KR101874594B1 - A composition for prevention or treating cognitive dysfunction comprising Annona atemoya leaf extract or fraction thereof - Google Patents
A composition for prevention or treating cognitive dysfunction comprising Annona atemoya leaf extract or fraction thereof Download PDFInfo
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- KR101874594B1 KR101874594B1 KR1020160166158A KR20160166158A KR101874594B1 KR 101874594 B1 KR101874594 B1 KR 101874594B1 KR 1020160166158 A KR1020160166158 A KR 1020160166158A KR 20160166158 A KR20160166158 A KR 20160166158A KR 101874594 B1 KR101874594 B1 KR 101874594B1
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- leaf extract
- atemoya
- extract
- disease
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- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
Abstract
The present invention relates to a composition for preventing or treating a cognitive dysfunction comprising atemoya leaf extract or a fraction thereof, a method for preventing or treating cognitive dysfunction using the composition, a cognitive dysfunction including an Atamoya leaf extract or a fraction thereof Prevention or amelioration of a health functional food composition.
Description
The present invention relates to a composition for preventing or treating a cognitive dysfunction including an Annona atemoya leaf extract, and more particularly to a composition for preventing or treating a cognitive dysfunction including the Atelope leaf extract or a fraction thereof A method for preventing or treating cognitive dysfunction, comprising the step of administering the pharmaceutical composition, and a health functional food composition comprising the extract or a fraction thereof.
Cognitive dysfunctions that lose the ability of cognitive function can be divided into dementia and mild cognitive impairment. Mild cognitive impairment refers to subjective memory impairment or abnormal findings on objective examination, but it does not interfere with the ability to carry out daily activities and maintains normal mental function. Although the process of killing neurons in the brain is already underway before the occurrence of mild cognitive impairment, there is no symptom at this time and it is difficult to distinguish it from memory impairment due to normal aging. Mild cognitive impairment is more common than dementia, with 15 to 30% of elderly people aged 60 years or older being associated with it and increasing with age. The state of mild cognitive impairment refers to a cognitive impairment that is currently intermediate between normal and Alzheimer's disease, and about 15% develop annually as symptoms of dementia. Dementia is expected to exceed 100 million people in the world in 2050 by 3.1 times the number of dementia patients in 2013. Korea is expected to be the fastest growing country in the world due to the aging population over 65% And is emerging as a major social concern.
Dementia refers to a specific state of cognitive decline, not a specific disease name, and there are about 100 causative diseases. Among them, Alzheimer's disease, a degenerative brain disease, accounts for more than 50% of the dementia. Alzheimer's irreversible behavior, change in personality, loss of thinking ability, Amyloid protein accumulation and oxidative stress caused by the hypofunction of the cholinergic nervous system, the neurotransmitter system, and the inflammatory response (Lancet, 21, 1403, 1976; J. Biol. Chem. 273, 29719, 1988; Science, 262, 689, 1993), it has been found that there is a close relationship with impairment of cognitive function. Thus, efforts to inhibit acetylcholinesterase (AChE) activity, acetylcholine concentration, and inhibition of beta-amyloid aggregation in the early stage of dementia in the brain have been actively conducted until recently. In order to measure the antioxidative activity, a method of controlling the electron transport system (DPPH, 1,1-diphenyl-2-picrylhydrazyl radical scavenging ability; ABTS, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid scavenging ability) (ROS), which may be a cause of cell death, is being sought.
However, to date, extensive and diverse studies have been conducted on the cause of dementia and its treatment, but the cause of dementia is insufficient and the development of effective therapies is insufficient. The currently used therapeutic agents are only limited effects such as delaying the progress of the disease and alleviating the symptoms under the premise that they are found at an early stage. In addition, the protective effect on nerve cells is affected by the effect of the drug And the effect is even weaker in severe dementia.
