KR102270028B1 - Compostion for Improving Muscle Strength or Muscular Atrophy Using an Extract of Ishige okamurae or Ishophloroglucin A - Google Patents

Abstract

Disclosed in the present invention is a composition for improving muscle strength or alleviating muscular atrophy, using an Ishige okamurae extract or ishophloroglucin A which alleviates muscle weakness or muscle atrophy caused by dexamethasone in muscular atrophy model animal experiments; promotes expression of muscle protein synthesis-related factors Akt, PI3K, and muscle growth-related factors TRPV4, and A1R; and also inhibits the expression of Myostatin and Sirt1, muscle protein synthesis inhibitors, or MuRF1, Atrogin1, a muscle protein degradation-related factor.

Description

Composition for improving muscle strength or improving muscle atrophy using shellfish extract or isophloroglucin A {Composition for Improving Muscle Strength or Muscular Atrophy Using an Extract of Ishige okamurae or Ishophloroglucin A}

The present invention relates to a composition for improving muscle strength or improving muscle atrophy using an extract of Ishige okamurae or isophloroglucin A.

Skeletal muscle is the largest tissue in our body, accounting for about 40-50% of the body weight of a normal person, and is responsible for essential functions such as movement, respiration, and heartbeat (Int J Biochem Cell Biol 37:1985-1996, 2005). ; Pharmacol Rev 61:373-393, 2009; Calcif Tissue Int 96:183-195, 2015). In the case of humans, the amount of muscle that is important for human activity starts to decrease by 1 to 2% every year after the age of 50, and by the age of 80, the amount decreases significantly to about half of the maximum muscle mass, and many elderly people suffer from sarcopenia (sarcopenia). ) or muscle atrophy, resulting in a decrease in physical function, disability, and deterioration in quality of life due to falls (Korean J Food and Nutr 4:133-139, 1991; J Nutr 127: 990S-991S, 1997; Curr Aging Sci 1:182-191, 2008) In particular, as life expectancy increases and the proportion of the elderly increases rapidly, muscular atrophy is recognized as an important aging disease (Curr Opin Clin Nutr Metab Care). 13:1-7, 2010).

The muscle mass of the human body is normally maintained by balancing protein synthesis and degradation, but when protein degradation increases or synthesis decreases, muscle atrophy occurs. In addition to aging, nutritional deficiencies, and decreased activity, muscle atrophy is commonly observed in chronic wasting diseases such as cancer, diabetes, uremia, chronic lung disease, heart failure, and AIDS, but also occurs in acute diseases such as sepsis, surgery, trauma, and burns (Int J Biochem Cell Biol 37:2156-68, 2005).

The occurrence of muscle atrophy is related to an increase in the expression of proteins such as Atrogin-1 and Murf-1, which promotes the breakdown of myofibrillar proteins, and inhibition of the PI3K-Akt-mTOR signaling pathway, which is involved in the synthesis of muscle-related proteins. ( Am J Physiol Cell Physiol 287:C834-843, 2004) Specifically, the ubiquitin-proteasome system that decomposes muscle proteins, including myosin, is activated in the muscle atrophy phenomenon to restore muscle. It was confirmed that the degradation of the constituent proteins was accelerated and, on the other hand, the activity of the PI3K-Akt-mTOR signaling pathway involved in muscle-related protein synthesis was lowered, and inhibition of muscle protein synthesis occurred together ( Proc Natl Acad Sci USA 98). :14440-14445, 2001; J Biol Chem 280: 2737-2744, 2005). Therefore, in order to effectively inhibit muscle atrophy, not only suppress the signaling pathway related to the proteolytic pathway, but also up-regulate the signaling pathways related to the biosynthesis of proteins essential for the increase in muscle mass and the activity of muscle cells. ) may be necessary.

The present invention discloses a muscle strength improvement or muscle atrophy improving activity of a shellfish extract or isolated therefrom or isophloroglucin A (Ishophloroglucin A).

