KR102467123B1 - Composition for improving endurance comprising limonium tetragonum extract - Google Patents

Abstract

The present invention relates to a composition for anti-fatigue or for enhancing endurance and a composition for preventing or for treating a muscle disease comprising Limonium tetragonum extract, wherein the Limonium tetragonum extract of the present invention increases an endurance through an increase of a motor ability of a mouse, increases a type 1 muscular fiber, advances/improves a new generation and function of mitochondria, and develops a muscle through muscle regeneration, thereby being used as a usage for anti-fatigue, enhancing endurance, and improving a motor ability, and being used as a usage for preventing or treating muscle diseases.

Description

Composition for enhancing endurance containing an extract of Gandhiko

The present invention relates to a composition for anti-fatigue or for enhancing endurance, and a composition for preventing or treating muscle diseases, which includes an extract of G.

Muscle is largely divided into skeletal muscle, cardiac muscle, and visceral muscle. Among them, skeletal muscle occupies a large part of the human body, accounting for 40% of the body weight, and together with the bones, holds the shape of the human body and enables exercise and movement. Together, these bones and skeletal muscles are called the musculoskeletal system. The basic cells of muscle are composed of myoblasts. When a muscle is injured or a muscle tissue is ruptured due to excessive exercise, a satellite cell, which is a stem cell of the muscle tissue, is activated and division of the satellite cell is promoted. Some of the increased satellite cells preserve the function of stem cells again, and some start to differentiate into muscle cells. At this time, several transcription factors related to the differentiation of muscle cells are activated, and the satellite cells differentiate into myoblasts, myocytes, and myotubes in order to refill the injured area and damaged muscle tissue with new muscle fibers. do. Muscles are largely composed of two types of muscle fibers, of which type 1 muscle fibers have many mitochondria and are essential for endurance exercise. The decrease in muscle fibers causes a decrease in endurance. On the other hand, muscle growth can be largely divided into two types. First, there is hyperplasia, which grows by increasing the number of muscle cells, and hypertrophy, which grows by increasing the size of cells. Hyperplasia mainly occurs during the growth phase, that is, from infancy to secondary sexual characteristics, and growing the size of muscles through exercise corresponds to hypertrophy. In addition, when an appropriate amount of exercise is continuously performed to stimulate muscle cells, factors involved in muscle development are continuously expressed. The size and number of muscle fibers, muscle development and muscle mass increase, as well as mitochondrial biosynthesis and function that synthesize ATP, which is important for muscle movement, are improved. Maintaining the homeostasis of these muscles is an essential condition for maintaining a smooth life, but in modern society, lack of exercise is increasing due to aging and changes in job distribution. As a result, muscle usage is reduced, and muscle mass and muscle function are lowered, so that fatigue is easily felt or incidents in which minor injuries are caused are increasing. In addition, behaviors that are harmful to the human body, such as irregular eating habits, stress, alcohol, and smoking, are also causes of weakening of muscle function. Muscular strength is the ability of a muscle, and mainly refers to the force that a muscle can produce at its maximum at one time. Exercise performance ability refers to the ability to perform an exercise using muscle strength. Weakening of muscle function and muscle weakness due to the above-mentioned problems leads to a decrease in muscle strength and exercise performance, which causes a decrease in physical strength, an increase in adult diseases, and a decrease in quality of life.

