KR20060072642A - Herb extract which are effective on improvement of brain function - Google Patents

Abstract

The present invention relates to a herbal extract having an effect of improving brain function, and more particularly, one or two or more herbal extracts or fractions selected from venom, mokduchae, Haedongpi, Sokdan, dew, and stomach cancer are neuronal cell protection, beta amyloid. Herbal extracts that can be used to improve brain function, such as prevention and treatment of mild cognitive impairment (MCI) or dementia, by revealing its beneficial effects on inhibiting (beta-amyloid) production and enhancing cognitive decline. It is about.

Improvement of brain function, virulence, sore throat, thawing skin, fasting, hyssop, gastric gland, neuron protection, inhibition of beta-amyloid production, cognitive function, mild cognitive impairment, dementia

Description

Herb extract which are effective on improvement of brain function

The present invention relates to a herbal extract having an effect of improving brain function, and more particularly, one or two or more herbal extracts or fractions selected from venom, mokduchae, Haedongpi, Sokdan, dew, and stomach cancer are neuronal cell protection, beta amyloid. Herbal extracts that can be used to improve brain function, such as prevention and treatment of mild cognitive impairment (MCI) or dementia, by revealing its beneficial effects on inhibiting (beta-amyloid) production and enhancing cognitive decline. It is about.

As the elderly population increases not only in Korea but also in the world, many degenerative diseases of the elderly are causing social and economic losses. Statistics released by the American Dementia Association and the National Institute of Aging indicate that 4 million Americans have dementia, typically dementia after age 60, but rarely start in their 50s and 10.3% of all Americans after age 65 The cost of treating dementia is $ 95 billion annually in the United States.                         

In Korea, a report by the Korea Institute for Health and Social Affairs showed that the dementia population has surged due to the aging population, and the prevalence of dementia in 1995 was 8.3% among the aged 65 and older. In addition, as a result of applying the prevalence of dementia to the prospective population revealed by the National Statistical Office, the number of elderly people with dementia in 2000 was 277,00048 (8.3% of the elderly aged 65 and over), 52,6868 (9%) in 2015 It is estimated that it will reach 61,132 (9%) in 2020. Dementia disease is a serious incurable disease that must be treated because it is a serious social and economic problem because it not only destroys the patient's own human life but also destroys the family life.

In addition, Mild Cognitive Impairment (MCI), a preliminary stage of dementia, refers to a condition in which cognitive functions such as memory, judgment, and learning ability are deteriorated compared to the normal elderly, but are not clinically satisfied with dementia criteria. Moreover, recent clinical studies suggest that patients with mild cognitive impairment are at high risk of developing dementia. Patients in this area transition to dementia disease at a rate of 10-15%, whereas normal controls convert to dementia at a rate of 1-2% each year. Therefore, early treatment for patients with mild cognitive impairment belonging to the high risk group of dementia is important for the prevention and treatment of dementia.

Alzheimer's disease can be caused by a variety of causes, but the most representative disease is Alzheimer's disease, characterized by the deposition of beta-amyloid proteins outside the brain cells, leading to degeneration of neurons. The symptoms are a marked decline in memory.                         

Tacrine, introduced in 1993, the first FDA-approved drug to treat Alzheimer's disease, inhibits the breakdown of acetylcholine produced in the brains of Alzheimer's disease patients in the early and mid-term by cognitive function in about 30% of patients. It has been able to slow down the loss of, but it is rarely used because it causes many side effects related to the liver. Aricept, which was approved by the US FDA in 1996, acts to increase the availability of acetylcholine, which can be taken once a day before bedtime. Side effects include nausea, diarrhea, and tiredness. Will disappear soon. However, tacrine, aricept and later developed reminil cannot stop or reverse Alzheimer's disease itself, and it is not yet clear how long patients should take these drugs and how long they will work. to be.

Therefore, the development of a new dementia treatment with fewer side effects and good efficacy is urgently needed.

