Application of tetrahydrocurcumin in preparation of medicine for treating Alzheimer disease

Abstract

The invention discloses an application of tetrahydrocurcumin in preparation of a drug for treating Alzheimer's disease, the drug for treating Alzheimer's disease takes tetrahydrocurcumin as a unique active ingredient, research finds that tetrahydrocurcumin can promote microglial cells to phagocytize beta-amyloid protein and reduce neuron damage and synaptic dysfunction, and the drug for treating Alzheimer's disease can be used for preparing drugs for treating Alzheimer's disease. According to the present invention, the tetrahydrocurcumin has characteristics of low molecular weight and good fat solubility, can easily penetrate through the cell membrane, can form hydrogen bonds and hydrophobic interaction with the biomacromolecule through the hydroxyl group and the methoxy group in the molecule, and further has characteristics of high bioavailability, good treatment effect, and good treatment effect on the Alzheimer's disease, and can be used for the treatment of the Alzheimer's disease. The problems that in the prior art, application of tetrahydrocurcumin serving as an active component to drugs for treating the Alzheimer disease is not reported yet, and the bioavailability of many natural compounds is low are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to application of tetrahydrocurcumin in preparing a drug for treating Alzheimer's disease. Background Art

[0002] Alzheimer's disease (AD) mainly affects people over 65 years old. As a degenerative disease of the central nervous system, AD not only causes great physical and mental pain to patients, but also brings heavy burdens to families and society. With the acceleration of global population aging, AD has become the leading chronic disease threatening the health and quality of life of humans in their later years.

[0003] The main clinical manifestations of AD are memory loss and cognitive dysfunction, and its core pathological features are: the formation of insoluble amyloid-β protein deposits (Aβ) in the brain, i.e., dense senile plaques, and filamentous neurofibrillary tangles formed by abnormal phosphorylation of Tau protein. Among them, the abnormal deposition of Aβ is considered to be the key starting link in the pathogenesis of AD, which can trigger a series of neurotoxic reactions, leading to neuronal dysfunction and death.

[0004] At present, curcumin has been proven to have certain therapeutic potential for Alzheimer's disease and to prevent the development of AD from the source. However, curcumin has poor water solubility and low bioavailability, which limits its clinical application. Tetrahydrocurcumin (THC) is a derivative of curcumin obtained by hydrogenation. Studies have confirmed that tetrahydrocurcumin has multiple physiological activities such as antioxidant, anti-inflammatory, and lipid metabolism regulation, and shows potential application value in the fields of cardiovascular disease, metabolic syndrome, etc. However, there are currently no reports on the direct use of tetrahydrocurcumin as an active ingredient to treat Alzheimer's disease. Summary of the invention

[0005] In view of the above-mentioned defects, the purpose of the present invention is to propose the use of tetrahydrocurcumin in the preparation of drugs for treating Alzheimer's disease, so as to solve the problem that there is no report on the use of tetrahydrocurcumin as an active ingredient in the prior art for treating Alzheimer's disease, and the bioavailability of many natural compounds is low.

[0006] To achieve this object, the present invention adopts the following technical solutions:

[0007] Application of tetrahydrocurcumin in the preparation of a drug for treating Alzheimer's disease, wherein the drug for treating Alzheimer's disease contains tetrahydrocurcumin as the only active ingredient.

[0008] Furthermore, the treatment of Alzheimer's disease is manifested as:

[0009] (a1) Reduce the production of β-amyloid protein;

[0010] (a2) inhibiting tau protein phosphorylation;

[0011] (a3) Promote the clearance of β-amyloid protein.

[0012] Furthermore, the (a3) ​​is specifically: tetrahydrocurcumin improves the phagocytic ability of microglia to β-amyloid protein.

[0013] Preferably, the drug further comprises a pharmaceutically acceptable carrier and / or excipient.

[0014] Preferably, the drug for treating Alzheimer's disease is used to treat Alzheimer's disease in mammals.

[0015] Preferably, the drug for treating Alzheimer's disease is used to improve cognitive dysfunction caused by Alzheimer's disease in mammals.

[0016] Furthermore, the mammal is a human or a mouse.

[0017] Preferably, the dosage form of the drug is an oral preparation.

