KR20190117262A - Composition for improvement of memory and cognition ability, prevention, delay, treatment or improvement of Alzheimer's disease, comprising extracts of Chionanthus retusa Lindl. & Paxton leaf - Google Patents

Abstract

The present invention relates to a composition for improving memory, improving cognitive ability, and preventing, delaying, treating or alleviating dementia containing a Chionanthus retusus extract as an active component. More specifically, the present invention relates to a pharmaceutical composition and a functional food composition which exhibit effects of improving memory, improving cognitive ability, and preventing, delaying, treating or alleviating dementia, containing the Chionanthus retusus extract as the active component. The composition of the present invention can improve memory and cognitive ability and can effectively prevent, delay, alleviate or treat dementia through acetylcholinesterase inhibitory activity, beta amyloid production and aggregation inhibitory activity, and beta amyloid plaque inhibitory activity without side effects.

Description

Composition for improvement of memory and cognition ability, prevention, delay, treatment or improvement of Alzheimer's disease, comprising extracts of Chionanthus retusa Lindl. & Paxton leaf}

The present invention relates to a composition for improving memory, improving cognitive ability, preventing dementia, delaying, treating or improving the composition of the poplar tree leaf extract as an active ingredient, and specifically, improving the memory of the poplar tree leaf extract as an active ingredient. A pharmaceutical composition and a functional food composition exhibiting an ability improvement, a dementia prevention, a delay, a treatment or an improvement effect.

Already in aging society, as of 2018, the elderly population accounted for 14.3% and the number of dementia patients is increasing rapidly. It is expected to increase to about 40% by 2060. As a result, the number of dementia patients is expected to increase significantly. This reality not only degrades the quality of life of individuals, but also becomes a big social and national problem due to the reduction of national competitiveness due to excessive medical expenses.

Dementia is caused by irreversible destruction of the brain's nerves due to brain atrophy, reduction of nerve cells, and the appearance of senile plaques, which accompany various acquired cognitive impairment symptoms such as memory, speech and behavioral disorders. Refers to the syndrome. Dementia is classified as Alzheimer's disease, degenerative diseases caused by vascular dementia and Parkinson's disease, metabolic diseases caused by hypothyroidism, brain tumors or infectious diseases, and the like.

Alzheimer's disease is the leading cause of dementia and is a degenerative neurodegenerative disorder of the brain that leads to the loss of intellectual capacity, such as memory loss and speech impairment, and eventually death, due to neuronal abnormalities caused by neuronal loss.

Beta-amyloid (Aβ), which is produced from Amyloid Precursor Protein (APP), is a major pathological marker of Alzheimer's disease and is known to be neurotoxic and cause dementia. If you look at the brains of dementia patients, you can see that Aβ is deposited with neurons, neurons. In particular, neuronal loss and Αβ deposition appear in the hippocampus, which is responsible for memory and cognition. In addition, dementia patients showed a decrease in neurotransmitter acetylcholine (ACh) by about 50% compared to normal. This may be due to abnormal concentrations of acetylcholinesterase (AChE), an enzyme that degrades ACh, and actually shows higher levels of AChE in patients with dementia than in normal people.

Therefore, inhibition of Aβ production and aggregation and inhibition of AChE may be potential strategies for the treatment of Alzheimer's disease.

Currently, dementia-improving drugs such as donepezil, galantamine, and rivastigmine, which are inhibitors of acetylcholinesterase, are used in clinical trials, but there are no effective treatments because of low treatment efficiency and severe side effects. to be.

Accordingly, the present inventors have searched for substances effective for dementia from plants in order to develop drugs that can effectively prevent, delay, treat or improve dementia without side effects, and through these results, Korean Patent Nos. 10-1194091, 10- He developed the same technology as 1480899.

The present inventors have attempted research on a variety of plants in order to develop new and more effective substances for dementia, and found that there is a possibility of these leaves. In addition it showed a background in a more detailed and full-scale research yipap leaf extract vitro (in vitro) AChE inhibitory activity, Aβ production-inhibiting activity and Aβ plaque production-inhibiting activity and Aβ aggregation inhibitory activity, antioxidant activity in the through animal experiments The results showed that they could improve memory and cognitive ability. Through this, the poplar tree leaf extract was confirmed that can effectively prevent, delay, improve or treat dementia without side effects and completed the present invention.

