WO2019212300A1 - Composition comprenant un extrait d'aster koraiensis nakai ou une fraction de celui-ci en tant que principe actif pour la prévention ou le traitement de la maladie de parkinson - Google Patents

Composition comprenant un extrait d'aster koraiensis nakai ou une fraction de celui-ci en tant que principe actif pour la prévention ou le traitement de la maladie de parkinson Download PDF

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WO2019212300A1
WO2019212300A1 PCT/KR2019/005352 KR2019005352W WO2019212300A1 WO 2019212300 A1 WO2019212300 A1 WO 2019212300A1 KR 2019005352 W KR2019005352 W KR 2019005352W WO 2019212300 A1 WO2019212300 A1 WO 2019212300A1
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disease
parkinson
extract
bee
protein
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PCT/KR2019/005352
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English (en)
Korean (ko)
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양현옥
박정윤
장리준
이주영
정상훈
천윤선
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한국과학기술연구원
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • 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
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • 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
    • 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

Definitions

  • the present invention relates to a composition for the prevention or treatment of Parkinson's disease, which comprises the bee herb extract or fractions thereof as an active ingredient.
  • Degenerative brain diseases are disorders in which motor, memory, and cognitive disorders are caused by neurodegenerative diseases caused by various causes.
  • Parkinson's disease is the most common neurodegenerative brain disease after Alzheimer's disease. .
  • Parkinson's disease was first described in 1817 by James Parkinson, a British medical doctor, about 60 years later, the term Parkinson's was used by J.Charout, and by Kinner wilson in 1912, Parkinson's disease It was found that the disease is related to the extrapyramidal system and not the pyramidal system (Habibi et al., 2011).
  • Parkinson's disease is classified as a progressive neurological disorder intractable disease without effective and effective long-term treatment (Pan et al., 2008, Habibi et al., 2011).
  • Parkinson's disease is caused by various pathological factors occurring in Parkinson's disease patients.
  • the abnormal killing of dopamine-releasing neurons among the neurotransmitters distributed in the melanoma of the midbrain is disrupted or destroyed by the substantia nigra par compacta (Camins et al., 2008, Smith). , 2008).
  • Abnormal death of dopamine neurons occurs through a series of processes.
  • mitochondria damaged by various factors such as the environment, heredity, and aging, cause functional degradation of the proteolytic system, which causes abnormal proteins and organelles. It is caused by accumulation and not decomposition. These causes raise the importance of proteolytic systems in the treatment and prevention of Parkinson's disease.
  • L-dopa is a treatment that increases the level of dopamine in the blood by direct injection of Levodopa, a precursor of dopamine neurons.
  • Direct infusion of Levodopa results in substantial symptomatic relief in Parkinson's patients, but increased doses are essential for long-term use and are known to cause a variety of unforeseen side effects as the dose increases (Rock and Peterson, 2006). , McGeer and McGeer, 2008). Therefore, it is urgent to develop more fundamental treatments and drugs that can suppress the protection and death of nerve cells that facilitate dopamine secretion, rather than the direct administration of L-dopa, which increases dopamine blood levels. As one of these attempts, research into the development of therapeutic agents targeting autophagy, one of the proteolytic systems, has recently attracted attention.
  • Autophagy or autophagy, is derived from the Greek word for "self,” meaning “self,” and “eating,” meaning to eat. It not only maintains the metabolic balance of the cell but also affects the fate of the cell. It is known as a mechanism of self-sacrifice that plays an important role (Eisenberg-Lerner et al., 2009).
  • This autophagy acts as a precursor to autophagosomes and is a morphological form of autophagosomes, which are independent bilayers, which gradually extend the edges of cells to completely surround unwanted proteins in the cell, forming vesicles. It has a characteristic structure.
  • autophagosomes move along microtubules to fuse with lysosomes in cells and form autolysosomes, which are reported to degrade proteins by proteolytic enzymes secreted inside lysosomes. It became.
  • Aster koraiensis Nakai is a compositae plant, also called Gymnaster koraiensis (Nakai) Kitamura, and is a native plant of Korea.