An object of the present invention is to provide a composition for improving muscle strength or muscle atrophy using a shellfish extract or isophloroglucin A (Ishophloroglucin A).

Other objects or specific objects of the present invention will be set forth below.

As confirmed in the Examples and Experimental Examples below, the present invention relates to IPA (Ishophloroglucin A, Hexadecaphlorethol) of Formula 1 below (refer to Korean Patent No. 10-1964080, which is separated from a shellfish extract or shellfish extract). Considered a part of the present specification) muscle atrophy model In animal experiments, dexamethasone-induced muscle weakness or muscle atrophy is improved, and the expression of Akt and PI3K, which are factors related to muscle protein synthesis, and TRPV4, A1R, which are factors related to muscle growth, are promoted, and This was completed by confirming that it inhibits the expression of Myostatin, Sirt1, muscle protein synthesis inhibitory factors, or MuRF1, Atrogin1 of muscle proteolysis-related factors.

<Formula 1>

Considering the above, the present invention can be identified as a composition for improving muscle strength or a composition for improving muscular atrophy comprising a shellfish extract or isophloroglucin A, a compound of Formula 1, as an active ingredient. .

As used herein, the term "shell extract" refers to a stem, leaf, fruit, flower, root, underground part, above-ground part, or a mixture thereof, which is an extraction target, water, a lower alcohol having 1 to 4 carbon atoms (methanol, ethanol, butanol, etc.), Methylene chloride, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol or these It refers to an extract obtained by leaching using a mixed solvent, an extract obtained using a supercritical extraction solvent such as carbon dioxide, pentane, or a fraction obtained by fractionating the extract, and the extraction method considers the polarity of the active material, the degree of extraction, and the degree of preservation. Thus, any method such as chilling, reflux, heating, ultrasonic radiation, and supercritical extraction can be applied. In the case of the fractionated extract, a fraction obtained by suspending the extract in a specific solvent and mixing and standing still with a solvent having a different polarity, and adsorbing the crude extract to a column filled with silica gel, etc., hydrophobic solvent, hydrophilic solvent, or a mixed solvent thereof It is meant to include the fraction obtained as a mobile phase. In addition, the meaning of the extract includes a concentrated liquid extract or solid extract from which the extraction solvent has been removed by freeze drying, vacuum drying, hot air drying, spray drying, or the like. Preferably, it means an extract obtained by using water, ethanol, or a mixed solvent thereof as an extraction solvent, and more preferably an extract obtained by using a mixed solvent of water and ethanol as an extraction solvent.

In addition, as used herein, the term "active ingredient" refers to a component capable of exhibiting the desired activity alone or in combination with a carrier that has no activity by itself.

Also in the present specification, "improving muscle strength" is meant to include muscle strength enhancement, muscle increase and/or muscle reduction inhibition.

Also, in this specification, "improving muscular atrophy" is meant to include prevention, treatment, and alleviation of symptoms of muscular atrophy caused by diseases such as aging, nutritional deficiency, decreased activity, cancer, diabetes, and the like.

The composition for improving muscle strength or the composition for improving muscular atrophy of the present invention may contain the active ingredient in any amount (effective amount) as long as it can exhibit the intended strength improvement activity or muscular atrophy improvement activity, etc. depending on the specific use, formulation, product form, etc. However, a typical effective amount will be determined within the range of 0.001% to 15% by weight based on the total weight of the composition. As used herein, the term "effective amount" refers to the intended medical and pharmacology effects such as muscle strength improvement effect or muscular dystrophy disease improvement effect when the composition of the present invention is administered to a mammal, preferably a human subject, during the administration period as suggested by a medical professional. Refers to the amount of the active ingredient included in the composition of the present invention, which can exhibit a negative effect. Such effective amounts can be determined empirically within the ordinary ability of one of ordinary skill in the art.

In a specific aspect, the composition of this invention can be grasped|ascertained as a food composition.

