Composition for alleviating, preventing, or treating alzheimer's disease comprising apigenin and oxyresveratrol

Abstract

The present invention relates to a composition for alleviating, preventing, or treating Alzheimer's disease, the composition comprising apigenin and oxyresveratrol. A composition according to the present invention is highly effective in reducing Alzheimer's disease pathology caused by β-amyloid, which is increased by aging and oxidative stress, and improving β-amyloid-induced memory loss and cognitive function.

Description

Composition for the improvement, prevention, or treatment of Alzheimer's disease comprising apigenin and oxyresveratrol

[0001] The present invention relates to a composition for the improvement, prevention, or treatment of Alzheimer's disease comprising apigenin and oxyresveratrol.

[0002] Alzheimer's disease is the form of dementia with the highest prevalence among the elderly population aged 65 and over in Korea, as well as in Western societies. The main symptom is difficulty in daily life caused by a decline in memory, learning ability, and cognitive function. According to the 'Dementia Status in Korea 2021' report published by the Korea Institute of Medical Information in 2023, there are over 840,000 dementia patients aged 65 and older in Korea, accounting for approximately one in ten elderly people aged 65. It is estimated that this number will exceed 1.36 million by 2030, 2.17 million by 2040, and 3 million by 2050; as the national cost of dementia management exceeded 17 trillion won in 2020, it poses a serious threat to the national economy.

[0003] Although the exact pathogenesis and causes of Alzheimer's disease, which accounts for 76% of dementia cases, are unknown, the accumulation of abnormal proteins such as amyloid-beta (Aβ) and hyperphosphorylated tau in the brain is considered the primary cause based on pathological findings in patients' brains. Compared to tau protein, beta-amyloid is reported to be important in the early and middle stages of Alzheimer's disease dementia; furthermore, while tau protein is associated with frontotemporal dementia and dementia with Lewy bodies, beta-amyloid is known to have high specificity for Alzheimer's disease.

[0004] To date, various clinical trials have been attempted for dementia treatments based on pathological hypotheses, including therapies targeting Aβ protein and tauopathy, cell therapies, neurotransmission pathways, and microglia activation. However, many drugs have failed to demonstrate efficacy or had their development discontinued due to side effects. Recently, antibody therapies targeting Aβ protein were attempted, but repeated failures in clinical trials have led to a situation where even the Aβ protein hypothesis regarding Alzheimer's disease is being shaken. Fortunately, however, in June 2021, aducanumab, a beta-amyloid monoclonal antibody, demonstrated efficacy in clinical trials as a fundamental treatment. It subsequently received conditional approval from the FDA, requiring mandatory additional Phase 4 clinical trials and a re-evaluation after 10 years. Currently, acetylcholine esterase inhibitors and NMDA receptor inhibitors are used in clinical trials for the treatment of Alzheimer's disease; however, these are considered merely symptom relievers and not fundamental treatments.

[0005] Therefore, there is a need to develop effective treatments for the increasing incidence of Alzheimer's disease.

[0006] The present invention aims to provide a composition comprising apigenin and oxyresveratrol for use in improving, preventing, or treating Alzheimer's disease.

[0007] The present invention aims to provide a memory-improving use of a composition comprising apigenin and oxyresveratrol.

[0008] The present invention provides a pharmaceutical composition for the prevention or treatment of Alzheimer's disease containing a mixture of apigenin and oxyresveratrol as an active ingredient.

[0009] In this case, the above Alzheimer's disease is preferably caused by the accumulation of beta-amyloid (β-amyloid).

[0010] The present invention provides a food composition for improving Alzheimer's disease comprising a mixture of apigenin and oxyresveratrol.

[0011] The present invention provides a food composition for improving memory comprising a mixture of apigenin and oxyresveratrol.

[0012] At this time, the above memory is preferably memory loss due to Alzheimer's disease.

[0013] The composition according to the present invention has the excellent advantage of reducing the pathological phenomena of Alzheimer's disease caused by beta-amyloid (β-amyloid), which increases due to aging and oxidative stress, and improving memory loss and cognitive function caused by beta-amyloid (β-amyloid).

[0014] Figure 1 shows the results of evaluating the effect of apigenin, oxyresveratrol, or a mixture thereof on the recovery of spatial memory in an Alzheimer's disease-induced mouse model by performing a Y maze test.