Fatigue is defined as a state in which physical and mental activity capacity is reduced, and physical fatigue, which means a state in which exercise performance is reduced report) is caused by the accumulation of fatigue substances such as lactic acid in muscles (Fitts et al., 1976; Savitski et al., 1979). Sufficient sleep and rest help to recover from fatigue, but unrecovered fatigue can cause various acute and chronic diseases. Fatigue can sometimes be defined as "a perception of reduced capacity for physical and mental activity due to an imbalance in the availability, utilization and recovery of resources necessary to perform an activity", specifically fatigue is primarily physical exhaustion at work. A state in which ability is reduced, and stress refers to a state in which acid resistance is disrupted due to mental fatigue (KFDA Health Functional Food Fatigue Recovery Related Functional Evaluation System Establishment, Research Report). Fatigue is classified into central nervous system fatigue, nerve-muscular junction fatigue, and peripheral fatigue of the limbs. Fatigue is a comprehensive physiological process including various physiological and biochemical factors, and is a mental physiological phenomenon that inevitably appears when the body's mental activity or physical activity reaches a certain level. This means that the original working capacity of the human body is temporarily lowered, and may be a symptom indicating that the body is developing into a damaged state. If fatigue continues to occur, it may develop into a disease called chronic fatigue syndrome when it becomes a chronic condition. Currently, the main symptom of Chronic Fatigue Syndrome (CFS) is long-lasting fatigue, which is a group of non-specific symptoms such as low-grade fever, headache, sore throat, muscle and joint pain, difficulty concentrating attention, memory loss, sleep disturbance, and depression. It is a syndrome, and there is usually no obvious abnormality in physical examination and routine examination (Holmes GO, er al, Amm. Intern Med, 1988, 108 (3)). There are many causes of fatigue, such as lack of sleep, lack of exercise, unbalanced diet, bad habits such as alcoholism, mental pressure, bad work environment, and work environment. There are several approaches to alleviating fatigue, including taking breaks, finding satisfying work, regular exercise, changing to a better diet and getting enough sleep. In addition, to relieve physical fatigue, the market for functional products focusing on improving exercise performance or products for suppressing the accumulation of fatigue substances in the body is being activated, but compounds such as steroids, caffeine, sodium bicarbonate and sodium citrate are included. While the product can significantly increase exercise performance when taken in a certain amount or more, the drug has a risk of ultimately harming health by accompanying fatal side effects. Therefore, in recent years, studies on the development of products for improving fatigue and improving exercise performance using natural products whose safety is guaranteed, such as plant extracts, have been actively conducted.

An object of the present invention is to provide a composition for anti-fatigue or endurance enhancement.

In addition, an object of the present invention is to provide a pharmaceutical composition for preventing or treating muscle diseases.

In addition, an object of the present invention is to provide a composition for improving exercise performance.

In order to solve the above problems, the present invention provides a composition for anti-fatigue or endurance enhancement comprising a galliformes extract as an active ingredient.

In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of muscle diseases comprising a galliformes extract as an active ingredient.

In addition, the present invention provides a composition for improving exercise performance containing an extract of Gajidaria as an active ingredient.

Since the pediatrician extract of the present invention increases endurance through an increase in exercise capacity of mice, increases type 1 muscle fibers, enhances/improves mitochondrial new generation and function, and develops muscles through muscle new generation, it is anti-fatigue , It can be used for enhancing endurance and improving exercise performance, and can also be used for preventing or treating muscle diseases.

Figure 1 is a diagram confirming the effect of increasing endurance by the administration of a hot water extract from Gaddifolia by increasing the running ability of mice (Values are mean ± SEM. *, p<0.05 and **, p<0.01):
A test drug administration and running exercise test protocol;
B and C: body weight and food intake after 4 weeks of administration of the hot water extract of Gaddiflora (n=8);
D Time taken to exhaustion in the forced running exercise test and percentage of mice at each time point (n=8);
E and F: Mean running time and distance in running exercise test (n=8);
LTE: Limonium tetragonum extracts (LTE);
LTE-30: 30 mg/kg administration group of sea bream extract; and
LTE-100: A group administered with 100 mg/kg of sea bream extract.
Figure 2 is a diagram confirming the change in the type and ratio of muscle fibers in mouse muscle tissue by administration of a galliformes extract (Values are mean ± SEM. *, p<0.05 and **, p<0.01):
A: Results of immunostaining of muscle fibers of each type (MyHC type I, IIa and IIb/x) in mouse gastrocnemius muscle tissue;
B: Results of SDH immunostaining in mouse gastrocnemius muscle tissue;
C: qPCR analysis of type 1 muscle fiber (slow fibers) and type 2 muscle fiber (fast fibers) specific gene mRNA expression; and
LTE-100: 100 mg/kg administration group of sea bream extract
Figure 3 is a diagram confirming mitochondrial neogeneration and functional changes in mouse muscle by the administration of a galliformes extract:
A: Ratio of mitochondrial DNA (mtDNA) to nDNA (nuclear DNA) (n=3-4);
B: Results of qPCR analysis of mRNA expression of genes related to mitochondrial neogenesis and oxidative phosphorylation (n=7-8); and
LTE-100: 100 mg/kg administration group of sea bream extract
Figure 4 is a diagram confirming changes in protein expression of cell signaling pathways and related transcription factors in mouse muscle by administration of a galliformes extract:
A: results of Western blot analysis of myogenesis-related proteins;
B: result of qPCR analysis of mRNA expression of myogenesis-related genes (n=7-8);
C: mRNA expression analysis of myogenesis-related genes in C2C12 cell line pre-treatment with SB203580 and treatment with 100 mg/kg of sea bream extract; and
LTE-100: A group administered with 100 mg/kg of sea bream extract.