  • Beetle odor is a perennial herb distributed mainly in Jeju Island and sub-Gyeonggi province, and is known to grow well in valleys and wetlands with high humidity.
  • the present inventors are conducting research on the development of a prophylactic and therapeutic agent for Parkinson's disease through induction of autophagy
  • the extract of Aster koraiensis Nakai plants induces autophagy and at the same time prevents and prevents Parkinson's disease.
  • the present invention was completed by confirming that it is very effective for treatment.
  • An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of Parkinson's disease comprising a bee odor extract or fractions thereof as an active ingredient.
  • Another object of the present invention is to provide a method for preventing or treating Parkinson's disease, comprising administering the pharmaceutical composition to a subject.
  • Still another object of the present invention is to provide a food composition for preventing or improving Parkinson's disease, which comprises a bee anesthetist extract or a fraction thereof as an active ingredient.
  • Still another object of the present invention is to provide a feed composition for preventing or improving Parkinson's disease, which comprises a bee anesthetist extract or a fraction thereof as an active ingredient.
  • Still another object of the present invention is to provide a composition for inhibiting brain cell death by in vitro autophagy inducing effect, which comprises a bee stinger extract or a fraction thereof as an active ingredient.
  • Beetle odor extract of the present invention increases the expression of LC3 protein, a membrane protein of autophagosome, induces autophagy through the increase of phosphorylated AMPK and UK1 which induces autophagy, and the reduction of mTOR that inhibits autophagy. Therefore, the composition including the same can be effectively used for the prevention or treatment of Parkinson's disease through induction of autophagy action.
  • Figure 1 shows the results confirmed by Western blotting to increase the expression of the autophagy membrane protein LC3 expression in accordance with the concentration of the bee odor extract in SH-SY5Y cell line (Control: control). ** indicates P ⁇ 0.01 for control and *** indicates P ⁇ 0.001.
  • Figure 2 is a result confirmed by Western blotting to increase the expression of the phosphorylated AMPK protein according to the concentration of the bee hijab extract (Control: control). *** indicates P ⁇ 0.001 for the control.
  • Figure 3 is the result confirmed by Western blotting to increase the expression of phosphorylated ULK1 protein expression according to the concentration of the bee sting odor extract (Control: control). *** indicates P ⁇ 0.001 for control
  • Figure 4 is a result confirmed by Western blotting to reduce the expression of mTOR protein expression according to the concentration of the bee sting odor extract (Control: control). * Indicates P ⁇ 0.05 for control and *** indicates P ⁇ 0.001.
  • Figure 6 shows the results confirmed by Western blotting to increase the expression of the autophagy membrane protein LC3 expression according to the bee odor fraction in SH-SY5Y cell line (Control: control).
  • Figure 7 is a result confirmed by Western blotting to reduce the amount of mTOR protein expression according to the addition concentration of the honey bee odor fraction (Control: control). ** indicates P ⁇ 0.01 for control and *** indicates P ⁇ 0.001.
  • FIG. 8 shows the effect of Western blotting on the expression of Tyrosine hydroxylase (TH) protein according to bee hives extracts and fractions in substantia nigra of C57BL / 6 mice induced Parkinson's disease by MPTP.
  • the result was confirmed (Control: control; MPTP: MPTP-treated group; Ropinirole: ropinirole + MPTP-treated group).
  • *** indicates P ⁇ 0.001 compared to the control group, ## indicates P ⁇ 0.01 for the MPTP treatment group and ### indicates P ⁇ 0.001 for the MPTP treatment group.
  • FIG. 11 shows the results of Western blotting confirming the effect of increasing the amount of phosphorylated AMPK protein expression according to bee hives extracts and fractions in substantia nigra of C57BL / 6 mice induced Parkinson's disease by MPTP.
  • Control control; MPTP: MPTP-only group; rofinirol: rofiniro + MPTP-treated group).
  • # Indicates P ⁇ 0.05 for MPTP alone treatment group.
