KR102445661B1 - Health functional food composition for improving cognitive ability comprising an extract of Allium hookeri - Google Patents

Abstract

The present invention relates to a health functional food composition for improving cognitive function containing an extract of samchae ( Allium hookeri ) as an active ingredient. By improving spatial perception ability, short-term memory cognition, spatial learning ability and explicit memory ability, the extract of the three plants can be usefully used as a health functional food composition for cognitive improvement, and the aging era due to the development of cognitive intelligence improvement materials It can contribute to reducing social costs and improving quality of life.

Description

Health functional food composition for improving cognitive ability comprising an extract of Allium hookeri

The present invention relates to a health functional food composition for improving cognitive ability containing an extract of Allium hookeri as an active ingredient.

Cognition is Latin for knowing, conceptualizing, or recognizing, and can be defined as the ability to apply knowledge in the process of processing information or to change applications. ability to acquire and use The meaning of cognition can vary depending on the field of use. For example, in cognitive science of psychology, it refers to an individual's information processing ability. may be included.

After the age of 30, cognitive ability declines and brain cells begin to decline, and continuous stress, excessive alcohol intake, drugs, lack of sleep, and depression can enhance the destruction of brain cells and reduce memory. The decline in cognitive ability makes it difficult for the intellectual function to be normal and social activities.

Alzheimer's disease (AD) is the most common disease associated with cognitive decline, and is usually chronic and progressive. see. The major neuropathological findings of AD are the aggregation and deposition of two proteins in the hippocampus and the cortex, with senile plaque (SP) composed of amyloid beta protein (Aß) outside the nerve cells and hyperphosphorylation inside the nerve cells. Neurofibrillary tangles (NFTs) made up of tau protein are accumulated. The cause and mechanism of AD have not been clarified yet, and it is known that the main causes are damage to nerve cells due to decreased synthesis of acetylcholine, a neurotransmitter, deposition of Aß, and hyperphosphorylation of Tau protein. In addition, changes in the apoE gene, α-synuclein protein, and destruction of myelin due to oxidative stress or aging are also known to affect brain cell damage and AD.

When the brain tissue of AD patients was observed, it was confirmed that the cholinergic nerve damage occurred. As such, the theory that explains the cause of AD according to the damage of the cholinergic nerve is called the Cholinergic Hypothesis in Alzheimer's disease. Based on this, many attempts have been made to inhibit the activity of acetylcholinesterase, which induces a decrease in the function of acetylcholine. Currently, drugs used for the treatment of AD are acetylcholinesterase inhibitors, such as tacrine, donepezil, rivastigmine, and galantamine. Among these, galantamine is the most recently approved and used by the FDA. Galantamine shows the effect of improving the cognitive function decreased by preventing the degradation of acetylcholine and maintaining the concentration of acetylcholine at the synapse. However, galantamine's efficacy and safety are questioned due to toxicity and side effects, and such side effects are raising public suspicion and fear. Therefore, there is a demand for the development of safer and more effective natural functional materials.

Samchae ( Allium hookeri ) is distributed in southern China, India, Bhutan, Sri Lanka, etc. in East Asia, and grows in forests, wetlands and grasslands at an altitude of 1400 to 4200 m above sea level. It is also called root leek. It is also called samchae (蔘菜) because it tastes and looks similar to ginseng, and is also called samchae (三菜) because it has three flavors: bitter, sweet and spicy. The height of the plant is about 0.6 to 1 m, and it is known that the three roots, leaves, and flowers can be used for food and medicine.

Accordingly, the present inventors, while trying to develop drugs and health functional foods derived from natural products that have no side effects to the human body and have a cognitive improvement effect, three fermented alcohol extracts were used to improve spatial perception ability and short-term memory recognition in dementia-inducing mice. The present invention was completed by confirming that it improves the ability to learn, spatial learning ability and explicit memory ability.

SUMMARY OF THE INVENTION It is an object of the present invention to provide a health functional food derived from a natural product that has no problems of toxicity and side effects of conventional compound therapeutics, is safer to the human body, and has an excellent cognitive ability improvement effect.