Hereinafter, the present invention will be described in detail as an embodiment of the present invention with reference to the accompanying drawings. However, the following embodiments are presented as examples of the present invention, and if it is determined that detailed descriptions of well-known techniques or configurations may unnecessarily obscure the gist of the present invention, the detailed descriptions may be omitted. , the present invention is not limited thereby. Various modifications and applications of the present invention are possible within the scope of the claims described below and equivalents interpreted therefrom.

In addition, the terms used in this specification (terminology) are terms used to appropriately express preferred embodiments of the present invention, which may vary according to the intention of a user or operator or customs in the field to which the present invention belongs. Therefore, definitions of these terms will have to be made based on the content throughout this specification. Throughout the specification, when a certain component is said to "include", it means that it may further include other components without excluding other components unless otherwise stated.

Throughout this specification, '%' used to indicate the concentration of a particular substance is solid/solid (w/w) %, solid/liquid (w/v) %, and Liquid/liquid is (v/v) %.

In one aspect, the present invention relates to a composition for anti-fatigue or endurance enhancement comprising Limonium tetragonum (Thumb.) AA Bullock) extract as an active ingredient.

In one embodiment, the rhododendron extract may be extracted with one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, a subcritical fluid and a supercritical fluid, and the organic solvent having 1 to 6 carbon atoms Anhydrous or hydrous alcohol having 1 to 6 carbon atoms, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane, cyclo It may be at least one selected from the group consisting of hexane (cyclohexane), glycerin, ethylene glycol, propylene glycol and butylene glycol.

In one embodiment, the rhododendron extract may be a hot water extract.

In one embodiment, the rhododendron extract can increase the proportion of type 1 muscle fibers in muscle tissue.

In one embodiment, the rhododendron extract can increase mitochondrial biogenesis in muscle tissue.

In one embodiment, the rhododendron extract can develop muscle through myogenesis.

In one embodiment, the rhododendron extract can increase the phosphorylation of p38, CREB or ATF2, and increase the expression of Mef2a or Mef2c.

In one embodiment, the composition may be a composition for fatigue recovery.

In one embodiment, the endurance may be muscular endurance.

In one embodiment, the anti-fatigue or endurance enhancing composition may be a food composition.

In the present invention, since endurance enhancement provides the ability to resist fatigue, substances that improve/enhance endurance not only improve overall muscle health, but can also be used as dietary supplements as fatigue recovery agents.

In one aspect, the present invention relates to a pharmaceutical composition for the prevention or treatment of muscle diseases comprising an extract of galliformes as an active ingredient.

In one embodiment, the muscle disease may be caused by muscle damage, decreased muscle function, muscle wasting or muscle degeneration, and may include atony, muscular atrophy, muscular dystrophy, muscle degeneration, It may be at least one selected from the group consisting of myasthenia, cachexia, and sarcopenia.

The "atony" refers to a state in which muscle tone is reduced or lost, as a disease also called atonicity, atonia, or hypotonia.

The "muscular atrophy" refers to a loss of muscle tissue caused by not using the muscle or a disease of the muscle itself or damage to the nerves that control the muscle, and includes both gradual muscle atrophy and muscle weakness. In general, there are cases in which severe muscle strength loss occurs due to not using muscles, which gradually progresses to muscular atrophy. Sometimes there are signs of deterioration.

In addition, muscular atrophy caused by the disease of the muscle itself may include myasthenia gravis, Duchenne type, Becker type, belt type, facial shoulder brachial type, and inflammation occurring in the muscle itself, and the nerves that control the muscles Muscular atrophy due to damage of spinal muscular atrophy (spinal muscular amyotrophy), Beradnig-Hoffmann type, Kugelberg-Welander disease, amyotrophic lateral sclerosis (ALS), Lou Gehrig's disease, spinal muscular atrophy ( spinobular muscular atrophy), Kennedy disease.