  • FIG. 12 shows Western blotting effect of increased phosphorylated ULK1 (s555) protein expression levels according to bee hives extract and fraction administration in substantia nigra of C57BL / 6 mice induced Parkinson's disease by MPTP administration. This was confirmed by (Control: control group; MPTP: MPTP treatment group; ropinillol: ropinillol + MPTP treatment group). * Indicates P ⁇ 0.05 compared to the control, ## indicates P ⁇ 0.01 for the MPTP-only group and ### indicates P ⁇ 0.001 for the MPTP-only group.
  • FIG. 13 shows the results of Western blotting confirming the reduction effect of mTOR protein expression according to bee hives extract and fraction administration in substantia nigra of C57BL / 6 mice induced Parkinson's disease by MPTP administration.
  • Control control; MPTP: MPTP alone group; ropinirol: rofiniro + MPTP treated group).
  • One aspect of the present invention for achieving the above object provides a pharmaceutical composition for the prevention or treatment of Parkinson's disease, including Aster koraiensis Nakai extract or a fraction thereof as an active ingredient.
  • the present invention provides a preventive or therapeutic use of Parkinson's disease of the composition comprising an extract of Aster koraiensis Nakai or fractions thereof as an active ingredient.
  • beetle odor is scientific name Aster koraiensis Nakai, but in the present invention can be used to extract the above-ground parts of the plant, more specifically, the leaves and stems of the plant can be used, preventing or treating Parkinson's disease As long as it has an effect, it is not specifically limited to this.
  • the hummingbird odor can be purchased commercially, or may be used collected or cultivated in nature.
  • extract refers to an extract, such as an extract obtained by extracting a bee odor, a diluent or concentrate of the extract, a dried product obtained by drying the extract, a modifier or purified product of the extract, or a mixture thereof. It includes extracts of all formulations that can be formed using extracts.
  • the method of extracting the hummingbird odor is not particularly limited, and may be extracted according to a method commonly used in the art.
  • Non-limiting examples of the extraction method may include hot water extraction, ultrasonic extraction, filtration, reflux extraction, etc., these may be carried out alone or in combination of two or more methods.
  • the type of extraction solvent used to extract the bee odor is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the extraction solvent may include water, alcohols of C1 to C4, mixed solvents thereof, and the like, which may be used alone or in combination of one or more thereof. Specifically, preferably 95% ethanol may be used, but is not limited thereto.
  • fraction refers to the result obtained by performing fractionation to separate a specific component or a specific group of components from a mixture comprising several various components.
  • the fractionation method of obtaining the fraction in the present invention is not particularly limited, and may be performed according to a method commonly used in the art.
  • Non-limiting examples of the fractionation method include a solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed through an ultrafiltration membrane having a constant molecular weight cut-off value, and various chromatography (size, charge, hydrophobicity). Or chromatographed fractions), and combinations thereof, which are prepared for separation according to affinity.
  • a method of obtaining a fraction from the extract by treating a predetermined solvent with an extract obtained by extracting the bee sting odor of the present invention are prepared for separation according to affinity.
  • the kind of the fractionation solvent used to obtain the fraction in the present invention is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the fractionation solvents include polar solvents such as water and alcohols having 1 to 4 carbon atoms; Nonpolar solvents such as hexane, ethyl acetate, chloroform and dichloromethane; Or a mixed solvent thereof. These may be used alone or in combination of one or more thereof, but is not limited thereto.
  • hexane, ethyl acetate, butanol or water may be used alone or in combination of one or more thereof, but is not limited thereto. It doesn't happen.
  • extract or fraction may be prepared and used in the form of a dry powder after extraction, but is not limited thereto.
  • Parkinson's disease means a degenerative brain disease of the nervous system caused by the loss of dopamine neurons. Stability, stiffness, slowness of movement (slowness of motion) and postural instability are characteristic, and clinical symptoms usually begin after age 60.
  • prevention means any action that inhibits or delays the progression of Parkinson's disease by the administration of a pharmaceutical composition of the present invention comprising a cane odor extract or a fraction thereof.
  • treatment means any action in which Parkinson's disease is ameliorated or beneficially altered by administration of the pharmaceutical composition.