[0015] Figure 2 shows the results of evaluating the effect of apigenin, oxyresveratrol, or a mixture thereof on the recovery of impaired object recognition ability in an Alzheimer's disease-induced mouse model by performing a novel object recognition test.

[0016] Figure 3 shows the results of evaluating the effects of apigenin, oxyresveratrol, or a mixture thereof on total antioxidant capacity in the cerebral cortex in an Izheimer's disease-induced mouse model.

[0017] Figure 4 shows the results of evaluating the effects of apigenin, oxyresveratrol, or a mixture thereof on AChE (Acetylcholinesterase) activity in the cerebral cortex in an Alzheimer's disease-induced mouse model.

[0018] In the following, redundant content has been omitted to prevent clutter. In other words, the content of the invention is not limited solely to the following, and should be interpreted in accordance with the overall context of the invention.

[0019]

[0020] In one embodiment according to the present invention, when a mixture of apigenin and oxyresveratrol was orally administered for two weeks to an Alzheimer's disease model prepared by inducing brain damage for one week by injecting aged beta-amyloid (β-amyloid) into the ventricles of a mouse via ICV, an excellent effect was observed in which antioxidant activity in the cerebral cortex increased rapidly and AChE (acetylcholine estasterase) activity, which increased rapidly due to beta-amyloid ventricular injection, was reduced. In addition, it was confirmed that there was a very excellent effect in restoring spatial memory and object recognition ability damaged by beta-amyloid (1-42) ventricular injection to the level of a normal mouse. It was observed that when a mixture of apigenin and oxyresveratrol was orally administered, the effects of increasing antioxidant activity, decreasing AChE activity, and restoring spatial memory and object recognition ability increased synergistically more than when apigenin or oxyresveratrol was orally administered alone.

[0021] Accordingly, the present invention aims to provide a mixture of apigenin and oxyresveratrol for use in improving, preventing, or treating Alzheimer's disease and for improving memory.

[0022]

[0023] As a preferred embodiment of the present invention, the present invention provides a pharmaceutical composition for the prevention or treatment of Alzheimer's disease containing a mixture of apigenin and oxyresveratrol as an active ingredient.

[0024] In this case, the above Alzheimer's disease is preferably caused by the accumulation of beta-amyloid (β-amyloid).

[0025] At this time, the above mixture of apigenin and oxyresveratrol is preferably apigenin and oxyresveratrol mixed in a mass ratio or molar ratio of 1 to 10:1 to 10.

[0026] Accordingly, the term "prevention" as used in the present invention refers to any act of suppressing or delaying the onset of a disease affected by the administration of the pharmaceutical composition according to the present invention, namely Alzheimer's disease.

[0027] Furthermore, the term "treatment" as used in this invention refers to any act in which the symptoms of Alzheimer's disease are improved or beneficially altered by the administration of a pharmaceutical composition according to this invention.

[0028] The mixture of apigenin and oxyresveratrol according to the present invention may additionally contain one or more active ingredients exhibiting the same or similar functions as the above ingredients.

[0029] The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier in addition to the mixture of apigenin and oxyresveratrol according to the present invention.

[0030] The types of carriers that can be used in the present invention are not particularly limited, and any carrier commonly used in the relevant technical field may be used. Non-limiting examples of the carriers include lactose, dextrose, sucrose, sorbitol, mannitol, saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, xylitol, erythritol, maltitol, maltodextrin, glycerol, ethanol, etc. These may be used alone or in a mixture of two or more types.

[0031] In addition, the pharmaceutical composition of the present invention may be used with other pharmaceutically acceptable additives, such as antioxidants, excipients, diluents, buffers, or bacteriostatic agents, if necessary, and may additionally be used with surfactants, binders, fillers, extenders, wetting agents, disintegrants, dispersants, or lubricants.

[0032] In the pharmaceutical composition of the present invention, the mixture of apigenin and oxyresveratrol according to the present invention may be included in an amount of 0.00001% to 99.99% by weight based on the total weight of the pharmaceutical composition, preferably 0.1% to 90% by weight, more preferably 0.1% to 70% by weight, and even more preferably 0.1% to 50% by weight, but is not limited thereto and may be varied depending on the condition of the subject to administration, the type of specific disease, the degree of progression, etc. If necessary, it may also be included as the total content of the pharmaceutical composition.