The "muscular dystrophy" is a kind of degenerative myopathy, and represents the necrosis of muscle fibers, and the damage to the muscle cell membrane causes muscle weakness and atrophy through necrosis and degeneration of the muscle fibers. Duchenne muscular dystrophy, Becker muscular dystrophy, Limb-girdle muscular dystrophy, Emery-Dreifuss muscular dystrophy, Facioscapulohumeral muscular dystrophy ), myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, distal muscular dystrophy, congenital muscular dystrophy, etc., and can appear in various forms depending on the site.

In addition, the muscle wasting or muscle degeneration occurs due to genetic factors, acquired factors, aging, etc., and includes both gradual loss of muscle mass and weakening and degeneration of muscles, particularly skeletal or voluntary muscles and cardiac muscles, resulting in muscle weakness. may include all.

The "muscular weakness" means a state in which the strength of one or more muscles is reduced. The muscle weakness may be limited to any one muscle, one side of the body, upper limbs or lower limbs, or may appear throughout the body. In addition, subjective muscle weakness symptoms including muscle fatigue or muscle pain can be quantified in an objective way through medical examination. Causes of muscle weakness include, but are not limited to, muscle damage, reduction in muscle mass due to reduced differentiation of muscle cells, and muscle aging.

The "myasthenia" is a disease in which muscles are weakened due to neurological disorders of the muscles, and at first, mild symptoms such as drooping eyelids (ptosis) and poor pupil rotation appear. Also, when speaking, the pronunciation is not accurate or the food is swallowed poorly. In addition, facial muscles are also weakened. When myasthenia gravis gets worse, the symptoms spread throughout the body, making it difficult to lift things well and fall easily because the arms and legs do not have strength. It can also cause dangerous conditions such as difficulty breathing and respiratory paralysis.

The "cachexia" refers to a condition that causes marked deterioration of the whole body, and causes include malignant tumor, Basedow's disease, hypothyroidism, malaria, hypoadrenocortical dysfunction, thymus insufficiency, and the like. Clinically, general weakness, anemia, and edema are the main signs. It is known that the anemia of malignant tumors, the local effect of the tumor itself, causes nutritional disorders, and systemically competes with the host's metabolism to cause host metabolic disorders and cachexia by the metabolites of the tumor.

In one embodiment, the rhododendron extract may be extracted with one or more solvents selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, a subcritical fluid and a supercritical fluid, and the organic solvent having 1 to 6 carbon atoms Anhydrous or hydrous alcohol having 1 to 6 carbon atoms, acetone, ether, benzene, chloroform, ethyl acetate, methylene chloride, hexane, cyclo It may be at least one selected from the group consisting of hexane (cyclohexane), glycerin, ethylene glycol, propylene glycol and butylene glycol.

In one embodiment, the rhododendron extract may be a hot water extract.

In one embodiment, the rhododendron extract can increase the proportion of type 1 muscle fibers in muscle tissue.

In one embodiment, the rhododendron extract can increase mitochondrial biogenesis in muscle tissue.

In one embodiment, the rhododendron extract can develop muscle through myogenesis.

In one embodiment, the rhododendron extract can increase the phosphorylation of p38, CREB or ATF2, and increase the expression of Mef2a or Mef2c.

As used herein, the term "extract" refers to a preparation obtained by squeezing into an appropriate leachate and concentrating the leachate by evaporation, but is not limited thereto. It may be a dried product obtained by drying, a crude product or a purified product thereof. The galliformes extract can be prepared using general extraction methods, separation and purification methods known in the art. The extraction method is not limited thereto, but preferably, hot water extraction, hot water extraction, cold needle extraction, reflux cooling extraction, or ultrasonic extraction may be used, and heating reflux extraction is most preferred.

In the present invention, the extract can be prepared by fractionation by adding a fractionation solvent to an extract prepared by extraction with an extraction solvent or extraction with an extraction solvent. The extraction solvent is not limited thereto, but water, an organic solvent, or a mixed solvent thereof may be used, and the organic solvent may be an alcohol having 1 to 6 carbon atoms, a polar solvent such as ethyl acetate or acetone, hexane or dichloro A non-polar solvent of methane or a mixture thereof may be used. In addition, preferably, water, alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof may be used, and more preferably, hot water may be used.

Prevention or treatment of muscle diseases It can be prepared as a pharmaceutical composition for use.

