CN111225667B

CN111225667B - Application of 1,2,3,6, 7-pentamethoxy benzophenone in preparation of medicine for preventing and treating hippocampal neuron related diseases

Info

Publication number: CN111225667B
Application number: CN201880034325.8A
Authority: CN
Inventors: 顾正兵; 梁延春; 陶月红; 刘艳芳; 曾铖
Original assignee: Taizhou Danding Biological Technology Co ltd
Current assignee: Taizhou Danding Biological Technology Co ltd
Priority date: 2018-09-26
Filing date: 2018-09-26
Publication date: 2023-08-04
Anticipated expiration: 2038-09-26
Also published as: WO2020061809A1; CN111225667A

Abstract

The invention discloses an application of 1,2,3,6, 7-pentamethoxy benzophenone in preparing a medicament for preventing and treating pathological feature diseases caused by damage or apoptosis of hippocampal neurons, wherein the chemical structural formula of the 1,2,3,6, 7-pentamethoxy benzophenone is shown as a formula I. Experiments show that the 1,2,3,6, 7-pentamethoxy benzophenone can promote the regrowth of hippocampal neurons, increase the expression of the related protein Bcl-2 of the apoptosis of the hippocampal neurons, reduce the expression of related proteins Bax and Caspase-8 of the apoptosis of the hippocampal neurons, and inhibit the apoptosis of the hippocampal neurons. Can be used for preventing and treating pathological characteristic diseases caused by hippocampal neuron injury, and provides experimental basis for clinically preventing and treating diseases such as depression, alzheimer disease, anxiety, parkinsonism and the like.

Description

Application of 1,2,3,6, 7-pentamethoxy benzophenone in preparation of medicine for preventing and treating hippocampal neuron related diseases

Technical Field

The invention relates to the field of medicines, in particular to application of 1,2,3,6, 7-pentamethoxy benzophenone in preparing medicines for preventing and treating diseases related to hippocampal neurons.

Background

The hippocampus is located in the temporal lobes of the left and right hemispheres of the brain, resembling the hippocampus, and plays an important role in learning, memory and emotion control. The prior researches show that the damage of the hippocampal neurons has close relation with diseases such as depression, alzheimer's disease, anxiety, parkinsonism and the like. Inhibition of hippocampal neuronal damage is an important strategy for the treatment of such diseases.

Apoptosis occurs by initiating intracellular regulation of various genes and protein expression, with Bcl-2 family and Caspase family related proteins and genes being major contributors. The Bcl-2 family has a plurality of members, mainly comprises anti-apoptosis genes Bcl-2 and pro-apoptosis genes Bax, and plays an important regulating role in the regulation of apoptosis. Bcl-2 and Bax act as an equilibrium system, the ratio of their expression largely affecting the onset of apoptosis [ 1]]. Bcl-2 protein is the coded product of Bcl-2 gene, belongs to an anti-apoptosis protein, mainly exists on mitochondria and endoplasmic reticulum, prevents the leakage of pro-apoptosis related protein in mitochondria by stabilizing mitochondrial membrane, and can block the release of Ca2+ from endoplasmic reticulum to ensure that Ca is dependent ²⁺ The reduction of endonuclease activity and the like to block apoptosis; the Bax protein is a homologous water-soluble related protein of Bcl-2, is mainly distributed in cytoplasm, has functions opposite to Bcl-2, can antagonize the protective effect of Bcl-2 by forming a heterodimer with Bcl-2, and belongs to a pro-apoptotic protein. Therefore, bcl-2/Bax is an important indicator of whether a cell will undergo apoptosis. Caspase is a recognized major related gene in the apoptosis process, wherein Caspase-8 is a core promoter of the Caspase cascade, which, upon activation, activates all caspases downstream of the apoptotic cascade, thereby inducing the onset of the apoptotic response, the encoded product of which belongs to the apoptosis-related protein.

Alzheimer's Disease (AD) is a progressive degenerative disease of the central nervous system, with progressive memory impairment, overall mental retardation, personality changes, and mental abnormalities as major clinical manifestations, bringing a heavy burden to patients, patient families, and the whole society. Studies have shown that: neuronal apoptosis is the primary pathway responsible for AD neuronal loss and is also the root cause of progressive decline in memory and cognitive function. The Bcl-2 family plays an important role in the hippocampal neuronal apoptosis process of alzheimer's disease. It has been found that beta-amyloid-beta, abeta treatment induces oxidative stress, leading to cell death of PC12, whereas PC12 (rat pheochromocytoma) cells transfected with the anti-apoptotic gene Bcl-2 have an enhanced anti-injury capacity [2].

