Composition for preventing, alleviating or treating muscle diseases, comprising lactobacillus gasseri strain and rice embryo bud extract as active ingredients

Abstract

The present invention relates to a composition for preventing, alleviating, or treating muscle diseases, comprising a Lactobacillus gasseri strain and a rice embryo bud extract as active ingredients. The composition according to the present invention contains a Lactobacillus gasseri strain and a rice embryo bud extract as active ingredients to increase muscle mass and muscle function, thereby preventing, treating, or alleviating muscle function decrease, muscle loss or reduction, and the like caused by various muscle diseases. The Lactobacillus gasseri strain and the rice embryo bud extract of the present invention are natural materials, and thus can be safely used without side effects, thereby being effectively used in the manufacture of medicines, foods or feed.

Description

A composition for the prevention, improvement, or treatment of muscle diseases comprising Lactobacillus gasseri strain and rice germ extract as active ingredients

[0001] The present invention relates to a composition for the prevention, improvement, or treatment of muscle diseases comprising a Lactobacillus gasseri strain and a rice germ extract as active ingredients.

[0002] Muscles are broadly classified into skeletal muscle, cardiac muscle, and visceral muscle. Among these, skeletal muscle is the most abundant tissue in the human body, accounting for 40–45% of body weight. Skeletal muscle attaches to bones via tendons and plays a role in generating bone movement or force. A single muscle is composed of numerous muscle fibers, which in turn are made up of numerous myofibrils composed of actin and myosin. When actin and myosin overlap and move, the muscle shortens or lengthens, inducing overall muscle contraction and relaxation. An increase in the size of myofibrils implies an increase in the thickness of the muscle fibers, resulting in muscle growth.

[0003] Muscle diseases follow a course in which the weakening of skeletal muscles gradually leads to impaired walking and mobility functions, making activities of daily living (ADL) difficult and ultimately rendering independent living impossible. Furthermore, since they cause cardiopulmonary dysfunction and co-occur with other complications, it is important to accurately understand the characteristics of each muscle disease and approach them accordingly.

[0004] South Korea entered an aging society in 2000 when the elderly population accounted for 7.2% of the total population, and it is predicted to enter a super-aging society (over 20%) by 2050 (2013 Statistics on the Elderly, Statistics Korea). Human muscle mass decreases with age (by about 10–15% between the ages of 50 and 70, and by more than 30% between the ages of 70 and 80), leading to a weakening of muscle strength and function; this condition is known as senile sarcopenia. Senile sarcopenia causes mobility and gait disorders, serving as a major cause that limits the independent living of the elderly. Furthermore, sarcopenia lowers the anaplastic mortality rate, increasing insulin resistance and accelerating the development of type 2 diabetes, while increasing the risk of hypertension and cardiovascular diseases by 3 to 5 times. Currently, there are no approved drugs for the treatment of sarcopenia, and drug repositioning technology is under development to apply myostatin inhibitors or existing FDA-approved treatments for other diseases to sarcopenia.

[0005] The inventors completed the present invention by confirming that while developing a treatment for muscle diseases using natural products safe for the human body, the combined use of a Lactobacillus gasseri strain and a rice germ extract promotes myogenesis and inhibits and improves muscle atrophy and age-related sarcopenia induced by dexamethasone in animal models.

[0006] The object of the present invention is to provide a food composition for the prevention or improvement of muscle diseases, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient.

[0007] Another objective of the present invention is to provide a food composition for increasing muscle mass or inhibiting muscle loss, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient.

[0008] Another objective of the present invention is to provide a feed composition for the prevention or improvement of muscle diseases, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient.

[0009] Another objective of the present invention is to provide a pharmaceutical composition for the prevention or treatment of muscle diseases, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a lysate thereof, a culture solution thereof, an extract of the culture solution, a concentrate of the culture solution, and a dried product of the culture solution; and (ii) a rice germ extract as an active ingredient.

[0010] To achieve the above objective, the present invention provides a food composition for the prevention or improvement of muscle diseases, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient.

[0011] According to one embodiment of the present invention, the strain may be a live strain or a dead strain.

[0012] According to one embodiment of the present invention, the rice germ extract may be extracted with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.

[0013] According to one embodiment of the present invention, the mixed solvent may be 20 to 80 volume% methanol, ethanol, butanol, or propanol.

[0014] According to one embodiment of the present invention, the composition may reduce the expression of one or more selected from Myostatin, MuRF1, and Atrogin-1, which are factors related to muscle protein degradation.

[0015] According to one embodiment of the present invention, the composition may increase muscle mass or inhibit muscle loss.

[0016] According to one embodiment of the present invention, the composition may increase one or more selected from muscle strength and muscle endurance.

[0017] According to one embodiment of the present invention, the muscle disease may be caused by aging, decreased muscle function, muscle reduction, muscle atrophy, muscle wasting, muscle degeneration, disused muscle, or muscle damage.

[0018] According to one embodiment of the present invention, the muscle disease may be caused by a glucocorticoid side effect.

[0019] According to one embodiment of the present invention, the glucocorticoid side effect may be caused by glucocorticoid treatment or an increase in the amount of glucocorticoid in the individual.

[0020] According to one embodiment of the present invention, the glucocorticoid may be one or more selected from cortisol, hydrocortin, cortisone, prednisolone, methylprednisolone, triamcinolone, triamcinolone acetonide, paramethasone, dexamethasone, betamethasone, hexastrol, methimazole, fluocinonide, fluocinolone acetonide, fluorometholone, beclomethasone dipropionate, estriol, diflorasone diacetate, diflucortolone valerate, and difluprednate.

[0021] According to one embodiment of the present invention, the muscle disease may be one or more selected from sarcopenia, muscular atrophy, muscular dystrophy, myopathy, myasthenia, cachexia, muscular injury, myotonia, atony, hypotonia, muscular weakness, myoneural conductive disease, diabetic amyotrophy, amyotrophic lateral sclerosis (ALS), and degenerative muscle diseases.

[0022] To achieve the other objectives mentioned above, the present invention provides a food composition for increasing muscle mass or inhibiting muscle loss, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient.

[0023] To achieve the other objectives mentioned above, the present invention provides a feed composition for the prevention or improvement of muscle diseases, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient.

[0024] To achieve the other objectives mentioned above, the present invention provides a pharmaceutical composition for the prevention or treatment of muscle diseases, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a lysate thereof, a culture solution thereof, an extract of the culture solution, a concentrate of the culture solution, and a dried product of the culture solution; and (ii) a rice germ extract as an active ingredient.

[0025] The composition according to the present invention contains Lactobacillus gasseri strain and rice germ extract as active ingredients, thereby increasing muscle mass and muscle function, and thus can prevent, treat, or improve the decline in muscle function, muscle loss, or reduction caused by various muscle diseases. Since the Lactobacillus gasseri CBT LGA1 strain and rice germ extract of the present invention are natural products, they can be used safely without side effects and can be usefully employed in the manufacture of pharmaceuticals, food, or animal feed.

[0026] Figure 1 is a graph showing the mRNA expression levels of Myogenin, a muscle protein synthesis factor, and Myostatin and MuRF1, muscle protein degradation factors, measured after treating a dexamethasone-induced sarcopenia cell model with the culture supernatant of a culture prepared by inoculating each of the 15 strains listed in Table 1 into a rice germ medium according to one embodiment of the present invention.

[0027] FIG. 2 is a graph showing the mRNA expression levels of MyoD, a muscle protein synthesis factor, and Myostatin and MuRF1, muscle protein degradation factors, measured after treating a dexamethasone-induced sarcopenia cell model with rice germ powder, a hot water extract of rice germ (W100), and 30% (E30), 50% (E50), 70% (E70), and 95% (E95) ethanol extracts of rice germ, respectively, according to one embodiment of the present invention.

[0028] Figure 3 is a graph showing the mRNA expression levels of muscle protein degradation factors Atrogin-1 and MuRF1 after treating a dexamethasone-induced sarcopenia cell model with a probiotic composition and a postbiotic composition prepared according to one embodiment of the present invention.

[0029] FIG. 4 is a graph showing changes in the weight of the gastrocnemius and quadriceps muscles of glucocorticoid (dexamethasone)-induced sarcopenia mice following the administration of rice germ extract (RGE), rice germ extract and Lactobacillus helveticus LH5 strain (LH5+RGE), rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE), and rice germ extract, Lactobacillus helveticus LH5 strain and Lactobacillus gasseri LGA1 strain (LH5+LGA1+RGE) according to one embodiment of the present invention.