Republic of Korea Patent No. 10-1194091 Republic of Korea Patent No. 10-1480899

The present invention provides a pharmaceutical composition and a functional food composition containing plant-derived substances which can improve memory and cognitive ability and can effectively prevent, delay, improve or treat dementia without side effects.

According to an aspect of the present invention, the present invention provides a pharmaceutical composition for improving memory, improving cognition, preventing dementia, delaying or treating a poplar tree leaf extract as an active ingredient.

In the pharmaceutical composition of the present invention, the extract is preferably 10 to 90% (v / v) ethanol extract of the poplar leaves.

In the pharmaceutical composition of the present invention, the extract was obtained by adding 1 to 20 times the weight of 10 to 90% (v / v) ethanol to the dried leaves of the poplar and extracting for 1 to 12 hours at 50 to 90 ℃ desirable.

According to another aspect of the present invention, the present invention provides a functional food composition for improving memory, improving cognitive ability, preventing dementia, delaying or improving, containing the Poplar leaf extract as an active ingredient.

In the functional food composition of the present invention, the extract is preferably 10 to 90% (v / v) ethanol extract of the poplar leaves.

In the functional food composition of the present invention, the extract is obtained by adding 1 to 20 times the weight of 10 to 90% (v / v) ethanol to the dry matter of the poplar leaves and extracted for 1 to 12 hours at 50 to 90 ℃ It is preferable.

The composition of the present invention can improve memory and cognitive ability, effectively prevent, delay, and improve dementia without side effects through acetylcholinesterase inhibitory activity, beta amyloid production and aggregation inhibitory activity, beta amyloid plaque inhibitory activity Or can be treated.

1 is a graph showing the results of acetylcholinesterase (AChE) inhibitory activity of the extract (CRE) according to an embodiment of the present invention. C, negative control group; 10 to 100, CRE-treated group by concentration (μg / ml); Tac 1 μM, positive control.
Figure 2 is a graph showing the results of the secretion inhibitory activity of Aβ 40 (A) and 42 (B) of the extract (CRE) according to an embodiment of the present invention. C, negative control group; 1 to 100, CRE-treated group by concentration (μg / ml); B-SI 10 μM, positive control.
Figure 3 is a TEM picture of 50,000 magnification showing the results of the Aβ aggregation inhibitory activity of the extract (CRE) according to an embodiment of the present invention. Aβ + DMSO, negative control group; Aβ + Cur, positive control (curcumin treated); Aβ + CRE, CRE treated group.
Figure 4 shows the results of the Aβ aggregation inhibitory activity of the extract (CRE) according to an embodiment of the present invention is a TEM picture of 100,000 magnification and a graph showing the numerical value thereof. Aβ + DMSO, negative control group; Aβ + Cur, positive control (curcumin treated); Aβ + CRE, CRE treated group.
Figure 5 is a graph showing the results of Aβ aggregation inhibitory activity through ThT analysis of the extract (CRE) according to an embodiment of the present invention. C, negative control (DMSO treatment); Aβ + Cur, positive control (curcumin treated); Aβ + CRE, CRE treated group.
Figure 6 is a graph showing the results of the antioxidant activity of the extract (CRE) according to an embodiment of the present invention. C, negative control (DMSO treatment); 1 to 100 CRE, CRE-treated group by concentration (μg / ml); 1 ~ 100 Vit C, L-ascorbic acid treatment group (positive control group) by concentration (㎍ / ㎖).
Figure 7 is a graph showing the results of the analysis of the short-term memory improvement effect of the extract (CRE) according to an embodiment of the present invention. Aβ-, normal group; Aβ +, negative control group; Aβ + CRE, CRE administration group; Aβ + PG, positive control.
8 is a graph showing the results of the analysis of the spatial cognitive ability improvement effect of the extract (CRE) according to an embodiment of the present invention. Graph A, a graph measuring the distance to reach the support; Graph B, a graph measuring the number of passes through where the support was located; Graph C, a graph of time taken to first reach where the support was located; Aβ-, normal group; Aβ +, negative control group; Aβ + CRE, CRE administration group; Aβ + PG, positive control.
Figure 9 is a graph (C) and immunohistostaining micrographs (A, B) showing the results of the Aβ plaque generation inhibitory activity in the brain tissue (cortex region) of the extract (CRE) according to an embodiment of the present invention. Aβ-, normal group; Aβ +, negative control group; Aβ + CRE, CRE administration group; Aβ + PG, positive control.
Figure 10 is a graph (C) and immunohistostaining micrographs (A, B) showing the results of Aβ plaque generation inhibitory activity in the brain tissue (hippocampus region) of the extract (CRE) according to an embodiment of the present invention. Aβ-, normal group; Aβ +, negative control group; Aβ + CRE, CRE administration group; Aβ + PG, positive control.