In the present invention, the term "prevention" refers to any action that inhibits or delays the occurrence, spread, and recurrence of muscle disease by administration of the pharmaceutical composition according to the present invention, and "treatment" refers to the administration of the composition of the present invention. Any action that ameliorates or beneficially alters the symptoms of muscle disease. Those of ordinary skill in the art to which the present invention pertains will be able to determine the degree of improvement, enhancement and treatment by knowing the exact criteria of the disease for which the composition of the present application is effective by referring to the data presented by the Korean Medical Association, etc. will be.

In the present invention, the term "therapeutically effective amount" used in combination with an active ingredient means an amount effective for preventing or treating muscle diseases, and the therapeutically effective amount of the composition of the present invention depends on several factors, such as the method of administration. , the target site, the condition of the patient, etc. Therefore, when used in the human body, the dosage should be determined in an appropriate amount considering both safety and efficiency. It is also possible to estimate the amount to be used in humans from the effective amount determined through animal experiments. These considerations in determining an effective amount can be found, for example, in Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; and E.W. Martin ed., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.

The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term "pharmaceutically effective amount" means an amount that is sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level is the patient's Factors including health condition, cause of onset of muscle disease, severity, activity of drug, sensitivity to drug, method of administration, time of administration, route of administration and excretion rate, duration of treatment, drugs used in combination or concurrently, and other medical fields are well known. It can be determined according to known factors. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or in multiple doses. Considering all of the above factors, it is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.

The pharmaceutical composition of the present invention may include a carrier, diluent, excipient, or a combination of two or more commonly used in biological preparations. As used herein, the term "pharmaceutically acceptable" means exhibiting non-toxic properties to cells or humans exposed to the composition. The carrier is not particularly limited as long as it is suitable for in vivo delivery of the composition. For example, Merck Index, 13th ed., Merck & Co. Inc. , saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components may be mixed and used. Customary additives may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate formulations for injection, such as aqueous solutions, suspensions, and emulsions, pills, capsules, granules, or tablets. Furthermore, it can be preferably formulated according to each disease or component by using an appropriate method in the art or by using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).

In one embodiment, the pharmaceutical composition may be one or more formulations selected from the group consisting of oral formulations, external preparations, suppositories, sterile injection solutions, and sprays, and oral formulations are more preferred.

As used herein, the term "administration" means providing a predetermined substance to an individual or patient by any suitable method, and parenteral administration (eg, intravenous, subcutaneous, intraperitoneal) according to the desired method Or it can be applied topically as an injection formulation) or administered orally, and the dosage varies depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and severity of the disease. Liquid formulations for oral administration of the composition of the present invention include suspensions, internal solutions, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, aromatics, and preservatives in addition to water and liquid paraffin, which are commonly used simple diluents etc. may be included. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, suppositories, and the like. The pharmaceutical composition of the present invention may be administered by any device capable of transporting an active substance to a target cell. Preferred administration methods and formulations include intravenous injections, subcutaneous injections, intradermal injections, intramuscular injections, drip injections, and the like. Injections are formulated with aqueous solvents such as physiological saline and IV, non-aqueous solvents such as vegetable oil, higher fatty acid esters (e.g., ethyl oleate, etc.), alcohols (e.g., ethanol, benzyl alcohol, propylene glycol, glycerin, etc.). Stabilizers (e.g., ascorbic acid, sodium hydrogensulfite, sodium pyrosulfite, BHA, tocopherol, EDTA, etc.) to prevent deterioration, emulsifiers, buffers to control pH, A pharmaceutical carrier such as a preservative (eg, phenylmercuric nitrate, thimerosal, benzalkonium chloride, phenol, cresol, benzyl alcohol, etc.) may be included.

As used herein, the term "subject" refers to monkeys, cows, horses, sheep, pigs, chickens, turkeys, quails, cats, dogs, mice, rats, rabbits, including humans who have or may develop the above muscle disease. or all animals including guinea pigs, and muscle diseases can be effectively prevented or treated by administering the pharmaceutical composition of the present invention to a subject. The pharmaceutical composition of the present invention may be administered in parallel with existing therapeutic agents.

The pharmaceutical composition of the present invention may further include pharmaceutically acceptable additives, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, and calcium hydrogen phosphate. , Lactose, Mannitol, Taffy, Gum Arabic, Pregelatinized Starch, Corn Starch, Powdered Cellulose, Hydroxypropyl Cellulose, Opadry, Sodium Starch Glycolate, Carnauba Lead, Synthetic Aluminum Silicate, Stearic Acid, Magnesium Stearate, Aluminum Stearate, Calcium stearate, white sugar, dextrose, sorbitol and talc may be used. The pharmaceutically acceptable additive according to the present invention is preferably included in an amount of 0.1 part by weight to 90 parts by weight based on the composition, but is not limited thereto.