[0030] FIG. 5 is a graph showing changes in Artogin-1 and MuRF1 mRNA expression levels in the gastrocnemius muscle of mice with glucocorticoid (dexamethasone)-induced sarcopenia following the administration of rice germ extract (RGE), rice germ extract and Lactobacillus helveticus LH5 strain (LH5+RGE), rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE), and rice germ extract, Lactobacillus helveticus LH5 strain and Lactobacillus gasseri LGA1 strain (LH5+LGA1+RGE) according to one embodiment of the present invention.

[0031] FIG. 6 is a graph showing changes in Artogin-1 and MuRF1 mRNA expression levels in glucocorticoid (dexamethasone)-induced sarcopenia mice following administration of rice germ extract (RGE), rice germ extract and Lactobacillus helveticus LH5 strain (LH5+RGE), rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE), and rice germ extract, Lactobacillus helveticus LH5 strain and Lactobacillus gasseri LGA1 strain (LH5+LGA1+RGE) according to one embodiment of the present invention.

[0032] FIG. 7 shows a rice germ extract (RGE) and a Lactobacillus gasseri LGA1 strain (LGA1, 1×10⁻⁶) according to one embodiment of the present invention. 8 ), Lactobacillus gasseri LGA1 strain (LGA1, 1×10 9 ), rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE, 1×10 8 ), and rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE, 1×10 9 This is a graph showing the weight changes of the gastrocnemius and quadriceps muscles in mice with glucocorticoid (dexamethasone)-induced sarcopenia following the administration of ).

[0033] FIG. 8 shows a rice germ extract (RGE) and a Lactobacillus gasseri LGA1 strain (LGA1, 1×10⁻⁶) according to one embodiment of the present invention. 8 ), Lactobacillus gasseri LGA1 strain (LGA1, 1×10 9 ), rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE, 1×10 8 ), and rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE, 1×10 9 This is a graph showing the changes in Artogin-1 and MuRF1 mRNA expression levels in the gastrocnemius muscle of glucocorticoid (dexamethasone)-induced sarcopenia mice following the administration of ).

[0034] FIG. 9 shows a rice germ extract (RGE) and a Lactobacillus gasseri LGA1 strain (LGA1, 1×10⁻⁶) according to one embodiment of the present invention. 8 ), Lactobacillus gasseri LGA1 strain (LGA1, 1×10 9 ), rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE, 1×10 8 ), and rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE, 1×10 9 This is a graph showing the changes in Artogin-1 and MuRF1 mRNA expression levels in the quadriceps of mice with glucocorticoid (dexamethasone)-induced sarcopenia following the administration of ).

[0035] FIG. 10 is a graph showing the weight changes of the gastrocnemius and quadriceps muscles of aged (Old) mice following the administration of Lactobacillus gasseri LGA1 strain (LGA1), rice germ extract (RGE), rice germ extract and Lactobacillus gasseri LGA1 strain (LGA1+RGE) according to one embodiment of the present invention.

[0036] FIG. 11 is a graph showing changes in Myostatin, MuRF1, and Artogin-1 mRNA expression levels in the gastrocnemius muscle of aged (Old) mice following administration of Lactobacillus gasseri LGA1 strain (LGA1), rice germ extract (RGE), rice germ extract, and Lactobacillus gasseri LGA1 strain (LGA1+RGE) according to one embodiment of the present invention.

[0037] FIG. 12 is a graph showing the change in expression levels of pro-inflammatory cytokines (IL1a, IL1b, and IL6) in the gastrocnemius muscle of aged (Old) mice following the administration of Lactobacillus gasseri LGA1 strain (LGA1), rice germ extract (RGE), rice germ extract, and Lactobacillus gasseri LGA1 strain (LGA1+RGE) according to one embodiment of the present invention.

[0038] FIG. 13 is a graph showing changes in MuRF1 and Artogin-1 mRNA expression levels in the quadriceps of an aged (Old) mouse following the administration of Lactobacillus gasseri LGA1 strain (LGA1), rice germ extract (RGE), rice germ extract, and Lactobacillus gasseri LGA1 strain (LGA1+RGE) according to one embodiment of the present invention.

[0039] FIG. 14 is a graph showing the change in expression levels of pro-inflammatory cytokines (IL1a, IL1b, IL6, and TNF-α) in the quadriceps of an aged (Old) mouse following the administration of Lactobacillus gasseri LGA1 strain (LGA1), rice germ extract (RGE), rice germ extract, and Lactobacillus gasseri LGA1 strain (LGA1+RGE) according to one embodiment of the present invention.

[0040] FIG. 15 is a graph showing the change in mRNA expression levels of IGF-1, Myogenin, and MyoD, which are markers for muscle protein synthesis and differentiation in the quadriceps femoris muscle, following the administration of Lactobacillus gasseri LGA1 strain (LGA1), rice germ extract (RGE), rice germ extract, and Lactobacillus gasseri LGA1 strain (LGA1+RGE) according to one embodiment of the present invention.

[0041] The present invention will be described in detail below.

[0042] The present invention provides a food composition for preventing or improving muscle disease, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient; a food composition for increasing muscle mass or inhibiting muscle loss; a feed composition for preventing or improving muscle disease; and a pharmaceutical composition for preventing or treating muscle disease.

[0043] In one embodiment, the strain may be the Lactobacillus gasseri CBT LGA1 strain deposited under accession number KCTC 12936BP.

[0044] In one embodiment, the strain may be a live bacterium or a dead bacterium. The dead bacterium may be a dead bacterium obtained by freeze-drying or heat treatment.

[0045] In this specification, the term “lysate” may refer to a product obtained by breaking the cell wall of the strain itself by chemical or physical force.

[0046] In this specification, the term “culture medium” may be used interchangeably with “culture supernatant” or “culture filtrate,” and may refer to the entire medium containing said strain, its metabolites, excess nutrients, etc., obtained by culturing said strain for a certain period in a medium capable of supplying nutrients so that the Lactobacillus gasseri strain can grow and survive in a test tube. Additionally, said culture medium may refer to a culture medium from which the cells have been removed from a cell culture medium obtained by culturing the strain. Meanwhile, the liquid from which the cells have been removed from said culture medium is also referred to as the “supernatant,” which may be obtained by leaving the culture medium undisturbed for a certain period to take only the liquid from the upper layer excluding the part that settled at the bottom, by removing the cells through filtration, or by centrifuging the culture medium to remove the lower precipitate and taking only the upper liquid. The “cells” refer to the strain of the present invention itself and include the strain itself isolated and selected from Korean feces or fermented foods, etc., or the strain isolated from the culture medium by culturing said strain. The above-mentioned bacterial cells can be obtained by centrifuging the culture medium and taking the portion that settles in the lower layer, or by letting them sit for a certain period of time and then removing the liquid from the top, as they sink to the lower layer of the culture medium due to gravity.

[0047] The above culture medium may include the culture medium itself obtained by culturing the strain, its concentrate or freeze-dried product, or the culture supernatant or culture filtrate obtained by removing the strain from the culture medium, its concentrate or freeze-dried product.

[0048] The above culture medium may be obtained by culturing the above Lactobacillus gasseri strain in a suitable medium (e.g., MRS medium, TSA medium, or R2A medium) at a temperature greater than 10°C or less than 40°C for a certain period of time, e.g., 4 to 50 hours. The above MRS medium may comprise any one selected from the group consisting of peptone, beef extract, yeast extract, glucose, sodium acetate, polysorbate 80, dipotassium hydrogen phosphate, ammonium citrate, magnesium sulfate, manganese sulfate, agar, and distilled water, a combination of two or more of these, or all of these. The concentrations of the components in the above-mentioned medium may be appropriately changed, and the term MRS medium may encompass all commercially available media referred to as MRS.

[0049] In one embodiment, the culture supernatant or culture filtrate of the strain may be obtained by removing the strain from the strain culture through centrifugation or filtration.

[0050] In this specification, the term “extract of a culture medium” means an extract obtained from said culture medium or its concentrate, and may include an extract, a diluted or concentrated extract, a dried product obtained by drying the extract, or a modified or purified product thereof, or a fraction obtained by fractionating the same.

[0051] In one embodiment, the rice germ or rice embryo is the embryonic part of rice and contains 60 to 70% of the total functional components of rice. The rice germ is rich in inositol (a water-soluble vitamin B complex), which provides nutrition to brain cells, helps in getting a good night's sleep, has therapeutic effects on depression and panic disorder, reduces sudden fear, and has been reported to have effects in preventing dementia and relieving fatty liver. In addition, it helps the body utilize fat and cholesterol, and has been reported to have effects such as preventing arteriosclerosis and reducing belly fat. Furthermore, the rice germ contains a large amount of gamma oryzanol, which is a powerful antioxidant with anticancer and anti-aging effects.