[0018] The technical solution provided by the present invention may include the following beneficial effects:

[0019] Tetrahydrocurcumin is used as the only active ingredient in drugs because it has a low molecular weight and good lipid solubility, can pass through the cell membrane relatively easily, and the hydroxyl and methoxy groups in its molecules can form hydrogen bonds and hydrophobic interactions with biological macromolecules, and have high bioavailability. At the same time, tetrahydrocurcumin can promote microglia to phagocytose beta-amyloid protein, reduce neuronal damage and synaptic dysfunction, thereby improving the cognitive function of Alzheimer's disease and achieving the purpose of treating Alzheimer's disease. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 This is a diagram showing the results of microscopic observation of Example Group 1-1 of the present invention.

[0021] Figure 2 It is a fluorescence intensity statistical graph of Example Group 1-1 of the present invention.

[0022] Figure 3 This is a diagram showing the results of microscopic observation of Example Group 1-2 of the present invention.

[0023] Figure 4 This is a diagram showing the results of microscopic observation of Example Group 1-2 of the present invention.

[0024] Figure 5 It is a statistical graph of the fluorescence intensity of Example Group 1-2 of the present invention.

[0025] Figure 6 It is a statistical graph of the escape latency of Example Group 2-1 of the present invention.

[0026] Figure 7 This is a statistical chart of the number of platform crossings on the sixth day of Example Group 2-1 of the present invention.

[0027] Figure 8 It is a statistical chart of the target quadrant stay time on the sixth day of Example Group 2-1 of the present invention.

[0028] Fig. 9 It is a swimming track diagram of Example Group 2-1 of the present invention.

[0029] Fig.10 It is a statistical graph of the average swimming speed of each group in Example Group 2 of the present invention.

[0030] Fig.11 It is a statistical chart of the arm advancement accuracy rate of Example Group 2-2 of the present invention.

[0031] Fig.12 It is a graph of the experimental results of Example Group 2-3 of the present invention.

[0032] Fig.13 This is a diagram showing the observation results of Example Group 3 of the present invention.

[0033] Fig.14 This is a statistical graph of the positive area of ​​β-amyloid protein in Example Group 3 of the present invention. DETAILED DESCRIPTION

[0034] The technical solution of the present invention is further illustrated below through specific implementation methods.

[0035] In order to facilitate the understanding of the present invention, the present invention is described more fully below. The present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0036] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0037] Application of tetrahydrocurcumin in the preparation of a drug for treating Alzheimer's disease, wherein the drug for treating Alzheimer's disease contains tetrahydrocurcumin as the only active ingredient.

[0038] Alzheimer's disease, as a degenerative disease of the central nervous system, not only causes great physical and mental pain to patients, but also brings a heavy burden to families and society. With the acceleration of global population aging, Alzheimer's disease has become the primary chronic disease threatening human health and quality of life in later years. Existing treatment technologies mainly relieve the symptoms of Alzheimer's disease but cannot prevent the progression of the disease. Specific natural compounds have certain therapeutic potential for Alzheimer's disease, but generally have low bioavailability and are limited in clinical application.

[0039] Among the natural compounds with therapeutic potential for Alzheimer's disease, curcumin protects neurons from damage by anti-oxidation, anti-inflammation, inhibiting β-amyloid protein aggregation and regulating tau protein phosphorylation, but curcumin has low bioavailability and poor water solubility, which limits its clinical application. When curcumin is used as a natural medicine to act on the disease, it will be converted into tetrahydrocurcumin in the body. As a reduced derivative of curcumin, tetrahydrocurcumin has better biological activity, but in addition to being converted into tetrahydrocurcumin, it is also converted into glucuronic acid conjugates, sulfate conjugates, etc. It is impossible to clarify the effect of tetrahydrocurcumin on Alzheimer's disease when it is the only active ingredient, and there is currently no report on the direct use of tetrahydrocurcumin as an active ingredient to treat Alzheimer's disease.

[0040] Tetrahydrocurcumin (THC) has a molecular formula of C 21 H 26 O6, with a molecular weight of 372.2, has a low molecular weight and good lipid solubility, can relatively easily pass through the cell membrane and act better on the cells, and its molecules do not contain carbon-carbon double bonds, which makes tetrahydrocurcumin more stable in chemical properties. At the same time, the hydroxyl and methoxy groups in its molecules can form hydrogen bonds and hydrophobic interactions with biological macromolecules, making its absorption and metabolism in the body more efficient, thereby improving its bioavailability. Therefore, compared with other natural compounds, tetrahydrocurcumin has a higher bioavailability and can act better at the desired location, solving the problem of low bioavailability of many natural compounds used in the treatment of Alzheimer's disease in the prior art.