The food composition of the present invention may be prepared in any form, for example, beverages such as tea, juice, carbonated beverages, and ionic beverages, processed oils such as milk and yogurt, gums, rice cakes, Korean sweets, bread, confectionery, noodles, etc. Foods, tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, and health functional food preparations such as bars can be prepared.

In addition, the food composition of the present invention may have any product classification in terms of legal and functional classification as long as it conforms to the enforcement laws at the time of manufacture and distribution. For example, it is a health functional food according to Korea's "Health Functional Food Act", or confectionery, beans, tea, and beverages according to each food type according to the Food Ordinance of Korea's Food Sanitation Act (Ministry of Food and Drug Safety Notification "Food Standards and Specifications") , food for special use, and the like.

The food composition of the present invention may contain food additives in addition to the active ingredients thereof. Food additives can be generally understood as substances that are added to and mixed with or infiltrated into food in manufacturing, processing or preserving food. Since they are consumed daily and for a long period of time with food, their safety must be ensured. Food additives with guaranteed safety are limited in terms of ingredients or functions in the Food Additives Ordinance in accordance with the laws of each country that regulates the manufacture and distribution of food (“Food Sanitation Act” in Korea). In the Korean Food Additives Code (“Food Additive Standards and Specifications” notified by the Ministry of Food and Drug Safety), food additives are classified into chemically synthetic products, natural additives, and mixed preparations in terms of ingredients. It is classified into an agent, a preservative, an emulsifier, an acidulant, and a thickener.

The sweetener is used to impart appropriate sweetness to food, and both natural and synthetic ones may be used in the composition of the present invention. Preferably, a natural sweetener is used. Examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.

Flavoring agents may be used to improve taste or aroma, and both natural and synthetic ones may be used. Preferably, it is a case where a natural thing is used. In the case of using a natural one, the purpose of nutritional enhancement in addition to flavor may be concurrently used. As a natural flavoring agent, it may be obtained from apple, lemon, tangerine, grape, strawberry, peach, etc., or it may be obtained from green tea leaf, dandelion, bamboo leaf, cinnamon, chrysanthemum leaf, jasmine, etc. In addition, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, ginkgo biloba, etc. can be used. The natural flavoring agent may be a liquid concentrate or a solid extract. Optionally, a synthetic flavoring agent may be used, and the synthetic flavoring agent may be an ester, an alcohol, an aldehyde, a terpene, or the like.

As a preservative, sodium calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc. can be used, and as an emulsifier, acacia gum, carboxymethylcellulose, xanthan gum, Pectin etc. are mentioned, and acidulant, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, etc. can be used as an acidulant. Acidulant may be added so that the food composition has an appropriate acidity for the purpose of inhibiting the growth of microorganisms in addition to the purpose of enhancing the taste.

As a thickening agent, a suspending agent, a settling agent, a gel former, a bulking agent, etc. can be used.

The food composition of the present invention may contain, in addition to the food additives as described above, physiologically active substances or minerals known in the art for the purpose of supplementing and reinforcing functionality and nutrition and guaranteed stability as food additives.

Examples of such physiologically active substances include catechins contained in green tea and the like, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, dibenzoylthiamine, and the like. Magnesium preparations, such as iron preparations, such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc, etc. are mentioned.

In the food composition of the present invention, the food additives as described above may be included in an appropriate amount to achieve the purpose of the addition according to the type of product.

In relation to other food additives that may be included in the food composition of the present invention, reference may be made to the national food regulations or food additives regulations.

The composition of the present invention may be identified as a pharmaceutical composition in another specific embodiment.

The pharmaceutical composition of the present invention may be prepared as an oral dosage form or a parenteral dosage form according to the route of administration by a conventional method known in the art, including a pharmaceutically acceptable carrier in addition to the active ingredient. Here, the route of administration may be any suitable route including topical route, oral route, intravenous route, intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination. An example of the combination of two or more routes is a case in which two or more formulations of drugs according to the route of administration are combined. For example, one drug is first administered by an intravenous route and the other drug is secondarily administered by a local route.

Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or formulation, and specifically, reference may be made to the pharmacopoeia of each country including the "Korea Pharmacopoeia".

When the pharmaceutical composition of the present invention is prepared as an oral dosage form, powders, granules, tablets, pills, dragees, capsules, liquids, gels, syrups, suspensions, wafers, together with a suitable carrier according to methods known in the art. It can be prepared in a formulation such as Examples of suitable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, and xylitol, starches such as corn starch, potato starch, wheat starch, cellulose, methylcellulose, ethylcellulose, sodium carboxymethylcellulose, Cellulose such as hydroxypropylmethylcellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable oil, ethanol, glycerol and the like. In the case of formulation, an appropriate binder, lubricant, disintegrant, colorant, diluent, etc. may be included as needed. Suitable binders include starch, magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, glucose, corn sweetener, sodium alginate, polyethylene glycol, wax, and the like, and lubricants include sodium oleate. , sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, silica, talcum, stearic acid, its magnesium salt and calcium salt, polyethylene glycol, etc., and the disintegrant includes starch, methyl cellulose, agar, bentonite, xanthan gum, starch, alginic acid or its sodium salt and the like. Examples of the diluent include lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, and the like.

When the pharmaceutical composition of the present invention is prepared for parenteral use, it may be formulated in the form of injections, transdermal administrations, nasal inhalants and suppositories together with suitable carriers according to methods known in the art. When formulated as an injection, an aqueous isotonic solution or suspension may be used as a suitable carrier, and specifically, PBS (phosphate buffered saline) containing triethanolamine, sterile water for injection, or isotonic solution such as 5% dextrose may be used. . When formulated for transdermal administration, it can be formulated in the form of ointments, creams, lotions, gels, external solutions, pasta agents, liniment agents, air rolls, and the like. In the case of a nasal inhalant, it can be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc., and when formulated as a suppository, the carrier is Witepsol ( witepsol), tween 61, polyethylene glycols, cacao fat, laurin fat, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearate, sorbitan fatty acid esters, and the like can be used.

Specific formulations of pharmaceutical compositions are known in the art, and reference may be made to, for example, Remington's Pharmaceutical Sciences (19th ed., 1995). This document is considered a part of this specification.

A preferred dosage of the pharmaceutical composition of the present invention is in the range of 0.001 mg/kg to 10 g/kg per day, preferably 0.001 mg/kg to 1 g, depending on the patient's condition, weight, sex, age, patient's severity, and administration route. It can be in the range /kg. Administration may be performed once or divided into several times a day. Such dosages should not be construed as limiting the scope of the invention in any respect.

As described above, according to the present invention, it is possible to provide a composition for improving muscle strength or muscle atrophy using a shellfish extract.

The composition of the present invention may be commercialized as food (especially health functional food) or medicine.

1 is a result showing the effect of shell extract and the like on body weight and muscle weight in a muscle atrophy model.
2 is a result showing the effect of a plaque extract and the like on the leg weight in the muscle atrophy model.
3 is a result showing the effect of a plaque extract and the like on the grip strength in the muscle atrophy model.
4 is a result showing the effect of shell extract and the like on the weight and thickness of gastrocnemius in the muscle atrophy model.
5 is a result showing the effect of shellfish extract and the like on the mRNA expression of factors related to protein synthesis and degradation in gastrocnemius muscle in a muscle atrophy model.
6 is a result showing the effect of the extract and the like on the mRNA expression of factors related to the promotion and inhibition of muscle growth of gastrocnemius muscle in a muscle atrophy model.
7 is a result showing the effect of shellfish extract and the like on the weight and thickness of soleus muscle in a muscle atrophy model.
8 is a result showing the effect of shellfish extract and the like on the mRNA expression of factors related to protein synthesis and degradation of soleus muscle in a muscle atrophy model.
9 is a result showing the effect of shellfish extract and the like on the mRNA expression of factors related to promoting and inhibiting muscle growth of soleus muscle in a muscle atrophy model.
10 is a result showing the effect of shellfish extract and the like on the level of LDH (Lactate dehydrogenase) production in the muscle atrophy model.

Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these Examples and Experimental Examples.

<Example> Preparation of shellfish extract and IPA (Ishophloroglucin A)

Shellfish (ishige okamurae , IO) collected in Seongsan-eup, Seogwipo-si, Jeju-do was decontaminated and dried, and 50% ethanol (alcohol) by weight of 10 times was added thereto, extracted at room temperature for 24 hours, filtered, and the extraction solvent was removed to prepare shellfish extract. did.

In addition, IPA was prepared by separating it according to the method described in the Examples of Korean Patent Registration No. 10-1964080.

<Experimental Example> Activity test for improving muscle strength or muscle atrophy of shellfish extract or IPA

<Experimental Example 1> Muscular atrophy model mouse experiment

1. Experimental method

1.1 Setting up the experimental group

After wearing 7-week-old ICR mice and acclimatizing them for 1 week, divide them into 7 groups as follows and measure their grip strength, and measure the weight of each group, muscle, leg muscle, gastrocnemius, soleus muscle, gastrocnemius and soleus muscle synthesis, growth, or decomposition or growth. An experiment was performed to measure the mRNA expression level of inhibitory factors.

① Group 1 (Saline administration group): Group administered saline once/day for 39 days

② Group 2 (Saline/Dexamethaone administration group): Administer saline once/day for 39 days, and subcutaneously dexamethaone (1mg/kg/day) for the last 10 days (29th to 38th) injection group.

③ Groups 3 to 5 (groups administered with shellfish extract 50, 100, and 200 mg/Kg/day): shellfish extract (50, 100, 200 mg/Kg/day) was administered once/day for 39 days, and the last 10 The group that received subcutaneous injection of dexamethaone (1mg/kg/day) daily (from the 29th to the 38th).

④ Group 6 (IPA) 3.5 mg/Kg/day administration group): IPA (3.5 mg/Kg/day) was administered once/day for 39 days, and dexamethaone (1 mg/kg/day) for the last 10 days (29 to 38 days) ) subcutaneously. IPA is a hexadecaphlorethol (HdP) compound isolated from plaque with Ishophloroglucin A (refer to Korean Patent No. 10-1964080)

⑤ Group 7 (oxymetholone 50 mg/Kg/day administration group): As a comparative drug, oxymetholone (50 mg/Kg/day), an oral muscle-increasing steroid, was administered once/day for 39 days, and the last Group subcutaneously injected with dexamethaone (1mg/kg/day) for 10 days (29th to 38th)

1.2 Measurement of body weight and muscle weight

After performing the 38-day test, the animals used were weighed, sacrificed, and total muscle was collected and weighed.

1.3 Measurement of grip strength

For the measurement of the forelimbs using a grip strength meter, after confirming that the animal has grasped the bar with its toes, grasp the origin of the tail of the animal and keep the body horizontal and pull at a constant speed (2.5 cm per second) to release the bar The values indicated on the gauge were recorded. The measurement of the hindlimb is carried out in the same manner as above by holding the animal's dorsal area and pulling it toward the tail. Each of the hind and forelimbs was measured and recorded three times, and the average value was evaluated.

1.4 Measurement of weight and thickness of gastrocnemius and soleus muscles

The gastrocnemius and soleus muscles among the leg muscles of the sacrificed animals were collected, weighed, and the diameter of the thickest thickness was measured several times, and the average value was used.