[0052] In one embodiment, the rice germ may be an embryo portion separated from non-glutinous rice.

[0053] In one specific example, the variety of non-glutinous rice may be one or more selected from Chucheong, Ilpum, Koshihikari, Koami, Onnuri, Odae, Dongjin, Junam, Samgwang, Gopum, Ungwang, Cheongdam, Cheonga, Chilbo, and Hopum, but it is preferable to use the Chucheong variety in terms of efficacy against muscle diseases. The Chucheong variety is a type of Japonica rice, which was introduced to Korea from Japan in the 1960s and began to be cultivated instead of Tongilbyeo.

[0054] In this specification, “rice germ extract” refers to a product obtained by extracting rice germ with a suitable solvent, and includes all forms such as an extract, a diluted or concentrated extract, a dried product obtained by drying the extract, or a modified or purified product thereof. Accordingly, in a broad sense, the rice germ extract of the present invention includes processed rice germ products formulated for administration to animals, such as rice germ powder.

[0055] In one embodiment, the rice germ extract of the present invention can be prepared by mixing rice germ powder with an extraction solvent in a weight ratio of 1:10 to 200 and then extracting at 70 to 100°C. If the weight ratio of the rice germ to the extraction solvent falls outside the above range, the active ingredients of the rice germ may be extracted in a small amount in the extract.

[0056] The extraction solvent for extracting the above extract may be water, a lower alcohol having 1 to 4 carbon atoms, or a mixture thereof. Although the above extraction solvent is not particularly limited, an extract obtained with 20 to 80 volume% methanol, ethanol, butanol, or propanol, preferably 20 to 80 volume% ethanol, shows excellent effects in terms of efficacy against muscle diseases.

[0057] The rice germ extract of the present invention may be prepared using conventional extraction methods in the art, such as heat extraction, cold maceration extraction, ultrasonic extraction, high-pressure extraction, and reflux extraction. For example, it may be obtained by extracting the rice germ under ultra-high pressure conditions of 100 MPa or more, preferably 100 MPa to 1000 MPa. If necessary, it may be prepared by additionally including filtration and concentration steps according to methods known in the art. The rice germ may be purchased from commercially available sources, or it may be collected from nature or separated from cultivated rice.

[0058] Meanwhile, in this specification, the term "containing as an active ingredient" means containing an amount sufficient to achieve the efficacy or activity of the Lactobacillus gasseri strain and the rice germ extract. For example, the composition of the present invention contains 1 × 10⁶ Lactobacillus gasseri strain. 7 Up to 1×10 10It may be included in CFU / g. In addition, the rice germ extract may be included at a concentration of 10 to 1000 mg / g. Since the Lactobacillus gasseri strain and the rice germ extract are natural products and do not cause adverse effects on the human body even when administered in excess, the quantitative upper limit of the active ingredients included in the composition of the present invention may be selected and implemented by a person skilled in the art within an appropriate range.

[0059] In this specification, "muscle" comprehensively refers to tendons, muscles, and tendons, and "muscle function" refers to the ability to exert force through muscle contraction. It includes muscle strength, which is the ability of a muscle to exert maximum contractile force to overcome resistance; muscle endurance, which is the ability of a muscle to repeat contraction and relaxation for a given weight for a certain period or many times; and explosiveness, which is the ability to exert strong force within a short period of time. The term "improvement of muscle function" in this specification refers to improving muscle functions, such as muscle strength, by increasing muscle mass.

[0060] In a specific embodiment of the present invention, the inventors specifically confirmed that treatment with a Lactobacillus gasseri strain and rice germ extract reduced the expression levels of muscle protein degradation factors Myostatin and MuRF1 in a dexamethasone-induced sarcopenia cell model (Fig. 3).

[0061] In addition, following the above in vitro experiment, the inventors verified the effect of co-administration of Lactobacillus gasseri strain and rice germ extract on muscle atrophy / muscle loss recovery in a glucocorticoid (dexamethasone)-induced sarcopenia mouse animal model.

[0062] In addition, in a specific embodiment of the present invention, when measuring muscle weight in glucocorticoid (dexamethasone)-induced sarcopenia mice, mice administered the Lactobacillus gasseri strain and rice germ extract of the present invention (Dex+LGA1+RGE) showed a significant increase in the weight of the gastrocnemius and quadriceps muscles compared to the sarcopenia-induced group (Dex) (see Figs. 4 and 7).

[0063] In addition, as a result of conducting an in vivo mechanism study in glucocorticoid (dexamethasone)-induced sarcopenia mice, it was confirmed that mice administered the Lactobacillus gasseri strain and rice germ extract of the present invention (Dex+LGA1+RGE) showed a significant decrease in the mRNA expression levels of Artogin-1 and MuRF1 in skeletal muscle compared to the sarcopenia-induced group (Dex) (see Figs. 5, 6, 8, and 9).

[0064] Following experiments in a glucocorticoid (dexamethasone)-induced sarcopenia mouse animal model, the inventors verified the sarcopenia-improving or therapeutic effects of the Lactobacillus gasseri strain and rice germ extract in an aging mouse animal model.

[0065] In addition, in a specific embodiment of the present invention, as a result of measuring the muscle weight of aging mice, mice (Old+LGA1+RGE) administered with the Lactobacillus gasseri strain and rice germ extract of the present invention showed a significant increase in the weight of the gastrocnemius and quadriceps muscles compared to the aging control group (see Fig. 10).

[0066] In addition, as a result of conducting in vivo mechanism studies in aging mice, it was confirmed that mice administered the Lactobacillus gasseri strain and rice germ extract of the present invention (Old+LGA1+RGE) showed a significant decrease in mRNA expression levels of Myostatin, MuRF1, and Atrogin-1 in skeletal muscle compared to the aging control group (Old Control) (see Figures 11 and 13). Furthermore, it was confirmed that mice administered the Lactobacillus gasseri strain and rice germ extract of the present invention (Old+LGA1+RGE) showed a significant increase in mRNA expression levels of IGF-1, Myogenin, and MyoD, which are markers for muscle protein synthesis and differentiation induction, in skeletal muscle compared to the aging control group (Old Control) (see Figure 15).

[0067] As described above, the composition comprising the Lactobacillus gasseri strain and rice germ extract of the present invention can be usefully used for the prevention, improvement, or treatment of muscle diseases because it reduces the expression of muscle atrophy and sarcopenia marker genes, or muscle protein degradation factors such as Myostatin, Artogin-1, and MuRF1, increases the expression of muscle synthesis-related proteins, increases muscle mass, inhibits muscle loss, and restores muscle atrophy and reduced muscle function.

[0068] The composition of the present invention may be used for the prevention, improvement, or treatment of muscle diseases caused by aging, decreased muscle function, muscle loss, muscle atrophy, muscle wasting, muscle degeneration, disused or damaged muscles, or muscle diseases caused by steroid side effects.

[0069] The aforementioned decline in muscle function, muscle loss, muscle atrophy, muscle wasting, or muscle degeneration occurs due to causes such as genetic factors, acquired factors, and aging, and is characterized by the progressive loss of muscle mass and the weakening and degeneration of muscles, particularly skeletal or voluntary muscles and cardiac muscles.

[0070] Specific examples of the above muscle diseases include, but are not limited to, sarcopenia, muscular atrophy, muscular dystrophy, myopathy, myasthenia, cachexia, muscular injury, myotonia, atony, hypotonia, muscular weakness, myoneural conductive disease, diabetic amyotrophy, amyotrophic lateral sclerosis (ALS), and degenerative muscle diseases.

[0071] In addition, the muscle disease of the present invention may be caused by steroid side effects, and more specifically, may be a muscle atrophy or sarcopenia disease caused by steroid side effects. The steroid may be a glucocorticoid.

[0072] In this specification, "glucocorticoid (GC)" may be a type of steroid hormone that binds to a glucocorticoid receptor (GR or GCR) present in most vertebrate cells. The glucocorticoid receptor is also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1) and is the receptor to which cortisol and other glucocorticoids bind. The glucocorticoid receptor may have the amino acid sequences NP_000167 (human) and NP_032199 (mouse). The glucocorticoid receptor may also be encoded by the nucleotide sequences NM_000176 (human) and NM_008173 (mouse).