[0041] At the same time, if Figure 1As shown in the figure, after the addition of tetrahydrocurcumin, the level of β-amyloid protein in microglia increased significantly. The higher the content of β-amyloid protein in microglia, the higher the content of β-amyloid protein phagocytosed by microglia. It can be seen that tetrahydrocurcumin can improve the phagocytic ability of microglia to β-amyloid protein and promote the clearance of β-amyloid protein. It is known that one of the main pathological characteristics of Alzheimer's disease is the abnormal deposition of β-amyloid protein in the brain. Promoting the clearance of β-amyloid protein can achieve the purpose of treating Alzheimer's disease. Therefore, compared with existing natural compounds, tetrahydrocurcumin has a higher bioavailability while achieving the treatment of Alzheimer's disease. It is also derived from turmeric rhizomes and has high safety. The application of tetrahydrocurcumin as the only active ingredient in the treatment of Alzheimer's disease provides a new research direction and potential drug selection for the treatment of Alzheimer's disease, which is expected to bring safer and more efficient treatment options to Alzheimer's patients, significantly improve the quality of life of patients, and reduce the burden on families and society.

[0042] Furthermore, the treatment of Alzheimer's disease is manifested as:

[0043] (a1) Reduce the production of β-amyloid protein;

[0044] (a2) inhibiting tau protein phosphorylation;

[0045] (a3) Promote the clearance of β-amyloid protein.

[0046] It is worth noting that the main clinical manifestations of AD are memory loss and cognitive dysfunction, and its core pathological characteristics are: the formation of insoluble β-amyloid protein deposits in the brain, namely dense senile plaques, and filamentous neurofibrillary tangles formed by abnormal phosphorylation of Tau protein. Among them, the abnormal deposition of β-amyloid protein is considered to be the key starting link in the pathogenesis of AD, which can trigger a series of neurotoxic reactions, leading to neuronal dysfunction and death.

[0047] Using tetrahydrocurcumin as the sole active ingredient in drugs for the treatment of Alzheimer's disease can reduce the production of β-amyloid protein and promote the clearance of β-amyloid protein, targeting the pathological characteristics of Alzheimer's disease, thereby reducing the insoluble β-amyloid protein plaques formed in the brain, that is, reducing the abnormal deposition of β-amyloid protein, preventing the onset of AD at the initial stage, avoiding a series of neurotoxic reactions caused by the abnormal deposition of β-amyloid protein, protecting neurons, and achieving the treatment of Alzheimer's disease.

[0048] At the same time, Tau protein is a low molecular weight microtubule-associated protein, mainly distributed in the central nervous system, and plays an important role in maintaining microtubule stability, promoting axon growth and neuronal plasticity. In Alzheimer's disease, abnormal phosphorylation and aggregation of Tau protein lead to the formation of neurofibrillary tangles, which in turn cause neuronal damage and death, and the synergistic effect with β-amyloid protein jointly promotes the pathogenesis of Alzheimer's disease. Tetrahydrocurcumin inhibits tau protein phosphorylation, reduces the resulting filamentous neurofibrillary tangles, and protects neurons.

[0049] Tetrahydrocurcumin treats Alzheimer's disease by reducing the production of β-amyloid protein, inhibiting tau protein phosphorylation, and promoting the clearance of β-amyloid protein, which can achieve the purpose of treating Alzheimer's disease to a certain extent.

[0050] Furthermore, the (a3) ​​is specifically: tetrahydrocurcumin improves the phagocytic ability of microglia to β-amyloid protein.

[0051] Specifically, β-amyloid protein is produced by the abnormal cleavage of amyloid precursor protein through β-secretase and γ-secretase. Under normal physiological conditions, the production and clearance of β-amyloid protein are in a dynamic balance. Under the pathological state of Alzheimer's disease, the production of β-amyloid protein increases and its clearance decreases, leading to the accumulation of β-amyloid protein in the brain. The deposition of β-amyloid protein can induce premature apoptosis of nerve cells, affect the normal physiological activities of neurons, interfere with the normal function of synapses between neurons, affect the transmission and signal transduction of neurotransmitters, damage the normal physiological activities of neurons, and even induce neuroinflammatory responses, further aggravating neuronal damage.

