KR101902510B1 - Composition for anti-stress effect, Functional Food and Pharmaceutical composition including the same - Google Patents

Abstract

The present invention relates to a composition for an anti-stress effect, and specifically, to a composition for an anti-stress effect, which comprises at least one selected from lupeol, isochlorogenic acid, chicoric acid as active ingredient/ingredients to lower the secretion of the stress hormone cortisol and to increase the secretion of the happy hormone serotonin, and to be free from side effects and safe for human body.

Description

[0001] The present invention relates to a composition for relieving stress, a functional food containing the composition, and a pharmaceutical composition,

The present invention relates to a composition for relieving stress, a functional food containing the same, and a pharmaceutical composition, and more particularly, to a composition for relieving stress, comprising at least one of Lupeol, Isochlorogenic acid, Chicoric acid, (Cortisol), which is a stress hormone, and increases secretion of serotonin, which is a happy hormone. The present invention relates to a composition for relieving stress, which is free from side effects and safe for human body.

 The origin of stress is 'Strictus' or 'Stringere: Tension', and in psychology Stress means the process of change of mind and body to cope with the stressor, which is also called mental pressure.

Stress is caused by the elements that are prevalent in everyday life and contributes to the occurrence of almost all diseases and medical diseases.

So far, many drug therapies such as sedatives, hypnotics, and hormone therapy have been studied to relieve stress. However, these pharmacologic therapies do not have side effects because they are resistant to drugs and risks of side effects during long-term use, A simple and effective way to take it is required.

The present inventors selected Lupeol, Isochlorogenic acid and Chicoric acid as effective materials for screening substances having a stress-relieving function based on the stress-related mechanism, The present invention has been completed based on these findings.

This product was funded by the Ministry of Food, Agriculture, Forestry, and Livestock and was supported by the Ministry of Agriculture, Forestry and Fisheries Technology Planning and Evaluation and supported by the High Value Added Food Technology Development Project (115036-3).

Domestic patent documents relating to Lupeol include registered patent No. 1582856 entitled " antiviral luperol-type triterpene derivative ", registered patent No. 0838435 entitled "Lupine seed pod extract containing lupeol ", registered patent No. 1598612 "Composition for prevention or treatment of vascular or heart valve calcification containing DPP-4 inhibitor", registered patent No. 1417310 "Composition for cosmetic composition containing extracts, fractions or compounds of avocet tree", registered patent No. 0941595 "Virus Triterpenoid compounds useful as inhibitors "and the like. Korean patent documents relating to Chicoric acid include patent application No. 2012-7033430 entitled " Use of chicory acid and derivatives for controlling skin pigmentation ", registered patent No. 1551238 "novel HIV reverse transcriptase inhibitor & Patent No. 1577698 entitled "Regulator of pharmacokinetic properties of therapeutic agent" and the like These patents are far from the stress reduction effect described in this patent.

The object of the present invention is to lower the secretion of Cortisol, which is a stress hormone, and to increase secretion of Serotonin, which is a happy hormone, to help alleviate stress, and to take it from time to time before onset, It is intended to provide a stress-relieving composition free from side effects and safe for human body.

In order to achieve the above object, the present invention provides a pharmaceutical composition comprising at least one of Lupeol, Isochlorogenic acid, Chicoric acid, A stress relieving composition is provided.

[Chemical Formula 1]

(2)

(3)

The isochlorogenic acid according to the present invention includes all of isomeric isochlorogenic acid A, isochorogenic acid B and isochorogenic acid C.

The luperol according to the present invention can be extracted from various plants such as soybean plants, dandelion roots and the like using an extraction solvent commonly used in the art.

Lupeol according to the present invention is useful for the production of plants such as mangoes, legumes, dandelion roots and the like, and isochlorogenic acid can be obtained from plants such as coffee beans, sweet potatoes, burdock, fruits, Can be extracted and used as an extraction solvent.