[0073] The above glucocorticoid may be one or more selected from, for example, cortisol, hydrocortin, cortisone, prednisolone, methylprednisolone, triamcinolone, triamcinolone acetonide, paramethasone, dexamethasone, betamethasone, hexastrol, methimazole, fluocinonide, fluocinolone acetonide, fluorometholone, beclomethasone dipropionate, estriol, diflorasone diacetate, diflucortolone valerate, and difluprednate, and preferably is cortisol, dexamethasone, betamethasone, prednisone, methylprednisolone, or prednisolone.

[0074] The above glucocorticoid side effects may be caused by glucocorticoid treatment or an increase in the amount of glucocorticoids in the individual.

[0075] Additionally, the above-mentioned glucocorticoid side effects may be caused by inhibition of S6K activity, inhibition of Akt1 activity, inhibition of 4EBP1 activity, increased Atrogin-1 activity, increased MuRF1 activity, or a combination thereof. In this specification, "increased activity" may be caused by increased biosynthesis of the protein itself or increased specific activity of the protein itself. The food composition of the present invention may cause increased activity of one or more selected from the group consisting of AKT, S6K, and 4EBP1, decreased activity of one or more selected from the group consisting of Atrogin-1 and MuRF1, or a combination thereof. Additionally, the composition may reduce phosphorylation of glucocorticoid receptors and / or reduce nuclear translocation of phosphorylated glucocorticoid receptors.

[0076] The above composition may be intended for administration before, concurrently with, or after the administration of a glucocorticoid drug. In the case of concurrent administration, it may be intended for administration as the same composition or as separate compositions.

[0077] The muscle disease resulting from the above-mentioned glucocorticoid side effects may be a muscle atrophy disease. The above-mentioned muscle atrophy disease may be muscular atrophy, myasthenia gravis, muscular dystrophy, myasthenia gravis, hypotonia, muscle weakness, muscular dystrophy, muscle degenerative atrophy, amyotrophic lateral sclerosis, spinal progressive muscular atrophy, or myasthenia gravis, or a combination thereof.

[0078] In addition, the muscle disease of the present invention may be due to aging, and more specifically, may be sarcopenia due to aging (age-related sarcopenia).

[0079] The composition of the present invention has the effect of increasing muscle mass and inhibiting muscle loss, and the type of muscle is not limited.

[0080] Since the composition of the present invention exhibits excellent effects in recovering muscle atrophy, increasing muscle mass, or inhibiting muscle loss, it can be usefully used as an active ingredient in food compositions for preventing or improving muscle diseases; food compositions for increasing muscle mass or inhibiting muscle loss; health functional food compositions for preventing or improving muscle diseases; health functional food compositions for improving muscle function; feed compositions for preventing or improving muscle diseases; and pharmaceutical compositions for preventing or treating muscle diseases.

[0081]

[0082] One aspect of the present invention relates to a food composition for the prevention or improvement of muscle diseases comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient.

[0083] The term "prevention" in this invention means anything that inhibits or delays the muscle disease.

[0084] The term "improvement" in the present invention means at least reducing parameters related to a condition treated by the administration of a composition comprising the Lactobacillus gasseri strain and rice germ extract of the present invention, such as the degree of symptoms.

[0085] The food composition of the present invention includes all forms such as functional food, nutritional supplement, health food, health functional food, food additives, and feed, and is intended for consumption by humans or animals including livestock. The above-mentioned types of food compositions can be manufactured in various forms according to conventional methods known in the industry.

[0086] The above-mentioned type of food composition can be manufactured in various forms according to conventional methods known in the art. General foods may be manufactured by adding the above-mentioned Lactobacillus gasseri strain and rice germ extract to beverages (including alcoholic beverages), fruits and their processed foods (e.g., canned fruit, bottled fruit, jam, marmalade, etc.), fish, meat and its processed foods (e.g., ham, sausage, corned beef, etc.), breads and noodles (e.g., udon, buckwheat noodles, ramen, spaghetti, macaroni, etc.), fruit juices, various drinks, cookies, malt syrup, dairy products (e.g., butter, cheese, etc.), edible vegetable oils, margarine, vegetable proteins, retort foods, frozen foods, and various seasonings (e.g., soybean paste, soy sauce, sauces, etc.). Additionally, nutritional supplements may be manufactured by adding the above-mentioned Lactobacillus gasseri strain and rice germ extract to capsules, tablets, pills, etc., although not limited thereto. In addition, as a health functional food, although not limited thereto, for example, the above-mentioned Lactobacillus gasseri strain and rice germ extract itself may be consumed by liquefying, granulating, encapsulating, and powdering so that they can be prepared in the form of tea, juice, and drink (health beverage). In addition, to use the above-mentioned Lactobacillus gasseri strain and rice germ extract in the form of a food additive, they may be prepared as a powder or prepared in the form of a concentrate after extraction. Furthermore, the above-mentioned Lactobacillus gasseri strain and rice germ extract may be prepared in the form of a composition by mixing them with a known active ingredient known to have an improving effect on muscle diseases.

[0087] When the food composition for preventing or improving muscle diseases according to the present invention is used as a health drink composition, the health drink composition may contain various flavoring agents or natural carbohydrates as additional ingredients, as in conventional beverages. The aforementioned natural carbohydrates may be monosaccharides such as glucose and fructose; disaccharides such as maltose and sucrose; polysaccharides such as dextrin and cyclodextrin; or sugar alcohols such as xylitol, sorbitol, and erythritol. Sweeteners may include natural sweeteners such as thaumatin and stevia extract; or synthetic sweeteners such as saccharin and aspartame. The proportion of the natural carbohydrates is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 mL of the composition of the present invention.

[0088] The Lactobacillus strain and rice germ extract of the present invention may be contained as active ingredients in a food composition for preventing or improving muscle diseases, and the amount is not specifically limited to an amount effective for achieving an improvement effect on muscle diseases, but may be 0.01 to 100 weight%, preferably 0.01 to 60 weight%, based on the total weight of the composition.

[0089] In addition to the above, the health functional food of the present invention may contain various nutritional supplements, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid, salts of pectic acid, alginic acid, salts of alginic acid, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, or carbonating agents. Furthermore, the health functional food of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice beverages, or vegetable beverages. These ingredients may be used independently or in combination. Although the proportion of these additives is not critical, it is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

[0090]

[0091] Another aspect of the present invention relates to a food composition for increasing muscle mass or inhibiting muscle loss, comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient. The descriptions of the “Lactobacillus gasseri strain,” “rice germ extract,” and “muscle disease” are omitted to avoid excessive duplication.

[0092]

[0093] Another aspect of the present invention relates to a feed composition for the prevention or improvement of muscle diseases comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a crushed liquid thereof, a culture medium thereof, an extract of the culture medium, a concentrate of the culture medium, and a dried product of the culture medium; and (ii) a rice germ extract as an active ingredient. The descriptions of the “Lactobacillus gasseri strain,” “rice germ extract,” and “muscle disease” are omitted to avoid excessive duplication.

[0094] In the present invention, the term "feed" refers to any natural or artificial prescribed food, single meal, etc., or a component of said single meal, intended for or suitable for animals to eat, consume, and digest. Feed containing the composition for preventing or improving muscle disease according to the present invention as an active ingredient can be manufactured in various forms of feed known in the art, and preferably may include concentrated feed, roughage, and / or special feed, but is not limited thereto.

[0095] Concentrated feeds include, but are not limited to, seed grains such as wheat, oats, and corn; bran, which is a byproduct obtained by refining grains and includes rice bran, wheat bran, and barley bran; oilseed meal, which is a byproduct obtained by extracting oil from soybeans, rapeseed, sesame, flaxseed, and coconut; residues such as residual starch, which is the main component of starch residue remaining after removing starch from sweet potatoes and potatoes; fish meal, fish residue; fish soluble, which is a concentrated fresh liquid obtained from fish; meat meal; blood meal; feather meal; skim milk powder; dried whey, which is the residue obtained when making cheese from milk or casein from skim milk; yeast, Chlorella, and seaweed.

[0096] Roughage includes raw grass feeds such as wild grass, pasture grass, and green cuts; root vegetables such as feed turnips, feed beets, and a type of turnip called lutea bearger; silage, which is a stored feed made by filling a silo with raw grass, green cut crops, and grains and fermenting them with lactic acid; hay made by cutting and drying wild grass and pasture grass; straw of livestock breeding crops; and leaves of legumes, but is not limited thereto. Special feeds include mineral feeds such as oyster shells and rock salt; urea feeds such as urea or its derivatives such as diuretic isobutane; feed additives, which are substances added in trace amounts to compound feed to supplement components that are prone to being deficient when only natural feed ingredients are mixed, or to improve the shelf life of the feed; and dietary supplements, but are not limited thereto.