[0052] Microglia are the main immune cells in the brain, responsible for clearing pathogens and cell debris. Tetrahydrocurcumin can effectively clear the deposition of beta-amyloid protein in the brain by enhancing the phagocytic ability of microglia to beta-amyloid protein, reduce neuronal damage and synaptic dysfunction, thereby improving the cognitive function of Alzheimer's disease and achieving the purpose of treating Alzheimer's disease.

[0053] Preferably, the drug further comprises a pharmaceutically acceptable carrier and / or excipient.

[0054] Specifically, pharmaceutically acceptable carriers and / or excipients are components of drugs, which not only contribute to the stability and solubility of drugs, but also improve the bioavailability and therapeutic effect of drugs. By combining with tetrahydrocurcumin, rationally selecting and using carriers and excipients, more ideal pharmaceutical preparations can be prepared to improve the efficacy and safety of drugs.

[0055] Preferably, the drug for treating Alzheimer's disease is used to treat Alzheimer's disease in mammals.

[0056] Since Alzheimer's disease mainly occurs in the human population and the research of the present invention is based on a mammalian model, the drug for treating Alzheimer's disease is used to treat Alzheimer's disease in mammals. In addition, the drug has potential therapeutic value for human Alzheimer's disease patients.

[0057] Preferably, the drug for treating Alzheimer's disease is used to improve cognitive dysfunction caused by Alzheimer's disease in mammals.

[0058] Specifically, tetrahydrocurcumin protects neurons, reduces neuronal damage and synaptic dysfunction by reducing the generation of β-amyloid protein, inhibiting tau protein phosphorylation and promoting the clearance of β-amyloid protein, thereby improving cognitive impairment caused by Alzheimer's disease in mammals, including memory loss and decreased learning ability.

[0059] Furthermore, the mammal is a human or a mouse.

[0060] Specifically, the experiment of the present invention uses a 3xTg-AD mouse model and BV-2 microglia. The mouse model highly simulates the pathological characteristics of human Alzheimer's disease and can effectively evaluate the therapeutic effect of drugs on Alzheimer's disease. In addition, BV-2 microglia play a key role in neuroimmune regulation. The drug for treating Alzheimer's disease is more capable of treating Alzheimer's disease in humans or mice.

[0061] Preferably, the dosage form of the drug is an oral preparation.

[0062] Beneficial effects: Specifically, Alzheimer's disease is a neurodegenerative disease with an insidious onset, a long course and a persistent condition. The dosage form of the drug is an oral preparation, which is suitable for long-term management and treatment of chronic diseases, that is, it is compatible with the course of Alzheimer's disease.

[0063] The technical solution of the present invention is further illustrated below through specific implementation methods.

[0064] Example Group 1

[0065] Group 1 of this embodiment investigated the ability of tetrahydrocurcumin to promote the phagocytosis of β-amyloid protein by microglia.

[0066] The microglial cell line used was the BV-2 cell line, purchased from Zhejiang Meisen Cell Technology Co., Ltd., and cultured in an appropriate 1640 culture medium containing 10% fetal bovine serum in a 37°C, 5% CO2 incubator.

[0067] Example Group 1-1

[0068] In order to explore the effects of different concentrations of tetrahydrocurcumin on the phagocytosis of β-amyloid protein by microglia, five groups were set up, namely blank control group, Aβ model group, 2nM THC group, 5nM THC group and 10nM THC group.

[0069] The specific grouping and processing methods are as follows:

[0070] Blank control group: microglia were not treated with tetrahydrocurcumin and no β-amyloid protein was added, and the incubation time was the same as that of other groups;

[0071] Aβ model group: After microglia were cultured for 24 h without tetrahydrocurcumin treatment, 0.5 μM β-amyloid protein with autofluorescence was added and incubated for 2 h;

[0072] 2nM THC group: microglia were pretreated with 2nM tetrahydrocurcumin for 24 hours, and then incubated with 0.5μM β-amyloid protein, which has autofluorescence, for 2 hours;

[0073] 5nM THC group: microglia were pretreated with 5nM tetrahydrocurcumin for 24 hours, and then incubated with 0.5μM β-amyloid protein, which has autofluorescence, for 2 hours;

[0074] 10nM THC group: microglia were pretreated with 10nM tetrahydrocurcumin for 24 hours, and then incubated with 0.5μM β-amyloid protein, which has autofluorescence, for 2 hours;

[0075] The phagocytosis of β-amyloid protein in the above groups was observed by laser confocal microscopy.

