WO2017183768A1

WO2017183768A1 - Pharmaceutical composition and health functional food comprising oat extract avenanthramide c or derivative thereof as effective ingredient for prevention or treatment of neurodegenerative disease

Info

Publication number: WO2017183768A1
Application number: PCT/KR2016/007196
Authority: WO
Inventors: 조지훈; 김형석; 이유영
Original assignee: 전남대학교산학협력단; 대한민국(농촌진흥청장)
Priority date: 2016-04-20
Filing date: 2016-07-04
Publication date: 2017-10-26

Abstract

The present invention relates to a pharmaceutical composition and a health functional food, both comprising an oat extract as an effective ingredient for prevention or treatment of neurodegenerative diseases. More particularly, the present invention relates to a pharmaceutical composition and a health functional food both of which comprise avenanthramide C, which is an oat extract, or a derivative thereof, e.g., avenanthramide C methyl ester, as an effective ingredient for preventing or treating Alzheimer disease.

Description

Pharmaceutical composition and health functional food for the prevention or treatment of degenerative neurological diseases comprising oat extract avenanthramid C or derivatives thereof as an active ingredient

The present invention relates to a pharmaceutical composition and health functional food for the prevention or treatment of degenerative neurological diseases comprising oat extract as an active ingredient. More specifically, the present invention provides a pharmaceutical composition for the prophylaxis or treatment of Alzheimer's disease comprising avenanthramide C (Avenanthramide C) or derivatives thereof, such as ebenanthramide C methyl ester as an active ingredient as an oat extract and It relates to health functional food.

Alzheimer's disease is a degenerative neurological disorder that causes memory, thinking and behavioral problems and is estimated to account for 60-80% of dementia cases (Blennow et al., 2006, Lancet 368: 387). Alzheimer's disease causes histopathologically the overall atrophy of the brain, enlargement of the ventricles, multiple lesions of nerve fibers (neural fiber distortion) and neuritic plaque. Many causes of Alzheimer's disease have been reported, but invention by accumulation of amyloid-β protein is reported to be the most likely cause. Accumulation of amyloid-β proteins causes damage to nerve cells and activates GSK3β enzymes, which are known to interfere with long term potentiation (LTP), which is required for memory formation. The onset of death after onset is usually 6-8 years, but sometimes over 20 years.

In the United States, more than 5 million people are known to have Alzheimer's disease, and the number of Americans with Alzheimer's disease and other dementia is expected to grow each year as the proportion of Americans age 65 and older continues to increase. In 2000, the elderly population aged 65 years or older exceeded 7.2% of the total population and entered an aging society.In 2010, the elderly population accounted for 11% of the total population, and an increase in dementia patients was predicted. A national epidemiological study conducted by the Ministry of Health and Welfare showed that the incidence of dementia among the elderly aged 65 or older was 540,755, or 9.18 per 100 people, and that Alzheimer's disease was 70.5% of all dementia. This is high compared to 50% to 70% of Alzheimer's disease patients among the dementia patients surveyed in overseas studies, suggesting that treatment of Alzheimer's disease is emerging as an important solution for the elderly population.

Accordingly, the present inventors have made efforts to develop a composition for preventing or treating neurodegenerative diseases using natural products. As a result, avenanthramid C or a derivative thereof such as avenanthramid C-methyl ester in oat extract is amyloid-β. The present invention was confirmed by inhibiting the activity of GSK3β (Glycogen synthase kinase-3β) activated by (Aβ) and also inducing LTP by interfering with the action of amyloid-β that inhibits long-term potentiation (LTP). The invention was completed.

