (1) 5-MIAA cytotoxicity results Figure 6 As shown, Figure 6 The figure is a schematic diagram of the effect of different concentrations of 5-MIAA on the survival rate of BV2 cells (Mean±SD, n=3). It can be seen from the figure that except for 7.5mM (P=0.0027) and 10mM (P<0.0001) 5-MIAA stimulation of cells for 24h, which significantly reduced the survival rate of cells, the other concentrations had no obvious toxicity to cells.

[0067] (2) Results of the dose screening of TBHP-induced oxidative stress injury Figure 7 As shown, Figure 7 The figure shows the effect of different concentrations of TBHP on cell survival rate (Mean±SD, n=3). It can be seen from the figure that TBHP above 200μM (P<0.0001) significantly affects cell survival rate and induces cell damage. 50 Between 200 μM and 300 μM, a concentration of 250 μM was selected in subsequent experiments to induce cell damage.

[0068] (3) The protective effect of 5-MIAA on TBHP-induced oxidative stress injury Figure 8 As shown, Figure 8 The figure is a schematic diagram of the effect of different concentrations of 5-MIAA on the survival rate of cells induced by 250μM TBHP (Mean±SD, n=3). It can be seen from the figure that 2.5mM (P=0.0052) and 5mM (P=0.0453) 5-MIAA can significantly reduce the cell damage induced by 250μM TBHP and improve the cell survival rate after stimulating the cells for 6 hours.

[0069] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment, it is not used to limit the present invention. Any technician familiar with this patent can make some changes or modify the technical contents suggested above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the solution of the present invention.

Claims

1. Use of 5-methoxyindole-3-acetic acid or a pharmaceutically acceptable salt thereof in the preparation of a drug for preventing and / or treating depression.

2. The use according to claim 1, characterized in that: The pharmaceutically acceptable salt refers to the following salts formed by 5-methoxyindole-3-acetic acid and the corresponding base: sodium salt, calcium salt, potassium salt, zinc salt or meglumine salt.

3. The use according to claim 1, characterized in that: The pharmaceutically acceptable salt refers to a salt formed by the reaction of 5-methoxyindole-3-acetic acid with a pharmaceutically acceptable inorganic acid or organic acid.

4. The use according to claim 3, characterized in that: The inorganic acid is at least one of hydrochloric acid, hydrobromic acid, phosphoric acid, carbonic acid, nitric acid or sulfuric acid.

5. The use according to claim 3, characterized in that: The organic acid is at least one of formic acid, acetic acid, propionic acid, succinic acid, 1,5-naphthalene disulfonic acid, asiatic acid, carbenoxolone acid, glycyrrhetinic acid, oleanolic acid, hawthorn acid, ursolic acid, corosolic acid, betulinic acid, boswellic acid, oxalic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, valeric acid, diethylacetic acid, malonic acid, succinic acid, fumaric acid, pimelic acid, adipic acid, maleic acid, malic acid, aminosulfonic acid, phenylpropionic acid, gluconic acid, ascorbic acid, stearic acid, nicotinic acid, isonicotinic acid, benzenesulfonic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, citric acid or amino acid.

6. The use according to claim 1, characterized in that: In the application, 5-methoxyindole-3-acetic acid or a pharmaceutically acceptable salt thereof is used as the only active ingredient.

7. A pharmaceutical preparation, characterized in that The invention is prepared from 5-methoxyindole-3-acetic acid or its pharmaceutically acceptable salt and medically acceptable auxiliary materials.

8. The pharmaceutical preparation according to claim 7, characterized in that The dosage form of the pharmaceutical preparation is injection, capsule, tablet, granule, pill, microcapsule preparation, microsphere preparation, and nano preparation.

9. Use of 5-methoxyindole-3-acetic acid or a pharmaceutically acceptable salt thereof in the preparation of a drug for preventing and / or treating mental illness and / or a drug for a disease associated with chronic stress.

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