Chicoric acid can be extracted from plants such as chicory, echinacea, dandelion, basil, lettuce and burdock through water extraction using an organic solvent commonly used, and water, supercritical extraction.

Lupeol, Isochlorogenic acid and Chicoric acid according to the present invention are preferably extracted with an organic solvent rather than with water.

Examples of the extraction solvent used for the extraction of Lupeol, Isochlorogenic acid, Chicoric acid, include purified water; Lower alcohols having 1 to 10 carbon atoms such as methanol, ethanol, isopropyl alcohol and butanol; Polyhydric alcohols having 2 to 30 carbon atoms such as glycerol, ethylene glycol, propylene glycol, and 1,3-butylene glycol; And hydrocarbon solvents having 1 to 30 carbon atoms such as petroleum ether, methyl acetate, ethyl acetate, benzene, hexane, methylene chloride, diethyl ether, dichloromethane and chloroform.

Also, one or two or more kinds of solvents may be mixed.

Lupeol, Isochlorogenic acid, Chicoric acid, or mixtures thereof according to the present invention may be present in an amount of 0.0001 to 50% by weight, preferably 0.001 to 50% by weight, based on 100% By weight to 10.0% by weight. If it is less than 0.0001% by weight, the effect of improving immunity is insignificant, and if it exceeds 50% by weight, it is difficult to apply the formulation.

The stress-relieving composition of the present invention has an excellent stress-relieving effect by lowering the secretion of Cortisol, which is a stress hormone, and increasing secretion of serotonin, which is a happy hormone. In particular, the composition of the present invention can be used for stress relief of modern people who are stressed, such as office workers, examinees, and housewives. In addition, the composition of the present invention is safe for the human body and has little side effects even if it is taken for a long time.

Therefore, the composition according to the present invention can be easily used as a functional food or pharmaceutical composition which can be effectively used by continuous administration. In addition, it can be obtained as a natural plant extract, and can be preferably used for a subject such as a child, an elderly person, or a pregnant woman who may have a side effect of a drug.

FIG. 1 shows the results of a change in IgA level in the stool due to consumption of Lupeol, Isochlorogenic acid, and Chicoric acid in a passive stress-induced mouse.
FIG. 2 shows the results of weight change test by intake of Lupeol, Isochlorogenic acid, and Chicoric acid in passivation stress-induced mice.
FIG. 3 is a graph showing the results of measurement of changes in blood cortisol and serotonin production by consumption of Lupeol, Isochlorogenic acid, and Chicoric acid in a passive stress-induced mouse.
FIG. 4 shows the result of the inflammatory cytokine gene expression test in spleen isolated from immobilized mice administered with Lupeol, Isochlorogenic acid, Chicoric acid.

Hereinafter, the present invention will be described in more detail.

According to the present invention, there is provided a stress relieving composition comprising at least one of Lupeol, Isochlorogenic acid and Chicoric acid as an active ingredient.

Preferably, Lupeol and Isochlorogenic acid are both included as active ingredients. Preferably, the Lupeol and isochlorogenic acid are contained in a weight ratio of 1: 1 to 1:10.

According to one embodiment of the present invention, at least one selected from the group consisting of Lupeol, Isochlorogenic acid and Chicoric acid is added to 100 weight% 0.0001 to 50% by weight.

According to one embodiment of the present invention, the isochlorogenic acid includes Isochlorogenic acid A, Isochlorogenic acid B, Isochlorogenic acid C, and the like.

The composition for relieving stress according to the present invention may be formulated into tablets, pills, powders, granules, powders, solutions, sprays, or capsules, and may be easily prepared and used according to purposes, May be applied.

Lupeol is a pharmacologically active Triterpenoid substance found in various plants such as mangoes, legumes, and dandelion roots. It is known to exhibit antibacterial, antiviral, anti-inflammatory and anti-cancer effects.