[0097] The feed composition for the prevention or improvement of muscle diseases according to the present invention can be prepared by adding Lactobacillus gasseri strain and rice germ extract in an appropriate effective concentration range according to various feed manufacturing methods known in the art.

[0098] The feed composition according to the present invention can be applied without limitation to any individual intended for the prevention or improvement of muscle diseases. For example, it can be applied to any individual, such as non-human animals like cattle, horses, pigs, goats, sheep, dogs, cats, rabbits, etc., as well as birds and fish.

[0099]

[0100] Another aspect of the present invention relates to a pharmaceutical composition for the prevention or treatment of muscle diseases comprising (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a lysate thereof, a culture solution thereof, an extract of said culture solution, a concentrate of said culture solution, and a dried product of said culture solution; and (ii) a rice germ extract as an active ingredient. The descriptions of the “Lactobacillus gasseri strain,” “rice germ extract,” and “muscle disease” are omitted to avoid excessive duplication.

[0101] The pharmaceutical composition for the prevention or treatment of muscle diseases of the present invention may be used for the prevention or treatment of muscle diseases caused by aging, decreased muscle function, muscle loss, muscle atrophy, muscle wasting, muscle degeneration, disused or damaged muscles, or muscle diseases caused by glucocorticoid side effects.

[0102] Specific examples of the above muscle diseases include sarcopenia, muscular atrophy, muscular dystrophy, myopathy, myasthenia, cachexia, muscular injury, myotonia, atony, hypotonia, muscular weakness, myoneural conductive disease, diabetic amyotrophy, amyotrophic lateral sclerosis (ALS), and degenerative muscle diseases. The composition of the present invention has the effect of recovering muscle atrophy, increasing muscle mass, or inhibiting muscle loss, and the type of muscle is not limited.

[0103] The term "prevention" in this invention means anything that inhibits or delays the muscle disease.

[0104] The term "treatment" in the present invention means reversing, alleviating, inhibiting, or preventing the symptoms of the muscle disease, unless otherwise stated.

[0105] The pharmaceutical composition for the prevention or treatment of muscle diseases of the present invention may include a pharmaceutically acceptable carrier.

[0106] Pharmaceutically acceptable carriers may additionally include, for example, carriers for oral administration or carriers for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, etc. Additionally, carriers for parenteral administration may include water, suitable oils, saline solution, aqueous glucose, and glycol, etc. Additionally, stabilizers and preservatives may additionally be included. Suitable stabilizers include antioxidants such as sodium bisulfite, sodium sulfite, or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-paraben, and chlorobutanol. For other pharmaceutically acceptable carriers, reference may be made to the following literature (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).

[0107] The pharmaceutical composition of the present invention can be administered to mammals, including humans, by any method. For example, it can be administered orally or parenterally, and parenteral administration methods may include, but are not limited to, intravenous, intramuscular, intra-arterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual, or rectal administration.

[0108] The pharmaceutical composition of the present invention may be formulated into an oral or parenteral administration formulation according to the administration route described above. When formulating, it may be prepared using one or more buffers (e.g., saline solution or PBS), antioxidants, bacteriostatic agents, chelating agents (e.g., EDTA or glutathione), fillers, extenders, binders, adjuvants (e.g., aluminum hydroxide), suspenders, thickeners, wetting agents, disintegrants or surfactants, diluents or excipients.

[0109] Solid dosage forms for oral administration include tablets, pills, powders, granules, liquids, gels, syrups, slurries, suspensions, or capsules, and such solid dosage forms may be prepared by mixing at least one excipient, for example, starch (including corn starch, wheat starch, rice starch, potato starch, etc.), calcium carbonate, sucrose, lactose, dextrose, sorbitol, mannitol, xylitol, erythritol, maltitol, cellulose, methyl cellulose, sodium carboxymethylcellulose and hydroxypropylmethylcellulose, or gelatin, with the pharmaceutical composition of the present invention. For example, a tablet or a sugar tablet may be obtained by combining an active ingredient with a solid excipient, grinding the mixture, adding a suitable auxiliary agent, and processing it into a granular mixture.

[0110] In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid formulations for oral administration include suspensions, oral liquids, emulsions, or syrups, and may contain various excipients, such as humectants, sweeteners, flavorings, or preservatives, in addition to commonly used simple diluents like water or liquid paraffin.

[0111] In addition, cross-linked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may be added as a disintegrant depending on the case, and may additionally include anticoagulants, lubricants, wetting agents, fragrances, emulsifiers, and preservatives.

[0112] When administered parenterally, the pharmaceutical composition of the present invention may be formulated in the form of an injectable, a transdermal agent, and a nasal inhalant with a suitable parenteral carrier according to methods known in the art. The injectable must be sterile and protected from contamination by microorganisms such as bacteria and fungi. Examples of suitable carriers for the injectable may be, but are not limited to, water, ethanol, polyols (e.g., glycerol, propylene glycol, and liquid polyethylene glycol), mixtures thereof, and / or solvents or dispersion media containing vegetable oils. More preferably, suitable carriers may include Hanks' solution, Ringer's solution, PBS (phosphate buffered saline) containing triethanolamine, sterile water for injection, isotonic solutions such as 10% ethanol, 40% propylene glycol, and 5% dextrose. To protect the above-mentioned injectable from microbial contamination, various antimicrobial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, etc. may be additionally included. In addition, the above-mentioned injectable may, in most cases, additionally include isotonic agents such as sugars or sodium chloride.

[0113] Transdermal formulations include forms such as ointments, creams, lotions, gels, topical solutions, pastes, liniments, and aerosols. In the above, 'transdermal administration' means administering a pharmaceutical composition topically to the skin so that an effective amount of the active ingredient contained in the pharmaceutical composition is delivered into the skin.

[0114] The pharmaceutical composition for the prevention and treatment of muscle diseases according to the present invention can provide desirable effects for the prevention and treatment of muscle diseases when it contains an effective amount of Lactobacillus gasseri strain and rice germ extract. In this specification, "effective amount" refers to an amount that exhibits a response greater than that of a negative control, and preferably refers to an amount sufficient to improve muscle function. The pharmaceutical composition of the present invention may contain Lactobacillus gasseri strain and rice germ extract in an amount of 0.01 to 99.99%, preferably 0.01 to 50% by weight, more preferably 0.1 to 20% by weight, even more preferably 0.2 to 10% by weight, and even more preferably 0.2 to 5% by weight, and the remainder may be occupied by a pharmaceutically acceptable carrier. The effective amount of Lactobacillus gasseri strain and rice germ extract included in the pharmaceutical composition of the present invention will vary depending on the form in which the composition is manufactured into a product, etc.

[0115] The total effective amount of the pharmaceutical composition of the present invention may be administered to a patient as a single dose, or administered via a fractionated treatment protocol involving multiple doses administered over a long period. The content of the active ingredient in the pharmaceutical composition of the present invention may vary depending on the severity of the disease. However, since the effective dosage for a patient is determined by considering various factors such as the patient's age, weight, health status, gender, severity of the disease, diet, and excretion rate, as well as the administration route and frequency of treatment of the pharmaceutical composition, a person of ordinary knowledge in the art would be able to determine an appropriate effective dosage of the Lactobacillus gasseri strain and rice germ extract for specific uses for the prevention and treatment of muscle diseases, taking these points into consideration. The pharmaceutical composition according to the present invention is not particularly limited in its formulation, administration route, and administration method as long as it exhibits the effects of the present invention.

[0116] The pharmaceutical composition for the prevention and treatment of muscle diseases of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, or biological response modifiers.

[0117] The pharmaceutical composition for the prevention and treatment of muscle diseases of the present invention can also be provided in the form of an external preparation containing a Lactobacillus gasseri strain and a rice germ extract as active ingredients.

[0118] When the pharmaceutical composition for the prevention and treatment of muscle diseases of the present invention is used as a topical application for the skin, it may additionally contain adjuvants commonly used in the field of dermatology, such as fatty substances, organic solvents, solvents, thickeners and gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic emulsifiers, non-ionic emulsifiers, fillers, metal ion chelating agents, chelating agents, preservatives, vitamins, blockers, humectants, essential oils, dyes, pigments, hydrophilic activators, lipophilic activators, or lipid vesicles. Furthermore, said ingredients may be introduced in amounts commonly used in the field of dermatology.

[0119] When the pharmaceutical composition for the prevention and treatment of muscle diseases of the present invention is provided as an external skin preparation, it may be in the form of an ointment, patch, gel, cream, or spray, but is not limited thereto.