As used herein, the term "oat" is believed to have spread from eastern to central Europe with barley around 5000 BC and is a plant that has been used for more than 800 years in Europe for nutritional and medical purposes. Oat is a monocotyledonous plant of the rice family Paddy, and it is an cultivated crop of two years. It is also called oat. There are about 70 species, but only a few of them are grown, mainly Wild oat (avena sativa L.). The height is about 90㎝, the leaves are 15 ~ 30㎝ long, the butterfly 6 ~ 12㎜, the leaf is flat, the leaf is long and the leaf lobe is short and finely divided. Flowers bloom in May-June, cone inflorescences, branches turn and split again. A glume has no ridges, many veins, and flanks. The fruit is wrapped inside and outside, with hairs and grooves on one side. Fruits are made from oatmeal and are used as alcohol, sweets and livestock feed. Ingredients of the oats include beta-carotene, vitamin C, niacin, riboflavin, thiamine, retinol, dietary fiber, avenanthhramide, etc. Among them, avenanthramide inhibits active oxygen as an antioxidant. It is known. The avenanthramides may be classified into avenanthramide-A, avenanthramide-B, avenanthramide C, avenanthramide-O, and avenanthramide-P.

As used herein, the term "neurodegenerative disease" refers to a disease in which the nervous system loses function due to degenerative changes in nerve cells. The degenerative neurological diseases include Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration, Parkinson's disease, and multiple system atrophy. multiple system atrophy, progressive supranuclear palsy, Huntington's disease, dentato-rubro-pallido-luysian atrophy, spinocerebellar ataxia, muscle atrophy It may be selected from the group consisting of amyotrophic lateral sclerosis, primary lateral sclerosis, and spinal muscular atrophy, but is not limited thereto.

As used herein, the term "Alzheimer's disease" is a disease that causes severe memory and other intellectual loss that interferes with daily life. Histopathologically, the general atrophy of the brain, the expansion of the ventricles, and multiple lesions of nerve fibers ( Neurodegenerative disease, characterized by neurofibrillation) and neuritic plaque.

As used herein, the term "amyloid-β" is a peptide consisting of 36-43 amino acids and is produced by degradation of an amyloid precursor protein (APP) by an enzyme such as secretase. The generated amyloid-β is agglomerated into several forms, and plaques having neurotoxicity are generated by multimers folded into wrong forms, causing neurological diseases.

As used herein, the term "GSK3β" refers to an enzyme that functions to phosphorylate other proteins and regulates various actions such as energy metabolism, cell proliferation and apoptosis.

As used herein, the term "long-term strengthening" refers to a phenomenon in which signal transmission of two neurons is continuously improved by stimulating neurons at the same time. Long-term strengthening is considered to be one of the major cellular mechanisms in learning and memory, and the formation of long-term strengthening strengthens synapses between neurons by new protein synthesis, leading to presynaptic neurons and postsynaptic neurons. ) Increases the ability to transmit signals through synapses. Long-term reinforcement applies to various types of learning, from classical conditioning to complex higher cognitive processes.

According to one aspect,

The present invention is to provide a pharmaceutical composition for preventing or treating neurodegenerative diseases comprising oat extract as an active ingredient. The oat extract is characterized in that the avenanthramid C or a derivative thereof represented by the following formula (1).

[Formula 1]

In the pharmaceutical composition for preventing or treating neurodegenerative diseases according to the present invention, the derivative of avenanthramid C is an avenanthramide C methyl ester represented by Formula 2 below. do.

[Formula 2]

In the pharmaceutical composition for preventing or treating degenerative neurological disease according to the present invention, the oat extract is characterized in that it is included at least 50μM.

In the pharmaceutical composition for preventing or treating neurodegenerative diseases according to the present invention, the oat extract is characterized by inhibiting the activity of GSK3β (Glycogen synthase kinase-3β) by accumulation of amyloid-β.

In the pharmaceutical composition for preventing or treating degenerative neurological disease according to the present invention, the oat extract is characterized by re-inducing long-term potentiation (LTP) inhibited by the accumulation of amyloid-β.

The pharmaceutical composition according to the present invention may further comprise a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier is commonly used, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpi Ralidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical compositions according to the invention can be administered orally or parenterally. In the case of parenteral administration, it can be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, topical administration, transdermal administration, nasal administration and the like. Most preferably, it is administered by nasal administration.