Isochlorogenic acid has a structure with an additional caffeic acid in the structure of chlorogenic acid. Isochlorogenic acid has three kinds of A, B and C depending on the position of caffeic acid group added to the structure of chlorogenic acid. Isochlorogenes are found in a variety of plants such as coffee beans, sweet potatoes, burdock, fruits and vegetables, and are known to exhibit anti-inflammatory, anti-cancer, anti-viral, anti-obesity, and liver protective effects.

Chicoric acid is found in various plants such as chicory, echinacea, dandelion, basil, lettuce, burdock, and edible plants and vegetables, and is known to exhibit antiviral, dementia prevention, antioxidant and anti-inflammatory effects.

Markers to identify the function of stress relief (reduction) are physiological indicators and behavioral indicators, and psychological indicators through surveys in human application tests.

Physiological indicators include brain neuron survival rate, lactate dehydrogenase (LDH), tissue weight, serotonin and its metabolites (5-HIAA), dopamine and its metabolites (DOPAC, HVA), norepinephrine, corticosterone / Corticotropin-releasing hormone (CRH), nerve growth factor (NGF), cortisol, cortisol, cytokine (IL-6 and TNF-α), adrenocorticotropic hormone (ACTH) ), Synaptophysin, saliva amylase, saliva IgA, blood pressure, island clapping, and brain waves.

Behavioral indicators include stress-related behaviors, elevated cross-lab tests, defensive store tests, sucrose preference tests, forced swimming tests, tail suspensions, novelty suppression of feeding (NSF), and resident-intruder testing .

Cerebral nerve cell survival rate can be evaluated by measuring the cell survival rate by treating the test substance with the brain nerve cell (SK-N-BE (2) C cell, PC12 cell, etc.), the main cell constituting the nervous system.

Lactate dehydrogenase (LDH) L is an enzyme that catalyzes the reaction of L-lactic acid to L-pyruvic acid by dehydrogenation. It exists in most tissues. When the tissue is damaged, the intracellular enzyme is released and the lactate dehydrogenase is also liberated. Generally, a high concentration of lactate dehydrogenase means that the cells are damaged.

The degree of stress can be measured by measuring the adipose and spleen tissue weights. The adrenal gland is a small endocrine gland with one each on the left and right side of the conus. Cortisol in the adrenal cortex is secreted in response to stress. Catecholamines in the adrenal gland secrete hormones that respond quickly to stress. Thus, in the spleen associated with adrenal hypertrophy and immunity due to stress, spleen atrophy may be caused by stress.

Serotonin is a 5-hydroxytryptamine (5HT) structure of physiologically active amine that is involved in functions related to mood, behavior, appetite, sleep and muscle contraction. Excessive serotonin stimulates the brain's function, stimulating it, and, if it is deficient, depresses the body's function. The serotonin metabolite is 5-hydroxy indolacetic acid (5-HIAA). Serotonin increases with increasing serenity.

Dopamine, a neurotransmitter, is a precursor of norepinephrine and epinephrine. Dopamine controls emotions in the body and makes them feel good, and they are involved in cognition, attention, concentration, compensation, and control of motor function. Dopamine metabolites include DOPAC (3,4-Dihydroxyphenyl acetic acid) and HVA (Homovanillic acid). An increase in dopamine means a decrease in stress.

Norepinephrine, also known as Noradrenaline, is a neurotransmitter. When stressed, norepinephrine increases the contractility and heart rate of the heart, contracts the blood vessels of the whole body, and increases blood pressure. It is also involved in mood. The higher the concentration of norepinephrine, the higher the stress.

Corticosterone or cortisol is a steroid hormone secreted from the adrenal cortex that is secreted in the form of corticosterone in rats and cortisol in humans and is the final agonist of the hypothalamus-pituitary-adrenal axis, It is involved in the regulation of the response and homeostasis of an individual. Corticosterone and cortisol increase micturition stress and increase blood pressure and pulse rate. The higher the concentration of corticosterone and cortisol, the higher the stress.