Atemoya is a tropical fruit of Annonaceae, a hybrid of annona squamosa and annona cherimola, originating from the American tropics. It is a variety of varieties including Hillary White and Pink Smoth. It is also known as the Buddha's head shape. It is also called as Buddha in China and Taiwan. It is also known that it has the highest sugar content among the fruits and it is cultivated in Jeju in Korea. Ately Moya's immature fruit is an antiseptic to stop the spasm by dripping water, dirt, tumors, and rash. The ethanol extract of seed is used for folk remedies as insecticide and insect repellent. Root is used for diarrhea and fever. And tumor suppression has been reported.
In addition, it can be used as an anticancer drug by confirming the antithrombotic effect of ethanol extract of Atemoya seed (BMC Complement Altern Med. 2014 Sep 23; 14: 353), antimicrobial, antioxidant and antimicrobial activities of compounds isolated from mature fruit of Atemoya Anti-inflammatory activity has been reported (Food Chem. 2016 Jul 1; 202: 176-83) and the treatment or prevention of degenerative brain disease of the active ingredient tryptamine of Atemoya seed extract has been reported U.S. Patent No. 8614246), the effect of the Atetamoya leaf extract on cognitive dysfunction has not been disclosed.
Under these circumstances, the present inventors have made efforts to find natural products harmless to the human body while exhibiting the effects of preventing, ameliorating or treating cognitive dysfunctions, and exhibiting the harmful effects on the human body. As a result, the inventors have found that the anti-amyloid beta- Non-toxic and nerve cell protective effect, and confirmed that it can be applied to medicines or foods using them, thus completing the present invention.
It is an object of the present invention to provide a pharmaceutical composition for preventing or treating cognitive dysfunction comprising an extract of Annona atemoya leaf or a fraction thereof.
It is another object of the present invention to provide a method for preventing or treating cognitive dysfunction, which comprises administering the composition to a subject.
It is still another object of the present invention to provide a health functional food composition for preventing or ameliorating cognitive dysfunction comprising an extract of Annona atemoya leaf or a fraction thereof.
One aspect of the present invention to attain the above object is to provide a pharmaceutical composition for preventing or treating cognitive dysfunction, which comprises an extract of Annona atemoya leaf or a fraction thereof.
The term " Annona atemoya " of the present invention is a tropical fruit of Annonaceae, a hybrid of annona squamosa and annona cherimola originating in the United States tropical regions. In order to investigate the effect of cetuximab, cetacea leaves, seeds and pulp extracts in the present invention, the inventors of the present invention firstly remarkably exerted a remarkable effect of Atemuya leaf extract on cognitive dysfunction. The attemoya leaves, seeds and flesh of the present invention can be purchased commercially and commercially available.
The term " extract " of the present invention means an extract obtained by extracting the Atelope leaf, a diluted solution or a concentrate of the extract, a dried product obtained by drying the extract, a preparation or a purified product of the extract, , The extract itself and extracts of all the formulations that can be formed using the extract. The extract or fraction of the present invention may be prepared in the form of a dry powder after extraction.
In the Atemoya leaf extract of the present invention, the method for extracting the Atelope leaf is not particularly limited, and may be extracted according to a method commonly used in the art. Nonlimiting examples of the extraction solvent include water, alcohol, or a mixed solvent thereof. When an alcohol is used as a solvent, C1 to C4 alcohols can be used as an example. As another example, the Atamoya leaf extract of the present invention may be an ethanol extract.
In addition, the extract may be subjected to extraction or fractionation, followed by a vacuum filtration process, or further concentrated and / or lyophilized to concentrate or remove the solvent. The obtained Atele moai leaf extract may be used It can be stored in a freezer refrigerator.
The term " fraction " of the present invention means a product obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.
The fractionation method for obtaining the fraction in the present invention is not particularly limited and may be carried out according to a method commonly used in the art. As a non-limiting example of the above-mentioned fractionation method, there is a method of obtaining a fraction from the extract by treating a predetermined solvent with the extract obtained by extracting atenza leaves.