The present invention provides a pharmaceutical composition for improving memory, improving cognitive ability, preventing dementia, delaying or treating containing Poplar leaf extract as an active ingredient.

Extract in the present invention means that the active ingredient is extracted using a solvent from the raw material.

This pop tree ( Chi : Chionanthus retusa Lindl. & Paxton) is a deciduous tree of the ash tree, Ash tree, which uses the leaf part in the present invention, and it is preferable to use the extract as a raw material by drying and crushing the leaves when preparing the extract.

In the present invention, it is preferable to use 10 to 90% (v / v) of ethanol as a solvent for the preparation of the extract. More preferably, 30 to 70% (v / v) ethanol, and more preferably 40 to 60% (v / v) ethanol are preferably used. In addition, the amount of the solvent as described above is preferably 1 to 20 times by weight of the extraction material, more preferably 5 to 15 times. 50-90 degreeC of extraction temperature is preferable, More preferably, it is 60-80 degreeC. The extraction time is preferably 1 to 12 hours, more preferably 5 to 7 hours. According to such extraction conditions, it is possible to efficiently extract the components exhibiting the effects desired in the present invention from the raw materials.

More preferably, the extract of the present invention is in the form of a lyophilized dried product after heating under reduced pressure the extract obtained after ethanol extraction.

At this time, the reduced-pressure heating concentration is preferably made under the conditions of 50 to 70 ℃, vacuum degree 100 to 200 torr so that the effect of the extract expected in the present invention can be sufficiently exhibited, the lyophilization is 24 to -50 to -100 ℃ It is preferable to make 48 hours.

The compositions of the present invention can be administered orally or parenterally during clinical administration and can be used in the form of general pharmaceutical formulations. The pharmaceutical composition of the present invention may contain 0.1 to 50% by weight of the extract as an active ingredient based on the total weight of the composition.

The pharmaceutical composition of the present invention may be formulated into a conventional pharmaceutical formulation by selecting one or two or more pharmaceutically acceptable conventional carriers and one or two or more additives into the extract, which is the main ingredient. The pharmaceutical compositions of the present invention may be used alone or in combination with other suitable pharmaceutically active compounds as well as with suitable substances.

The pharmaceutical compositions of the present invention may be in various oral or parenteral formulations. When formulated, it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. which are commonly used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose), gelatin and the like can be mixed. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like can also be used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

In addition to the main components, the pharmaceutical composition of the present invention may include mineral-containing compounds such as vitamins B, C, E, beta carotene, Ca, Mg, and Zn, phospholipids such as lecithin, or compounds such as maltol and amino acids, as auxiliary components. Among them, the use of a mixture of two or three components of vitamin C, E or beta carotene, maltol and the like is more preferable because it can increase or enhance the bioactive effect.

In addition to the above ingredients, in order to enhance the taste as a known additive, natural flavors such as plum, lemon, pineapple or herb, or natural fruit juice, natural pigments such as chlorophyllin, flavonoid, and fructose, sweet sugar, Honey, sugar alcohols, sugars, and other acidifying agents such as citric acid and sodium citrate can be used.

The subject to which the pharmaceutical composition of the present invention can be applied is a vertebrate, preferably a mammal, more preferably an experimental animal such as a rat, mouse, rabbit, guinea pig, hamster, dog, cat, and most preferably It is ape-like, such as chimpanzees and gorillas.