Cytokine is a protein that mediates intercellular signaling, including interleukin (IL), interferon (IFN), and tumor necrosis factors (TNF). Not only immune cells but also neurons secrete cytokines and are involved in the regulation of cranial nerve function. The inflammatory cytokines IL-1β, IL-2, IL-6, and TNF-α are secreted by the central nervous system during the stress response. The greater the amount of IL-1β, IL-2, IL-6, and TNF-αβγ, the inflammatory cytokines, the greater the degree of stress.

Adrenocorticotropic hormone (ACTH) secreted from the pituitary gland stimulates the adrenal cortex to release steroid hormones such as cortisol. When the human body is stressed, the secretion of this hormone is promoted through the central nervous system.

Corticotropin-releasing hormone (CRH) is secreted into the pituitary portal system by the hypothalamic-pituitary nervous system and is involved in the secretion of adrenocortical stimulating hormone. The secretion is regulated by the concentration of adrenocortical hormone in the blood.

Nerve growth factor (NGF) is a neuro-trophic protein that plays a key role in neural development and maintenance of the sensory and sympathetic nerves. It is also transported into nerve cells from tissue and nerve fiber ends and contributes to the development of sensory neurons, peripheral adrenergic neurons and cholinergic nerve fibers of the central nervous system.

Synaptophysin is a glycoprotein present in the vesicle of neurons or neuroendocrine cells, which increases in proportion to the degree of neuronal synaptogenesis during development and is consistent with the distribution of neuronal synapses. It is a widely used protein.

Salivary amylase is an enzyme that hydrolyzes the α-1,4-glycosidic bond of starch and is produced in the glandular cells of the parotid gland and submandibular gland. Salivary amylase is secreted by sympathetic stimulation and increases secretion of saliva amylase under stress conditions.

Immunoglobulin A (IgA) is contained in mucous secretions such as serum, saliva, colostrum, tears, bile, urine, and feces and plays a defense role against various pathogens. Increased cortisol in stress conditions inhibits the secretion of salivary IgA.

The blood pressure is the pressure on the wall of the blood vessel, that is, the systolic blood pressure, which is the blood pressure when the ventricle contracts, and the diastolic blood pressure, which is the blood pressure when relaxing. Normal blood pressure is about 120-130 mmHg in systolic blood pressure, and 80-85 mmHg in diastolic blood pressure. Higher than a certain level of high blood pressure, low blood pressure is said. Stress stimulates the sympathetic nerves and causes an increase in blood pressure.

The heart rate refers to the number of times the heart plays for one minute, and the normal person is about 70 times / minute when stable, but the difference is large among individuals, so the normal range is about 50-100 times. Heart rate variability factors include body temperature, exercise, sleep, feeding, and emotions. Stress may stimulate sympathetic nerves and increase heart rate.

EEG records the currents that occur according to the activity of the brain. EEG has α, β, γ, δ, θ. As the power of the EEG wave increases, the stress decreases as the power of the EEG decreases.

According to still another aspect of the present invention, there is provided a functional food for relieving stress.

The food composition according to the present invention can be prepared in the form of a composition by mixing with known active ingredients known to be effective for fatigue recovery or stress relaxation, and can be used as a functional food, a nutritional supplement, food, and food additives. Food compositions of this type may be prepared in a variety of forms according to conventional methods known in the art. For example, the health food may be prepared in the form of tea, juice and drink containing at least one active ingredient selected from the group consisting of Lupeol, Isochlorogenic acid and Chicoric acid, A food composition containing at least one of Lupeol, Isochlorogenic acid and Chicoric acid as an active ingredient may be granulated, encapsulated or powdered.

The food composition of the present invention may contain one or more active ingredients selected from the group consisting of Lupeol, Isochlorogenic acid and Chicoric acid, as well as vitamin A, B, C, D, E, beta carotene, It is possible to use minerals containing compounds such as Ca, Mg and Zn, and it is also possible to use extracts such as Rhodiola, Ashishima, stone outer leaves and Hovenia dulcis extract or L-theanine and milk hydrolysates May be mixed and used.