The kind of the fraction solvent used for obtaining the fraction in the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the fraction solvent include polar solvents such as water and alcohol; And non-polar solvents such as hexane, ethyl acetate, chloroform, and dichloromethane. These may be used alone or in combination of two or more. When an alcohol is used in the fraction solvent, C1 to C4 alcohols can be preferably used. As another example, fractions of the Atmo moai leaf extract of the present invention may specifically be hexane, ethyl acetate, water-saturated butanol, and water fractions.
The term " cognitive function " of the present invention refers to various intellectual abilities such as attention, perception, memory, language ability, and executive ability. For the purpose of the present invention, cognitive dysfunction is a state in which the above- A disease associated therewith, and all diseases in which it is a symptom. The term " disorder " For example, the cognitive dysfunction may be degenerative brain disease selected from the group consisting of forgetfulness, Alzheimer's disease, dementia, Parkinson's disease, peak disease, and Huntington's disease.
Dementia refers to a syndrome in which the cognitive functions of various areas such as memory, language, and judgment are reduced and thus does not function properly in daily life. As a result of various causes, brain function is impaired, And it may cause considerable difficulties in daily life. The above-mentioned dementia is classified into a causal disease, and there are dozens of cases. Among them, Alzheimer's disease is the most frequent cause and more than 50%. In addition, dementia can be caused by various causes such as degenerative brain diseases such as Lewy body dementia, anterior temporal lobe, Parkinson's disease, normal pressure hydrocephalus, head trauma, brain tumor, metabolic disease, have. In a specific example of the present invention, the atemoyaya leaf extract of the present invention was found to have remarkably superior amyloid beta aggregation inhibitory activity (Fig. 2); It was confirmed that ABTS and DPPH radical scavenging ability had a high antioxidant activity (FIGS. 3 and 4). In addition, Atemoya leaf extract did not show toxicity to nerve cells (Fig. 5); It was confirmed that the survival rate of neurons was improved using HT22 cells induced with neuronal damage (FIG. 6). This suggests that the Atelope leaf extract can be very useful for preventing, treating or improving cognitive dysfunction.
In addition, in a specific example of the present invention, the fraction of Atmo moai leaf extract of the present invention was treated, and as a result, it was confirmed that the ethyl acetate fraction was superior to hexane, water-saturated butanol and water fraction, 7); ABTS and DPPH radical scavenging ability (FIG. 8 and FIG. 9). This suggests that the fractions of the Athermoya leaf extract, specifically the ethyl acetate fraction, can be very useful for preventing, treating or improving cognitive dysfunction.
The term " prevention " of the present invention means all actions that inhibit or delay the cognitive dysfunction by administration of the pharmaceutical composition comprising the Atamoya leaf extract of the present invention or its fractions.
The term " treatment " of the present invention means any action that improves or alters the cognitive dysfunction by the administration of the pharmaceutical composition.
The pharmaceutical composition of the present invention may contain 0.01% to 100% by weight of Atmeoya leaf extract or fraction thereof, relative to the weight of the total composition, and may include, but is not limited to, 1% to 80% by weight.
The pharmaceutical composition for preventing or treating cognitive function related diseases according to the present invention may further comprise a pharmaceutically acceptable carrier and may be formulated together with the carrier to provide a food, a medicine, a feed additive, a drinking water additive, etc. .
The term " pharmaceutically acceptable carrier " of the present invention may mean a carrier or diluent that does not disturb the biological activity and properties of the compound being injected, without irritating the organism. The type of the carrier that can be used in the present invention is not particularly limited, and any carrier conventionally used in the art and pharmaceutically acceptable may be used. Non-limiting examples of the carrier include saline, sterilized water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol and the like. These may be used alone or in admixture of two or more. Compositions comprising a pharmaceutically acceptable carrier may be of various oral or parenteral formulations. At this time, the carrier may comprise a non-naturally occuring carrier. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used. The carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, But may be at least one selected from the group consisting of polyvinylpyrrolidone, physiological saline, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol and liquid paraffin, But are not limited to, ordinary carriers, excipients or diluents. The components may be added to the active ingredient Atemoya leaf extract independently or in combination.