In order to achieve the above object,

The present invention provides a health functional food composition for improving cognitive ability containing an extract of samchae ( Allium hookeri ) as an active ingredient.

Samchae ( Allium hookeri ) extract of the present invention by improving spatial perception ability, short-term memory cognition, spatial learning ability and explicit memory ability, the samchae extract can be usefully used as a health functional food composition for cognitive improvement, The development of materials for improving cognitive intelligence can contribute to reducing social costs and improving the quality of life in an aging society.

1 is a diagram showing the number of times each experimental group (normal group, negative control group, positive control group, low concentration sample administration group, and high concentration sample administration group) entered each maze in the Y-maze test.
1a is a graph showing the number of times each experimental group (normal group, negative control group, positive control group, low concentration sample administration group, and high concentration sample administration group) entered each maze in the Y-maze test using a dementia-induced mouse model. ( p < 0.05).
1b is a graph showing the number of times each experimental group (normal group, negative control group, positive control group, low concentration sample administration group and high concentration sample administration group) entered each maze in the Y-maze test using a genetically modified mouse model. ( p < 0.05).
2 is a graph showing the number of times each experimental group (normal group, negative control group, positive control group, low concentration sample administration group and high concentration sample administration group) reached the 8-room maze in a radial arm maze test using a genetically modified mouse model; is ( p <0.05).
3 is a diagram showing the time for each experimental group (normal group, negative control group, positive control group, low concentration sample administration group and high concentration sample administration group) to reach the escape zone in the water maze test.
Figure 3a is a graph showing the time to reach the escape zone in each experimental group (normal group, negative control group, positive control group, low concentration sample administration group and high concentration sample administration group) in the underwater maze test using a dementia-induced mouse model ( p <0.05).
Figure 3b is a graph showing the time to reach the escape zone of each experimental group (normal group, negative control group, positive control group, low concentration sample administration group, and high concentration sample administration group) in the underwater maze test using a genetically modified mouse model ( p <0.05).
4 is a diagram showing the time for each experimental group (normal group, negative control group, positive control group, low concentration sample administration group, and high concentration sample administration group) to escape and escape in a passive avoidance test.
Figure 4a is a graph showing the time for each experimental group (normal group, negative control group, positive control group, low concentration sample administration group, and high concentration sample administration group) to escape to a bright box in a passive avoidance test using a dementia-induced mouse model ( p <0.05) ).
Figure 4b is a graph showing the step-through latency time of each experimental group (normal group, negative control group, positive control group, low concentration sample administration group and high concentration sample administration group) in a passive avoidance test using a dementia-induced mouse model ( p <0.05).
Figure 4c is a graph showing the time for each experimental group (normal group, negative control group, positive control group, low concentration sample administration group, and high concentration sample administration group) to escape to the bright box in the passive avoidance test using the genetically modified mouse model ( p <0.05) ).

Hereinafter, the present invention will be described in detail.

The present invention provides a health functional food composition for improving cognitive ability, containing an extract of samchae ( Allium hookeri ) as an active ingredient.

Here, as for the three chaes, cultivated ones or commercially available ones may be used, and any of leaves, roots, stems, and branches may be used, and preferably, the roots of three chaes may be used.

The three plants extract may be prepared using a conventionally known extraction method of a plant extract, and alcohol extraction, shaking extraction, Soxhlet extraction, or reflux extraction may be used. Preferably, the extract may use alcohol extraction.

In one aspect of the present invention, the three-chae extract may be an additionally separated or purified fraction, or a fractionated material. Here, the fraction, or the fraction material, refers to a fraction, or a fraction material, that can be used for the prevention or improvement of degenerative brain disease and the use of improving cognitive ability, as in the experimental example shown in the experiment of the present invention, and also, the following Experimental Example of the present invention As shown in the effect, it can exhibit the effect of improving spatial perception ability, short-term memory cognition, spatial learning ability and explicit memory ability. It means that it is separated and purified to contain the active ingredient from the extract of three chae.