Suitable dosages of the pharmaceutical compositions according to the invention may be prescribed in various ways, such as by the method of formulation, the age, weight, sex, morbidity of the patient, food, time of administration, route of administration, rate of excretion and response to reaction. have. On the other hand, when the pharmaceutical composition of the present invention is used as a composition for nasal administration, the preferred unit spray amount is 20 to 500 μg, and the most preferable unit spray amount is 50 to 200 μg. It is difficult to achieve the desired effect at a small amount of the composition of the spray amount of less than 20 μg, the unit spray amount of more than 500 μg is difficult to administer because the composition flows out of the nasal cavity when spraying intranasally.

The pharmaceutical composition according to the invention may be formulated in unit dose form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Can be prepared.

According to another aspect,

The present invention is to provide a health functional food for preventing or improving degenerative neurological disease comprising oat extract as an active ingredient. The oat extract is characterized in that the avenanthramid C or a derivative thereof represented by Formula 1 below:

[Formula 1]

In the health functional food for preventing or improving degenerative neurological disease according to the present invention, the derivative of avenanthramid C is an avenanthramide C methyl ester represented by Formula 2 below. do.

[Formula 2]

In the health functional food for preventing or improving degenerative neurological disease according to the present invention, the derivative of avenanthramid C includes avenanthramid C-methyl ester, avenanthramid A or avenanthramid B It features.

The health functional food according to the present invention includes not only the above-mentioned effective ingredient, but also ingredients normally added during food preparation, and may include, for example, proteins, carbohydrates, fats, nutrients, seasonings, and flavoring agents. The carbohydrates are monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agents [tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, if the health functional food of the present invention is prepared with a drink, in addition to the active ingredient of the present invention, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract, jujube extract or licorice extract, etc. Can be included.

Avenanthramid C, an oat extract according to the present invention, inhibits the activity of GSK3β induced by amyloid-β and induces LTP inhibited by the accumulation of amyloid-β. It can be usefully used for the prevention or treatment of. In particular, the oat extract according to the present invention is a natural product having stability without cytotoxicity, so the composition of the present invention comprising it as an active ingredient has a safe advantage even for long-term use without side effects to the human body.

Figure 1 shows the results of LTP induction experiments using hippocampal sections of normal mice not treated with amyloid-β and avenanthramid C according to Experimental Example 1.

Figure 2 shows the results of LTP induction experiments using hippocampal sections of mice treated with 500 nM amyloid-β according to Experimental Example 1.

Figure 3 shows the results of LTP induction experiment using hippocampal sections of mice treated with 500 nM amyloid-β and 50 μM avenanthramid C according to Experimental Example 1.

4 shows the results of LTP induction experiments using hippocampal sections of mice treated with 50 μM of avenanthramid C according to Experimental Example 1. FIG.

FIG. 5 shows the results of LTP induction experiments using hippocampal sections of mice treated with 500 nM amyloid-β and 10 μM avenanthramid C according to Experimental Example 1. FIG.

6 shows the results of LTP induction experiments using hippocampal sections of mice treated with 500 μM of avenanthramid C according to Experimental Example 1. FIG.

Figure 7 shows the results of LTP induction using hippocampal sections of mice treated with 500 nM amyloid-β and 500 μM avenanthramid C according to Experimental Example 1.

8 shows the results of GSK3β activity when 500 nM of amyloid-β and 50 μM of avenanthramid C were treated according to Experimental Example 2. FIG.

9 shows the results of GSK3β activity when 500 nM amyloid-β and 500 μM avenanthramid C were treated according to Experimental Example 2. FIG.

10 shows the results of avenanthramid C on LTP in Alzheimer's induced mice according to Experimental Example 3 (FIG. 10A: Avenanthramid C untreated hippocampal section, FIG. 10B: Avenanthramid C treated hippocampal section).

11 shows the results of Western blotting according to Experimental Example 3.

12 shows the results of avenanthramid C on LTP in Alzheimer's induced mice according to Experimental Example 4 (FIG. 12A: Avenanthramid C untreated hippocampal section, FIG. 12B: Avenanthramid C treated hippocampal section).

13 shows the results of Western blotting according to Experimental Example 4.

FIG. 14 shows the results of abenanthramid C-methyl ester on LTP in mice according to Experimental Example 5 (FIG. 14A: Amyloid-β and Avenanthramid C untreated hippocampal sections, FIG. 14B: 500 nM amyloid-β) Treated hippocampal sections, FIG. 14C: 50 μM of avenanthramide C-methyl ester and 500 nM amyloid-β treated hippocampal sections).