In one aspect, the present invention relates to a composition for improving exercise performance comprising an extract of galliformes as an active ingredient.

In one embodiment, the improvement in exercise performance may have one or more effects selected from the group consisting of an increase in exercise endurance, strengthening of muscle strength, enhancement of a sense of balance, and enhancement of exercise adaptation.

In one embodiment, the improvement of motor performance may mean preventing or treating one or more diseases selected from the group consisting of mitochondrial abnormalities, neurodegenerative diseases, hypostamina, and hypoacuity.

As used in the present invention, the term "exercise performance ability" refers to the ability to quickly, strongly, accurately, and for a long time, when physical motions seen in daily life or sports are externally classified into running, jumping, throwing, swimming, etc. , It indicates the degree to which one can do it proficiently, and exercise performance is defined by factors such as muscle strength, agility, and endurance, and "improvement of exercise performance" means improving or improving exercise performance.

The "mitochondrial disease" is a disease caused by mitochondrial dysfunction, which is caused by phosphate swelling due to abnormal mitochondrial membrane potential, dysfunction due to oxidative stress caused by reactive oxygen species or free radicals, and damage to mitochondrial DNA or cell nuclei. Functional abnormalities due to genetic factors such as genetic mutations related to mitochondrial function, diseases caused by defects in mitochondrial oxidative phosphorylation function for energy generation, and the like may all be included.

Mitochondria are essential organelles that generate ATP, which is cellular energy. Dysfunction of mitochondria gradually reduces the energy produced within cells, leading to cell damage or even cell death. Accordingly, mitochondrial dysfunction inhibits all cell functions including mitochondria other than mitochondria-less red blood cells, and in particular, causes fatal damage to organs with high energy demand, such as muscles or brains. Almost all tissues can be affected by mitochondrial dysfunction, and very diverse symptoms may exist depending on the extent to which tissues are involved. Examples of specific mitochondrial abnormalities include Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), Dominant Optic Atrophy (DOA); Mitochondrial Myopathy, Encephalopathy, Lactacidosis, Stroke (MELAS), Myoclonus Epilepsy Associated with Ragged-Red Fibers (MERRF) Syndrome, Ray ( Leigh syndrome and oxidative phosphorylation disorders, and most mitochondrial diseases are known to be capable of representing neurodegenerative diseases, stroke, blindness, hearing impairment, diabetes, and heart failure.

In one aspect, the present invention relates to a food composition for the prevention or improvement of muscle disease containing a galliformes extract as an active ingredient.

In the case of using the composition of the present invention as a food composition, the Gaddicorus extract may be added as it is or used together with other foods or food ingredients, and may be appropriately used according to a conventional method. In addition to the active ingredient, the composition may include food additives acceptable in food science, and the mixing amount of the active ingredient may be appropriately determined depending on the purpose of use (prevention, health or therapeutic treatment).

The term "food supplement additive" used in the present invention refers to a component that can be added to food supplementally, and can be appropriately selected and used by those skilled in the art as being added to prepare a health functional food of each formulation. Examples of food additives include various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners , pH regulators, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, etc. are included, but the types of food additives of the present invention are not limited by the above examples.

The food composition of the present invention may include health functional food. The term "health functional food" used in the present invention refers to food prepared and processed in the form of tablets, capsules, powders, granules, liquids and pills using raw materials or ingredients having useful functionalities for the human body. Here, 'functionality' means obtaining useful effects for health purposes, such as adjusting nutrients for the structure and function of the human body or physiological functions. The health functional food of the present invention can be manufactured by a method commonly used in the conventional technical field, and can be prepared by adding raw materials and components commonly added in the conventional technical field at the time of manufacture. In addition, the formulation of the health functional food may also be manufactured without limitation as long as the formulation is recognized as a health functional food. The composition for food of the present invention can be prepared in various types of formulations, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long period of time by using natural substances as raw materials, and has excellent portability. Health functional foods of can be consumed as supplements to enhance the effectiveness of muscle disease treatments.