The rapid development of society and the acceleration of life rhythm lead to the annual increase of incidence of depression, and clinical symptoms are often manifested as low emotion, cognitive dysfunction, despair and the like. Major depressive patients often develop light ideas that adversely affect individuals and society. The effect of treating depression by the traditional monoamine transmitter and receptor theory is limited, so that the pathogenesis of depression is further explored, and searching for a new treatment way is urgent. The proposal of the nerve depression theory in 2000 proves that adult hippocampal neuron injury can cause depression [3], each research student establishes a rat depression model through repeated constraint stress, chronic unpredictable warm stress, corticosterone injection and other chronic stress, and the phenomenon of hippocampal neuron injury is found in model animals. Therefore, the change of the hippocampal neurons is closely related to depression, and promotion of the regeneration of the hippocampal neurons is also an important therapeutic strategy for treating depression. Through observation and analysis of Bcl-2 expression in hippocampal tissues of stressed rats and the intervention effect of fluoxetine on the same, the fluoxetine is found to play a role in treating depression by inhibiting the expression of hippocampal Bax and simultaneously enhancing the expression of Bcl-2, promoting the regeneration of neurons and inhibiting the apoptosis of hippocampal neurons [4].

It has been found that when mice are inhibited in their hippocampal neuronal regeneration, the peak of corticosterone in plasma is elevated under mild stress, suggesting that inhibition of hippocampal neuronal regeneration has a direct modulating effect on the hypothalamic-pituitary-adrenal (HPA) axis [5]. The HPA axis is involved in endocrine regulation of the body and is mainly regulated by the hippocampus, which is divided into CA1, CA2, CA3 and Dentate Gyrus (DG), and each region has different functions. In addition, mineralocorticoid receptors and glucocorticoid receptors of the parathalamus nucleus and anterior pituitary promote regeneration and differentiation of DG neoneurons by causing elevation of glucocorticoid through negative feedback regulation on the HPA axis. The quantitative analysis and comparison of three metabolites of N-acetyl aspartic acid (NAA), choline (Cho) and creatine (Cr) of forehead and hippocampal brain tissues of anxiety patients are carried out by domestic scholars by using a magnetic resonance proton spectrum analysis technology (1H-MRS), and the results show that the left hippocampus of the anxiety group, the Cho, NAA/Cr and the Cho/Cr are obviously higher than those of a normal control group, and the difference has statistical significance (Cho: P <0.05; NAA/Cr: P <0.05; cho/Cr: P < 0.01), which indicates that the hippocampus of the anxiety patients possibly participates in the pathophysiological process of the anxiety disease [6]. Animal experiments also show that anxiety-related behavior is significantly enhanced after adult hippocampal neuronal injury, suggesting that hippocampal nerves play an important role in the modulation of emotional states, possibly as a novel therapeutic strategy for the treatment of anxiety disorders [7].

The literature cited in the description of the invention summarises the following:

[1]Dey S,Mactutus CF,Booze RM,et al.Cocaine exposure in vitro induces apoptosis in fetal locus coeruleus neurons by altering the Bax/Bcl-2 ratio and through caspase-3 apoptotic signaling[J].Neuroscience,2007,144(2):509-521.

[2]Jang JH,Surh YJ.Bcl-2 protects against Abeta(25-35)-induced oxidative PC12 cell death by potentiation of antioxidant capacity[J].Biochem Biophys Res Commun,2004,320(3):880-886.

[3]Jacobs BL,Henriette VP,Gage FH,et al.Adult brain neurogenesis and psychiatry:a novel theory of depression[J].Mol Psychiatry,2000,5(3):262-269.

[4] zhong Detai, zhang Qi. Effect of fluoxetine on the expression of Bax and Bcl-2mRNA in hippocampal tissue of rats in a model of depression [ J ]. Zizikhaki medical college, 2008,29 (22): 2689-2690.

[5]Jason SS,Amelie S,Michelle B,et al.Adult hippocampal neurogenesis buffers stress response and depressive behavior[J].Nature,2011,476(7361):458-461.

[6] Yu Hua Liang research on magnetic resonance proton Spectroscopy of the frontal lobe and Hippocampus of anxiety patients Zhejiang university Shuoshi article 2007.