  • the "pharmaceutical composition” of the present invention may further comprise a pharmaceutically acceptable carrier, excipient or diluent commonly used in the manufacture of a pharmaceutical composition, which carrier is a non-naturally occuring carrier. It may include.
  • the pharmaceutical composition may be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. .
  • “Pharmaceutically acceptable” means to exhibit properties that are not toxic to cells or humans exposed to the composition.
  • the type of the carrier is not particularly limited, and any carrier can be used as long as it is a conventionally used and pharmaceutically acceptable carrier in the art.
  • Non-limiting examples of the carrier include saline, sterile 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 combination of two or more thereof.
  • ком ⁇ онентs such as antioxidants, buffers and / or bacteriostatic agents may be added and used, and diluents, dispersants, surfactants, binders, lubricants, and the like may be additionally added to provide a solution such as an aqueous solution, a suspension, an emulsion, or the like. It may be formulated into a use formulation, pills, capsules, granules or tablets.
  • the mode of administration of the pharmaceutical composition for preventing or treating Parkinson's disease according to the present invention is not particularly limited and may be in accordance with a method commonly used in the art.
  • the composition may be administered by oral or parenteral administration.
  • the composition for preventing or treating Parkinson's disease of the present invention can be prepared in various formulations according to the desired mode of administration.
  • Another aspect of the invention provides a method of preventing or treating Parkinson's disease comprising administering the pharmaceutical composition to a subject.
  • Parkinson's disease prevention and treatment is as described above.
  • the term "administration” means the introduction of certain substances into an individual in a suitable manner.
  • the term "individual” means all animals, such as rats, mice, and livestock, including humans who may or may develop Parkinson's disease. As a specific example, it may be a mammal including a human.
  • the "individual” may include a companion animal.
  • the companion animal refers to an animal that lives together with a human, and includes, but is not limited to, a mammal such as a dog, a cat, a hamster, and a guinea pig, a bird such as a parrot, a canary, and the like.
  • the method for preventing or treating Parkinson's disease of the present invention may include administering to the individual a pharmaceutically effective amount of a medicinal composition comprising a bee herb extract or a fraction thereof.
  • the "pharmaceutically effective amount” means an amount sufficient to treat the disease at a reasonable benefit / risk ratio applicable to the medical treatment and not causing side effects, and the effective dose level refers to the sex, age, weight, Well-known in the field and other medical fields, including health status, type of disease, severity, drug activity, drug sensitivity, method of administration, time of administration, route of administration, and rate of release, duration of treatment, combination or drug used simultaneously Depending on the factor, it can be readily determined by one skilled in the art.
  • the pharmaceutical composition of the present invention may be administered at 0.0001 to 500 mg / kg body weight per day, more specifically at 0.01 to 500 mg / kg body weight, based on solids. Dosing may include administering the recommended dose once a day or in several divided doses.
  • compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. It may also be single or multiple doses. Taking all of these factors into consideration it is important to administer an amount that will achieve the maximum effect in a minimum amount without causing side effects, which can be readily determined by one skilled in the art.
  • the route of administration and the mode of administration of the composition are not particularly limited, and any route of administration can be reached as long as the composition comprising the composition can be reached at the desired site.
  • the composition may be administered through various routes, oral or parenteral, and non-limiting examples of the route of administration include oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, nasal What is administered through intralateral or inhalation etc. are mentioned.
  • Yet another aspect of the present invention provides a food composition for preventing or improving Parkinson's disease, comprising a bee odorous extract or a fraction thereof as an active ingredient.
  • the term " improvement" means any action that at least reduces the parameters associated with the condition to be treated with the administration of the compositions of the present invention, eg the extent of symptoms.
  • the term "food” of the present invention meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, drinks, tea, drinks, alcoholic beverages , Vitamin complexes, nutraceuticals and health foods, and includes all foods in the usual sense.
  • the food composition of the present invention can be consumed on a daily basis, a high Parkinson's disease improvement effect can be expected, and thus can be very useful for health promotion purposes.
  • the functional food is the same term as a food for special health use (Food for special health use, FoSHU), in addition to the nutritional supply, the processed food, so that the bioregulatory function appears efficiently, high medical effect Means food.