The pharmaceutical composition of the present invention may be administered orally or parenterally, and when parenteral administration, it is preferable to select external or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection methods. Preferably used for oral administration.

The dosage of the pharmaceutical composition of the present invention varies depending on the weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of the disease, but the amount of the extract in a daily dosage It is preferably 0.1 to 10 mg / kg, more preferably 3 to 9 mg / kg, more preferably 5 to 6 mg / kg, can be administered 1 to 6 times a day have.

The dosage unit may be, for example, one, two, three or four times the individual dosage, or one half, one third or one quarter. The individual dosage is preferably such that the effective drug is administered in one dose, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dose.

The pharmaceutical composition of the present invention may further contain one or more active ingredients exhibiting the same or similar functions.

The pharmaceutical composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers.

In addition, the present invention provides a functional food composition for improving memory, improving cognitive ability, preventing dementia, delaying or improving, containing the poplar leaf extract as an active ingredient.

The functional food according to the present invention may be, for example, various functional foods such as chewing gum, caramel products, candy, ice cream, confectionery, beverage products such as soft drinks, mineral water, alcoholic beverages, and health functional foods including vitamins and minerals. Can be.

The extract of the present invention may be added as it is or used with other food or food ingredients, and may be appropriately used according to conventional methods. The blending amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or hygiene). In general, the extract of the present invention in the preparation of food or beverage may be added in an amount of up to 15% by weight, preferably up to 10% by weight relative to the raw material. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.

The functional food of the present invention may contain various flavors, natural carbohydrates, and the like as additional ingredients. The above-mentioned natural carbohydrates may be glucose, monosaccharides such as fructose, maltose, disaccharides such as sucrose, and polysaccharides such as dextrin, cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used.

The ratio of the natural carbohydrate is preferably selected in the range of 0.01 to 0.04 parts by weight, preferably about 0.02 to 0.03 parts by weight, per 100 parts by weight of the health food of the present invention.

In addition to the above, the functional food of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols. And carbonation agents used in carbonated beverages. In addition, the functional food of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is usually selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the functional food of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. Since these examples are only for illustrating the present invention, the scope of the present invention is not to be construed as being limited by these examples.

Example 1. Extract Preparation

The raw poplar leaves were dried and crushed to prepare extracts. 10% (10 kg) of 50% (v / v) ethanol was added based on the weight of the leaf shreds (1 kg) of the poplar tree, followed by extraction for 6 hours at 70 ° C. and filtration with a 1 μm pore filter to obtain an extract. Then, the same amount (10 kg) of 50% (v / v) ethanol was again added to the extraction residue, followed by extraction and filtration in the same manner to obtain an extract, which was then combined with the extract obtained first.

The extract obtained through two extractions was concentrated under reduced pressure under the conditions of about 60 ° C. and vacuum degree of about 145 torr, and then dried in a freeze dryer at about −80 ° C. for 36 hours. It was then crushed with a grinder and wrapped in aluminum foil for use in subsequent experiments. The final prepared extract was named 'CRE'.

In addition, the extract was prepared in the same manner as above, but the extract was prepared using only red ginseng as a raw material and used as a positive control group.

Experimental Example 1. Evaluation of acetylcholinesterase inhibitory activity

The purpose of this study was to determine the effect of extracts on acetylcholinesterase (AChE), the most important enzyme in neuronal response and function. After diluting the CRE with the buffer solution so that the final concentration was 10, 50, and 100 ㎍ / ml, respectively, add 30 µl of the diluted extract, 10 µl of 0.3% acetylcholine esterase positive control, and 50 µl of the reaction mixture to 96 wells. After reacting at 占 폚 for 20 minutes, the absorbance was measured at a wavelength of 570 nm, and the enzyme activity inhibition was calculated. At this time, tacrin was used at a concentration of 1 μM as a positive control.

As a result, as shown in FIG. 1, CRE was shown to inhibit the activity of acetylcholinesterase in a concentration-dependent manner, and the IC 50 was calculated to be 103.48 µg / ml.