1.5 Measurement of mRNA expression levels of gastrocnemius and soleus muscle protein synthesis factors

After adding 1.0ml of Trizole to the muscle tissue crushed using a stick, and leaving it for 10 minutes at room temperature, 0.2ml of chloroform is added and vortexed vigorously for 15 seconds to completely dissolve (Lysis) did it This was left at room temperature for 10 minutes, and then centrifuged at 14,000 x g, 4°C for 15 minutes. The supernatant was transferred to a new tube, 0.5 ml isopropyl alcohol was added, and left at room temperature for 10 minutes, followed by centrifugation at 14,000 x g, 4°C for 10 minutes. After removing the supernatant, after washing the pellet with 1.0ml of 75% alcohol, 30 μl of DEPC-treated sterile distilled water was added to dissolve the pellet, and then used in subsequent tests.

Using each isolated RNA as a template, cDNA was synthesized according to the manufacturer's instructions using PrimeScript™ 1st strand cDNA Synthesis Kit. Using the cDNA as a template, a real-time polymerase chain reaction was performed as follows. Including oligonucleotide and SYBR Green I, real-time polymerase chain reaction was performed under conditions of denaturation at 95°C for 30 seconds, annealing at 58°C for 30 seconds, and elongation at 72°C for 30 seconds.

2. Experimental results

2.1. Effect of plaque extract and IPA on muscle weight and leg muscle thickness in muscle atrophy model

Changes in body weight and muscle weight were confirmed compared to the group treated with shellfish extract and IPA, and the group treated with only dexamethasone, which induces muscle atrophy, for 10 days. As a result, as the significantly decreased body weight and muscle weight in the model inducing muscle atrophy increased significantly in the group administered with the sample and the group administered with oxymetholone as a comparative drug (p<0.01), shellfish extract It was confirmed that muscle atrophy caused by dexamethasone was inhibited by , IPA, and the comparative drug oxymetholone (FIG. 1).

These changes were also observed in changes in the thickness of the leg muscles. In the leg muscle thickness reduced by dexamethasone, a significant improvement effect was confirmed in the group administered with shellfish extract, IPA, and the comparative drug oxymetholone (FIG. 2).

2.2. Effect of plaque extract and IPA on grip strength in a muscle atrophy model

As a result of checking the grip strength to check whether it affects muscle strength as well as significant external muscle changes in the shell extract and IPA groups, it was confirmed that the grip strength decreased by muscle atrophy was significantly increased in the sample and control group (Fig. 3). Accordingly, it was confirmed that the loss of grip strength could be prevented by significantly inhibiting the decrease in grip strength due to muscle atrophy by administering shellfish extract or IPA.

2.3. Effect of shellfish extract and IPA on gastrocnemius and soleus muscle in muscle atrophy model

In the muscle atrophy model, changes were confirmed in the gastrocnemius muscle, which is a fast muscle for agility, and the soleus muscle, a slow muscle for endurance. A significant decrease in gastrocnemius muscle was observed in the group induced by dexamethasone, and a significant improvement effect was observed in the group administered with cncnfanf, IPA, and the comparative drug oxymetholone (Fig. 4). ). In particular, the weight and thickness of gastrocnemius in the group administered with 100 and 200 mg/Kg/day shellfish extract were improved to a level similar to that of the group administered with the comparative drug oxymetholone.

In addition, in the muscle atrophy model, the effect on the mRNA expression levels of Akt and PI3K, protein synthesis-related factors of gastrocnemius muscle, and the mRNA expression levels of MuRF1 and Atrogin1, which are degradation-related factors, was confirmed in the group administered with shellfish extract and IPA. As a result, it was confirmed that the mRNA expression of the gastrocnemius protein synthesizing factor increased and the mRNA expression of the degradation-related factor decreased (FIG. 5). Accordingly, it was confirmed that the decreased gastrocnemius protein synthesis promotion and degradation inhibition in the muscle atrophy model could be improved by the administration of shellfish extract and IPA.