[7]Reverst JM,Dupret D,Koehl M,et al.Adult hippocampal neurogenesis is involved in anxiety-related behaviors[J].Mol Psychiatry,2009,14(10):959-967.

[8]Iro H,Taniguchi H,Kita T,et al.Xanthone and a cinnamic acid derivative from Polygala tenuifolia[J].Phytochemistry,l977,16(10):1614-1616.

[9] Jiang Yong, liu Lei, tu Pengfei. Chemical composition research of Polygala tenuifolia. Chinese Natural medicine, 2003,1 (3): 142-145.

[10] Ren Tieling, huqingsheng, fu Hongjun, et al, establishment of serum-free primary culture technique for rat hippocampal neurons, journal of Chinese health examination 2004,14 (2): 178-179.

[11]Sanna E,Mostallino MC,Busonero F,et al.Changes in GABA(A)receptor gene expression associated with selective alterations in receptor function and pharmacology after ethanol withdrawal.J.Neuroscience,2003,23(37):11711-11724.

Disclosure of Invention

The invention provides application of a benzopyrazolone compound 1,2,3,6, 7-pentamethoxy benzopyrazolone as a related medicament of a hippocampal neuron protective agent. By protecting and promoting regeneration of hippocampal neurons, enhancing expression of anti-apoptosis related protein Bcl-2, inhibiting expression of apoptosis related protein Bax and Caspase-8, and inhibiting apoptosis of hippocampal neurons, the preparation method can be used for preparing medicines for preventing and treating pathological characteristic diseases caused by hippocampal neuron injury or apoptosis.

In order to achieve the above object, the present invention provides the following technical solutions:

the application of 1,2,3,6, 7-pentamethoxy benzophenone in preparing medicine for preventing and treating pathological characteristic diseases caused by hippocampal neuron injury or apoptosis is provided, the chemical structural formula of the 1,2,3,6, 7-pentamethoxy benzophenone is shown in formula I,

the molecular formula of the 1,2,3,6, 7-pentamethoxy diphenyl pyridone is as follows: c (C) ₁₈ H ₁₈ O ₇ The molecular weight is: 346.33. the 1,2,3,6, 7-pentamethoxy benzophenone is a chemical component of plants of the genus Polygala Polygala tenuifolia (Polygala tenuifolia) or Polygala sibirica L (Polygala tenuifolia), and can also be obtained by chemical synthesis.

The invention adopts a conventional extraction and separation method well known in the field of natural product research to separate 1,2,3,6, 7-pentamethoxy benzophenone from polygala tenuifolia, wherein the ultraviolet spectrum is shown in figure 1, the nuclear magnetic resonance spectrum is shown in figure 2, and the data are consistent with those reported in documents [8,9 ].

Further, the pathological characteristic disease caused by damage or apoptosis of hippocampal neurons is one or more of depression, alzheimer's disease, anxiety and Parkinson's disease. That is, the present invention employs 1,2,3,6, 7-pentamethoxy benzophenone for the preparation of a medicament for the prevention and treatment of diseases characterized by pathological characteristics caused by damage or apoptosis of hippocampal neurons, which are selected from one or more of depression, alzheimer's disease, anxiety and Parkinson's disease.

Further, the medicine comprises 1,2,3,6, 7-pentamethoxy benzophenone shown in the formula I and pharmaceutically acceptable auxiliary materials.

A method of preparing a medicament for a disease characterized by pathology resulting from hippocampal neuronal damage or apoptosis, comprising the steps of: the medicine is prepared into clinically acceptable dosage forms by taking 1,2,3,6, 7-pentamethoxy diphenyl pyridone as a main component and adding auxiliary materials according to a selected prescription amount and a conventional process.

Further, the auxiliary materials comprise one or a mixture of more of a filler, a disintegrating agent, a lubricant, a binder, a flavoring agent, a suspending agent, a preservative or a matrix.

The auxiliary materials comprise one or a mixture of more of a filler, a disintegrating agent, a lubricant, an adhesive, a flavoring agent, a suspending agent, a preservative or a matrix;

the filler includes, but is not limited to, one or more of starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose;

the disintegrants include, but are not limited to, one or more of starch, crospovidone, hydroxypropyl cellulose, sodium carboxymethyl starch;

the lubricant includes, but is not limited to, one or more of magnesium stearate, talc, silica, sodium lauryl sulfate;

the binder includes, but is not limited to, one or more of starch slurry, polyvinylpyrrolidone, hydroxypropyl methylcellulose;

such flavoring agents include, but are not limited to, sweeteners and/or flavors; the sweetener is one or more of saccharin sodium, aspartame, sucrose and sodium cyclamate;

the suspending agent comprises, but is not limited to, polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose or a mixture of one or more of them;

the preservative includes, but is not limited to, a mixture of one or more of parabens, benzoic acid, sodium benzoate, sorbic acid, sorbate;

the matrix comprises one or a mixture of PEG and insect wax.