Experimental Example 2 Evaluation of Aβ Secretion Inhibitory Activity

Human APP with the Swedish mutation (APPswe) cells were used. Similar to the pathology of dementia patients, the APPswe cell line was used to detect Aβ42 secretion more than twice that of normal cells. Sandwich ELISA was performed to measure the amount of Aβ secreted from the APPswe cell line. 1 × 10 ⁶ cells were cultured in a 60 mm dish and exchanged with serum-free DMEM. After 16 hours, CRE dissolved in dimethyl sulfoxide (DMSO) was treated at a concentration of 1, 10, 50, 100 µg / ml. It was. 10 μM of β-secretase inhibitor III (B-SI) (Calbiochem, Darmstadt, Germany) was used as a positive control. After 24 hours incubation and the culture was recovered in the presence of PMSF (phenylmethanesulfonylfluoride) was used as a sample.

As a result, as shown in FIG. 2, CRE inhibited Aβ secretion in a concentration-dependent manner, and ED 50 of Aβ 40 was 78.94 μg / ml, and ED 50 of Aβ 42 was 86.93 μg / ml.

Experimental Example 3. Evaluation of Aβ aggregation inhibitory activity (TEM analysis)

In order to analyze the effect of CRE on Aβ aggregation, Transmission electron microscopy (TEM) analysis was performed after inducing Aβ aggregation as follows.

After reacting Aβ 42 (20 μM) diluted with PBS for 15 minutes at room temperature, 5 μl of CRE (10 μg / ml) and curcumin (10 μM), a positive control group, were added thereto and reacted at 37 ° C. for 0, 5 or 24 hours. . After the reaction was completed, 10µl of the sample was placed on 400mesh Copper grids (Formvar / Carbon, Electron Microscopy Science), dried, and washed twice with 5µl of Milli-Q water. Grids from which Milli-Q water was removed were stained with 10 μl of 1% uranyl acetate for 1 minute, and dried at room temperature for 15 minutes to obtain an image with a FEI G2 Spirit Twin microscope (Hitachi H-7650, Japan). At this time, three or more Aβ aggregates were secured for each sample, and three images were randomly selected, and the degree of Aβ aggregation was quantified by Image J2 (NIH).

As a result, as shown in FIGS. 3 and 4, CRE showed an excellent Aβ aggregation inhibitory activity of 46.5% compared to the negative control group (Aβ + DMSO) after 24 hours. Curcumin used as a positive control showed 29.58% inhibitory activity at the same time.

Experimental Example 4. Evaluation of Aβ aggregation inhibitory activity (ThT analysis)

Another method, Thioflavine T (ThT) method, was used to analyze the effect of CRE on the aggregation of Aβ.

After reacting Aβ 42 (20 μM) diluted with PBS for 15 minutes at room temperature, 5 μl of CRE (10 μg / ml) and curcumin (10 μM), a positive control group, were added thereto and reacted at 37 ° C. for 0, 5 or 24 hours. . After the reaction was completed, 10 μl of the sample, 30 μl of ThT 1 μM solution, and 10 μl of PBS were placed in a black 96 well, and the fluorescence absorbance was measured at ex: 485 nm / em: 535 nm. The degree of aggregation was quantified based on the negative control group based on the absorbance values obtained at this time.

As a result, as shown in Fig. 5, CRE showed excellent Aβ aggregation inhibitory activity.

Experimental Example 5. Evaluation of Antioxidant Activity

Dementia is a disease associated with aging, and aging is closely related to oxidative stress. Therefore, we tried to confirm the antioxidant activity of CRE by evaluating DPPH radical scavenging activity. Dilute CRE and positive control (vitamin C; ascorbic acid) with DMSO to final concentrations of 1, 10, 50, and 100 µg / ml, add 2.5 µl and 247.5 µl of 100 µM DPPH solution, respectively, to 96 wells for 20 minutes. After the reaction, the absorbance was measured at a wavelength of 415 nm, and the inhibition of oxidation activity was calculated.

As a result, as shown in FIG. 6, CRE showed an excellent antioxidant activity in a concentration-dependent manner, and an IC 50 was calculated to be 47.4 µg / ml.

Experimental Example 6. Short-term memory capacity test (passive avoidance test)

To summarize the animal experiments to demonstrate the effect of improving the memory and cognition of CRE is shown in Table 1.