Solid formulations for oral administration may include tablet pills, powders, granules, capsules, and the like, which may contain one or more excipients, such as starch, calcium carbonate, sucrose, Lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.
The pharmaceutical composition of the present invention may also be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, Or a pharmaceutically acceptable salt thereof.
The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. There is no particular restriction on the dosage, and it may vary depending on the body's absorption, body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, severity of disease and the like. The pharmaceutical composition of the present invention is prepared in consideration of an effective dose range, and the unit dosage formulations thus formulated are classified according to the judgment of the expert who monitors or observes the administration of the drug, if necessary, Or may be administered several times at a predetermined time interval. Specifically, the pharmaceutical composition of the present invention may be administered at a dose of 0.0001 to 1000 mg / kg, more specifically, 0.01 to 100 mg / kg per day, based on the amount of Atemoya leaf extract, Or may be divided into several doses.
In another aspect of the present invention, there is provided a method of treating a cognitive disorder comprising administering to a subject a pharmaceutical composition comprising the Atelope leaf extract or a fraction thereof as an active ingredient.
At this time, the atmo moai, extract, fraction, cognitive function, prevention and treatment are as described above.
The term "administering" of the present invention means introducing a predetermined substance into a subject by an appropriate method, and the administration route of the composition can be administered through any conventional route so long as it can reach the target tissue. But are not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, oral, topical, intranasal, intrathecal, rectal.
The term "individual" of the present invention means all animals, including humans, who have developed or are capable of developing cognitive dysfunction. As a specific example, it may be a mammal including a human.
Another aspect of the present invention provides a health functional food composition for preventing or ameliorating a cognitive dysfunction including Atemoya leaf extract.
At this time, the atmo moai, extract, fraction, cognitive function, prevention and treatment are as described above.
The term "improvement" of the present invention means all actions that at least reduce the degree of symptom associated with the condition to be treated by administration of the composition comprising the Atamoya leaf extract or its fractions of the present invention.
When the composition of the present invention is used as an additive for health functional food, the Atele moai leaf extract or its fraction may be used as it is, or may be used together with other foods or food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (preventive, health or therapeutic treatment), and the composition of the present invention is environmentally friendly and has no problem in terms of stability.
Since the health functional food composition of the present invention can be routinely ingested, the effect of improving the cognitive dysfunction can be expected, and thus it can be very usefully used for health promotion purposes.
The term " health functional food " of the present invention is the same term as a food for special health use (FoSHU). In addition to nutrition, . Here, the term 'function' means that the structure and function of the human body are controlled to have nutrients and have a beneficial effect on health uses such as physiological actions. The health functional food of the present invention can be prepared by a method commonly used in the art and can be prepared by adding raw materials and ingredients that are conventionally added in the art. In addition, the formulation of the health functional food may also be produced without restrictions as long as it is a food product. The composition for a health functional food of the present invention can be manufactured in various forms, and unlike a general medicine, there is an advantage that a food is used as a raw material and there are no side effects that may occur when a medicine is taken over a long period of time. , The health functional food of the present invention can be taken as an adjuvant for improving the cognitive dysfunction improving effect.
The health functional food refers to a food having an active health maintenance or promotion effect as compared with a general food, and a health supplement food refers to a food for health assistance. In some cases, the terms health functional foods, health foods, and health supplements are used.
Specifically, the health functional food is a food prepared by adding the compound of the present invention to a food material such as a beverage, a tea, a spice, a gum, confectionery, or the like, or encapsulated, powdered or suspended therein. But it has the advantage that there is no side effect that can occur when the food is used as a raw material and long-term use of the drug.
The health functional food composition may further include a physiologically acceptable carrier. The carrier is not particularly limited, and any carrier conventionally used in the art can be used.
In addition, the health functional food composition may contain additional components that are commonly used in food compositions and can improve odor, taste, visual appearance, and the like. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid and the like. Minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn) and copper (Cu); And amino acids such as lysine, tryptophan, cysteine, valine, and the like.