Further, the dosage form of the medicine is an oral preparation or an injection preparation.

Further, the oral preparation is a tablet, an oral liquid, a pill, a capsule, a granule, a paste, a syrup, a powder, a granule, a tincture or a dripping pill.

Further, the injection preparation is powder injection or injection. The injection mode of the injection preparation is intramuscular injection, for example.

It should be noted that the auxiliary materials include, but are not limited to, the above listed ranges, and those skilled in the art may make suitable selections and adjustments according to practical situations.

The pharmaceutical unit preparation contains 1,2,3,6, 7-pentamethoxy benzophenone in an amount of 1-10 mg/day according to daily administration dosage. The pharmaceutical unit preparation of the invention is that capsules are each capsule, tablets are each tablet, injection is 10 ml/piece or granules are 25 g/bag.

Experiments show that the 1,2,3,6, 7-pentamethoxy benzophenone of the invention can promote the regrowth of hippocampal neurons, increase the expression of the related protein Bcl-2 of the apoptosis of the hippocampal neurons, reduce the expression of the related protein Bax and Caspase-8 of the apoptosis of the hippocampal neurons, and inhibit the apoptosis of the hippocampal neurons. Can be used for preventing and treating pathological characteristic diseases caused by hippocampal neuron injury, and provides experimental basis for clinically preventing and treating diseases such as depression, alzheimer disease, anxiety, parkinsonism and the like.

Drawings

The drawings referred to below are explained.

FIG. 1 is an ultraviolet spectrum of 1,2,3,6, 7-pentamethoxy benzophenone.

FIG. 2 is a nuclear magnetic resonance spectrum of 1,2,3,6, 7-pentamethoxy benzophenone.

FIG. 3 is a graph showing the effect of PMT on hippocampal neuronal cell viability. Among them, DAPI-stained cells, which represent nuclei of all cells, are blue. Red spots are PI stained nuclei, representing apoptotic cells. The scale is 10m.

FIG. 4 is a graph of the Bcl-2 protein expression (400) of hippocampal neurons from each group of rats. Wherein, C is the reference substance; m model group; f fluoxetine group; and a P PMT group.

FIG. 5 is a graph of hippocampal neuronal Bax protein expression (400) for each group of rats. Wherein, C is the reference substance; m model group; f fluoxetine group; and a P PMT group.

FIG. 6 is a graph of hippocampal neuronal Caspase-8 protein expression (400) in each group of rats. Wherein, C is the reference substance; m model group; f fluoxetine group; and a P PMT group.

Detailed Description

The invention is further illustrated below in connection with examples, but the scope of the invention is not limited thereto.

Example 1 tablet

Taking 10g of 1,2,3,6, 7-pentamethoxy diphenyl pyrrolidone, taking starch, talcum powder, microcrystalline cellulose, hydroxypropyl methyl cellulose and sucrose as auxiliary materials in a medicine dosage, and preparing the auxiliary materials into tablets according to a conventional process. Each tablet contains 1mg of 1,2,3,6, 7-pentamethoxy diphenyl pyrrolidone, and each time, 1 tablet is used for 2 times a day.

Example 2 Capsule

Taking 10g of 1,2,3,6, 7-pentamethoxy diphenyl pyridone, taking microcrystalline cellulose, crosslinked povidone, magnesium stearate, polyvinylpyrrolidone and sorbic acid as auxiliary materials, and preparing the auxiliary materials into capsules according to the conventional process. Each capsule contains 0.5mg of 1,2,3,6, 7-pentamethoxy benzophenone and is 2 granules each time, 3 times daily.

Example 3 granules

Taking 100g of 1,2,3,6, 7-pentamethoxy diphenyl pyridone, taking starch, crospovidone, magnesium stearate, sucrose and sorbic acid as auxiliary materials in a medicine dosage, and preparing the auxiliary materials into granules according to a conventional process. The granule dosage per bag is 25g, the content of 1,2,3,6, 7-pentamethoxy diphenyl pyrrolidone is 3mg, 1 bag each time is 3 times daily.