On the other hand, the herbal medicine used in the present invention ( Aralia cordata radix) belongs to the family Arboraceae and is called jeopduum or ground gulum is effective in the pain in the lower back and thigh due to the custom. In oriental medicine and private medicine, keunpi (根 해) is used as medicine for fever, tonic, expectoration, stomach cancer, diabetes. Aralia elata cortex is the bark of Aralia elata , which has analgesic and anti-inflammatory effects on customary arthritis, lowers blood sugar and is used to treat diabetes. It is a herbal medicine used in seawater, colitis, and stomach cancer. Kalopanax pictus cortex is a bark of the moth tree ( Kalopanax pictus ) and is known to improve symptoms such as numbness of limbs, pain in the lower back and knees, eczema and skin diseases caused by customs. In addition, cough, sputum, kidney disease, diabetes, gastritis, gastric ulcers, urination disorders, neuralgia, rheumatism is effective. Dipsacus asper radix is the root of Dipsacus asperoides and is effective for knee pain and bruises caused by customs. Achyranthes japonica radix is the root of Achyranthes japonica , which helps to circulate blood and eliminates blood loss. Clematis mandshurica radix is the root of the genus Clematis mandshurica , which acts on the circulatory system to reduce blood pressure, diuresis, hypoglycemia, analgesic and antibacterial activity. In addition, it is known that it is effective in removing customs, relieving pain in joints and limbs, and relieving muscle paralysis and bruises.

Research reports on the effects of improving the brain function of herbal medicines are not known yet.

Accordingly, the present inventors screened various herbal medicines to develop a dementia medicament that has little toxicity and is useful for protecting neuronal cell toxicity by powerful beta amyloid and enhancing the declining memory, Aralia cordata radix, Useful for protecting nerve cells, inhibiting beta amyloid production and enhancing decayed memory from Aralia elata cortex, Kalopanax pictus cortex, Dipsacus asper radix, Achyranthes japonica radix or Clematis mandshurica radix The present invention has been completed by extracting and purifying extracts and fractions.

Accordingly, an object of the present invention is to provide a method for preparing one or two or more extracts or fractions selected from poisonous bowels, soybeans, thawed bark, sokdan, wort and gastric glands.

In addition, the present invention is another object to provide a brain function improving agent and health food containing one or two or more extracts or fractions selected from poisonous bowels, soybeans, thaw skin, sokdan, wort and gastric glands.

The present invention is selected from Aralia cordata radix, Aralia elata cortex, Kalopanax pictus cortex, Dipsacus asper radix, Achyranthes japonica radix, and Clematis mandshurica radix. At least two herbal extracts, characterized in that the method for producing a fraction.

In addition, one or more selected from Aralia cordata radix, Aralia elata cortex, Kalopanax pictus cortex, Dipsacus asper radix, Achyranthes japonica radix, and Clematis mandshurica radix Brain function improvers and dry foods containing two or more herbal extracts or fractions.

Referring to the present invention in more detail as follows.

The present invention is one or two or more herbal extracts or fractions selected from venom, mokduchae, Haedongpi, Sokdan, Wooseon, and gastric ulcer are useful for protecting neurons, inhibiting beta-amyloid production and enhancing cognitive function. By revealing that there is, it relates to a herbal extract that can be used for improving brain function, such as prevention and treatment of mild cognitive impairment (MCI, Mild Cognitive Impairment) or dementia.

The present invention relates to the efficient separation of more active extract components from the herbal medicine by the following method as follows.

First, finely pulverize one or two or more herbal medicines selected from poisonous, soybean meal, thaw skin, sokdan, wort, and gastrointestinal tract, and then add about 5 to 10 times the amount of lower alcohol solution, preferably methanol or ethanol, Four times solvent extraction, followed by filtration and concentration under reduced pressure to completely remove the alcohol in the extract, thereby removing the alcohol components remaining more than necessary in the alcohol extract can be made easier solvent fractions to be carried out next. The extract is completely dissolved or suspended in water with distilled water of about 3-5 times (v / w) relative to the weight of the original herbal medicine. At this time, to completely dissolve the extract in water, a large amount of water is required or must be heated, but it can be carried out the next step even if the extract is not completely dissolved because of the inconvenience of handling. Then, the suspension of the extract and the same amount of saturated lower alcohol is added and stirred for about 10 to 20 minutes at 30 to 50 rpm, and the mixture is left to stand. After separating the layers, the saturated lower alcohol layer is filtered and concentrated under reduced pressure to obtain an active purified fraction. The saturated lower alcohol used in this case is a saturated aqueous solution of lower alcohol, which is diluted with distilled water by adding distilled water to the lower alcohol, stirring it, and taking a lower alcohol layer saturated with distilled water. For example, propanol, butanol, etc. may be used. Carry out 2-3 times. If a small amount of lower alcohol is used to obtain the lower alcohol solvent fraction, the purification efficiency is lowered, and the yield and the content of the active ingredient are lowered. When the lower alcohol is used, the economical efficiency is increased by using excessive alcohol compared to the purification efficiency. Dropped. Therefore, it is advisable to use 3-5 times the weight of the lower alcohol (v / w) of the crude drug, the amount described above being consistent with such purification efficiency and economics.