[0033] That is, the pharmaceutical effective amount and effective dosage of the pharmaceutical composition of the present invention may vary depending on the formulation method, administration method, administration time and / or administration route, etc., and may vary depending on various factors including the type and degree of response to be achieved by administering the pharmaceutical composition, the type of individual to be administered, age, body weight, general health condition, symptoms or severity of disease, gender, diet, excretion, and components of other compositions used simultaneously or at different times with the individual, as well as similar factors well known in the pharmaceutical field, and a person with ordinary knowledge in the art can easily determine and prescribe a dosage effective for the intended treatment. For example, the daily dosage of the pharmaceutical composition of the present invention is about 0.01 to 1,000 mg / kg, preferably 0.1 to 100 mg / kg, and may be administered once or several times a day.

[0034] The pharmaceutical composition of the present invention may be administered once a day or divided into several doses. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. Taking all of the above factors into consideration, an amount that can obtain maximum effect with a minimum amount without side effects may be administered, and this can be easily determined by a person skilled in the art.

[0035] The pharmaceutical composition of the present invention may be used in combination with various methods, such as hormone therapy and drug therapy, to prevent or treat Alzheimer's disease.

[0036] As used in the present invention, the term "administration" means introducing the pharmaceutical composition of the present invention to a patient by any appropriate method. The route and method of administration of the pharmaceutical composition of the present invention may be independent of each other, and any route and method of administration may be followed without special limitation as long as the pharmaceutical composition can reach the intended site.

[0037] The above pharmaceutical composition may be administered orally or parenterally, and may be formulated into various suitable formulations for oral or parenteral administration.

[0038] Non-limiting examples of oral formulations using the pharmaceutical composition of the present invention include oily suspensions, troches, lozenges, tablets, water-soluble suspensions, prepared powders, granules, emulsions, hard capsules, soft capsules, syrups, or elixirs.

[0039] To formulate the pharmaceutical composition of the present invention for oral administration, binders such as sorbitol, mannitol, starch, amylopectin, cellulose, lactose, saccharose, or gelatin; lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate, or polyethylene glycol wax; excipients such as dicalcium phosphate; disintegrants such as corn starch or sweet potato starch may be used, and flavorings, syrups, sweeteners, etc. may also be used. Furthermore, in the case of capsules, in addition to the materials mentioned above, liquid carriers such as fatty oils may be additionally used.

[0040] Methods of parenteral administration of the pharmaceutical composition of the present invention may include intramuscular administration, transdermal administration, intravenous administration, intraperitoneal administration, or subcutaneous administration, and methods of applying, spraying, or inhaling the composition to a diseased area may also be used, but are not limited thereto.

[0041] Non-limiting examples of parenteral formulations using the pharmaceutical composition of the present invention include injectable solutions, suppositories, ointments, topical powders, oils, powders for respiratory inhalation, aerosols for sprays, creams, etc.

[0042] To formulate the pharmaceutical composition of the present invention for parenteral administration, sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, topical agents, etc. may be used, and as the non-aqueous solvents and suspensions, vegetable oils such as olive oil, propylene glycol, polyethylene glycol, injectable esters such as ethyl oleate, etc. may be used.

[0043] When formulating the pharmaceutical composition of the present invention into an injectable solution, the pharmaceutical composition of the present invention may be mixed in water with a stabilizer or a buffer to prepare a solution or suspension, and formulated for unit administration in an ampoule or vial.

[0044] When the pharmaceutical composition of the present invention is formulated as an aerosol, it may be combined with additives such as propellants so that the dispersed concentrate or wet powder is dispersed.

[0045] When the pharmaceutical composition of the present invention is formulated into an ointment, oil, cream, topical powder, external skin preparation, etc., it may be formulated using animal oil, vegetable oil, wax, paraffin, polyethylene glycol, silicone, bentonite, silica, talc, starch, tragacanth, cellulose derivative, zinc oxide, etc. as a carrier.

[0046]

[0047] In another preferred embodiment of the present invention, the present invention provides a food composition for improving Alzheimer's disease comprising a mixture of apigenin and oxyresveratrol.

[0048] In addition, as another preferred embodiment of the present invention, the present invention provides a food composition for improving memory comprising a mixture of apigenin and oxyresveratrol. In this case, the memory is preferably memory loss due to Alzheimer's disease.

[0049] At this time, the above mixture of apigenin and oxyresveratrol is preferably apigenin and oxyresveratrol mixed in a mass ratio or molar ratio of 1 to 10:1 to 10.

[0050] The term "improvement" in this invention refers to any act in which Alzheimer's disease or memory is improved or beneficially altered by the administration of the composition of this invention.