In addition to the above components, natural additives such as natural flavors such as plum, lemon flavor, pineapple flavor or herb flavor, natural fruit juice, natural pigments such as Chlorophyllin and Flovonoid and sweetness components such as fructose , Honey, sugar alcohol, sugar and the like may be mixed with an acid agent such as citric acid or sodium citrate.

The preferred content of the active ingredient of at least one of lupeol, isochorrogenic acid and chicoric acid in the food composition of the present invention is about 0.0001 to 50% by weight based on the total weight of the food . Preferably 0.01 mg / kg / day to 10 mg / kg / day, may result in fatigue recovery or stress relief.

The present invention provides a functional food in a form selected from the group consisting of tablets, pills, granules, powders, powders, capsules, sprays, and solutions containing the above food composition.

Functional foods are foods that are designed and processed so that they can fully exercise their biological control functions, such as bio-defense, regulation of biorhythms, prevention and recovery of diseases, etc. of food components.

The above-mentioned functional food preparation is not particularly limited except that the food composition of the present invention is included, and it is possible to additionally contain ingredients necessary for each food as a conventional food-acceptable food supplementary additive.

Tablets are made from a flaky or crystalline material and are pressed into a circular or conical shape, which is easy to take and dose is accurate. The functional food tablets of the present invention may include excipients such as lactose, starch, white sugar, mannitol, sorbitol, inorganic salt, and the like, and magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, Sodium carboxymethylcellulose and / or polyvinylpyrrolidine, and may optionally contain a disintegrating or boiling mixture such as starch, agar, alginic acid or its sodium salt and / or an absorbing agent, a colorant, a flavoring agent, And sweeteners. The formulations may be prepared by conventional mixing, granulating or coating methods.

Granules are round, granular formulations, and in the case of mixed preparations, they can always take a certain proportion and are easy to take. A coloring agent, a fragrance, etc. may be added to the granule of the present invention as needed, and the granules may be prepared by a suitable sheath agent or the like. It is preferable that 20% of the granules of the granules have a size of 355um or more and 1400um or less. A liquid preparation refers to a liquid formulation, and a stabilizer, a mating agent, a preservative, and the like may be added according to the necessity of the present invention. In addition, the functional beverage composition of the present invention may further comprise an fruit extract for improving flavor. Fruit extracts have the advantage of being able to use various active ingredients of fruit together with improving flavor. Fruit roots used in the fruit extract include at least one selected from pineapple, lemon, citrus, orange, apple, pear, grapefruit, apricot, strawberry, peach, melon, guava, lemon and plum . Other functional beverage compositions of the present invention may contain known additives. Examples of the known additives include nicotinamide, vitamin A, B, C, D, E and folic acid. Vitamins include L-glycine, L-lysine, DL- L-cystine, L-tryptophan, L-threonine, L-phenylalanine and the like can be used as the herbicide. Examples of the herbicide include Gugija, Ogapi, Baekje, And flavoring agents may be used. Examples of sweetening agents include, but are not limited to, mixture and flavor, apple flavor, yoghurt flavor, and drink flavor. Sweeteners include sweet potato, glucose, fructose, fructooligosaccharide, isomaltooligosaccharide, maltooligosaccharide, Chitosan oligosaccharide, chito oligosaccharide, soy oligosaccharide, xylooligosaccharide, isomerized sugar (high fructose), phosgene, aspartame, stevioside, sorbitol, mannitol and the like can be used. Citric acid, DL-malic acid, Gt; stabilization < / RTI > Include polysorbate flow of polysorbate 20, polysorbate 40, polysorbate 80, it can be used.

According to another aspect of the present invention, there is provided a pharmaceutical composition for relieving stress.

The pharmaceutical composition of the present invention can be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned active ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, A lubricant or a flavoring agent can be used.