Searching for the activity of the herbal extracts and fractions prepared according to the above method, there was a neuroprotective effect, inhibiting the production of beta amyloid and cognitive function.

In addition, in animal experiments, scopolamine (scopolamine) and the control group (drug not administered) were 100%, and scoflavin (1 mg / kg), which is known to reduce memory through interference with neurotransmitters, was used. When the group administered to 0% was evaluated for memory enhancement of the butanol fraction one hour after the administration of scoflavin, the activity was 42-50%.

Accordingly, the brain function improvement (prevention of mild cognitive impairment and dementia) containing one or two or more herbal extracts (or fractions) selected from the virulence, soybeans, thawed bark, sokdan, dew and gastric glands according to the present invention as active ingredients. It can be used as a therapeutic medicine and health food.

When prepared as a pharmaceutical, the herbal extract (or fraction) of the present invention may be administered orally or parenterally during clinical administration and may be provided in the form of a general pharmaceutical formulation.

One or two or more herbal extracts (or fractions) selected from the virulence, soybeans, thawed bark, sokdan, wedge and gastric glands of the present invention can be administered in various dosage forms, oral or parenteral, in actual clinical administration. In this case, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants are usually used.

Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose in lignans and lactone compounds and derivatives thereof. Mixed with gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solvents, emulsions, and syrups. In addition to the commonly used simple diluents, water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. have.

Formulations for parenteral administration include sterile aqueous solutions, water-insoluble solvents, suspensions, emulsions, lyophilizers, suppositories. As the non-aqueous and suspending solvent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like can be used. As the base of the suppository, utopsol, macrogol, tween 61, cacao butter, laurin butter, glycerol gelatin and the like can be used.

The content in the preparation of the active ingredient according to the present invention can be appropriately selected depending on the absorbency, inactivation rate, excretion rate, age, sex and condition of the user in the body. In the case of the herbal extract (or fraction) of the present invention, it is 1 to 100 mg / kg, preferably 20 to 60 mg / kg, and can be administered 1 to 3 times a day.

In addition, the present invention includes a healthy food for improving brain function as an active ingredient of one or two or more herbal extracts (or fractions) selected from venom bowels, soybeans, Haedongpi, Sokdan, Wooseon, and stomach cancer.

The health food is a food prepared by adding the herbal extract (or fractions) to a general food, or by encapsulating, powdering, or suspensioning, and ingesting it to have a specific effect on health. Unlike the food as a raw material has the advantage that there is no side effect that can occur during long-term use of the drug.

Hereinafter, the present invention will be described in more detail based on the following examples, but the present invention is not limited thereto.

Example 1: Preparation of herbal extracts and fractions

2 kg of dry weight of finely pulverized venom, soybeans, thawed bark, sokdan, hyssop or lieutenant gland were extracted with reflux for 4 hours in 14 L of 50% ethanol aqueous solution. In addition, two herbal medicines (dockbow, thawed blood), three herbal medicines (headache, thawed blood, right dew) and all six of the herbal medicines were mixed in the same amount, and 2 kg of the extract was extracted in the same manner to obtain a herbal extract. The extract was filtered and concentrated under reduced pressure at 50 ° C. with a rotary evaporator to obtain an ethanol extract. In addition, water is added to the extract and suspended to about 5 times the original herbal weight (V / W), and then mixed with the same amount of saturated normal-butanol and placed in a separation funnel, and stirred for 24 hours. It was left to separate only the butanol layer of the upper layer. Re-fractionation was performed 2-3 more times, and the butanol fraction was concentrated using a distillation machine. The ethanol extract and the butanol fraction were dried by removing the solvent completely in a vacuum oven, and then powdered and stored at -20 ° C.