15 shows western blotting results according to Experimental Example 5. FIG.

Figure 16 shows the results of avenanthramid-B on LTP in Alzheimer's-induced mice according to Experimental Example 6 (Fig. 16a: Avenanthramid-B untreated hippocampal section, Fig. 16b: Avenanthramid-B treated hippocampus) Intercept).

17 shows the results of avenanthramid-A on LTP in Alzheimer's induced mice according to Experimental Example 7 (FIG. 17A: Avenanthramid-A untreated hippocampal section, FIG. 17B: Avenanthramid-A treated hippocampus Intercept).

18 shows the results of LTP induction experiments using hippocampal sections of normal mice not treated with amyloid-β and glucan according to Experimental Example 8. FIG.

19 shows LTP induction experiments using hippocampal sections of 500 nM amyloid-β-treated mice according to Experimental Example 8. FIG.

20 shows LTP induction experiments using hippocampal sections of mice treated with 500 nM amyloid-β and 80 nM β-glucan according to Experimental Example 8. FIG.

Figure 21 shows the results of LTP induction experiment using hippocampal sections of mice treated with 80 nM β-glucan only according to Experimental Example 8.

Fig. 22 shows the results of β-glucan on LTP in Alzheimer's induced mice according to Experimental Example 9 (Fig. 22a: β-glucan untreated hippocampal sections, Fig. 22b: β-glucan treated hippocampal sections).

Hereinafter, the present invention will be described in detail by the following examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited by the following examples.

<실시예 1><Example 1>

Example 1 Preparation of Experimental Animals

C57BL / 6 mice (Central Laboratory Animals) and 5X FAD mice (Jackson Laboratory) were used, and diet and drinking water were freely consumed in a controlled feeding room with a temperature of 23 ± 3 ° C, 60 ± 10% humidity, and a 12 hour light / dark cycle. Adapted for 7 days after import and used for the experiment. Management and maintenance of experimental animals and experimental procedures were carried out with the approval of Chonnam National University Ethics Committee.

Example 2. Preparation of Hippocampal Sections

The mice of Example 1 were decapitation after anesthesia and brains were extracted. The extracted brain was stored with 95% oxygen in cooled aCSF (124 mM NaCl, 3 mM KCl, 26 mM NaHCO3, 2 mM CaCl2, 1 mM MgSO4, 10 mM Glucose, 1.25 mM NaH2PO4, and 2 mM CaCl ₂ ). Samples were made to a thickness of 400 μm, and then supplied with 95% oxygen, 22-25 ° C. aCSF (124 mM NaCl, 3 mM KCl, 26 mM NaHCO 3, 2 mM CaCl 2, 1 mM MgSO 4, 10 mM Glucose, 1.25 mM NaH 2 PO 4, and 2 mM CaCl _2). ) Was recovered for 1 hour and then used for the experiment.

<실험예>Experimental Example

Experimental Example 1. According to the present invention Abenanthramid Long-term strengthening by treatment of C LTP ) compare

Hippocampal sections of 4-month-old C57BL / 6 mice were treated with amyloid-β and avenanthramid C 2 hours prior to LTP comparison experiments as shown in Table 1 below.

TABLE 1

LTP induction was observed by analyzing the field excitatory postsynaptic potential (fEPSP) by Schaffer-Collateral fiber stimulation after placing the hippocampal sections in recording chambers. It was applied every 200ms for 90 minutes. During the experiment, 30 ° C. aCSF was supplied by perfusion at a rate of 2-3 ml / min, and the obtained experimental results were compared and analyzed using ANOVA tests known in the art, which are shown in FIGS. 1 to 7.