  • Food for special health use Food for special health use, FoSHU
  • the term 'function (sex)' refers to obtaining a useful effect for health purposes such as nutrient control or physiological action on the structure and function of the human body.
  • the food of the present invention may be prepared by a method commonly used in the art, and the preparation may be performed by adding raw materials and ingredients commonly added in the art.
  • the formulation of the food may be prepared without limitation as long as the formulation is recognized as a food.
  • Food composition of the present invention can be prepared in a variety of dosage forms, unlike the general medicine has the advantage that there is no side effect that can occur when taking a long-term use of the drug as a natural product, and because the portability is excellent,
  • the food of the invention can be taken as an adjuvant for enhancing the Parkinson's disease improving effect.
  • the health food refers to foods having active health maintenance or promotion effect as compared to general foods
  • the health supplement food refers to foods for health supplementation purposes.
  • nutraceutical, health food, dietary supplement are used interchangeably.
  • the health functional food is a food prepared by adding the extract of the present invention to food materials such as beverages, teas, spices, gums, confections, or the like, encapsulated, powdered, suspensions, etc.
  • food materials such as beverages, teas, spices, gums, confections, or the like, encapsulated, powdered, suspensions, etc.
  • the food composition may further include a physiologically acceptable carrier, and the type of carrier is not particularly limited and may be any carrier that is commonly used in the art.
  • the food composition may include additional ingredients that are commonly used in food compositions to improve the smell, taste, time and the like.
  • additional ingredients may include 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), copper (Cu) and chromium (Cr); And amino acids such as lysine, tryptophan, cysteine, valine and the like.
  • the food composition is a preservative (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetic acid, etc.), fungicides (bleaching powder and highly bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisol (BHA), butylhydride) Oxytoluene (BHT), etc.), colorants (such as tar pigments), colorants (sodium nitrite, sodium nitrite, etc.), bleach (sodium sulfite), seasonings (such as MSG glutamate), sweeteners (ducin, cyclate, saccharin Foods such as sodium, etc.), fragrances (vanillin, lactones, etc.), swelling agents (alum, potassium D-tartrate, etc.), reinforcing agents, emulsifiers, thickeners (foils), coatings, gum herbicides, foam inhibitors, solvents, modifiers, etc. It may include food additives.
  • the additive may
  • Another aspect of the present invention provides a feed composition for the prevention or improvement of Parkinson's disease comprising a bee anesthetized extract or a fraction thereof as an active ingredient.
  • composition comprising the honey bee odor extract or fractions thereof of the present invention can be used for the prevention or treatment of the development of Parkinson's disease in individuals other than humans, such as livestock or companion animals, can be utilized as a functional feed additive, or a feed composition.
  • the content of the bee-flavored extract or fractions thereof in the feed composition according to the present invention can be appropriately adjusted according to the type and age of the livestock, the type of application, the desired effect, and the like, for example, 1 to 99% by weight, preferably 10 to 90% by weight. %, More preferably 20 to 80% by weight, but is not limited thereto.
  • diluents, dispersants, surfactants, binders or lubricants may be additionally added to formulate injectable formulations, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.
  • the feed composition of the present invention is a supplementary ingredient such as amino acids, inorganic salts, vitamins, antioxidants, antifungal agents, antibacterial agents, and vegetable protein feed such as milled or crushed wheat, barley, corn, blood meal, meat meal, fish meal as auxiliary ingredients.
  • a supplementary ingredient such as amino acids, inorganic salts, vitamins, antioxidants, antifungal agents, antibacterial agents, and vegetable protein feed such as milled or crushed wheat, barley, corn, blood meal, meat meal, fish meal as auxiliary ingredients.
  • animal protein feed animal fat and vegetable fat, such as can be used with nutritional supplements, growth promoters, digestive absorption accelerators, disease prevention agents.
  • the feed composition of the present invention When the feed composition of the present invention is used as a feed additive, the feed composition may be added as it is or used together with other ingredients, and may be suitably used according to a conventional method.