Example 2: Determination of Neurocytotoxicity Inhibition by Beta Amyloid

The ethanol extract and normal butanol fractions obtained in Example 1 were dissolved in 50% ethanol, diluted in cell medium (MEM-α) to a final concentration of 20 or 10 μg / ml, and pretreated to 50 μl cells (ethanol final Concentration of 0.5% confirms no vehicle effect on the cells). Cells used were aliquoted with SK-N-SH human neuroblastoma cell line in 96 well plates at 5 × 10 ³ cell concentration (3 wells in each group).

After 2 hours, the cells were treated with beta amyloid dissolved in 100% DMSO to a final concentration of 40 μM and incubated for 48 hours (37 ° C., 5% CO ₂ incubator).

After incubation, 25 μl of MTT solution (5 mg / ml) was treated per well to measure the viability of the cells, followed by incubation for 4 hours to allow for MTT to form formazan in the cells. Then, the cell medium was removed, and the cells were lysed with 100% DMSO to measure UV absorbance at 550 nm by ELISA.

In addition, the beta amyloid and the drug-free group was used as a control, and when the cell survival rate was 100%, the cytotoxicity caused by beta amyloid was beta amyloid (%), and the cell survival rate (%) due to the fraction was determined. It is shown in Table 1 below (each value is the average of three wells).

division Cell survival rate (%) Ethanol Extract (20 μg / mL) Butanol fraction (10 μg / ml) Poisonous 82.4 ± 5.6 85.1 ± 6.3 Neck 80.5 ± 6.3 83.7 ± 5.7 Thawed blood 84.7 ± 4.9 86.2 ± 6.2 Fast 79.2 ± 5.7 81.4 ± 5.5 A lieutenant ship 78.9 ± 9.2 81.8 ± 7.5 Dew 78.1 ± 3.7 79.1 ± 6.3 Poison + Thawing Blood 83.4 ± 6.6 87.4 ± 6.1 Neckduple + thawed skin + dew 81.1 ± 4.9 84.2 ± 7.8 Six kinds of compound herbal medicine 80.2 ± 6.8 80.6 ± 7.3 Control 67.4 ± 5.3

As shown in Table 1, it was found that ethanol extract (20 ㎍ / ㎖) strongly inhibits beta amyloid-induced neuronal cell toxicity by improving the cell survival rate due to beta amyloid toxicity 78 ~ 85% to a significant level. Could. In particular, in the case of normal-butanol fraction (10 ㎍ / ㎖) it can be seen that the cell viability value is 79 ~ 86% more effective than the ethanol extract.

Example 3: Passive Avoidance Test

Passive Avoidance Test of the extracts and butanol fractions of Example 1 was performed to determine whether the extracts and fractions of venom, soybeans, thawed bark, sesame, hyssop or gastric glands were effective in enhancing memory and learning ability in vivo. Was carried out.

The experimental apparatus used a shuttle box having a width, length, and height of 50, 15, and 40 cm. The box is divided into two rooms using a guillotine door, one of which is illuminated, which makes it a bright room, and the other is covered by a black cloth, making it a dark room. To make it possible.

First, put a rat in a bright room, turn on the lights, open the partition door, and the rat will enter the dark room within 20 seconds according to the instinct to find a dark place, and the partition door will close as soon as the mouse moves to the dark room. In this way, the time required for the rats to enter the dark room from the light room is measured as the latency time, and a training trial was conducted on the first day of the experiment to make sure that all the mice fit within 20 seconds.

The next day, put the above trained rats back in the bright room and turn them on in the dark room. At this point, an electric stimulus of 0.8 mA is applied for 3 seconds through an electronic grid installed on the floor of a dark room, and the mice are shocked at the sole of the foot.

After 24 hours of this acquisition trial, rats were placed in a bright room, turned on, and led to a dark room. Normal rats remembered the shock of the previous day and hesitated to enter the dark room. It measured again by maximizing the reaching time of 300 second at this time.