[0120]

[0121] Another aspect of the present invention relates to a method for treating a muscle disease comprising the step of administering to a mammal (i) one or more selected from the group consisting of a Lactobacillus gasseri strain, a lysate thereof, a culture solution thereof, an extract of the culture solution, a concentrate of the culture solution, and a dried product of the culture solution; and (ii) administering an effective amount of a pharmaceutical composition comprising a rice germ extract as an active ingredient.

[0122] As used herein, the term "mammal" refers to a mammal that is the subject of treatment, observation, or experiment, preferably a human.

[0123] As used herein, the term "effective dose" refers to the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal, or human as conceived by a researcher, veterinarian, physician, or other clinician, and includes an amount that induces the alleviation of symptoms of the relevant disease or disorder. The effective dose and frequency of administration for the active ingredient of the present invention may vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by a person skilled in the art and may be adjusted according to various factors including the type of disease, the severity of the disease, the content of the active ingredient and other ingredients contained in the composition, the type of formulation, and the patient's age, body weight, general health status, gender and diet, time of administration, route of administration and secretion rate of the composition, duration of treatment, and concurrently used drugs. In the preventive or therapeutic method of the present invention, for adults, it is preferable to administer a pharmaceutical composition containing a Lactobacillus gasseri strain and a rice germ extract as active ingredients at a dose of 0.1 to 1,000 mg / kg once to several times a day.

[0124] In the treatment method of the present invention, a pharmaceutical composition comprising a Lactobacillus gasseri strain and a rice germ extract as active ingredients can be administered in a conventional manner via oral, rectal, intravenous, arterial, abdominal, intramuscular, sternal, transdermal, topical, ocular, or intradermal routes.

[0125]

[0126] The present invention will be described in detail below by way of examples, but the present invention is not limited by the following examples.

[0127]

[0128] <Example>

[0129] Experimental method

[0130] (1) Preparation of strain

[0131] Fifteen types of probiotics isolated from Korean feces or fermented foods, held by the Cell Biotech Research Institute, were used (see Table 1).

[0132] Among the above probiotics, CBT BL3, BF3, BR3, BG7, and BT1 strains of the genus Bifidobacterium were inoculated into glucose Blood Liver medium (KisanBio, Korea) and anaerobically cultured at 37°C for 48 hours.

[0133] CBT LC5, LPC5, and LR5 strains of the genus Lacticaceibacillus, CBT LP3 strain of the genus Lactibactibacillus, CBT LA1, LGA1, and LH5 strains of the genus Lactobacillus, CBT SL6 strain of the genus Lactococcus, CBT LU4 strain of the genus Limosi-Lactobacillus, and CBT ST3 strain of the genus Streptococcus were inoculated into MRS medium (BD Difco, USA) and aerobically cultured at 37°C.

[0134] In summary, the L series and cocci were inoculated into MRS medium and aerobically cultured at 37°C for 24 hours, and the B series were inoculated into BL medium and anaerobically cultured at 37°C for 48 hours.

[0135] Number Strain Accession Number (KCTC No.) 1Bifidobacterium animalissubsp.lactisCBT BL311904BP2Bifidobacterium bifidumCBT BF312199BP3Bifidobacterium breveCBT BR312201BP4Bifidobacterium longumCBT BG712200BP5Bifidobacterium longum subsp. InfantisCBT BT111859BP6Lacticaseibacillus caseiCBT LC512398BP7Lacticaseibacillus paracaseiCBT LPC512451BP8Lacticaseibacillus rhamnosusCBT LR512202BP9Lactiplantibacillus plantarumCBT LP310782BP10Lactobacillus acidophilusCBT LA111906BP11Lactobacillus gasseriCBT LGA112936BP12Lactobacillus helveticusCBT LH512670BP13Lactococcus lactissubsp.lactisCBT SL611865BP14Limosilactobacillus reuteriCBT LU412397BP15Streptococcus thermophilusCBT ST311870BP

[0136] (2) Cell culture

[0137] Myoblasts C2C2 were purchased from the Korean Cell Line Bank (Seoul, Korea), inoculated into DMEM medium (Dulbecco's modified Eagle's minimum essential medium, Life Technologies Inc., NY, USA) supplemented with 10% FBS (fetal bovine serum, Hyclone™, GE healthcare life sciences, Chicago, USA), 100 U / ml penicillin (Hyclone™, GE healthcare life sciences, Chicago, USA), and 100 μg / ml streptomycin (Hyclone™, GE healthcare life sciences, Chicago, USA), and cultured in a 37°C, 5% CO2 incubator.

[0138]

[0139] (3) Cytotoxicity measurement

[0140] The cytotoxicity of the samples was confirmed after treating C2C12 cells with the samples at concentrations increasing in 10% increments from 0% (v / v) to 100% (v / v). The lowest concentration of the sample that exhibited more than 90% cell proliferation compared to the untreated control group after treatment was set as the minimum non-cytotoxic concentration. As a result of the experiment, it was confirmed that the minimum non-cytotoxic concentration for each sample was 10% (v / v). In the following experiments, the C2C12 cells were treated with the samples at a concentration of 10% (v / v), which is the concentration with no cytotoxicity.

[0141]

[0142] (4) Induction of cell differentiation and atrophy

[0143] C2C12 cells were inoculated into a differentiation medium containing 2.5% horse serum and 1% P / S (penicillin / streptomycin) in DMEM, and cultured at 37°C under 5% CO2 conditions to induce differentiation. The cells in which differentiation was completed were inoculated into DMEM containing 10 μM of dexamethasone (Dex), and simultaneously treated with test substances (each strain and / or rice germ extract) at a non-cytotoxic concentration. After culturing for 24 hours, the inhibitory effect of dexamethasone on atrophy induced by the dexamethasone was confirmed. In this case, Cont (control group) refers to differentiated C2C12 cells not treated with dexamethasone and / or test substances, and DEX (negative control group) refers to the group treated with dexamethasone alone.

[0144]

[0145] (5) mRNA analysis by Quantitative RT-PCR

[0146] RNA extraction (Quiagen) and cDNA synthesis (Takara) from C2C12 cells or muscle tissues (gastrocnemius, quadriceps femoris) were prepared according to the respective manufacturers' instructions. RT-PCR (Bio-rad) was performed using SYBR Green PCR master mix (Genetbio) to measure mRNA expression of each target. Primers were manufactured and purchased from Cosmo Genetech (see Table 2). After the reaction was completed, single amplification curves were verified and CT values ​​were recorded as data; mRNA expression levels were quantified and corrected as a relative ratio to the CT value of GAPDH.

[0147] 타겟 유전자프라이머 서열(5' - 3')AtroginForwardCTC TGT ACC ATG CCG TTC CTReverseGGC TGC TGA ACA GAT TCT CCMuRF1ForwardTGT CTG GAG GTC GCC GTT TGC GTC ACT GTC ATC TMyostatinForwardACG CTA CCA CGG AAA CAA TCReverseAAA GCA ACA TTT GGG CTT TCMyoDForwardCTA CAT CGA AGG TCT GCA GReverseAAT CCA TCA TGC CAT CAG AGMyogeninForwardAAA ACT ACC TTC CTG TCC ACReverse ACCAT CCT TCTG CCIL1aForwardTCT GAA GAA GAG ACG GCT GAReverseACA AAC TTC TGC CTG ACG AGIL1bForwardAAA ATA CCT GTG GCC TTG GGReverseGCT TGT GAG GTG CTG ATG TAIL6ForwardATA CCA CTC CCA ACA GAC CCA CTRA GAAGAGC GAAGA AATNFaForwardGGT GCC TAT GTC TCA GCC TCT TReverseGCC ATA GAA CTG ATG AGA GGG AGIGF1ForwardTGC TCT TCA GTT CGT GTGReverseACA TCT CCA GTC TCC TCAGAPDHForwardGCC TTC CGT GTT CCT ACCReverse CTT CACTT CTC GTT GTT

[0148] 통계 분석

[0149] All of the following research results were analyzed using one-way ANOVA with GraphPad Prism 7 (GraphPad Software Inc., San Diego, CA, USA), and statistical significance was verified using the Tukey multiple comparison post test, indicated as *p<0.05, **p<0.01, and ***p<0.001.

[0150]

[0151] In vitro test

[0152] Test Example 1: Screening of strains effective for the prevention, improvement, or treatment of muscle diseases

[0153] 1-1: Preparation of the sample (culture supernatant of strain cultured in rice germ medium)

[0154] A rice germ medium was prepared by adding rice germ powder of the Chucheong variety to distilled water at a concentration of 200 mg / 10 mL. Each strain of Table 1 was inoculated into the rice germ medium to achieve an absorbance value of 1.0 at 610 nm. Subsequently, L-series and cocci-series strains were aerobically cultured at 37°C for 24 hours, and B-series strains were anaerobically cultured at 37°C for 48 hours. Afterward, the culture solution of each strain was filtered, and the culture filtrate obtained was centrifuged (4,255 xg, 10 min), and the supernatant obtained therefrom was freeze-dried.