The pharmaceutical composition may be suitably formulated into pharmaceutical compositions containing at least one pharmaceutically acceptable carrier in addition to the above-described effective ingredients for administration.

The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, natural and synthetic gums such as corn sweeteners, acacia, tracker candles or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like.

Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile solutions suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like.

Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.

The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, the composition can be administered by intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, transdermal administration, etc., .

The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.01 to 10 mg / kg / day.

The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions or emulsions in oils or aqueous media, or in the form of excipients, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.

delete

Hereinafter, the present invention will be described in more detail with reference to examples and comparative examples. It should be understood, however, that the present invention is not limited to the above-described embodiments, and that various changes and modifications may be made without departing from the spirit and scope of the invention as defined in the appended claims. It is to be understood that equivalents and modifications are possible.

Example : Lupeol ( Lupeol ), Isochlorogen ( Isochlorogenic  acid, Chicoric acid  Produce

Lupeol, Isochlorogenic acid and Chicoric acid were purchased from Sigma Aldrich and the following experiments were carried out.

Experimental Example  One: dissimilation  In stress-induced mice Lupeol ( Lupeol ), Isochlorogen (Isochlorogenic acid), Chicoric acid  During the intake of feces IgA  Level change test

Lupeol, Isochlorogenic acid, Chicoric acid) were added to 8-week-old C57BL / 6 mice, which had reduced immune system, by allowing them to move for 2 days in a narrow frame for 21 days. (10 mg / day), and a sample of 1: 1 mixture of Lupeol and Isochlorogenic acid was orally administered at 5 mg / day, 10 mg / day and 20 mg / day for 21 days each day .

The feces of the mouse were collected IgA levels were measured by ELISA, and statistically significant differences were observed in all experimental groups treated with lupeol, isochlorogenic acid, and chicoric acid compared to the immobilized control (IM_S-IM_S-control) And increased IgA levels.

In particular, the highest IgA level was observed in the 20 mg / kg sample of 1: 1 mixture of Lupeol: Iso-chlordenic acid.

The results are shown in FIG.

Experimental Example  2: dissimilation  In stress-induced mice Lupeol ( Lupeol ), Isochlorogen (Isochlorogenic acid), Chicoric acid administration Weight change test by

Lupeol, Isochlorogenic acid, Chicoric acid) were added to 8-week-old C57BL / 6 mice, which had reduced immune system, by allowing them to move for 2 days in a narrow frame for 21 days. (10 mg / day), and a sample of 1: 1 mixture of Lupeol and Isochlorogenic acid was orally administered at 5 mg / day, 10 mg / day and 20 mg / day for 21 days each day .

The body weight was measured once a week for 3 weeks after the administration and the change was observed.

The body weight change was measured in the passive control group (IM_S-IM_S-control) compared with the normal control group (C57bl / 6_Nr), and Lupeol, Isochlorogenic acid, Chicoric acid ) Had less weight loss than the passive control group (IM_S-IM_S-control).

In particular, the lowest weight loss was observed in the 20 mg / kg group of 1: 1 mixture of Lupeol: Iso-chlogenic acid.

The results are shown in Fig.

Experimental Example  3: dissimilation  In stress-induced mice Lupeol , Isochlorogen , Kikoric acid On administration  Blood by Cortisol and  Serotonin ( Serotonin ) Production change measurement test

Lupeol, Isochlorogenic acid, Chicoric acid) were added to 8-week-old C57BL / 6 mice, which had reduced immune system, by allowing them to move for 2 days in a narrow frame for 21 days. (10 mg / day), and a sample of 1: 1 mixture of Lupeol and Isochlorogenic acid was orally administered at 5 mg / day, 10 mg / day and 20 mg / day for 21 days each day .