On the other hand, the fraction or fraction material may refer to a more isolated/purified form. For example, a fraction obtained by passing the three plant extracts through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (prepared for separation according to size, charge, hydrophobicity or affinity), etc. Fractions obtained through various purification methods are also included in the fractions or fractions of the three plants.

In one embodiment of the present invention, the three-chae extract, a fraction thereof, or a fraction thereof may be obtained as follows.

The present invention comprises the steps of preparing all or at least part of the three plants;

immersing the whole or at least part of the prepared three plants so that at least a part can be immersed in a solvent; and

After the immersion step, the step of filtration to obtain a filtrate; provides a method for preparing the extract comprising a samchae.

Here, the preparation step may be prepared by cutting the whole plant, such as the leaves, stems, roots, etc. of the three plants, or a part thereof, and additionally grinding it, and the immersion step is such that at least a part of the prepared thing is immersed in a solvent However, the solvent may use the solvent presented herein, for example, (a) anhydrous or hydrated lower alcohols having 1-4 carbon atoms (eg, methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol and normal-butanol), (b) a mixed solvent of the lower alcohol and water, (c) acetone, (d) ethyl acetate, (e) chloroform, (f) 1,3-butylene glycol, (g) hexane, (h) diethyl ether, (i) butyl acetate, or (j) water may be used as the extraction solvent.

On the other hand, the step of obtaining the filtrate may use a conventional filtration separation method, for example, a conventional method used for separating or filtering a solid component and a liquid component, for example, using filter paper It can be separated into a filtrate and a residue. In addition, the filtration here may be a filtration step in which the extraction is repeated in the first, second, or higher order, and a method in which many active ingredients can be extracted from the residue to preferably become a filtrate may be used.

On the other hand, the filtrate itself may be a three-chae extract, but alternatively, by further performing a step of concentrating and lyophilizing it, an extract can be obtained, which again according to the intended use, in a separate solvent It can be used by dissolving or suspending. For example, in order to obtain a higher concentration of the active ingredient, a method for preparing a fraction or a fraction described herein or a conventional method for preparing a fraction or a fractional material may be used.

In another aspect of the present invention, the Samchae extract may be obtained by extracting the fermented Samchae. Preferably, the fermented three vegetables may be extracted and dried for 24 hours after repeated steaming and drying.

In another aspect of the present invention, the three-chae extract can be extracted using any one solvent selected from the group consisting of water, C 1 (C ₁ ) to 4 (C ₄ ) alcohol, and a mixed solvent thereof. Preferably, the alcohol may be extracted using C ₁ to C ₂ lower alcohol, and more preferably, may be extracted using ethanol.

In one embodiment of the present invention, the extract of the three plants can be extracted using ethanol, for example, 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more , 70% or more, 80% or more, or 90% or more of ethanol may be used for extraction, and preferably, it may be extracted using 50% ethanol.

On the other hand, it should be understood that the parts that can be easily changed and applied by ordinary technicians such as the extraction time and the number of times of extraction of the extraction method of the present invention are to be understood as included in the present invention, but the extraction time is preferably 10 to 48 time, more preferably 15 to 30 hours, and most preferably 24 hours. In addition, the number of extractions may be 1 to 5 times, preferably 2 to 4 times repeated extraction, and more preferably 2 times repeated extraction.

The health functional food composition of the present invention may be used as it is, or may be used with other foods or food ingredients, and may be appropriately used according to a conventional method.

The health functional food may be as follows. Examples of foods to which the three vegetable extracts can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks , alcoholic beverages and vitamin complexes, and includes all health functional foods in the ordinary sense.

In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, It may contain alcohol, a carbonation agent used in carbonated beverages, and the like. In addition, it may contain the pulp for the production of natural fruit juice, fruit juice beverage and vegetable beverage. These components may be used independently or in combination.