  • Dosage forms of the feed composition may be prepared in immediate release or sustained release formulation in combination with a nontoxic pharmaceutically acceptable carrier.
  • a nontoxic pharmaceutically acceptable carrier may be corn starch, lactose, sucrose, propylene glycol.
  • a solid carrier it may be a dosage form such as a tablet, a powder, a torokee agent, or the like, and in the case of a liquid carrier, it may be a dosage form of a syrup, a liquid suspension, an emulsion, or a solution.
  • the dosage may contain preservatives, lubricants, solution promoters, stabilizers, and may also contain other inflammatory disease ameliorating agents and substances useful for virus prevention.
  • the feed composition of the present invention is applicable to a number of animal diets, ie feeds, including mammals, poultry, fish and shellfish.
  • animal diets including mammals, poultry, fish and shellfish.
  • Commercially important mammals such as pigs, cows and goats, zoo animals such as elephants and camels, and livestock such as dogs and cats.
  • Commercially important poultry includes chickens, ducks, geese and the like, and may include commercially raised fish and crustaceans such as trout and shrimp.
  • the feed composition according to the present invention may be mixed in a livestock feed in an amount of about 10 to 500 g, preferably 10 to 100 g per kg, on a dry weight basis, and then thoroughly mixed and then fed into a mesh or further processing. Palletization, expansion, extrusion through the process is preferred.
  • the composition of the present invention increases the protein expression level of phosphorylated ULK1 and inhibits mTOR protein expression by increasing the protein expression level of phosphorylated AMPK in dopaminergic cell lines, and autophagy in an animal model induced by Parkinson's disease through MPTP. Through the induction of the brain cell death can be effectively suppressed, it was confirmed that it has an excellent effect on the prevention, treatment and improvement of Parkinson's disease.
  • the bee anesthetized extract of the present invention has an excellent effect of inducing autophagy and promoting the degradation of alpha-synuclein protein, which is known as the ultimate cause of Parkinson's disease, thereby preventing or treating Parkinson's disease. It was confirmed that the composition can be effectively used for improvement.
  • Beetle odor was cultivated in Bukpyeong-myeon, Jeongseon-gu, Gangwon-do, and washed and dried completely to obtain 15 kg of dry weight. The sample was crushed in a grinder and extracted with 95% ethanol twice under reduced pressure for 2 hours at 60 ⁇ 70 °C. kg was obtained.
  • Example 1-2 Effect of Increasing the Expression Level of LC3 Protein by the Beetle Odor Extract
  • the dopaminergic cell line SH-SY5Y cell line was 10% heat-inactivated fetal bovine serum of Gibco (Grand Island, NY, USA) Dulbecco's modified eagle medium nutrient mixture F-12 (Ham) 1 ⁇ containing 1% penicillin / streptomycin (hereinafter referred to as P / S, Gibco); Cultured in DMEM / F12 (Gibco) medium was used.
  • This cell line was purchased from ATCC: The Global Bioresource Center (CRL-2266 TM) (Manassas, Virgina 20108, USA).
  • the bee-flavored extract obtained in Example 1 was added to the cell line (SH-SY5Y) in the amount shown in FIG. 1, then incubated at 5% CO 2 , 37 ° C. for 24 hours, and collected for 6 minutes at 13,000 rpm. Centrifugation was washed twice with Dulbecco's phosphate buffered saline (DPBS). After lysis solution (1X lysis buffer, 1X Protease inhibitor cocktail, 1x Phenylmethyl sulfonyl fluoride) was added to the obtained cells, the cells were reacted at 4 ° C for 30 minutes, and then completely lysed while shaking at the same 4 ° C for 30 minutes. Centrifugation was performed at 13,000 rpm for 20 minutes to obtain the supernatant from which the protein was released. The supernatant was quantified by Bradford method using Protein assay dye Reagent concentrate (Bio-Rad).