[0155]

[0156] 1-2: Analysis of Expression Levels of Muscle Protein Degradation / Synthesis Factors by Strain Type

[0157] We intended to compare the effects of each sample prepared in 1-1 above on changes in the expression levels of muscle protein degradation and synthesis factors in a dexamethasone-induced sarcopenia cell model.

[0158] Specifically, differentiated C2C12 cells were inoculated into DMEM containing 10 uM of dexamethasone to induce muscle atrophy / sarcopenia, and each sample prepared in 1-1, raw rice germ, or rice germ powder at a concentration of 10% (v / v), and cultured for 24 hours at 37 ℃ under 5% CO2 conditions. Subsequently, total RNA was extracted from each C2C12 cell, and the mRNA expression levels of the muscle protein degradation factors Myostatin, MuRF1, and the muscle protein synthesis factor Myogenin were confirmed by RT-PCR analysis (Fig. 1).

[0159] In Figure 1, considering both the aspect of increasing the mRNA expression of Myogenin, a muscle protein synthesis factor, and the aspect of decreasing the expression of Myostatin and MuRF1, muscle protein degradation factors, it can be confirmed that LH5 and LGA1 have excellent efficacy in preventing, improving, or treating muscle atrophy and sarcopenia induced by dexamethasone.

[0160]

[0161] Test Example 2: Efficacy of rice germ extract on muscle diseases

[0162] 2-1: Preparation of Samples (Raw Rice Germ and Extract)

[0163] 100 times the weight of purified water and 30% (w / w), 50% (w / w), 70% (w / w), and 95% (w / w) ethanol were added to rice germ powder of the Chucheong variety, and the extracts were obtained by extracting at 80°C for 6 hours. The obtained extracts were filtration and vacuum concentration, and then powdered by freeze-drying for use.

[0164]

[0165] 2-2: Analysis of Expression Levels of Muscle Protein Degradation / Synthesis Factors in Raw Rice Germ and Extracts

[0166] We intended to compare the effects of rice germ powder and each of the rice germ extracts prepared in 2-1 above (hot water extract, 30%, 50%, 70%, and 95% ethanol extracts) on changes in the expression levels of muscle protein degradation and synthesis factors.

[0167] Specifically, differentiated C2C12 cells were inoculated into DMEM containing 10 μM of dexamethasone to induce sarcopenia and each sample prepared in 2-1 at a concentration of 10% (v / v), and cultured for 24 hours at 37°C under 5% CO2 conditions. Subsequently, total RNA was extracted from each C2C12 cell, and the mRNA expression levels of the muscle protein degradation factors Myostatin, MuRF1, and the muscle protein synthesis factor MyoD were confirmed by RT-PCR analysis (Fig. 2).

[0168] Looking at Figure 2, considering both the aspect of increasing the mRNA expression of MyoD, a muscle protein synthesis factor, and the aspect of decreasing the expression of Myostatin and MuRF1, muscle protein degradation factors, it can be confirmed that the 30%, 50%, and 70% ethanol extracts of rice germ, especially the 50% ethanol extract, have superior efficacy in preventing, improving, or treating muscle atrophy and sarcopenia induced by dexamethasone compared to rice germ powder, rice germ hot water extract, and rice germ 95% ethanol extract.

[0169]

[0170] Test Example 3: Efficacy of probiotics / postbiotics utilizing two selected strains and / or rice germ extract against muscle diseases

[0171] 3-1: Preparation of Samples (Probiotics and Postbiotics)

[0172] Probiotic and postbiotic compositions were prepared, respectively, using the two selected strains (LH5, LGA1), their complex (LH5+LGA1), and a 50% ethanol extract of rice germ.

[0173] The probiotic composition comprises 200 mg / 10 mL of 50% ethanol extract of rice germ and 1 x 10 7 It was manufactured by adding CFU.

[0174] The postbiotic composition was prepared by adding 200 mg / 10 mL of 50% ethanol extract of rice germ to distilled water, inoculating each strain into the medium at 610 nm so that the absorbance value was 1.0, and aerobically culturing at 37 ℃ for 24 hours. The culture medium was filtered, and the culture filtrate was centrifuged (4,255 xg, 10 min) and freeze-dried, and the filtrate was added to DPBS at 10% (v / v) to prepare the composition.

[0175]

[0176] 3-2: Analysis of Muscle Protein Degradation Factor Expression Levels

[0177] We intended to investigate the effects of the above probiotic composition and postbiotic composition on changes in the expression levels of muscle protein degradation factors.

[0178] Specifically, differentiated C2C12 cells were inoculated into DMEM containing 10 μM of dexamethasone to induce sarcopenia and each sample prepared in 3-1 at a concentration of 10% (v / v), and cultured for 24 hours at 37°C under 5% CO2 conditions. Subsequently, total RNA was extracted from each C2C12 cell, and the mRNA expression levels of the muscle protein degradation factors Atrogin-1 and MuRF1 were confirmed by RT-PCR analysis (Fig. 3).

[0179] Looking at Figure 3, it can be seen that both the probiotic composition and the postbiotic composition exhibit significant efficacy in inhibiting the degradation of muscle proteins induced by dexamethasone. In particular, it can be seen that the muscle protein inhibitory activity of the probiotic composition is significantly higher than that of the postbiotic composition.

[0180]

[0181] In vivo test

[0182] Test Example 4: Effect of increasing muscle function and muscle mass in a dexamethasone-induced muscle atrophy / sarcopenia animal model (1)

[0183] 4-1: Design of Animal Experiments

[0184] (1) Experimental animals: male mice C57BL / 6J mice, 10 mice / group, Initial weight: 24 ~ 27g / mice

[0185] (2) Experiment period: 5 weeks (Week 1: Adaptation period, Week 4: Injection and administration of experimental substance)

[0186] (3) Administered substances: Dexamethasone (Dex, muscle atrophy / sarcopenia-inducing substance), 50% ethanol extract of rice germ (RGE), probiotics (LH5, LGA1), positive control (turmeric extract, AriBio), feed (AIN-93G), saline solution (0.9% NaCl)

[0187] (4) Dosage and method of administration:

[0188] - Dexamethasone (Dex): 25 mg / kg, daily intraperitoneal administration for 4 weeks

[0189] - LH5, LGA1: 1×10 9 CFU / head, daily oral administration for 4 weeks

[0190] - RGE: 6.15 mg / dead, daily oral administration for 4 weeks

[0191] No. Test Group - Weeks 1 ~ 0 Weeks 0 ~ 4 1 Normal Group (Control) Indication - 2 Muscle Loss Inducing Group (Dex) Administered substance daily for 4 weeks 3 Dex + RGE 4 Dex + RGE + LH5 5 Dex + RGE + LGA16 Dex + RGE + LH5 + LGA17 Dex + Positive Control

[0192]

[0193] 4-2: Effects of increasing muscle mass

[0194] After the administration of the sample was completed, mice in each test group were anesthetized and dissected, and the left and right gastrocnemius and quadriceps muscles were harvested and weighed. Subsequently, the weight of each measured tissue was divided by the body weight on the day the experiment ended to express the ratio of muscle tissue to body weight (Fig. 4).

[0195] Looking at Figure 4, it can be seen that the weight of the gastrocnemius and quadriceps muscles in the sarcopenia-induced group (Dex) was significantly reduced compared to the normal group (Control), whereas the weight of the gastrocnemius and quadriceps muscles in the rice germ extract and LGA1 administration group of the present invention (LGA1+RGE) was significantly increased compared to the sarcopenia-induced group.

[0196]

[0197] 4-3: Analysis of Expression Levels of Muscle Protein Degradation Factors in Muscle Tissue

[0198] Total RNA was extracted from muscle tissues (gastrocnemius and quadriceps femoris) collected from each experimental group using the RNeasy mini kit (Qiagen, Germany) according to the manufacturer's instructions. Then, cDNA was synthesized using the PrimeScript 1st Strand cDNA Synthesis Kit (TaKaRa, 6210A, Japan), and qRT-PCR was performed using Prime Q-Mastermix (Genet Bio, Korea) to measure the mRNA expression levels of Atrogin-1 and MuRF1 (Muscle RING-finger protein 1) (Figs. 5 and 6).