As a result, LTP was induced in Sample 1 not treated with amyloid-β and avenanthramid C (FIG. 1), but LTP was not induced in Sample 2 treated with 500 nM amyloid-β (FIG. 2). LTP was induced in Sample 3 treated with 500 nM amyloid-β and 50 μM avenanthramid C (FIG. 3). In addition, LTP was induced in Sample 4 in which only 50 μM of avenanthramid C was treated (Fig. 4). On the other hand, LTP was not induced in Sample 5 treated with 500 nM of amyloid-β and 10 μM of avenanthramid C (FIG. 5). That is, when amyloid-β and avenanthramid C are given together, 10 μM of avenanthramid C supply does not prevent LTP formation by amyloid-β, but 50 μM of avenanthramid C supply is caused by amyloid-β. It has been confirmed that it can block interference with LTP formation.

On the other hand, Sample 5 treated with only 500μM avenanthramid C showed no toxicity and confirmed that LTP was induced like Sample 1 (FIG. 6). In addition, LTP was also induced in Sample 6 treated with 500 nM of amyloid-β and 500 μM of avenanthramid C (FIG. 7).

Experimental Example 2. According to the present invention Abenanthramid According to the processing of C Of GSK3β Active comparison

Hippocampal sections of 4-month-old C57BL / 6 mice were treated with amyloid-β and avenanthramid C as shown in Table 1 above, followed by grinding with a homogenizer on ice with RIPA buffer 4 RIPA [50 mM Tris-HCl (pH 7.5), 150 mM NaCl, 1% Nonidet P-40, 0.5% sodium deoxycholate, 0.1% SDS, 1 mM PMSF (phenylmethylsulfonyl fluoride), 1 mM DTT and Lupeptin 2 [mu] g of tinine each. Crushed cells were centrifuged at 12,000 g for 20 minutes at 4 ° C., and the resulting soluble fractions were denatured in Laemmli buffer and subjected to SDS-PAGE. After gel electrophoresis, the separated proteins were transferred to polyvinylidenedifluoride (PVDF) membranes using electroblotting. The membrane was blocked with amresco, rapidblock solution (pH 7), and blotting was performed using enhanced chemiluminescence (ECL). For blotting, the results are shown in FIGS. 8 and 9 using an antibody against GSK3αβ and an antibody against phosphorylated GSK3β (S9). GSK3β is an enzyme whose activity is inhibited by phosphorylation of the serine residue 9 and is known as a regulator of a wide range of functions such as energy metabolism, cell proliferation and apoptosis.

As a result, the amyloid-β treatment activated GSK3β, and when 500nM amyloid-β was treated with 50μM avenanthramid C, the GSK3β activity was inhibited (FIG. 8). In addition, even when 500 nM amyloid-β was treated with 500 μM of avenanthramid C, it was confirmed that GSK3β activity was suppressed and not toxic (FIG. 9).

Experimental Example 3. According to the present invention Abenanthramid Effect of C on Alzheimer's Induced Mouse (5X FAD Mouse)

(1) Long-term strengthening (LTP) comparison

In order to investigate the effect of avenanthramid C according to the present invention on the long-term potentiation of hippocampal sections of 4 month-old 5 X FAD Alzheimer's-induced mice, the comparison of LTP in the same manner as in Experiment 1 using hippocampal sections of genetically modified mice The experiment was performed and shown in FIG. 10.

As a result, Alzheimer's-induced mice failed to form LTP (FIG. 10A), but it was confirmed that LTP was induced when 50 μM of avenanthramid C was treated (FIG. 10B).

(2) GSK3β activity comparison

In order to determine the effect of avenanthramid C according to the present invention on GSK3β activity in hippocampal sections of 4 month-old 5 X FAD Alzheimer's-induced mice, the same western blotting as Experimental Example 2 was performed using hippocampal sections of genetically modified mice. This was done and shown in FIG. 11.

As a result, it was confirmed that the treatment of 50 μM of avenanthramid C inhibited the activity of GSK3β as compared with the case of no treatment of avenanthramid C (FIG. 11).

Experimental Example 4. According to the present invention Abenanthramid Effect of C on Another Alzheimer's Induced Mouse (Tg2576 Mouse)

(1) Long-term strengthening (LTP) comparison

In order to determine the effect of avenanthramid C according to the present invention on the organ reinforcement in hippocampal sections of 7-month-old Tg2576 Alzheimer's-induced mice, a comparative experiment of LTP was carried out in the same manner as in Experiment 1 using hippocampal sections of genetically modified mice. This was done and shown in FIG. 12.