Example 4 effect of 1,2,3,6, 7-pentamethoxy benzophenone (PMT) on the survival of hippocampal nerve cells in neonatal rats.

(1) Culture of neonatal rat hippocampal nerve cells [10,11]

New 1-3d SD rats were sterilized by soaking in 70% ethanol for several seconds. The hippocampus was removed and placed in 10ml of dissecting solution. Washing Hippocampus tissue pieces with dissecting solution, removing connective tissue such as meningal blood vessel, cutting into paste, transferring into another centrifuge tube together with dissecting solution, centrifuging at 4deg.C for 5min after blowing for several times, discarding supernatant, blowing with 10ml dissecting solution, adding 0.25% Trypsin-EDTA 2.5ml and DNase 25l, gently blowing, and digesting in water bath at 37deg.C for 5-10min; adding 5ml of planting culture medium to stop digestion, sieving with 70m sieve, collecting liquid in another centrifuge tube, centrifuging at 4deg.C and 1000g for 5min; removing supernatant, adding 15ml of culture solution, gently beating, centrifuging at 4deg.C and 1000g for 5min; the supernatant was discarded, 10ml of plating medium was added, blown into single cell suspensions and counted, and cells were plated into 96 empty plates coated with Poly-lysine at a density of 5X 104 cells/ml, 200l per well, 1X 104 cells per well. Placing the mixture in a CO2 incubator for culture; after 4 hours, the culture solution is completely changed into a maintenance culture solution, the culture solution is changed for 1 time every 3 days, and half of the culture solution is changed each time. Cell growth was observed daily under an inverted microscope.

(2) Protection detection of neural cells by PMT

Hippocampus cells were seeded at a density of 5X 104/mL in 96-well plates pre-plated with 0.01% polylysine, 200 μl per well, 1X 104 cells per well. After 5d culture in an incubator at 37℃with CO2, hippocampal neurons were divided into 5 groups: blank control group, corticosterone group (10 mol/L), corticosterone+5 mol/L PMT group, corticosterone+10 mol/L PMT group, corticosterone+20 mol/L PMT group, 20 wells each; the blank group was given the same volume of D-PBS, and after 48 hours of administration, DAPI and PI staining was performed to examine the number of apoptosis. The results show that, compared with the corticosterone group, after PMT acts on hippocampal nerve cells, the number of apoptotic cells is obviously reduced, and a certain dose correlation is presented. PMT was suggested to have the effect of protecting and promoting the growth of hippocampal nerve cells (see fig. 3, table 1).

TABLE 1 Effect of PMT on hippocampal neuronal cell viability

# compared to blank, P <0.05; * P <0.05 compared to corticosterone group

Experimental example 5 influence of 1,2,3,6, 7-pentamethoxy-benzophenone (PMT for short) on the behavior of depressed rats.

SD rats were divided into four groups, namely, 40 SD rats, age of 8-12 weeks, weight (220 th.) g, and 1 week of adaptive feeding, and randomly divided into a blank control group, a model control group, a fluoxetine group (1 mg/kg) and a PMT group (0.2 mg/kg). The control group was fed normally. The model group, the fluoxetine group and the PMT group are fed in single cages, and 1 PMT group is fed in each cage.

The model group, fluoxetine group and PMT group rats were randomly given a plurality of chronic mild unpredictable stress factors in 21d of feeding (60 s high-speed horizontal concussion and tail clamping, fasted 24h, water forbidden 24h, ice water swimming at 4 ℃ for 5min, 10 times per interval of 10s of electric shock to the sole of foot for 0s at 36v voltage, constraint stress for 6h, squirrel cage tilting for 24h, suspension for 5min and black and white inversion for 24 h). One stimulus was given daily, each of which was used 3 times per day, in a random order. The model group was fed with water and PMT was infused at 0.2mg/kg starting on day 2 of PMT group. Fluoxetine group was infused with 1mg/kg at day 2. PMT and fluoxetine groups were gavaged 1 time per day for 20 days.

After 21d, the behaviours of each group were assessed using open field experiments. A25 cm square was drawn on the bottom of a square cardboard box with a darkened four walls of 80cm by 40cm, and the rats were placed in the bottom of the box and were recorded in a resting state for the number of horizontal, vertical movements and finishing times within 3 minutes. Then, a sugar water consumption experiment was performed, and the rats were given pure water and 1% sucrose water, and the consumption amount was recorded for 24 hours. Sugar water preference = 1% sucrose water/total water x 100%.