Laboratory animals ICR mice Experimental drug CRE Dosage 500mg / kg Reference drug Red Ginseng Extract 100mg / kg Causes nerve cell damage β-Amyloid (1-42) 10 nM Dosing method Administered in a dose of 200 μl / kg body weight based on the weight of the day
The method of administration is to fix the animal by the method of fixation of the back of the neck and inject it directly into the stomach using a metal oral administration

Experimental Animals: Male ICR mice, 3 weeks old, were purchased from Korea Experimental Animal Co., Ltd., and were acclimated according to the management criteria of the Laboratory Animal Laboratory, Woosuk University.

Sample administration: Mice were divided into groups (n = 10) so that the average body weight and dispersion were uniform, and placebo and CRE were dissolved orally in a solvent (water). Behavioral experiments were performed after administration of CRE (500 mg / kg). The positive control group was administered red ginseng extract (100mg / ㎏), the negative control group was administered distilled water.

Preparation of Aβ infarction model by icv administration of beta amyloid (β) -42 After anesthetizing the mice, the epidermis of the bregma section was dissected by fixation to the stator. 5μl of Aβ42 (25ng / ml in saline) was taken with a specially prepared Hamilton syringe and injected into the auto injector (1μl / sec) at a depth of 2.4mm to be used as a model for behavioral experiments.

Passive avoidance test: Passive avoidance test was performed using the Gemini avoidance system. In the training experiment on the first day, the mice were placed in a bright box, acclimated for 30 seconds, automatically opened the door to move to a dark box, and when moved to a dark box, 0.8 mA of electrical stimulation was applied for 3 seconds. In the test experiments after 24 hours, mice were allowed to acclimate to a light box for 30 seconds and then the door was opened to move to a dark box. At this time, no electrical stimulation was performed, and the time taken to move to the dark box was measured.

As a result, as shown in Figure 7 CRE showed an excellent effect on improving memory.

Experimental Example 7. Spatial Cognitive Ability Test (Maritime Water Maze)

A circular bath was prepared and the water temperature was adjusted to about 25 ° C., and then milk powder or vegetable dye was added to the water so that the water became cloudy, and a small escape support (about 11 cm in diameter) was placed about 2 cm below the water surface. Mice use visual information to find clues in the lab where the support is located. The swimming path was recorded using a video tracking system, and the path length, swimming speed, time spent in each quadrant, and various variables were measured. The faster the animal finds its support, the shorter the swimming time (usually training to be 2 minutes). Removing the support will increase swimming time in the quadrant where the support was located. Finally, experiments with the flagged support can be used to evaluate sensory motor skills.

As shown in Experiment 6, CRE, red ginseng extract, and beta amyloid-treated mice were subjected to underwater testing. As shown in FIG. 8, CRE showed an excellent effect on improving cognitive ability.

Experimental Example 8. Evaluation of inhibitory activity of Aβ plaque in brain tissue

After performing the animal experiments of Experimental Examples 6 and 7, the brain tissues of the mice were taken, and immunohistostaining was performed using an antibody against Aβ.

As a result, as shown in Figs. 9 and 10, CRE was found to be excellent in the inhibitory activity of Aβ plaque in brain tissue.

Claims (6)

A pharmaceutical composition for improving memory, improving cognition, preventing dementia, delaying or treating the composition containing the extract of Poppy tree as an active ingredient. The method of claim 1,
The extract is a composition, characterized in that 10 to 90% (v / v) ethanol extract of the poplar leaves. The method of claim 2,
The extract is obtained by adding 1 to 20 times the weight of 10 to 90% (v / v) ethanol to the dry matter of the poplar leaves and extracting for 1 to 12 hours at 50 to 90 ℃. Functional food composition for improving memory, improving cognitive ability, preventing dementia, delaying or improving the composition containing the poplar leaf extract as an active ingredient. The method of claim 4, wherein
The extract is a composition, characterized in that 10 to 90% (v / v) ethanol extract of the poplar leaves. The method of claim 5,
The extract is obtained by adding 1 to 20 times the weight of 10 to 90% (v / v) ethanol to the dry matter of the poplar leaves and extracting for 1 to 12 hours at 50 to 90 ℃.

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