[0076] Example Group 1-2

[0077] In order to explore the phagocytosis of β-amyloid protein by microglia at different time points after treatment with the same concentration of tetrahydrocurcumin, on the basis of Example 1-1, the Aβ model group and the 10 nM THC group were observed, and the phagocytosis of β-amyloid protein by microglia was observed by laser confocal microscopy at the time points of 1h, 2h, 3h, 4h and 6h of incubation with self-fluorescent β-amyloid protein.

[0078] Example Group 2

[0079] Group 2 of this example investigated the effect of tetrahydrocurcumin on cognitive function in 3xTg-AD mice.

[0080] The experimental animals used were 3xTg-AD mice, purchased from Jiangsu Ailingfei Biotechnology Co., Ltd., with a production license number of SCXK(E)2021-0025, and were kept in an environment that meets the standards for experimental animals, with free access to food and water. In addition, there were corresponding wild-type mice from the same litter that did not carry transgenic genes as normal controls for 3xTg-AD mice.

[0081] Before conducting the experiment of Group 2 of this embodiment, mice were bred to 10 months of age and then given oral gavage treatment for one month, once a day. Then mice with normal bilateral eyes and no lesions, normal limb movement ability, and no wounds on the body were selected. A total of 6 groups were set up, and the swimming speed of mice in different groups was tested. If there was no significant difference, subsequent experiments were carried out.

[0082] The specific groups are:

[0083] Control group: wild-type mice of the same littermate that do not carry the transgene and are not treated with tetrahydrocurcumin;

[0084] Tetrahydrocurcumin-20mg / kg group: wild-type mice of the same littermate that do not carry the transgene were treated with 20mg / kg of tetrahydrocurcumin by gavage;

[0085] Model group: 3xTg-AD mice, not treated with tetrahydrocurcumin;

[0086] Model group + tetrahydrocurcumin-5 mg / kg: 3xTg-AD mice were treated with 5 mg / kg tetrahydrocurcumin by oral gavage;

[0087] Model group + tetrahydrocurcumin-10 mg / kg: 3xTg-AD mice were treated with 10 mg / kg tetrahydrocurcumin by oral gavage;

[0088] Model group + tetrahydrocurcumin-20 mg / kg: 3xTg-AD mice were treated with 20 mg / kg tetrahydrocurcumin by oral gavage.

[0089] Example Group 2-1

[0090] The Morris water maze test is an indicator for detecting the working memory and spatial memory of mice.

[0091] Water maze: The water maze has a diameter of 1.5m, the platform has a diameter of 10cm, and the platform plane is 2cm underwater. Before testing 3xTg-AD mice, an appropriate amount of edible titanium dioxide was added to the pool to increase the contrast between the animals and the background. Markers of different colors and shapes were affixed to the side walls of the water maze to help the mice remember the relative position of the platform. Indoor lights were prevented from directly shining on the water surface. The camera was above the center of the pool, and the camera focus and clarity were adjusted to identify the movement state of the mouse. The camera was connected to a computer, and the tracking system of the camera was used to record and analyze the movement trajectory of the mouse.

[0092] The mouse water maze experiment is divided into two stages: the training stage and the detection experiment.

[0093] During the training phase, mice need to be trained for 5 consecutive days so that they can remember the location of the platform through the prompts of surrounding landmarks. During these 5 days, mice need to be put into the water from the quadrant opposite the platform every day to start the test. When the mouse is put into the water against the side wall of the pool, keep the mouse's back facing the side wall of the pool. At the same time, turn on the software and record for 60 seconds. If the mouse climbs onto the platform and persists for 3 seconds, it is considered that the mouse can successfully find the platform and stop the software timing. If the mouse fails to successfully find the platform after 60 seconds, it needs to be guided to find the platform in the water and stay for 1 minute.

[0094] On the sixth day, the detection experiment was conducted, and the start time of the detection experiment should be at least 24 hours after the last mouse training. Remove the platform from the water, put the mouse into the water from the quadrant opposite the platform, and time it for 60 seconds. Then, pick up the mouse, dry its hair, and put it back into the cage.

[0095] During the training phase, the time from when the mouse entered the water to when it climbed onto the platform was the latency period; during the detection experiment, the number of times the mouse shuttled back and forth between the original platform location was recorded as the "number of platform crossings", and the time the mouse stayed in the quadrant of the area where the original platform was located was recorded as the "target quadrant stay time", and the corresponding time was recorded according to the mouse's actions.