Improve spatial perception ability and short-term memory cognition by using the functional food composition for cognitive improvement containing the extracts of three plants (see FIGS. 1a, 1b and 2), and improve the reduced spatial learning ability ( FIGS. 3a and 3a and 3b), it is possible to restore the reduced explicit memory capacity (see FIGS. 4a, 4b and 4c), so the composition can be used for cognitive improvement purposes.

Hereinafter, the present invention will be described in detail by way of Examples and Experimental Examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

<Example 1> Three fermented vegetables ( Allium hookeri ) extract preparation

1-1. Preparation of fermented three vegetables

Each 1×10 ^8~9 cfu/g number of bacteria, each of Lactobacillus acidophilus MG501 and Bifidobacterium longum MG723, Enterococcus faecium MG89, Streptococcus thermophilus MG510, and Saccharomyses cerevisiae MG111 yeast, were added to 50mL purified water. After homogenization by stirring at room temperature, persimmons in a greenish state before maturation grown without pesticides were mixed with persimmon fermented undiluted solution prepared by fermenting persimmons with sugar for about 6 months and the extract of ginseng leaves, diluted 20 times in purified water. 950 mL of a mixture of the fermented broth and the three-leaf extract was mixed to prepare 1,000 mL of a microbial mixture.

200 g of dried ginseng root was placed in a tray for fermentation, immersed in 400 mL of the prepared microbial mixture, left at room temperature for 24 hours, placed on a shelf inside the fermenter, and primary fermented for 3 days while maintaining 40 to 50 ° C. , After evenly spraying 300 mL of the microbial mixture on the roots of the three vegetables fermented in the first place by spraying, leaving it at room temperature for 24 hours, placing it on the shelf inside the fermenter again, and fermenting it for the second time for 3 days while maintaining 40 ℃ ~ 50 ℃, The second fermentation process was repeated one more time, and the third fermentation was performed to prepare fermented three pieces.

1-2. Preparation of fermented ginseng extract

Fermented ginseng ( Allium hookeri ) was used as a sample to confirm the effect of preventing or treating degenerative brain disease and improving the cognitive decline. After repeated steaming and drying, the three fermented vegetables were extracted and dried for 24 hours, and the extract was extracted twice at room temperature for 24 hours in 50% ethanol for use. After filtration, all samples were concentrated and freeze-dried (PVTFD 10R, Ilsin Lab, Yangju, Korea) to form dry powder and used for each experiment. .

<Example 2> Preparation of experimental group

2-1. Manufacture of short-term memory deterioration model using dementia-inducing drug (Scopolamine)

A mouse was selected as an experimental animal for the experiment to confirm the effect of preventing or treating degenerative brain disease and improving cognitive ability of fermented three chae. C57BL/6 male black mice (12 weeks old) were used as mice, and the normal group and the dementia-inducing group were bred in aseptic conditions under ad libitum feeding conditions. To induce memory impairment in the dementia-induced group, scopolamine (Sigma Aldrich, S0929) was intraperitoneally administered to a body weight of 2 mg/kg BW 120 minutes before the behavioral evaluation test. Scopolamine is a drug that impairs memory by inhibiting the binding of Ach (neurotransmitter) and muscarinic receptor. All experimental procedures and procedures related to animal experiments used in this study were carried out in compliance with the regulations of the Animal Experimental Ethics Committee (NAS-201906) of the National Academy of Agricultural Sciences, Rural Development Administration.

2-2. Dementia-induced transgenic mouse (C57BL/6-Tg) model preparation

Genetically modified experimental animals (NSE-hps2*N1411) were purchased from the Food and Drug Administration (NIFDS) and used to confirm the effects of preventing or treating degenerative brain disease and improving cognitive abilities of fermented three plants. For the normal group model, 16-week-old C57BL/6 male black mice were used, and the normal group and the dementia-inducing group were bred in aseptic conditions under ad libitum feeding conditions. During the breeding period, general solid feed (Central Experimental Animals, Seoul, Korea) and water were freely ingested, temperature 23±2℃ and humidity 50±10% were controlled, and the light-dark cycle was adjusted in 12-hour units. All experimental procedures and procedures related to animal experiments in this study were performed in accordance with the regulations of the Animal Experimental Ethics Committee (NAS-201906) of the National Academy of Agricultural Sciences, Rural Development Administration.