[0051] In the food composition for improving Alzheimer's disease or memory according to the present invention, the mixture of apigenin and oxyresveratrol according to the present invention is preferably included in an amount of 0.00001 to 50 weight% relative to the food composition. If the amount is less than 0.00001 weight%, the effect is negligible, and if the amount exceeds 50 weight%, the increase in effect relative to the amount used is insignificant and therefore uneconomical.

[0052] The food composition of the present invention may be, for example, any one selected from noodles, chewing gum, dairy products, ice cream, meat, grains, caffeinated beverages, general beverages, chocolate, bread, snacks, confectionery, candy, pizza, jelly, alcoholic beverages, alcohol, vitamin complexes, and other health supplements, but is not necessarily limited thereto.

[0053] When the food composition of the present invention is used as a food additive, it may be added as is or used together with other foods or food ingredients, and may be used appropriately according to conventional methods.

[0054] The food composition according to the present invention preferably includes a health functional food. The term "health functional food" refers to a food manufactured and processed using raw materials or ingredients having functional properties useful to the human body as defined in Article 6727 of the Health Functional Foods Act, and the term "functional properties" refers to consuming the food for the purpose of obtaining useful effects for health purposes, such as regulating nutrients or physiological actions on the structure and function of the human body.

[0055] The health functional food of the present invention may include additional ingredients that can improve the smell, taste, and appearance. For example, it may include biotin, folate, pantothenic acid, vitamins A, C, D, E, B1, B2, B6, B12, niacin, etc. In addition, it may include minerals such as chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn), iron (Fe), and calcium (Ca). In addition, it may include amino acids such as cysteine, valine, lysine, and tryptophan. In addition, food additives such as preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dihydroacetate, etc.), coloring agents (tar dyes, etc.), colorants (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), disinfectants (bleaching powder and high-grade bleaching powder, sodium hypochlorite, etc.), leavening agents (alum, potassium hydrogen tartrate, etc.), reinforcing agents, emulsifiers, thickeners (sizing agents), coating agents, antioxidants [butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), etc.], seasonings (MSG, monosodium glutamate, etc.), sweeteners (dulcin, cyclamate, saccharin, sodium, etc.), flavorings (vanillin, lactones, etc.), gum bases, antifoaming agents, solvents, and improvers may be added. The above additives may be selected according to the type of food and used in appropriate amounts.

[0056] In the health functional food of the present invention, the content of the mixture of apigenin and oxyresveratrol according to the present invention is not particularly limited and can be varied depending on the condition of the subject to administration, the specific type of disease, the degree of progression, etc. If necessary, it may also be included in the total content of the food.

[0057]

[0058] The contents of the present invention will be explained in more detail below through the following examples of embodiments or experiments. However, the scope of the present invention is not limited to the following examples of embodiments or experiments, but also includes variations of equivalent technical concepts.

[0059]

[0060] [Example 1: Preparation of an Alzheimer's disease-induced mouse model and administration of apigenin, oxyresveratrol, or a mixture thereof]

[0061] In the experiment, 6-week-old mice were used, which were 5-week-old male normal mice (C57BL / 6N) purchased from Orient Bio Co., Ltd. and adapted for 1 week.

[0062] To induce Alzheimer's disease, 5 μl (500 pmol) of β-Amyloid Peptide (1-42 (Sigma-Aldrich A9810, dissolved in physiological saline at 100 μM and aged at 37°C for 3 days)) was injected into the ventricles of 6-week-old mice using an ICV (Intracerebroventricular) Hamilton syringe, and brain damage was induced for 1 week to create an Alzheimer's disease mouse model.

[0063] For two weeks starting one week after the injection of β-Amyloid Peptide, each group was administered a standard diet, a diet containing apigenin (20 mg / kg body / day), a diet containing oxyresveratrol (20 mg / kg body / day), and a diet containing a mixture of apigenin and oxyresveratrol (20 mg / kg body / day each or 40 mg / kg body / day each).

[0064] The control group and experimental group designed in the present invention are as shown in Table 1 below.