[0096] Example Group 2-2

[0097] Y-maze spontaneous alternation test.

[0098] The Y-maze includes three identical arms (labeled A, B, and C respectively), with the length, width, and height of each arm being 30 cm, 5 cm, and 15 cm respectively, and the angles between the arms being equal. The mice were placed at the intersection of the three arms and allowed to explore freely for 6 minutes. The total number of times the mice entered the arms and the order in which they entered the arms each time were recorded. If all four limbs of the mouse entered an arm, it was considered to have entered the arm once, and if the mouse entered different arms three times in a row, it was considered to have entered the arm correctly. The correct rate of mouse entering the arm was calculated, and the correct rate of entering the arm = the number of correct times of entering the arm / (total number of times entering the arm-2). After the experiment, the excrement of each mouse was removed and wiped with 75% alcohol to eliminate odor. Mice that entered the arm less than 15 times were not included in the statistical analysis.

[0099] Example Group 2-3

[0100] Y-maze spatial recognition experiment.

[0101] The test was carried out in stages. The first stage was the training stage. One of the arms (B) was closed and all groups remained unchanged. The mice were placed at the intersection of the three arms and allowed to explore freely for 15 minutes. They were randomly wiped with 75% alcohol to eliminate odor. After the training of the same group of mice was completed, the second stage of the test was carried out. The arm (B) was opened and the mice were placed at the intersection of the three arms. The mice were allowed to explore freely for 5 minutes. The total time the mice spent in each arm was counted separately. The time the mice spent in B was calculated as a percentage of the total time.

[0102] Example Group 3

[0103] Group 3 of this example investigated the effect of tetrahydrocurcumin on the level of Aβ oligomers in the cerebral cortex of 3xTg-AD mice.

[0104] The mice that completed the experiment of Example Group 2 were subjected to immunohistochemistry experiments to detect the expression level of Aβ in the mouse brain.

[0105] According to the above-mentioned embodiment groups, experiments were conducted and the experimental results were recorded and analyzed as follows.

[0106] Example Group 1 investigated the ability of tetrahydrocurcumin to promote the phagocytosis of β-amyloid protein by microglia, wherein Example Group 1-1 observed the phagocytosis of β-amyloid protein in each group by laser confocal microscopy. Figure 1 As shown, according to Figure 1 The fluorescence intensity of β-amyloid protein in each group was obtained Figure 2 .exist Figure 2 In the figure, from left to right, the fluorescence intensity of β-amyloid protein in the blank control group, Aβ model group, 2nM THC group, 5nM THC group and 10nM THC group are respectively shown. The fluorescence intensity is positively correlated with the content of β-amyloid protein. Figure 2In the experiment, compared with the Aβ model group, the β-amyloid protein level in the microglia of the 2nM THC group, 5nM THC group and 10nM THC group was significantly increased, and among the three groups, the β-amyloid protein phagocytosed by the microglia in the 10nM THC group was the highest, indicating that tetrahydrocurcumin can enhance the ability of microglia to phagocytize β-amyloid protein in a dose-dependent manner.

[0107] Example Group 1-2 The phagocytosis of β-amyloid protein in the Aβ model group and 10 nM THC group at the corresponding time points was observed by laser confocal microscopy. Figure 3 and Figure 4 As shown, according to Figure 3 and Figure 4 The fluorescence intensity of β-amyloid protein in each group was obtained Figure 5 By Figure 5 It can be seen that in the 10nM THC group, that is, microglia treated with tetrahydrocurcumin, began to phagocytose at 1 hour, and the fluorescence intensity was the highest at 2 hours, indicating that the phagocytosis result was the best, and the fluorescence intensity decreased at 3 hours, indicating that the β-amyloid protein substrate began to be digested by the cells, and at 6 hours the substrate was completely digested by the cells, while there was no significant difference in the Aβ model group from 1 to 6 hours. Compared with the Aβ model group and the 10nM THC group, it can be clearly seen that the ability of microglia to phagocytose Aβ was improved after tetrahydrocurcumin treatment.

[0108] Therefore, by Figures 1 to 5 It can be seen that tetrahydrocurcumin can promote the ability of microglia to phagocytize β-amyloid protein.

[0109] Example 2 investigated the effect of tetrahydrocurcumin on cognitive function of 3xTg-AD mice, wherein the swimming speed of mice in each group was as follows: Fig.10 As shown, there is no significant difference in the swimming speed of mice in each group, which has little impact on subsequent experiments.