In the above experiments, scopolamine and the non-drug negative control group were 100%, and scoflavin (1 mg / kg) group, which is known to decrease memory through interference with neurotransmitters, was administered. At 0%, the memory-improving effect of the group administered with the extracts of venom, soybean, thawed bark, fasting, hyssop or gastric glands was measured one hour after the administration of scoflavin. As a positive control, Aricept (1 mg / kg) was administered in the same manner and the memory enhancement effect was measured.

division Cognitive Enhancement (%) Ethanol Extract (200 mg / kg) Butanol Fraction (100 mg / kg) Poisonous 43.4 ± 9.2 47.1 ± 8.9 Neck 35.5 ± 7.7 49.7 ± 7.1 Thawed blood 39.7 ± 9.4 44.2 ± 9.5 Fast 40.2 ± 11.5 48.4 ± 8.8 A lieutenant ship 36.9 ± 8.9 43.8 ± 10.2 Dew 38.1 ± 6.6 42.1 ± 8.6 Poison + Thawing Blood 42.4 ± 7.2 48.7 ± 7.8 Neckduple + thawed skin + dew 45.5 ± 6.7 45.1 ± 6.1 Six kinds of compound herbal medicine 40.1 ± 9.6 45.8 ± 6.4 Positive control (aricept, 1 mg / kg) 35.2 ± 11.1

As shown in Table 2, Aricept, a positive control group, has an effect of preventing 35% memory loss. The 50% ethanol extract (200 mg / kg) and butanol fraction (100 mg / kg) of Example 1 showed 35 to 46% and 42 to 50% of activity, respectively.

In other words, the extracts and fractions of venom, mokduchae, Haedongpi, Sok, Wooseon, or stomach gland were higher than the control drug Aricept, which prevents memory loss caused by scoflavin, which interferes with the transfer of acetylcholine from the brain. there was.

These results indicate that extracts and fractions of venom, mokduchae, thaw, sesame, hyssop, or gastrointestinal tract have the effect of enhancing the reduced memory in symptoms such as mild cognitive impairment and dementia.

Example 4 Confirmation of Increased Activity of Alpha Secretase

Beta-amyloid, a major source of dementia, is produced by the process of alpha-secretase by the precursor amyloid protein precursor (APP). Normally, APP is processed by alpha secretase to become secreted Amyloid Precursor Protein α (sAPPα). Beta amyloid induces toxicity such as necrosis of neurons, while sAPPα has neurotrophic activity such as promoting neuronal proliferation. Therefore, the activity of alpha secretase is important for the prevention and treatment of dementia.

In order to determine the effect of the butanol fraction of the herbal medicine on the APP process, the following experiment was performed using a W4 cell line expressing a large amount of APP.

After treatment with butanol fraction (20 ㎍ / ㎖) to the W4 cell line for 12 hours, the culture medium was concentrated by TCA, Western blotting, and the band was quantified by densitometry to determine the amount of sAPPα in the culture. sAPPα is the product of alpha-secretase degrading beta amyloid proprotein (APP), the amount of this protein indirectly confirms the activity of alpha-secretase. In this case, as a positive control, a culture medium of cells treated with PDBu (Phorbol 12, 13-dibutyrate), which is an inducer of alpha secretase, with 1 mM was concentrated. Based on the amount of sAPPα of the cell culture (negative control) treated with nothing, the amount of sAPPα of each experimental group was compared to indicate the activity of alpha secretase (each value is an average of three wells).

division sAPPα band density (relative to negative control) Poisonous 224 ± 36 Neck 217 ± 54 Thawed blood 196 ± 47 Fast 178 ± 41 A lieutenant ship 201 ± 26 Dew 189 ± 43 Poison + Thawing Blood 215 ± 51 Neckduple + thawed skin + dew 221 ± 57 Six kinds of compound herbal medicine 193 ± 46 Positive control (PDBu 1 mM) 312 ± 56

As shown in Table 3, the butanol fraction of the virulence, the head, the thaw, the stomach, the dew, or the gastrointestinal tract increased the alpha secretase activity of the W4 cell line, which increased the activity of the alpha secretase and This increase in sAPPα means a decrease in the production of beta amyloid, a cause of dementia. For reference, it is well known that increased alpha secretase activity contributes to the prevention and treatment of dementia [Lichtenthaler SF, Haass C., J Clin Invest., 2004 MAY; 113 (10): 1384-7.