In addition, there is no limitation on the type of health food in which the composition of the present invention can be used. In addition, the composition containing the Gadizolifolia extract of the present invention as an active ingredient can be prepared by mixing suitable other auxiliary ingredients that can be contained in health functional foods and known additives according to the selection of those skilled in the art. Examples of foods that can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, and There are vitamin complexes, etc., and it can be prepared by adding the extract according to the present invention to juice, tea, jelly, juice, etc. prepared as a main component.

The present invention will be described in more detail through the following examples. However, the following examples are only for specifying the content of the present invention, and the present invention is not limited thereto.

Example 1. Preparation of galliformes extract

Chonbuk National University LED plant factory ( Limonium tetragonum ) was dried and refluxed for 1 hour while boiling at 100 ° C. Thereafter, the product was filtered under reduced pressure, concentrated under reduced pressure, freeze-dried, and powdered, and the yield was 28.3%.

Example 2. Confirmation of the effect of increasing the endurance of the galliformes extract

20-week-old male C57BL/6J mice were purchased from Samtako (Korea) and fed a regular diet under standard conditions (22±2° C., 50-60% humidity, 12-hour light/dark cycle) throughout the experiment. After adapting the mice to a single-lane treadmill (Jeong-do Bio & Plant, Korea) by running for 30 minutes every day at 10 m/min for 7 days, the powdered hydrangeas hot-water extract prepared in Example 1 was dissolved in PBS. Limonium tetragonum extracts (LTE) were orally administered to the test group at a dose of 30 or 100 mg/kg once a day for 4 weeks while running on a treadmill every day. Endurance was measured by recording the running time and distance of each mouse while running at 10 m/min for the first 10 minutes and increasing by 2 m/min every 10 minutes to 16 m/min until the mouse was exhausted.

As a result, it was found that the time taken to exhaustion and the average running time and distance significantly increased in a concentration-dependent manner of the hot water extract of the galliformes (Fig. 1).

Example 3. Confirmation of changes in the ratio of muscle fibers in muscle tissue by the Gaddolidaria extract

In order to confirm the change in muscle tissue by administration of the Gypsy sp. extract, immunochemical staining and quantitative RT- Analyzed by PCR. Specifically, the gastrocnemius muscle tissue was extracted by sacrificing the mouse after the 4-week running exercise test of Example 2, and immediately after extraction, it was placed in a 30% sucrose solution and cooled in liquid nitrogen with isopentane. Fixed. Thereafter, frozen tissue sections cut to a thickness of 10 μm were stained with SDH (Succinate dehydrogenase), immunostained with antibodies to MyHC type I, IIa and IIb/x, which are markers for each muscle fiber type, and each stained image was captured using a Leica DM750 microscope. After observation using iSolution DT software, it was quantitatively analyzed. In addition, after extracting total RNA from muscle tissue using TRIzol reagent, mRNA expression of genes specific to type 1 muscle fibers (slow fibers) and type 2 muscle fibers (fast fibers) was analyzed through qRT-PCR analysis. Confirmed.

As a result, it was found that the ratio of type 1 muscle fibers (oxidative muscle fibers) was significantly increased by the administration of the Gaddifolia extract (FIG. 2).

Example 4. Confirmation of mitochondrial neogeneration and functional improvement in muscle by Gadidopsis extract

In order to confirm the changes in the mouse muscle by the administration of the galliformes extract, the expression of genes related to mitochondrial biogenesis and mitochondrial regeneration were confirmed. Specifically, total DNA was extracted with a genomic DNA purification kit (Qiagen, Hiaden, Germany) from the gastrocnemius tissue of the mouse after the 4-week running exercise test in Example 2, and mitochondrial DNA (mtDNA) compared to nDNA (nuclear DNA) by qPCR Relative mtDNA was identified through the ratio of mtDNA, and mRNAs of genes related to mitochondrial neogenesis and oxidative phosphorylation were analyzed. In addition, the mitochondrial encoded gene Cox2 (cytochrome oxidase 2) was quantified through Ppia (nuclear-encoded gene cyclophilin A).

As a result, it was found that the mitochondrial content and the expression of mitochondrial regeneration-related genes were increased in the mouse muscle by the administration of the sea bream extract (FIG. 3). From this, it can be seen that the Gajidaria extract improved the new generation and function of muscle mitochondria, promoted the development of type 1 oxidative muscle fibers, and as a result, improved endurance exercise such as running.