[0110] In the training phase, the escape latency of mice in group 2-1 of the embodiment was as follows: Figure 6 As shown in Figure 2, during the detection experiment, the number of times the mouse shuttled back and forth between the original platform and the original platform was as follows: Figure 7 As shown in Figure 2, the time that the mouse stayed in the quadrant of the original platform was as follows: Figure 8 As shown. Figure 6-8It can be seen that, under the premise that the motor ability of mice in each group is equivalent, when detecting the escape latency of mice, the time it takes for mice to reach the platform gradually decreases as the experiment progresses. Compared with the model group, the time it takes for mice treated with tetrahydrocurcumin to reach the platform is significantly reduced; during the detection experiment, compared with the model group, the time that mice treated with tetrahydrocurcumin stay in the target quadrant and the number of times they cross the platform are significantly increased. In short, it can be seen that mice treated with tetrahydrocurcumin have better memory than mice in the model group.

[0111] In Example Group 2-1, the swimming trajectory of mice on the sixth day is shown in FIG. Fig. 9 As shown, the green line represents the swimming trajectory of the mouse, and the red circle represents the escape platform. It can be seen that the swimming trajectories of the mice treated with tetrahydrocurcumin are more concentrated in the target quadrant, especially the swimming trajectories of the mice in the model group + tetrahydrocurcumin-10 mg / kg and the model group + tetrahydrocurcumin-20 mg / kg are more concentrated in the target quadrant.

[0112] In Example Group 2-2, the correct arm entry rate of each group of mice was as follows: Fig.11 As shown in the figure, compared with the model group, the correct rate of arm entry in the group treated with tetrahydrocurcumin was improved.

[0113] In Example Groups 2-3, the statistical results of the time each group of mice spent in B as a percentage of the total time are as follows: Fig.12 As shown by Fig.12 It can be seen that after treatment with tetrahydrocurcumin, the percentage of time spent by mice in B increased.

[0114] The experimental results of Example 2 are as follows Figure 6-12 As shown above, in summary, tetrahydrocurcumin enhances the ability of 3xTg-AD mice to explore new things and significantly improves the spatial cognitive impairment of 3xTg-AD mice.

[0115] The observation results of Example 3 are as follows Fig.13 As shown, statistics Fig.13 The positive area of ​​β-amyloid protein in Fig.14 ,Depend on Fig.14 It can be seen that a large amount of β-amyloid protein appeared in the cerebral cortex of the 3xTg-AD mice in the model group, and after treatment with tetrahydrocurcumin, the expression level of β-amyloid protein was significantly reduced. According to Example Group 3, it is shown that tetrahydrocurcumin can reduce the aggregation of β-amyloid protein plaques in the cerebral cortex of mice.

[0116] The technical principle of the present invention is described above in conjunction with specific embodiments. These descriptions are only for explaining the principle of the present invention and cannot be interpreted as limiting the scope of protection of the present invention in any way. Based on the explanations herein, those skilled in the art can associate other specific implementations of the present invention without paying creative labor, and these methods will fall within the scope of protection of the present invention.

Claims

1. The use of tetrahydrocurcumin in the preparation of a drug for treating Alzheimer's disease, characterized in that: The drug for treating Alzheimer's disease contains tetrahydrocurcumin as the only active ingredient.

2. The use of tetrahydrocurcumin according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The treatment of Alzheimer's disease is manifested by: (a1) Reduce the production of β-amyloid protein; (a2) inhibiting tau protein phosphorylation; (a3) Promote the clearance of β-amyloid protein.

3. The use of tetrahydrocurcumin according to claim 2 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The (a3) ​​is specifically: tetrahydrocurcumin improves the phagocytic ability of microglia to β-amyloid protein.

4. The use of tetrahydrocurcumin according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The medicine further comprises a pharmaceutically acceptable carrier and / or excipient.

5. The use of tetrahydrocurcumin according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The drug for treating Alzheimer's disease is used for treating Alzheimer's disease in mammals.

6. The use of tetrahydrocurcumin according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The drug for treating Alzheimer's disease is used to improve cognitive dysfunction caused by Alzheimer's disease in mammals.

7. The use of tetrahydrocurcumin according to claim 5 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The mammal is a human or a mouse.

8. The use of tetrahydrocurcumin according to claim 1 in the preparation of a drug for treating Alzheimer's disease, characterized in that: The dosage form of the drug is an oral preparation.

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