In addition, the health functional food composition may contain antiseptic agents (such as potassium sorbate, sodium benzoate, salicylic acid, and sodium dehydroacetate), bactericides (such as bleaching powder and highly bleached white powder, sodium hypochlorite), antioxidants (butylhydroxyanilide (BHA) (Sodium hypophosphite, etc.), coloring agent (tar pigment, etc.), coloring agent (sodium nitrite, sodium nitrate), bleaching agent (sodium sulfite), seasoning (sodium MSG glutamate etc.) (Antimicrobial agents such as alginate, sodium saccharin, etc.), perfumes (vanillin, lactones, etc.), swelling agents (alum and potassium hydrogen D-tartrate), emulsifiers, thickeners Of food additives. The additives may be selected and used in appropriate amounts depending on the type of food.
As an example of the health functional food composition of the present invention, it can be used as a health beverage composition. In this case, various flavors or natural carbohydrates can be added as an additional ingredient like ordinary drinks. The above-mentioned natural carbohydrates include monosaccharides such as glucose and fructose; Disaccharides such as maltose, sucrose; Polysaccharides such as dextrin, cyclodextrin; Xylitol, sorbitol, erythritol, and the like. Sweeteners include natural sweeteners such as tau Martin and stevia extract; Synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate may be generally about 0.01 to 0.04 g, specifically about 0.02 to 0.03 g per 100 mL of the health beverage composition of the present invention.
In addition to the above, the health beverage composition may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acid, protective colloid thickener, pH adjuster, stabilizer, Alcohols or carbonating agents, and the like. It may also contain flesh for the production of natural fruit juices, fruit juice drinks, or vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the health beverage composition of the present invention.
The composition comprising the Atamoya leaf extract or the fractions thereof according to the present invention inhibits amyloid beta aggregation and exhibits high antioxidant efficacy, non-toxicity to nerve cells, and protection of nerve cells from external stimuli, The present invention can be applied to medicines or health functional foods for treatment or improvement.
FIG. 1 shows a process for producing a fraction according to an embodiment of the present invention.
Figure 2 is a graph showing the effect of Atemoya leaves, seeds and flesh extracts on amyloid beta aggregation (Morin; positive control, the same hereinafter).
Figure 3 is a graph showing the antioxidant efficacy of Atemoya leaves, seeds and pulp extracts through DPPH radical scavenging activity (Vit. C; positive control, the same shall apply hereinafter).
4 is a graph showing the antioxidant activity of Atemoya leaves, seeds and pulp extracts through DPPH radical scavenging ability.
5 is a graph showing cytotoxicity of Atemoya leaves, seeds and pulp extracts on neuronal hippocampal cell lines ( ** P < 0.01).
6 is a graph showing the cytoprotective effect of atelope leaf, seed and pulp extract using HT22 cells (Carvedilol: positive control, ### P <0.001 vs. no extract treatment, ** P <0.01, ***) P < 0.001 vs. H 2 O 2 alone)
Figure 7 is a graph showing the effect of the Atemoya leaf extract fraction on amyloid beta aggregation.
FIG. 8 is a graph showing the antioxidative activity of the fraction of Atemoya leaves on ABTS radical scavenging ability.
FIG. 9 is a graph showing the antioxidant efficacy of the Atemoya leaf extract fraction through DPPH radical scavenging ability.
Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited by these examples.
Manufacturing example One : Atemoya Preparation of extract
To 500.0 g of dried Atelope leaf, seed, and flesh, 5 L of 70% (v / v) ethanol was added and ultrasonication was performed three times for 1 hour using an ultrasonic extractor. The supernatant extract was filtered using Advantec No. 2 (110 mm) filter paper to remove insoluble matter, and then concentrated under reduced pressure at 40 ° C with a condenser equipped with a cooling condenser. To completely remove the solvent of the concentrated extract, 500 mL of purified water was added to suspend it and then concentrated using a freeze dryer. Table 1 shows the yields of extracts of each part of Atmoya.