As a result, Alzheimer's-induced mice failed to form LTP (FIG. 12A), but it was confirmed that LTP was induced when 50 μM of avenanthramid C was treated (FIG. 12B).

(2) GSK3β activity comparison

In order to determine the effect of avenanthramid C according to the present invention on GSK3β activity in hippocampal sections of 7-month-old Tg2576 Alzheimer's-induced mice, the same Western blotting as in Experiment 2 was performed using hippocampal sections of genetically modified mice. This is shown in FIG. 13.

As a result, it was confirmed that the treatment of 50 μM of avenanthramid C inhibited the activity of GSK3β as compared to the case of no treatment of avenanthramide C (FIG. 13).

Experimental Example 5. According to the present invention Abenanthramid C- methyl Comparison of long-term potentiation (LTP) and GSK3β activity according to ester treatment

(1) Long-term strengthening (LTP) comparison

In order to determine the effect of avenanthramid C-methyl ester according to the present invention on organ reinforcement in hippocampal sections of mice, LTP comparison experiments were carried out in the same manner as in Experimental Example 1 and shown in FIG. 14.

As a result, LTP was induced when the amyloid-β and avenanthramid C-methyl esters were not treated (FIG. 14A), and LTP was not induced when the 500 nM amyloid-β was treated (FIG. 14B). It was confirmed that LTP was induced when treated with 50 μM of avenanthramid C-methyl ester and 500 nM amyloid-β (FIG. 14C).

(2) GSK3β activity comparison

In order to determine the effect of avenanthramid C-methyl ester according to the present invention on GSK3β activity in hippocampal sections of mice, the same Western blotting as in Experimental Example 2 was performed and this is shown in FIG. 15.

As a result, it was confirmed that the activity of GSK3β was inhibited when treated with 50 μM of avenanthramid C-methyl ester and 500 nM amyloid-β (FIG. 15).

Experimental Example 6. As a comparative example Abenanthramid Of B-B on Alzheimer's Induced Tg2576 Mouse

In order to investigate the effects of avenanthramid-B according to the present invention on the organ reinforcement in hippocampal sections of 7-month-old Tg2576 Alzheimer's-induced mice, LTP comparison experiments were performed in the same manner as Experimental Example 1 using hippocampal sections of genetically modified mice. Was performed and shown in FIG. 16.

As a result, Alzheimer's-induced mice failed to form LTP (FIG. 16a), and when 50 μM of avenanthramid-B was treated, LTP was slightly induced but did not recover completely unlike avenanthramide C. It was confirmed not to (FIG. 16B).

Experimental Example 7. As a comparative example Abenanthramid Of A-A on Alzheimer's Induced Tg2576 Mouse

In order to investigate the effect of avenanthramid-A according to the present invention on the long-term strengthening of hippocampal sections of 7-month-old Tg2576 Alzheimer's-induced mice, LTP comparison experiments were carried out in the same manner as in Experiment 1 using hippocampal sections of genetically modified mice. Was performed and shown in FIG. 17.

As a result, Alzheimer's-induced mice failed to form LTP (FIG. 17A), but it was confirmed that LTP was not induced when 50 μM of avenanthramid-A was treated (FIG. 17B).

Experimental Example 8. As a comparative example Long-term reinforcement following treatment of β-glucan (β-glucan) LTP ) compare

Except for using β-glucan instead of avenanthramid C according to the present invention, LTP was treated with amyloid-β and β-glucan according to Experimental Example 1 and 2 hours before, using LTP. Comparative experiments were performed. The results are shown in FIGS. 18 to 21.

TABLE 2

As a result, LTP was induced in Sample 6 not treated with amyloid-β and β-glucan (FIG. 18), but LTP was not induced in Sample 7 treated with 500 nM amyloid-β (FIG. 19). On the other hand, LTP was not induced even in Sample 8 treated with 500 nM of amyloid-β with 80 μg / ml of β-glucan (FIG. 20). In addition, LTP was induced in Sample 9 treated with 80 μg / ml β-glucan only (Sample 21). That is, as shown in Experiment 1, the avenanthramid C according to the present invention may block the interference of LTP formation by amyloid-β, but β-glucan, one of oat extracts, prevents the interference of LTP formation by amyloid-β. It was confirmed that it could not be blocked.