2-3. Experimental group preparation

For the cognitive improvement effect test, after 1 week of adaptation period, healthy animals without weight loss were selected, and 5 experimental groups (normal group, negative control group, positive control group, The low-concentration sample administration group and the high-concentration sample administration group) were divided. For the normal group, mice that did not induce dementia were used, and for the negative control group, the positive control group and the sample administration group, a mouse model using a dementia-inducing drug or a dementia-inducing genetically modified mouse (C57BL/6-Tg) was used. The sample administration group dissolved the fermented ginseng extract in a solvent (Phosphate Buffer Saline, PBS) and fed at 150mg/kg (low concentration) or 300mg/kg (high concentration) BW level, and the negative control group fed only the same amount of PBS, A positive control group (positive control) was fed with tacrine (tacrine, Sigma-Aldrich, A3773) at 1 mg/kg BW level. Tacrine is a drug that can slow the loss of cognitive function in patients with Alzheimer's by inhibiting the breakdown of acetcholine produced in the brain of Alzheimer's patients in the early and middle stages. The drug and the fermented ginseng extract were orally administered 5 times a week at a fixed time every day.

<Experimental Example 1> Confirmation of improvement in spatial perception ability and short-term memory cognitive ability according to administration of fermented ginseng extract

1-1. Y-maze test to confirm improvement of spatial perception ability and short-term memory cognitive intelligence

In order to determine whether the reduced spatial perception ability and short-term memory ability are restored according to the administration of the fermented ginseng extract, the dementia-inducing drug (scopolamine) administration model of Example 2-1 or the dementia-inducing gene of Example 2-2 A Y-maze test was performed using a modified mouse, respectively. The Y-maze test is one of the behavioral types measurement methods, and is the most basic method used because several neuroprotective mechanisms, including tolerance to brain damage and improved function, are related to motility (Nichol, K. E. 2007), the The test relies on the natural exploratory behaviors and tendencies of mice and is considered the most basic test to evaluate spatial working memory (Webster, S. J. 2014).

Specifically, the Y-shaped maze consists of three Y-shaped passageways, each of which is 50 cm long, 20 cm high, and 10 cm wide, made of white plastic material. Mice were placed at the end of one starting point and the number and sequence of entering each maze were measured to evaluate the ability to change behavior. A score of 1 was given for entering the other two domains sequentially, and 0.5 points for entering only one domain. The inventor established the basic conditions in the learning and memory ability evaluation criteria and verified the rationality, accuracy, and reproducibility of the test method.

All data were expressed as Mean±SE, and statistical processing was performed at the p <0.05 level after one-way ANOVA was performed using the SPSS program (Statistical Package for the Science ver. 24, IBM Corp, Armonk, NY, USA). Significance was indicated.

As a result of the Y-maze test using the dementia-inducing drug (scopolamine) administration model of Example 2-1, the negative control group repeatedly entered one area many times, and the sample administration group reached areas A, B and C, respectively. The average low concentration group increased by 35.4% compared to the negative control group, and the high concentration group increased by 39.78% compared to the negative control group (FIG. 1a).

In addition, as a result of performing the Y-maze test using the dementia-induced genetically modified mouse of Example 2-2, the number of times reaching the three areas of the Y-maze for 1 minute was significantly higher in the sample administration group, indicating that the average low concentration The group increased by 47.5% compared to the negative control group, and the high concentration group increased by 21.5% compared to the negative control group. In the case of the low concentration sample administration group, a higher score was obtained compared to the normal control group (FIG. 1b).

This indicates that when the fermented ginseng extract is administered, short-term memory and cognitive ability are improved, and the reduced spatial perception ability is also restored. And it suggests that it can be used as a health functional food composition.