Manufacturing example 2 : Atemoya Of leaf extract Fraction Produce
200 mL of purified water was suspended in 10 g of the Atele moai leaf extract prepared in Preparation Example 1, 200 mL of n-hexane was added thereto three times, and the mixture was divided into an aqueous layer and an organic layer using a separatory funnel, The organic layer fractions were concentrated under reduced pressure at 40 ° C with a condenser equipped with a cooling condenser to obtain 413 mg of n-hexane fraction. Then, 200 mL of ethyl acetate was added to the water layer repeatedly three times, and the water layer and the organic layer were separated by using a fractionating funnel. The organic layer fractions were concentrated under reduced pressure at 40 ° C with a condenser equipped with a cooling condenser to obtain 424 mg of ethyl Acetate fraction. 200 mL of n-butanol saturated with water was added to the water layer repeatedly three times, and the organic layer fraction and the organic layer were separated by using a fractionating funnel. The organic layer fraction and the water layer were concentrated under reduced pressure at 40 ° C with a condenser equipped with a cooling condenser 1.373 g of a water-saturated n-butanol fraction and 5.209 g of a water fraction were obtained (Fig. 1). The yields of fractions of Atemoya leaf extract are shown in Table 2.
Example One : Atemoya Analysis of cognitive dysfunction physiological index of extracts by site
Example 1-1: Measurement of amyloid beta aggregation inhibitory effect
The amyloid beta coagulation inhibition assay was performed using a fluorescence assay (Thioflavin T assay). Amyloid beta (A β 1 -42) peptide was stored at
As shown in FIG. 2, the amyloid beta agglutination inhibitory activity of Atemoya leaf extract at a concentration of 100 ug / mL of the sample showed a significant activity of 69.7% of the positive control activity in the leaf extract, At 100 ug / mL, the concentration-dependent tendency of amyloid beta aggregation inhibitory activity was increased with increasing concentration. In addition, IC 50 for inhibition of beta aggregation of Atemoya leaf extract was 87.19 ug / mL.
On the other hand, the extracts of Atemoya seed showed a rather increase in aggregation of amyloid beta, and the extracts of Atemoya pulp showed no effect on aggregation of amyloid beta.
From the above results, it was found that the Ateta Moya leaf extract has superior amyloid beta aggregation inhibitory effect and is effective in the prevention of cognitive disorders compared to the seed and pulp extract.
Example 1-2: Antioxidant efficacy measurement
Example 1-2-1: ABTS Radical Scatters Measure
The antioxidant activity of ABTS (3-ethyl-benzothiazoline-6-sulfonic acid) was measured by ABTS + cation decolorization. 7 mM ABTS and 2.45 mM potassium persulfate were uniformly mixed and allowed to stand at room temperature for 24 hours to form ABTS cation (ABTS +). It was then diluted with PBS to have an absorbance value of 0.7 at 743 nm. The ABTS + solution and each of the samples of Preparation Example 1 were mixed in the same volume of 100 μl each in a 96-well plate, reacted at room temperature for 30 minutes, and the absorbance was measured at 743 nm using an Epoch microplate spectrophotometer. The radical scavenging activity of each sample was expressed as a percentage of the radical scavenging activity relative to the control group using PBS as a control. Vitamin C was used as a positive control for activity comparison.
As shown in FIG. 3, the concentration of Athermoya leaves, seeds and pulp extract increased, and the concentration of ABTS radical scavenging activity increased. The radical scavenging ability of ABTS was 46.74% and 76.74% when treated with 100 ug / mL of seed and flesh extract, respectively. The radical scavenging ability of ABTS with 100% The extracts of the pulp, as well as 77.05% of the ABTS radical scavenging ability.
Example 1-2-2: DPPH Radical Scatters Measure
DPPH (1-1-diphenyl-2-picrylhydrazyl) radical was used to evaluate the antioxidant activity using a 96-well plate. 0.15 mM DPPH solution and a sample of Preparation Example 1 were mixed in the same volume of 100 μl each in the same volume, and reacted at room temperature for 30 minutes, and the absorbance was measured at 517 nm. The antioxidative activity of each extract was expressed as a percentage of the radical scavenging activity of the control group using DMSO as a control. Vitamin C was used as a positive control for activity comparison.