Example 5: Toxicity Test

For ICR mice (body weight: 25-30 g, 5 males per unit dose, BGI, Korea), 1.0 g / Kg, 500 mg / Kg, 250 mg / Kg A total of seven oral administrations were performed once a week, and visually observed at 30 minute intervals on the day of administration. In addition, two weeks after the end of drug administration, mortality, general symptoms, and body weight were measured, and autopsy confirmed abnormalities of each organ.

LD ₅₀ of the ethanol extract and butanol fraction of Example 1 was found to be 1.0 g / Kg or more and did not show any unusual symptoms at all doses and the autopsy showed no change from the control.

Preparation Example 1 Preparation of Powder and Capsule

100 mg of the ethanol extract and butanol fraction of Example 1 were mixed together with 14.8 mg of lactose, 3 mg of crystalline cellulose, and 0.2 mg of magnesium stearate. The mixture was filled into No. 5 gelatin capsules using a suitable apparatus.

Formulation Example 2: Preparation of Ointment

Using the ethanol extract and butanol fraction of Example 1 to prepare an ointment in the following composition.

[Furtherance]

Active ingredient 5 g, cetyl palmitate 20 g, cetanol 40 g, stearyl alcohol 40 g, myristan isopropyl 80 g, monostearic acid sorbitan 20 g, polysorbate 60 g, paraoxybenzoic acid propyl 1 g, para 1 g of methyl oxyanate, phosphoric acid and purified water

Formulation Example 3 Preparation of Injection

An injection was prepared in the following composition using the ethanol extract and butanol fraction of Example 1.

[Furtherance]

Active ingredient 100 mg, mannitol 180 mg, sodium dihydrogen phosphate 25 mg, purified water for injection 2974 mg

Preparation Example 4 Preparation of Health Food

The ethanol extract of Example 1 and 0.3 g of butanol fraction, powdered vitamin E, iron lactate, zinc oxide, nicotinic acid amide, vitamin A, vitamin B1 and vitamin B2 were prepared on a daily dosage basis.

The components of the health food is as follows (per person daily dose basis).

300 mg of active ingredient

Ginseng Extract 100 mg                     

Green Tea Extract 100 mg

Vitamin C 100 mg

Powdered Vitamin E 120 mg

Iron lactate 2 mg

Zinc oxide 2 mg

20 mg nicotinic acid

Vitamin A 5 mg

Vitamin B1 2 mg

Vitamin B2 2 mg

Corn starch 200 mg

20 mg magnesium stearate

As described above, one or two or more herbal extracts or fractions selected from venom bowels, soybeans, haejupi, sesame, dew and gastric glands according to the present invention protect neurons, inhibit the production of beta amyloid and enhance memory. It is very useful for the use of medicines and health foods for improving brain function, such as mild cognitive impairment and dementia-related diseases.

Claims (7)

1 or 2 or more selected from Aralia cordata radix, Aralia elata cortex, Kalopanax pictus cortex, Dipsacus asper radix, Achyranthes japonica radix, and Clematis mandshurica radix Brain function improving agent comprising an extract. 1) 1 or 2 selected from Aralia cordata radix, Aralia elata cortex, Kalopanax pictus cortex, Dipsacus asper radix, Achyranthes japonica radix, Clematis mandshurica radix Extracting at least one species with an aqueous lower alcohol solution to obtain an alcohol extract; 2) concentrating the obtained alcohol extract under reduced pressure and then separating the layers with saturated lower alcohol to obtain an alcohol fraction. Method of producing a fraction, characterized in that it comprises a. Brain function improving agent, characterized in that it contains the product obtained in each extraction fraction step according to claim 2. The brain function improving agent according to claim 1 or 2, wherein the brain function improving agent is an agent for preventing and treating mild cognitive impairment or dementia. 1 or 2 or more selected from Aralia cordata radix, Aralia elata cortex, Kalopanax pictus cortex, Dipsacus asper radix, Achyranthes japonica radix, and Clematis mandshurica radix Health foods for improving brain function, comprising the extract. Health food for improving brain function, characterized in that it contains the obtained product obtained in each extraction fraction step according to claim 2. The health food according to claim 5 or 6, wherein the improvement of brain function is for preventing and treating mild cognitive impairment or dementia.