Also, in the muscle atrophy model, the effect on the mRNA expression levels of TRPV4 and A1R, which are factors related to the promotion of muscle growth in gastrocnemius muscle, and the mRNA expression levels of Myostatin and Sirt1, which are factors related to inhibition, was confirmed in the group treated with shellfish extract and IPA. As a result, it was confirmed that the mRNA expression of the gastrocnemius muscle growth promotion-related factor increased and the mRNA expression of the inhibition-related factor decreased (FIG. 6). Accordingly, it was confirmed that the decreased gastrocnemius muscle growth promotion and inhibition inhibition in the muscle atrophy model could be improved by the administration of shellfish extract and IPA.

As such, it was confirmed that the gastrocnemius and soleus muscles were significantly improved by the administration of shellfish extract and IPA.

Also, significant changes in weight and thickness were observed in the soleus muscle, which is a slow muscle, by the administration of shellfish extract and IPA. It was confirmed that the decrease in soleus muscle due to dexamethasone was significantly inhibited in the shell extract administered groups at 100 and 200 mg/Kg/day (FIG. 7). In addition, it was observed that in the group administered with IPA, the weight and thickness of the soleus muscle could be protected at a level similar to that of the group administered with the comparative drug oxymetholone (FIG. 7). These results suggest that shellfish extract or IPA can inhibit the decrease in gastrocnemius caused by dexamethasone.

Also, in the muscle atrophy model, the effect on the mRNA expression levels of Akt and PI3K, which are factors related to protein synthesis in soleus muscle, and the mRNA expression levels of MuRF1 and Atrogin1, which are factors related to degradation, was confirmed in the group treated with shellfish extract and IPA. It was confirmed that the mRNA expression of the factor related to the protein synthesis of the soleus muscle increased and the mRNA expression of the factor related to the degradation was decreased (FIG. 8). Accordingly, it was confirmed that the promotion of protein synthesis and inhibition of the degradation of soleus muscle protein, which were decreased in the muscle atrophy model, could be improved by the administration of shellfish extract and IPA.

In addition, in the muscle atrophy model, the effect on the mRNA expression levels of TRPV4 and A1R, which are factors that promote muscle growth in the soleus muscle, and the mRNA expression levels of Myostatin, Sirt1, which are inhibitory factors, was confirmed. It was confirmed that the mRNA expression of the soleus muscle growth promoting factor increased and the mRNA expression of the inhibitory factor decreased ( FIG. 9 ). Accordingly, it was confirmed that the promotion and inhibition of soleus muscle growth, which was decreased in the muscle atrophy model, could be improved by the administration of shellfish extract and IPA. Accordingly, it was confirmed that the ability to significantly improve soleus muscle, which is the slow muscle that affects endurance, was confirmed by shellfish extract and IPA.

3.4. Effect of shellfish extract and IPA on muscle strength improvement biomarkers in muscle atrophy model

Lactate dehydrogenase (LDH), an evaluation index of blood energy metabolism, decreased in the muscle atrophy model, but a significant increase was confirmed in the group administered with shellfish extract and IPA (FIG. 10). LDH is used as an indicator of histological damage analysis and physical strength evaluation of muscles according to exercise intensity, exercise duration, and recovery from fatigue, suggesting that muscle atrophy due to muscle atrophy can be suppressed by shellfish extract and IPA.

Claims (8)

A composition for inhibiting muscle increase or muscle loss comprising an active ingredient in water, ethanol, or a mixed solvent thereof, or isophloroglucin A (Ishophloroglucin A).
delete According to claim 1,
The composition is a pharmaceutical composition, characterized in that the composition.
According to claim 1,
The composition is a food composition, characterized in that the composition.
A composition for improving muscular atrophy comprising an extract or isophloroglucin A (Ishophloroglucin A) by water, ethanol, or a mixed solvent thereof.
6. The method of claim 5,
The extract is a composition, characterized in that the extract obtained by extraction with a mixed solvent of water and ethanol.
7. The method according to claim 5 or 6,
The composition is a pharmaceutical composition, characterized in that the composition.
7. The method according to claim 5 or 6,
The composition is a food composition, characterized in that the composition.

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