The level of Cortisol, a stress hormone in serum, was measured by ELISA and compared with that of the immobilized control (IM_S-IM_S-control), Lupeol, Isochlorogenic acid, Chicoric acid There was a statistically significant reduction in Cortisol levels in all study groups. In particular, Cortisol levels were significantly decreased in the 20 mg / kg sample of 1: 1 mixture of Lupeol: Iso-chlogenic acid.

Serotonin, a hormone that makes people feel happy in their serum, was measured by Lupeol, Isochlorogenic acid and Chicoric acid compared with the immobilized control (IM_S-IM_S-control) Serotonin levels were significantly increased in all experimental groups. In particular, serotonin (serotonin) levels were significantly increased in the 20 mg / kg group of 1: 1 mixture of Lupeol: Iso-chlogenic acid.

The results are shown in Fig.

Experimental Example  4: dissimilation  In stress-induced mice Lupeol ( Lupeol ), Isochlorogen (Isochlorogenic acid), Chicoric acid administration Inflammation in the spleen by Cytokine  Gene expression test

Lupeol, Isochlorogenic acid, Chicoric acid) were added to 8-week-old C57BL / 6 mice, which had reduced immune system, by allowing them to move for 2 days in a narrow frame for 21 days. (10 mg / day), and a sample of 1: 1 mixture of Lupeol and Isochlorogenic acid was orally administered at 5 mg / day, 10 mg / day and 20 mg / day for 21 days each day .

The expression of inflammatory cytokine-related genes was confirmed by Real-Time PCR in each immune organ cell isolated from the immobilized mouse model.

In spleen, mRNA expression of TNF-a, IL-6, and IL-1b mRNA in inflammatory cytokines was increased in the immobilized control (IM_S-control) compared to the normal control (C57bl / 6_Nr) TNF-a, IL-6, and IL-1b mRNA gene expression was lower in the experimental group treated with isoleucine (Lupeol) and isochlorogenic acid (Isochlorogenic acid). In particular, it was confirmed that mRNA gene expression was lowered in the 20 mg / kg group in which 1: 1 mixture of Lupeol: Iso-chlogenic acid was mixed.

The results are shown in Fig.

Formulation example :

[ Formulation example  One] Sanje  Produce

20 mg of a 1: 1 mixture of lupeol and isochlorogenic acid

Lactose 100mg

Talc 10mg

The above components are mixed and filled in airtight bags to prepare powders.

[ Formulation example  2] Preparation of tablets

10 mg of a 1: 1 mixture of lupeol and isochlorogenic acid

Corn starch 100 mg

Lactose 100 mg

1 mg of magnesium stearate

Microcrystalline cellulose 84 mg

Povidone 3 mg

Sodium starch glycolate 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

 [ Formulation example  3] Manufacture of health food

1000 mg of a 1: 1 mixture of lupeol and isochlorogenic acid

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

24.8 mg of magnesium chloride

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

 [ Formulation example  4] Manufacture of health drinks

1000 mg of a 1: 1 mixture of lupeol and isochlorogenic acid

Citric acid 1000 mg

100 g of oligosaccharide

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated for about 1 hour at 85 DEG C with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Nr in the drawing is an abbreviation denoting Normal.
IM_S in the drawing is an abbreviation for immobilization stress.

Claims (9)

delete delete delete Wherein the weight ratio of Lupeol to Isochlorogenic acid is 1: 1. The stress relieving composition according to claim 4, wherein Lupeol and Isochlorogenic acid are contained in an amount of 0.0001 to 50% by weight based on 100% by weight of the total composition on the basis of solid content. The stress relieving composition according to claim 4, wherein the isochlorogenic acid is Isochlorogenic acid A, Isochlorogenic acid B, or Isochlorogenic acid C. The stress relieving composition according to claim 4, wherein the composition is in the form of tablets, pills, powders, granules, powders, solutions, sprays or capsules. A functional food for stress relief comprising the composition according to any one of claims 4 to 7. A pharmaceutical composition for the prevention or treatment of a stress disorder, which comprises the composition according to any one of claims 4 to 7.

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