1-2. Additional test (Radial arm maze test) to confirm improvement of short-term memory and cognitive ability following administration of fermented ginseng extract

In order to further confirm that short-term memory cognitive ability is improved by administration of the fermented ginseng extract, a radial arm maze test was performed using the dementia-induced genetically modified mouse of Example 2-2. The radial maze test uses an eight-way radial maze widely used in rodent models as a method for testing short-term memory tests (Huang, J. 2007).

Specifically, the 8-room maze used in the test consists of a central platform made of transparent acrylic material and eight identical poles radially diverging from it, and the time taken from the moment each experimental group is placed at the starting point. (Latency; reaction latency) was measured, and the number and frequency of visits to the end point of each of the eight states were measured, and these were used as indicators of learning performance. Visiting the same route more than twice was considered an error and allowed to wander freely for 5 minutes. Experimental data was measured in the same manner as in Experimental Example 1-1.

As a result of performing the radial maze test using the dementia-inducing genetically modified mouse of Example 2-2, the sample administration group showed significant significance at low concentrations (7.84 points) and high concentrations (7.57 points) compared to the scores (5.48 points) obtained by the negative control group. was significantly higher (FIG. 2).

This indicates that the fermented ginseng extract has the effect of restoring and improving short-term memory ability, and based on this, it is suggested that the fermented ginseng extract can be used for the prevention or treatment of degenerative brain diseases.

<Experimental Example 2> Confirmation of recovery of spatial learning ability by administration of fermented ginseng extract

In order to determine whether spatial learning ability and spatial memory cognitive ability are restored by administration of the fermented ginseng extract, the dementia-inducing drug (scopolamine) administration model of Example 2-1 or the dementia-inducing genetically modified mouse of Example 2-2 A water maze test was performed using each. The underwater maze test is the most preferred and clear behavioral type evaluation method to evaluate spatial learning ability (Higaki, Akinori. 2018, Smith, S. 2000). Based on the previous study that the effects of treatment can be compared in the underwater maze examination (Jolkkonen, J. 2003, Jiwa, N. S. 2010), this study was performed to measure the hippocampal dependence and spatial learning ability of mice.

Specifically, the underwater maze test consisted of a rectangular water tank and an escape platform, and the examination space was made of white acrylic with a diameter of 42 cm and a height of 18 cm, and a height and diameter of the escape platform of 10 cm. An escape platform was installed at one reaching point of the tank, filled with 15 cm of water, and the temperature of the water was maintained at 22±3°C during the experiment, and the position of the inspector was also the same. The mice of the experimental group were started from the opposite section, and the time the mice reached the escape zone by free swimming for 60 seconds was measured (seconds). Experimental data was measured in the same manner as in Experimental Example 1-1.

As a result of performing the water maze test using the dementia-inducing drug (scopolamine) administration model of Example 2-1, the final measurement was compared with the negative control group (25.16 seconds), in the low concentration sample administration group 16.59 seconds, in the high concentration sample administration group After recognizing the escape zone at 16.07 seconds, the arrival time decreased to a significant level (Fig. 3a). In addition, as the sample administration period increased, the escape zone was recognized and the average escape latency did not show a significant difference from that of the normal control group (14.75 seconds).

In addition, in the underwater maze test using the dementia-induced genetically modified mouse of Example 2-2, a total of 5 measurements were performed for 10 weeks at an interval of 2 weeks. The average visiting time decreased by 20.00 seconds, and in particular, the low concentration sample administration group decreased by 30.64 seconds, showing a significantly significant difference (FIG. 3b). And, as the administration period increased, the performance of the mice in finding the escape zone was improved through learning training through repetition.

These experimental results indicate that spatial cognitive memory was strengthened through purposeful training in the sample administration group administered with the fermented ginseng extract, suggesting that the fermented ginseng extract is related to the prevention or treatment of degenerative brain disease.