The results show that: after 21d, the behavioral index of the PMT group and fluoxetine group rats was significantly higher than that of the model group (P < 0.01). PMT was shown to improve behaviours in depressed model rats. See table 2.

TABLE 2 influence of PMT on the behaviours of depressed ratsn＝10)

^## P compared with blank group<0.01； ^** P compared with the model group<0.01

Experimental example 6 influence of 1,2,3,6, 7-pentamethoxy-benzophenone (PMT for short) on the expression of Bcl-2 protein, bax protein and Caspase-8 protein in hippocampal neurons of depressed rats.

After the behavioural test of each rat in the test group in example 5 is completed, brain tissues are taken, frozen storage tubes are split-packed and stored in liquid nitrogen. Thawing, grinding brain tissue, adding precooled protein lysate, centrifuging at 4deg.C for 20min at 10000r/min, collecting supernatant, and detecting by High Content Analysis (HCA).

The results showed (see figures 4, 5, 6) that the relative fluorescence intensity of the rat neuronal Bcl-2 protein was significantly increased in the fluoxetine and PMT groups compared to the model group, significantly decreased in the model group compared to the blank group (< 0.05, #p0.05), and significantly decreased in Bax protein and Caspase-8, and significantly increased in the model group compared to the blank group (< 0.05, #p0.05). PMT was shown to inhibit hippocampal apoptosis.

Example 7 behavioural effect of 1,2,3,6, 7-pentamethoxybenzophenone (PMT for short) on appwe transgenic mice.

80 single transgenic APPSwe mice 9 months old were randomly divided into a control group, a PMT low dose group, a PMT medium dose group and a PMT high dose group, and the number of animals fed per cage was controlled at 5. The control group does not have any intervention, and standard laboratory special feed and drinking water are given in the experimental process; PMT low, medium, and high dose groups were infused with 0.05mg.kg-1.D-1, 0.2mg.kg-1.D-1, and 0.5mg.kg-1.D-1 PMT, respectively, except for the special feed and drinking water.

Each group of mice was randomly selected from 12 Morris water maze tests and Y maze tests according to the experimental design. The test results show that: PMT significantly improved cognitive function in AD transgenic mice. The results are shown in tables 3 and 4.

Table 3. Morris water maze escape latency comparisons for each group of mice (n=12,)

^* p compared with the control group<0.05。 ^** P compared with the control group<0.01

TABLE 4Y maze of mice of each groupComparison of the test results (n=12,)

Example 8 Effect of 1,2,3,6, 7-pentamethoxybenzophenone (PMT for short) on apoptosis of hippocampal neurons in APPswe transgenic mice

The experimental mice of example 7 were evaluated behaviorally, 10 more mice per group were taken, the brain was broken after anesthesia, and the brain sagittal plane was sectioned and PI stained with a frozen microtome. The results showed that the numbers of apoptotic cells in the medium and high dose groups CA1, CA3 of PMT were significantly reduced compared to the control group (P < 0.01). PMT was shown to be capable of inhibiting apoptosis in hippocampal cells in appwe transgenic mice.

While particular embodiments of the present invention have been illustrated and described, it will be appreciated that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention.

Claims

1. The application of 1,2,3,6, 7-pentamethoxyl benzophenone in preparing a medicament for preventing and treating pathological characteristic diseases caused by hippocampal neuron injury or apoptosis is provided, wherein the chemical structural formula of the 1,2,3,6, 7-pentamethoxyl benzophenone is shown as formula I, and the active ingredient of the medicament is 1,2,3,6, 7-pentamethoxyl benzophenone; the pathological characteristic diseases caused by the damage or the apoptosis of the hippocampal neurons are one or more of depression and Alzheimer disease

2. The use according to claim 1, wherein the medicament comprises pharmaceutically acceptable excipients.

3. The use according to claim 2, wherein the auxiliary material is one or more of a filler, a disintegrant, a lubricant, an adhesive, a flavoring agent, a suspending agent, a preservative or a matrix.

4. The use according to claim 2, wherein the medicament is in the form of an oral or injectable formulation.

5. The use according to claim 4, wherein the oral preparation is a tablet, an oral liquid, a pill, a capsule, a granule, a paste, a syrup, a powder, a granule, a tincture or a drop pill.

6. The use according to claim 4, wherein the injectable formulation is a powder injection or an injectable solution.