[0065] β-Amyloid Peptide (µL) Apigenin (body / day) Oxyresveratrol (body / day) Normal Group (untreated, Normal) --- Aβ-Treated Group (Aβ) 5 --- Aβ+apigenin-Treated Group (A) 520 mg / kg --- Aβ+oxyresveratrol-Treated Group (O) 5 20 mg / kg --- Aβ+apigenin-oxyresveratrol-1-Treated Group (AO1) 520 mg / kg 20 mg / kg --- Aβ+apigenin-oxyresveratrol-2-Treated Group (AO2) 540 mg / kg 40 mg / kg

[0066]

[0067] [Experimental Example 1: Cognitive Function Test]

[0068] A Y-maze test and a novel object recognition test were performed on the control group and the experimental group according to Example 1.

[0069] 1. Y-maze test

[0070] The Y-maze test is constructed of black acrylic with three identical arms and can evaluate the animal's spontaneous alteration ability to find new things based on its spatial memory.

[0071] Specifically, the number of times the mouse started from the starting point and entered passages A, B, and C (three arms) for 8 minutes was recorded, and the change behavior ability based on memory was measured as shown in Equation 1 below, and the results are shown in Table 2 below.

[0072] [Mathematical Formula 1]

[0073] Alteration Rate (%) = Actual Alteration / Maximum Alteration × 100

[0074] NormalAβAOAO1AO2lteration Index32.51418.518.7532.2532.55Standard deviation0.701.001.410.951.521.00

[0075]

[0076] Experimental results showed that spatial memory in the Aβ-treated group decreased to 43% of that of normal mice compared to the normal group (Normal), spatial memory in the Aβ+apigenin-treated group (A) recovered to 57% of that of the normal group, and spatial memory in the Aβ+oxyresveratrol-treated group (O) recovered to 58% of that of the normal group.

[0077] In addition, in the Aβ+apigenin-oxyresveratrol-1 treatment group (AO1), spatial memory was found to be restored to 100% of the normal group, and in the Aβ+apigenin-oxyresveratrol-2 treatment group (AO2), spatial memory was found to be restored to 100% (Fig. 1). Fig. 1 shows the results of evaluating the effect of apigenin, oxyresveratrol, or a mixture thereof on the recovery of spatial memory in an Alzheimer's disease-induced mouse model by performing a Y maze test.

[0078] That is, when apigenin or oxyresveratrol was administered alone, it showed a slight recovery effect, but when a mixture of apigenin and oxyresveratrol was administered, it showed an excellent therapeutic effect that synergistically restored spatial memory damaged by the injection of Aβ (1-42) into the ventricles to the level of normal mice.

[0079]

[0080] 2. Object Recognition Function Test

[0081] The Novel object recognition test consists of three stages: habituation, familiarization, and testing, and evaluates object recognition memory ability based on the mouse's curiosity about new objects.

[0082] Specifically, the subjects were acclimatized to an empty test box for 10 minutes on the first day, and on the second day, during the familiarization phase, they were instructed to explore two identical objects for 10 minutes. On the third day, during the test phase, one of the two objects was replaced with a new object, and subjects were instructed to explore it for 10 minutes; the contact time with the objects was recorded and used as data. The Object Recognition Function (ORT) index was calculated using the formula shown in Equation 2 below, and the results are shown in Table 3 below.

[0083] [Mathematical Formula 2]

[0084] Recognition index in ORT = (NF) / (N+F)

[0026]

[0085] N: New object search time, F: Familiar object search time

[0086] NormalAβAOAO1AO2Recognition Index0.7630.3920.4720.4930.7730.770Standard deviation0.0410.0340.0230.0350.0410.042

[0087]

[0088] Experimental results showed that object recognition ability in the Aβ-treated group decreased to 51% of the normal group (Normal), and object recognition ability in the Aβ+apigenin-treated group (A) and the Aβ+oxyresveratrol-treated group (O) recovered to approximately 62% and 65% of the normal group, respectively.

[0089] In addition, in the Aβ+apigenin-oxyresveratrol-1 treatment group (AO1) and the Aβ+apigenin-oxyresveratrol-2 treatment group (AO2), it was confirmed that object recognition ability reduced by Aβ (1-42) injection was restored to a level similar to that of the normal group by 100% (Fig. 2). Fig. 2 shows the results of evaluating the effect of apigenin, oxyresveratrol, or a mixture thereof on the recovery of impaired object recognition ability in an Alzheimer's disease-induced mouse model by performing a novel objective recognition test.

[0090] That is, when apigenin or oxyresveratrol was administered alone, it showed a slight recovery effect, but when a mixture of apigenin and oxyresveratrol was administered, it showed an excellent therapeutic effect that synergistically restored spatial memory damaged by injection into the ventricles of Aβ (1-42) to the level of normal mice, which means that when apigenin and oxyresveratrol are mixed, there is a synergistic effect that is greatly improved compared to using them alone.