  • Example 1-3 Effect of Increasing Phosphorylated AMPK Protein Expression by Beetle Anesthetic Extract
  • Example 2 In order to measure the effect of increasing the expression level of phosphorylated AMPK protein of the bee-flavored extract obtained in Example 1, it was added to the cultured SH-SY5Y cell line in the amount of the bee-flavored extract described in Figure 2, at 5% CO 2 , 37 °C Incubated for 24 hours, and experimented in the same manner as in Example 2.
  • Primary antibodies used in this experiment are AMPK, p-AMPK, GAPDH (Cell signaling technology), GAPDH was used as a loading control.
  • Example 1-4 Effect of Increasing Phosphorylated ULK1 Protein Expression by Beetle Odor Extract
  • Example 1-5 Effect of Increasing Expression of mTOR Protein by Beetle Odor Extract
  • Example 1-6 Effect of Induction of Autophagy Action on Beetle Anesthetic Extracts Through Autophagy Inhibitor Bafilomycin A
  • Example 2 In order to confirm whether the effect of inducing autophagy action of the bee-flavored extract was a non-specific result of false positive or true autophagy induction effect, the cultured SH-SY5Y cell line was obtained in Example 1 Beetle odor extract was treated for 18 hours at 50 ⁇ g / ml concentration as described in Figure 5 and then treated with 100nM bafilomycin A1 (hereinafter, baf A1) and incubated for 6 hours. Thereafter, the amount of LC3 protein expression was measured by Western blotting in the same manner as in Example 2.
  • bafilomycin A1 hereinafter, baf A1
  • Baf A1 is an autophagy inhibitor that inhibits the fusion of autophagosomes and lysosomes, thereby inhibiting the maturation of autophagic vacuoles. Specifically, autophagy flux occurs only at the last stage of the autophagy route, but autophagy induction occurs. However, when baf A1 is treated, LC3 protein expression is increased as autophagy flux is suppressed.
  • the bee-flavored fraction was added to the cell line (SH-SY5Y cell) at 5, 10, 25, 50, and 100 ⁇ g / ml depending on the fraction toxicity. After the addition, 5% CO 2 , and incubated for 24 hours at 37 °C, it was confirmed through the Western blotting experiment of the same method as Example 2.
  • Example 7 In order to determine the effect of reducing mTOR protein expression of the hummingbird BuOH fraction obtained in Example 7 at all, the hummingbird fraction was added to the SH-SY5Y cell line as described in FIG. 7, followed by 24% at 5% CO 2 , 37 ° C. The culture was carried out in the same manner as in Example 2. Primary antibodies used in this experiment are mTOR, GAPDH (Cell signaling technology), GAPDH was used as a loading control.
  • mice C57BL / 6 male mice (8 weeks old) were used and feed and water were freely ingested. Mice were divided into seven groups, six in each group.
  • the control group and the MPTP-treated group were orally administered with saline once 3 days, the bee odor extract (200 mg / kg) group obtained in Example 1-1 and the bee odor fraction obtained in Example 2-1 (25, 50, 100 mg / kg) group was dissolved orally in each saline extract and fractions and administered once orally for 3 days.
  • rofinirol was dissolved in physiological saline and administered once orally for 3 days.
  • MPTP (30 mg / kg) dissolved in physiological saline was administered orally to all groups except the control group 1 hour after drug administration, and to all groups except the control group on the 9th to 10th day of drug administration. The same amount of drug was administered orally once.
  • mice in each group were killed and brain tissues were separated into substantia nigra and striatum.
  • the isolated brain tissue was homogenized with PRO-PREPTM Lysis Buffer (iNtRON, Gyeonggi, Korea) supplemented with Phosphatase Inhibitor Cocktail Set I (Sigma-Aldrich, MO, USA).
  • the homogenate was left at 4 ° C. for 30 minutes and then the supernatant was collected by centrifugation at 13,000 rpm, 4 ° C. for 30 minutes, and the supernatant was quantitated by Bradford method using Protein assay dye Reagent concentrate (Bio-Rad). It was.
  • Example 1-2 The mixture was mixed with a predetermined amount of SDS loading buffer and heated at 99 ° C. for 5 minutes, and protein expression was measured by Western blotting in the same manner as in Example 1-2.