Example 5. Confirmation of the mechanism of muscle development by gallidal medulla extract

In order to analyze the mechanism of muscle development by the administration of the gallbladder extract, the gastrocnemius tissue of the mouse after the 4-week running exercise test of Example 2 was ground, separated by 10% SDS-PAGE, and then transferred to a PVDF membrane. After blocking with 5% skim milk, reacted with the following primary antibodies: p38 (#9212), p-p38 (#9211), CREB (#9197), p-CREB (#9198) (Cell Signaling Technology, Beverly , MA, USA), ATF2 (sc-242), p-ATF2 (sc-8398) (Santa Cruz Biotrchnology, Dallas, TX, USA)), MEF2C (ab227085), MEF2A (ab109420), T-OXPHOS (ab110413) , Mfn1 (ab567602) (Abcam, Cambridge, UK), OPA1 (#612606, BD Biosciences, Franklin Lakes, NJ, USA), HSP90 (#ADI-SPA-836-F, Enzo Life Sciences, Plymouth Meeting, PA, USA) ), PGC-1α (#AB-3242, Millipore, Danvers, MA, USA) and α-myosin (#M4276) (Sigma-Aldrich). Then, after simple washing, the membrane was reacted with a secondary antibody, horseradish peroxidase (HRP)-IgG for 1 hour at room temperature, followed by color development using an ECL solution. Protein signals were confirmed using a Las-4000 imager (GE Healthcare Life Science, Pittsburgh, PA, USA). In addition, the expression of myogenesis-related genes was analyzed by qPCR. In addition, the C2C12 cell line, a muscle cell line, was pretreated with SB203580, a p38 inhibitor, and then treated with a galliformes extract (100 μg/ml) for 24 hours, and the mRNA expression level of myogenesis-related genes was analyzed by qPCR.

As a result, phosphorylation of p38 was increased in the muscle of the mouse to which the extract was administered, and phosphorylation of CREB and ATF2, which are important transcription factors for muscle development, and protein expression of Mef2a and Mef2c were significantly increased (FIG. 4A). In addition, it was found that the mRNA expression of myogenesis-related genes was significantly increased in mouse muscles by the administration of the sea bream extract (FIG. 4B), and the increased expression was reduced by p38 inhibitors (FIG. 4C), indicating that p38 It was inferred that the rhododendron extract plays an important role in the muscle development mechanism.

Claims (14)

An anti-fatigue or endurance enhancing composition comprising Limonium tetragonum (Thumb.) AA Bullock) extract as an active ingredient. The anti-fatigue or stamina enhancing composition according to claim 1, wherein the galliformes extract is extracted with at least one solvent selected from the group consisting of water, an organic solvent having 1 to 6 carbon atoms, a subcritical fluid, and a supercritical fluid. The composition for anti-fatigue or endurance enhancement according to claim 1, which increases the ratio of type 1 muscle fibers in muscle tissue. The composition for anti-fatigue or endurance enhancement according to claim 1, which increases mitochondrial biogenesis in muscle tissue. delete Containing galliformes extract as an active ingredient,
A pharmaceutical composition for the prevention or treatment of muscle disease, which is caused by decreased muscle function, muscle wasting or muscle degeneration. Containing galliformes extract as an active ingredient,
The muscular disease is at least one muscle disease selected from the group consisting of atony, muscular atrophy, muscular dystrophy, muscle degeneration, myasthenia, cachexia and sarcopenia. A pharmaceutical composition for the prevention or treatment of The pharmaceutical composition for preventing or treating muscle diseases according to claim 6 or 7, which increases the ratio of type 1 muscle fibers in muscle tissue. The pharmaceutical composition for preventing or treating muscle diseases according to claim 6 or 7, which increases mitochondrial biogenesis in muscle tissue. The pharmaceutical composition for preventing or treating muscle diseases according to claim 6 or 7, which develops muscles through muscle regeneration. The pharmaceutical composition for preventing or treating muscle diseases according to claim 6 or 7, which increases phosphorylation of p38, CREB or ATF2. The pharmaceutical composition for preventing or treating muscle diseases according to claim 6 or 7, which increases the expression of Mef2a or Mef2c. A composition for improving exercise performance containing an extract of Gajidaria as an active ingredient. The method of claim 13, wherein the exercise performance improvement has one or more effects selected from the group consisting of exercise endurance increase, muscle strength enhancement, balance enhancement, and exercise adaptation ability enhancement. A composition for improving performance.

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