<Experimental Example 3> Confirmation of improvement of explicit memory ability by administration of fermented ginseng extract

In order to determine whether the explicit memory ability is improved by administration of the fermented ginseng extract, the dementia-inducing drug (scopolamine) administration model of Example 2-1 or the dementia-inducing genetically modified mouse of Example 2-2 A passive avoidance test was performed. The passive avoidance experiment is an experiment using the characteristics of mice that prefer dark places. It is one of the common methods for evaluating memory enhancement and explicit memory. Shuttle box is used to screen for symptoms of diseases including memory loss or dementia. The passive avoidance test using a simple and efficient method has been used in many previous studies (Shudo, K. 2004). The passive avoidance response to an aversive stimulus was reported to have a similarity to the memory impairment phenomenon of vascular dementia (Shinjeong Kang 2013, Kimura S. 2000), and a correlation between the passive avoidance response and hippocampal acetylcholine levels in mice with reduced memory was reported. (Kimura, S. 2000).

Specifically, in the manual avoidance test, between two acrylic boxes consisting of a dark box and a light box, a guillotine door through which the mouse can move is installed, and a stainless steel rod is laid on the bottom of the acrylic box to apply an electric shock according to the inventor's condition. capable device is connected. Before the start of the experiment, the mice of each experimental group were acclimatized to the dark box for 10 seconds, then the light was lit through the light in the bright box, the guillotine door was opened and an aversive stimulus (electric shock, 0.3 mA) was applied to move the mouse to the opposite box. The step through latency is measured within 1 minute. In addition, it was measured within 1 minute whether the mouse moved to the light box remembered the electrical memory of the dark box, suppressed the nature of wanting to go to the dark box, and then returned to the dark box within 1 minute. After that, the experiment was stopped if there was no movement. Experimental data was measured in the same manner as in Experimental Example 1-1.

As a result of performing a passive avoidance test using the dementia-inducing drug (scopolamine) administration model of Example 2-1, the average time for the negative control group to come out from the dark space to which the aversive stimulus was applied to the bright space was 8.76 seconds, but the sample administration group 3.85 seconds (low concentration) and 3.80 seconds (high concentration) showed a significant improvement in explicit memory compared to the negative control group ( FIGS. 4a and 4b ).

In addition, in the passive avoidance test using the dementia-induced genetically modified mouse of Example 2-2, the passive avoidance response was evaluated every two weeks in order to measure the explicit memory enhancement effect of the fermented three vegetables. In the final measurement, compared to the negative control group (8.00 seconds), the movement time from the dark box to the light box that applied the aversive stimulus was significantly reduced in the low concentration sample administration group (5.57 seconds) and the high concentration sample administration group (5.57 seconds) (Fig. 4c) ).

This suggests that fermented ginseng extract can improve explicit memory ability, and that the extract effectively prevents memory impairment and that the memory function is related to hippocampal neurogenesis (Lee, Kwang-Sik. 2005). , suggests that the extract can be used as a pharmaceutical composition for preventing or treating degenerative brain disease and a health functional food composition.

Claims (6)

1) In a solution obtained by homogenizing lactic acid bacteria Lactobacillus acidophilus and Bifidobacterium longum, enterococcus faecium and Streptococcus thermophilus, and yeast Saccharomyses cerevisiae, a mixture of persimmon fermentation undiluted solution and extract from three leaf extracts was mixed in a volume ratio of 1:19 to obtain a mixture of microorganisms. obtaining;
2) immersing the dried samchae ( Allium hookeri ) roots in the microbial mixture of step 1), followed by primary fermentation at 40° C. to 50° C. for 3 days;
3) Spraying the microbial mixture on the first fermented saengchae in step 2, leaving it at room temperature for 24 hours, and repeating the process of fermenting at 40°C to 50°C for 3 days 2 to 4 times to obtain fermented saengchae ;
4) repeating the steaming and drying of the fermented three chaes in step 3) to obtain the steamed fermented three chae; and
5) A method for producing a fermented ginseng extract, characterized in that it comprises the step of extracting the fermented ginseng steamed in step 4) with 50 to 100% ethanol solvent at room temperature for 15 to 30 hours.
delete delete delete delete A health functional food composition for improving cognitive function, characterized in that it contains the fermented ginseng extract obtained by the manufacturing method of claim 1 as an active ingredient.

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