[0091]

[0092] [Experimental Example 2. Analysis of Total Antioxidant Activity and AChE Activity in the Cerebral Cortex]

[0093] 1. Analysis of total antioxidant activity

[0094] After the behavioral test according to Experimental Example 1, mice were slaughtered by cervical dislocation, and the hippocampus and cerebral cortex were immediately isolated and stored at -20℃. The total antioxidant capacity was analyzed using an antioxidant assay kit (sigma Aldrich CS0790K), and the results are shown in Table 4 below.

[0095] NormalAβAOAO1AO2Total antioxidant capacity0.1240.0950.2150.2180.8740.915Standard deviation0.0190.0060.0060.0070.0220.016

[0096]

[0097] As a result of the experiment, the total antioxidant activity in the Aβ-treated group was found to be reduced to about 76% of the normal group compared to the normal group (Normal), while the Aβ+apigenin-treated group (A) increased to 173% of the normal group, and the Aβ+oxyresveratrol-treated group (O) also increased to about 176% of the normal group.

[0098] In addition, in the Aβ+apigenin-oxyresveratrol-1 treated group (AO1) and the Aβ+apigenin-oxyresveratrol-2 treated group (AO2), it was confirmed that the total antioxidant activity reduced by Aβ (1-42) injection increased to more than 700% of the normal group level (Fig. 3). Fig. 3 shows the results of evaluating the effect of apigenin, oxyresveratrol, or a mixture thereof on total antioxidant capacity in the cerebral cortex in an Alzheimer's disease-induced mouse model.

[0099] That is, when apigenin or oxyresveratrol was administered alone, it showed a slight increase effect, but when a mixture of apigenin and oxyresveratrol was administered, it showed a very excellent effect of synergistically increasing the antioxidant activity reduced by injection into the ventricles of Aβ(1-42) to 700% of the normal mouse level.

[0100]

[0101] 2. AChE Activity Analysis

[0102] After the behavioral test according to Experimental Example 1, the mouse was slaughtered by cervical dislocation, and the cerebral cortex was immediately isolated and stored at -20℃. Then, AChE (acetylcholine esterase) activity was analyzed using an AChE assay kit (Sigma-Aldrich Acetylcholinesterase Assay Kit, CS003-KT).

[0103] NormalAβAOAO1AO2AChE activity0.0050.8180.5940.5760.0920.022Standard deviation0.00040.0320.0230.0080.0120.001

[0104]

[0105] Experimental results showed that AChE activity increased 160-fold in the Aβ-treated group compared to the normal group (Normal), AChE activity in the Aβ+apigenin-treated group (A) decreased to 72% of the level of the Aβ-treated group, and AChE activity in the Aβ+oxyresveratrol-treated group (O) also decreased to 70% of the level of the Aβ group.

[0106] In addition, in the Aβ+apigenin-oxyresveratrol-1 treated group (AO1), AChE activity decreased to 11% of the level of the Aβ treated group, and in the Aβ+apigenin-oxyresveratrol-2 treated group (AO2), AChE activity decreased to 2.5% of the level of the Aβ treated group, showing activity similar to that of the normal group (Fig. 4). Fig. 4 shows the results of evaluating the effects of apigenin, oxyresveratrol, or a mixture thereof on AChE (Acetylcholinesterase) activity in the cerebral cortex in an Zheimer's disease-induced mouse model.

[0107] That is, when apigenin or oxyresveratrol was administered alone, it showed a slight reduction effect, but when a mixture of apigenin and oxyresveratrol was administered, it showed an excellent effect of synergistically reducing the AChE activity, which had surged due to injection into the ventricles of Aβ (1-42), to 10% of the normal mouse level.

Claims

1. A pharmaceutical composition for the prevention or treatment of Alzheimer's disease containing a mixture of apigenin and oxyresveratrol as an active ingredient.

2. A pharmaceutical composition according to claim 1, wherein the Alzheimer's disease is caused by the accumulation of beta-amyloid (β-amyloid).

3. A food composition for improving Alzheimer's disease comprising a mixture of apigenin and oxyresveratrol.

4. A food composition for improving memory comprising a mixture of apigenin and oxyresveratrol.

5. In Paragraph 4, The above memory is, A food composition for memory loss due to Alzheimer's disease.

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