Experimental Example 9. As a comparative example Effects of Beta Glucan (β-Glucan) on Alzheimer's Induced Mice

LTP comparison experiments were performed on hippocampal sections of Alzheimer's-induced mice using the same method as Experimental Example 3 except that β-glucan was used instead of avenanthramid C according to the present invention. The results are shown in FIG. 22.

As can be seen from FIG. 22, Alzheimer's-induced mice that did not process anything failed to form LTP (22a), and even when treated with 80 μg / ml β-glucan, LTP was not induced as in the case where nothing was treated. It was confirmed (FIG. 22B).

So far I looked at the center of the preferred embodiment for the present invention. Those skilled in the art will appreciate that the present invention can be implemented in a modified form without departing from the essential features of the present invention. Therefore, the disclosed embodiments should be considered in descriptive sense only and not for purposes of limitation. The scope of the present invention is shown in the claims rather than the foregoing description, and all differences within the scope will be construed as being included in the present invention.

Avenanthramide C (Avenanthramide C), an oat extract according to the present invention, inhibits the activity of GSK3β induced by amyloid-β and induces LTP inhibited by the accumulation of amyloid-β. It can be usefully used in the pharmaceutical composition and health functional food for the prevention or treatment of Alzheimer's disease.

Claims

Pharmaceutical composition for preventing or treating neurodegenerative diseases comprising oven extract as an active ingredient avenanthramid C or a derivative thereof represented by the following formula (1).

[Formula 1]
The method of claim 1,

The derivative of avenanthramid C is characterized in that the avenanthramid C-methyl ester represented by the following formula (2), pharmaceutical composition.

[Formula 2]
The method of claim 1,

The avenanthramid C is characterized in that it comprises 50μM or more, pharmaceutical composition.
The method of claim 1,

The avenanthramid C is characterized in that to inhibit the activity of GSK3β (Glycogen synthase kinase-3β) by the accumulation of amyloid-β, pharmaceutical composition.
The method of claim 1,

The avenanthramid C is characterized in that the induction of LTP (Long-term potentiation) inhibited by the accumulation of amyloid-β again, pharmaceutical composition.
The method of claim 1,

The neurodegenerative diseases include Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration, Parkinson's disease, and multiple system atrophy. multiple system atrophy, progressive supranuclear palsy, Huntington's disease, dentato-rubro-pallido-luysian atrophy, spinocerebellar ataxia A pharmaceutical composition, characterized in that it is selected from the group consisting of amyotrophic lateral sclerosis, primary lateral sclerosis and spinal muscular atrophy.
A functional health food for preventing or improving degenerative neurological disease, comprising oven extract as Avenanthhramide C or a derivative thereof represented by the following Chemical Formula 1 as an active ingredient.

[Formula 1]
The method of claim 7, wherein

Derivatives of the avenanthramid C is characterized in that the avenanthramid C-methyl ester represented by the following formula (2), health functional food.

[Formula 2]
The method of claim 7, wherein

The avenanthramid C is characterized in that it is contained 50μM or more, health functional food.
The method of claim 7, wherein

The avenanthramid C is characterized by inhibiting the activity of GSK3β (Glycogen synthase kinase-3β) by the accumulation of amyloid-β, health functional food.
The method of claim 7, wherein

The avenanthramid C is characterized in that induces LTP (Long-term potentiation) inhibited by the accumulation of amyloid-β again, health functional food.
The method of claim 7, wherein

The neurodegenerative diseases include Alzheimer's disease, frontotemporal dementia, dementia with Lewy bodies, corticobasal degeneration, Parkinson's disease, and multiple system atrophy. multiple system atrophy, progressive supranuclear palsy, Huntington's disease, dentato-rubro-pallido-luysian atrophy, spinocerebellar ataxia A health functional food, characterized in that it is selected from the group consisting of amyotrophic lateral sclerosis, primary lateral sclerosis and spinal muscular atrophy.