As shown in FIG. 4, the Atetamoya leaf extract showed a DPPH radical scavenging activity remarkably higher than that of the seed and pulp extract, and the DPPH radical scavenging activity was increased with increasing concentration of Attermoya leaf extract.
As can be seen from the results of Examples 1-2-1 and 1-2-2, the antioxidative activity of Leaf Extract of Leaf, Seed and Flesh of Atemoya is particularly excellent. In addition, with respect to the reason that the ABTS scavenging ability (100%) at the same concentration is higher than the DPPH scavenging ability (79.86%) of 100 ug / mL Atelope leaf extract, DPTS scavenges free radicals, but ABTS scavenges cation radical And there is a difference in the radical scavenging ability due to the difference in the degree of binding to the reactants reacting with the two substrates. (J Korean Soc Food Sci Nutr 36, 250-254).
Example 2: Neuroprotective effect by HT22 cells
Example 2-1: HT22 cell culture
HT22 cells were cultured in DMEM supplemented with 10% FBS in a 5% CO 2 incubator at 37 ° C.
Example 2- 1: cell Toxicity measurement
Cell Counting Kit-8 (CCK-8) was used according to the manufacturer's method to examine the cytotoxicity of each sample of Preparation Example 1 above. The HT22 cell line (5 × 10 3 cells / well), which had been divided into 96-well plates, was treated with the samples at different concentrations and cultured for 24 hours. After incubation for 4 hours with 10 μL of CCK-8 solution, the absorbance was measured at 450 nm and the relative cell viability (%) was compared with each control group (0 ug / mL) (Fig. 3).
As shown in FIG. 5, cell viability was markedly lowered to 56.20% when treated with 100 ug / mL of Atele moai seed extract, compared with the respective extracts and the control group, and cytotoxicity was the highest, , But cell viability was 86.37% and slightly cytotoxic, but cell viability was almost 100% when treated with 100 ug / mL of Atemoya leaf extract.
From the above results, the cell survival rate of Atemoya leaf extracts was almost 100% at all concentrations of 12.5-100 ug / mL, indicating that the extracts showed no harmful effects to human body as compared with Atetamoya seed and pulp extract.
Example 3: Measurement of nerve cell protection activity
HT22 cells were treated with 250 μM hydrogen peroxide (H 2 O 2 ) for 6 hours in order to induce neuronal cell damage, and H 2 O 2 alone group and sample And H 2 O 2 were compared to determine cell protection efficacy. Carvedilol was used as a positive control.
As shown in Fig. 6, in the case of Atemoya seed and pulp extract, the cell survival rate was lower than the cell survival rate in the H 2 O 2 alone treatment group compared to the control group in which no treatment was performed at all the concentrations of 25 to 100 ug / mL , It was not possible to confirm the cell protection effect by the extracts.
On the other hand, in the group treated with Atemoya leaf extract and H 2 O 2 , the cell survival rate gradually increased with increasing concentration in the group treated with H 2 O 2 alone compared to the control group treated with no treatment And at a concentration of 50 and 100 ug / mL, a survival rate of about 80% similar to that of the positive control group showed a protection effect of about 40% against the H 2 O 2 treatment group.
From the above results, it can be seen that the Ateta Moya leaf extract has an effect of enhancing the survival rate of neurons by protecting nerve cells against external stimuli.
Example 4 : Atemoya Leaf extract Fraction Analysis of Physiological Indices of Cognitive Dysfunction
Example 4-1: Measurement of amyloid beta aggregation inhibitory effect
The measurement of inhibition of amyloid beta aggregation of the Atmo moai leaf extract fraction of Preparation Example 2 was performed using a fluorescence assay (Thioflavin T assay), and a specific experimental method was performed in the same manner as in Example 1-1.
As a result, as shown in Fig. 7, the amyloid beta agglutination inhibitory activity of each fraction of 100 ug / mL of Atele moai leaf extract was superior to the positive control in the ethyl acetate fraction.