  • Primary antibodies used in this experiment include TH, Beclin-1, p-mTOR, Mtor, p-ULK1 (s555), ULK1, p-AMPK, AMPK, LC3, ⁇ -synuclein, Cell signaling technology (GAPDH). GAPDH was used as loading control.

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Abstract

La présente invention concerne une composition pharmaceutique comprenant un extrait d'Aster koraiensis Nakai ou une fraction de celui-ci en tant que principe actif pour la prévention ou le traitement de la maladie de Parkinson, un procédé de prévention ou de traitement de la maladie de Parkinson à l'aide de la composition pharmaceutique, et une composition alimentaire et une composition d'aliment pour animaux pour la prévention ou le soulagement de la maladie de Parkinson. Un extrait d'Aster koraiensis Nakai ou une fraction de celui-ci selon la présente invention est caractérisé par l'augmentation spécifique de la quantité d'une protéine impliquée dans l'autophagie qui prévient la mort des neurones dopaminergiques, qui constitue une cause de la maladie de Parkinson. En particulier, l'extrait d'Aster koraiensis Nakai ou une fraction de celui-ci présente d'excellents effets de régulation à la hausse de l'expression de la protéine LC, qui est une protéine membranaire d'un autophagosome, et l'expression de protéines p-AMPK et p-ULK1, qui induisent l'autophagie, et régulent remarquablement l'expression de la protéine mTOR, qui inhibe l'autophagie, ce qui permet de trouver des applications avantageuses dans la prévention ou le traitement de la maladie de Parkinson. De plus, la composition de la présente invention est dérivée d'une substance naturelle et peut donc être utilisée en toute sécurité pour la prévention, le traitement et le soulagement de la maladie de Parkinson, sans effets secondaires.
PCT/KR2019/005352 2018-05-04 2019-05-03 Composition comprenant un extrait d'aster koraiensis nakai ou une fraction de celui-ci en tant que principe actif pour la prévention ou le traitement de la maladie de parkinson WO2019212300A1 (fr)

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KR102234494B1 (ko) * 2019-10-02 2021-03-31 대한민국 까실쑥부쟁이 추출물을 유효성분으로 포함하는 인지능력 개선용 조성물
KR102335690B1 (ko) * 2020-03-12 2021-12-07 한국과학기술연구원 신규한 트리테르펜 사포닌 유도체 및 이의 용도

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050007955A (ko) * 2003-07-12 2005-01-21 충남대학교산학협력단 뇌 항산화활성을 가지는 참취 추출물
KR20120067183A (ko) * 2010-12-15 2012-06-25 상지대학교산학협력단 섬쑥부쟁이 추출물, 이의 분획물, 또는 이로부터 분리된 화합물을 함유하는 항경련용 조성물
KR20120095251A (ko) * 2011-02-18 2012-08-28 한국과학기술연구원 벌개미취 추출물 또는 이의 분획물을 포함하는 망막질환 예방 및 치료용 조성물

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20050007955A (ko) * 2003-07-12 2005-01-21 충남대학교산학협력단 뇌 항산화활성을 가지는 참취 추출물
KR20120067183A (ko) * 2010-12-15 2012-06-25 상지대학교산학협력단 섬쑥부쟁이 추출물, 이의 분획물, 또는 이로부터 분리된 화합물을 함유하는 항경련용 조성물
KR20120095251A (ko) * 2011-02-18 2012-08-28 한국과학기술연구원 벌개미취 추출물 또는 이의 분획물을 포함하는 망막질환 예방 및 치료용 조성물

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KIM, KYUNG-A ET AL.: "Edible wild vegetable, Gymnaster koraiensis protects retinal ganglion cells against oxidative stress", FOOD AND CHEMICAL TOXICOLOGY, vol. 49, 2011, pages 2131 - 2143, XP028266613 *
ZHANG, HONG-TAO ET AL.: "Effect of Aster tataricus on production of inflammatory mediators in LPS stimulated rat astrocytoma cell line (C6) and THP-1 cells", SAUDI PHARMACEUTICAL JOURNAL, vol. 25, 2017, pages 370 - 375, XP029945119 *

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