From the above results, it can be seen that the fractions of Atmo moai leaf extract, specifically, the ethyl acetate fraction have excellent amyloid beta agglutination inhibitory effect and thus can be effective in the prevention of cognitive dysfunction.
Example 4-2: Antioxidant efficacy measurement
Example 4-2-1: ABTS Radical Scatters Measure
The antioxidative activity of the Attemoya leaf extract fraction using the ABTS radical was determined by modifying the ABTS + cation decolorization assay according to the method using a 96-well plate. The specific experimental method was the same as in Example 1-2-1 Respectively.
As a result, as shown in FIG. 8, all the fractions of Atemoya leaf extract showed the radical scavenging ability of ABTS, and in particular, the ethyl acetate fraction and then the water saturated butanol fraction showed superior radical scavenging ability of ABTS.
Example 4-2-2: DPPH Radical Scatters Measure
The antioxidant activity of the Atemoya leaf extract fraction was measured using a DPPH (1-1-diphenyl-2-picrylhydrazyl) radical using a 96-well plate.
As a result, as shown in FIG. 9, the fractions of Atemoya leaf extract showed excellent DPPH radical scavenging activity, and in particular, superior DPPH radical scavenging ability of the ethyl acetate fraction and then the water saturated butanol fraction was confirmed.
The antioxidative activity of the fractions of Atemoya leaf extract was confirmed by this.
From the above description, it will be understood by those skilled in the art that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. In this regard, it should be understood that the embodiments described above are illustrative in all aspects and not restrictive. The scope of the present invention should be construed as being included in the scope of the present invention without departing from the scope of the present invention as defined by the appended claims.
Claims (11)
Wherein said Atemoya leaf extract is obtained by extracting Atemoya leaves with water, C1 to C4 alcohols or a mixed solvent thereof.
Wherein the Atetamoya leaf extract is obtained by extracting with ethanol.
Wherein the fraction of the Atmo moai leaf extract is at least one fraction selected from the group consisting of hexane, ethyl acetate, butanol and water fraction.
Wherein said fraction is an ethyl acetate fraction.
Wherein said fraction is a water saturated butanol fraction.
Wherein the Atelope leaf extract or fraction thereof has acetylcholinesterase inhibition, amyloid beta aggregation inhibition, antioxidant and nerve cell protection.
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| KR1020160166158A KR101874594B1 (en) | 2016-12-07 | 2016-12-07 | A composition for prevention or treating cognitive dysfunction comprising Annona atemoya leaf extract or fraction thereof |
| PCT/KR2017/013247 WO2018105929A1 (en) | 2016-12-07 | 2017-11-21 | Composition for preventing or treating cognitive impairment including atemoya leaf extract or fraction thereof |
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| KR1020160166158A KR101874594B1 (en) | 2016-12-07 | 2016-12-07 | A composition for prevention or treating cognitive dysfunction comprising Annona atemoya leaf extract or fraction thereof |
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| JP4711272B2 (en) * | 2000-05-29 | 2011-06-29 | 沖縄食糧株式会社 | Angiotensin converting enzyme inhibitor |
| WO2009132051A1 (en) * | 2008-04-21 | 2009-10-29 | Signum Biosciences, Inc. | Compounds, compositions and methods for making the same |
| FR2942625B1 (en) * | 2009-03-02 | 2013-11-22 | Centre Nat Rech Scient | INDOLIC DERIVATIVES FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
| JP2012116761A (en) * | 2010-11-29 | 2012-06-21 | Wamiles Cosmetics Kk | Cosmetic containing plant-originated steam-distillation fraction |
| KR20150064314A (en) * | 2013-12-03 | 2015-06-11 | 한국콜마주식회사 | Cosmetic Composition Comprising Mangifera indica L. Extract, Passiflora edulis Sims Extract, Hylocereus undatus (Haw.) Britt. and Rose Extract, Actinidia chinensis Planch. Extract and Annona Squamosa Extract |
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