[0199] Looking at Figure 5, it can be seen that in the gastrocnemius muscle tissue, the mRNA expression of the muscle protein degradation factors MuRF1 and Atrogin-1 was significantly increased in the sarcopenia-induced group (Dex) compared to the normal group (Control), whereas the mRNA expression of MuRF1 and Atrogin-1 was significantly decreased in the rice germ extract and LGA1 administration group of the present invention (LGA1+RGE) compared to the sarcopenia-induced group.

[0200] In addition, looking at Figure 6, it can be seen that in the quadriceps femoris tissue, the mRNA expression of the muscle protein degradation factors MuRF1 and Atrogin-1 was significantly increased in the sarcopenia-induced group (Dex) compared to the normal group (Control), whereas the mRNA expression of MuRF1 and Atrogin-1 was significantly decreased in the rice germ extract and LGA1 administration group of the present invention (LGA1+RGE) compared to the sarcopenia-induced group.

[0201]

[0202] 4-4: Sintering

[0203] Based on the above results, it can be seen that the muscle mass increase effect of the rice germ extract and LGA1 administration group (LGA1+RGE) of the present invention is the most superior.

[0204]

[0205] Test Example 5: Effect of increasing muscle function and muscle mass in a dexamethasone-induced muscle atrophy / sarcopenia animal model (2)

[0206] We intended to confirm the effects of the LGA1 strain on the selected rice germ extract and LGA1 complex according to the dosage.

[0207] 5-1: Design of Animal Experiments

[0208] (1) Experimental animals: male mice C57BL / 6J mice, 10 mice / group, Initial weight: 21 ~ 23g / mice

[0209] (2) Experiment period: 5 weeks (Week 1: Adaptation period, Week 4: Injection and administration of experimental substance)

[0210] (3) Administered substances: Dexamethasone (Dex, muscle atrophy / sarcopenia-inducing substance), 50% ethanol extract of rice germ (RGE), probiotics (LGA1), feed (AIN-93G), saline solution (0.9% NaCl)

[0211] (4) Dosage and method of administration:

[0212] - Dexamethasone (Dex): 25 mg / kg, daily intraperitoneal administration for 4 weeks

[0213] - LGA1: 1×10 8 CFU / head or 1×10⁻⁶ 9 CFU / head, daily oral administration for 4 weeks

[0214] - RGE: 6.15 mg / dead, daily oral administration for 4 weeks

[0215] No. Test Group - Weeks 1 ~ 0 Weeks 0 ~ 4 1 Normal Group (Control) Indication - 2 Muscle Loss Inducing Group (Dex) Administered substance daily for 4 weeks 3 Dex + RGE 4 Dex + LGA1 (1 × 10⁻⁶ 8 CFU)5Dex + LGA1(1×10 9 CFU)6Dex + RGE + LGA1(1×10 8 CFU)7Dex + RGE + LGA1(1×10 9 CFU)

[0216]

[0217] 5-2: Effects of increasing muscle mass

[0218] After the administration of the sample was completed, mice in each test group were anesthetized and dissected, and the left and right gastrocnemius and quadriceps muscles were collected and weighed. Subsequently, the weight of each measured tissue was divided by the body weight on the day the experiment ended to express the ratio of muscle tissue to body weight (Fig. 7).

[0219] Referring to Fig. 7, it can be seen that the sarcopenia-induced group (Dex) showed a significant decrease in the weight of the gastrocnemius and quadriceps muscles compared to the normal group (Control), whereas all test groups of the present invention showed a significant increase in the weight of the gastrocnemius and quadriceps muscles compared to the sarcopenia-induced group. In particular, the groups administered with a combination of rice germ extract and LGA1 (LGA1+RGE (1×10⁻¹⁰) 8 ), LGA1+RGE(1×10 9 In the case of )), the weight of the gastrocnemius and quadriceps muscles was found to have increased significantly compared to the sarcopenia-induced group.

[0220]

[0221] 5-3: Analysis of Expression Levels of Muscle Protein Degradation Factors in Muscle Tissue

[0222] The mRNA expression levels of Atrogin-1 and MuRF1 were measured for muscle tissues (gastrocnemius and quadriceps femoris) collected from each experimental group (Figs. 8 and 9).

[0223] Referring to Fig. 8, in the gastrocnemius muscle tissue, the sarcopenia-induced group (Dex) showed a significant increase in mRNA expression of the muscle protein degradation factors MuRF1 and Atrogin-1 compared to the normal group (Control), whereas the group administered with the rice germ extract and LGA1 complex of the present invention (LGA1+RGE) (1×10⁻¹⁰ 9 It can be confirmed that the mRNA expression of MuRF1 was significantly reduced compared to the sarcopenia-induced group.

[0224] In addition, looking at Fig. 9, in the quadriceps femoris tissue, the sarcopenia-induced group (Dex) showed a significant increase in mRNA expression of the muscle protein degradation factors MuRF1 and Atrogin-1 compared to the normal group (Control), whereas the group administered with the rice germ extract and LGA1 complex of the present invention (LGA1+RGE) (1×10⁻¹⁰⁻¹⁰⁴ 9 It can be confirmed that the mRNA expression of Atrogin-1 and MuRF1 was significantly reduced compared to the sarcopenia-induced group.

[0225]

[0226] 5-4: Sintering

[0227] Based on the above results, the rice germ extract of the present invention and the LGA1 administration group (LGA1+RGE(1×10) 9 It can be seen that the muscle mass increase effect of )) is the most excellent.

[0228]

[0229] Test Example 6: Effect of increasing muscle function and muscle mass in an aging animal model

[0230] Rice germ extract and LGA1 complex (LGA1+RGE(1×10⁻¹⁰) finally selected using an aging animal model 9 We intended to verify the effect of )).

[0231] 6-1: Design of Animal Experiments

[0232] (1) Experimental animals: male mice C57BL / 6J mice, 10 mice / group, Initial weight: 23 ~ 26 g / young mice, 38 ~ 52 g / old mice

[0233] (2) Experiment period: 9 weeks (Week 1: Adaptation period, Week 8: Administration of experimental substance)

[0234] (3) Administered substances: 50% ethanol extract of rice germ (RGE), probiotics (LGA1), feed (AIN-93G), saline solution (0.9% NaCl)

[0235] (4) Dosage and method of administration:

[0236] - LGA1: 1×10 9 CFU / head, daily oral administration for 8 weeks

[0237] - RGE: 6.15 mg / dead, daily oral administration for 8 weeks

[0238] No. Test Group - Weeks 1 ~ 0 Weeks 0 ~ 8 1 Normal Group (Young Control) Indication - 2 Aging Control Group (Old Control) Administered substance daily for 8 weeks 3 Old + LGA1 4 Old + RGE 5 Old + RGE + LGA1

[0239]

[0240] 6-2: Effects of increasing muscle mass

[0241] After the administration of the sample was completed, mice in each test group were anesthetized and dissected, and the left and right gastrocnemius and quadriceps muscles were harvested and weighed. Subsequently, the weight of each measured tissue was divided by the body weight on the day the experiment ended to express the ratio of muscle tissue to body weight (Fig. 10).

[0242] Looking at Figure 10, it can be seen that the weight of the gastrocnemius and quadriceps muscles in the aging control group (Old Control) was significantly reduced compared to the normal group (Young Control), whereas the weight of the gastrocnemius and quadriceps muscles in the rice germ extract and LGA1 administration group of the present invention (RGE + LGA1) was significantly increased compared to the aging control group.

[0243]

[0244] 6-3: Analysis of Expression Levels of Muscle Protein-Related Biomarkers in Muscle Tissue

[0245] 6-3-1: Calf muscles

[0246] mRNA expression levels of muscle protein degradation factors (Myostatin, Atrogin-1, and MuRF1) and pro-inflammatory cytokines (IL1a, IL1b, IL6) in muscle tissue (gastrocnemius) collected from each experimental group were measured (Figs. 11 and 12).

[0247] Looking at Figure 11, it can be seen that the mRNA expression of muscle protein degradation factors Myostatin, MuRF1, and Atrogin-1 was significantly increased in the aging control group (Old Control) compared to the normal group (Young Control), whereas the mRNA expression of Myostatin, MuRF1, and Atrogin-1 was significantly decreased in the rice germ extract and LGA1 administration group of the present invention (RGE + LGA1) compared to the aging control group.

[0248] In addition, looking at Figure 12, it can be seen that the mRNA expression of the pro-inflammatory cytokines IL1a, IL1b, and IL6 was significantly increased in the aging control group (Old Control) compared to the normal group (Young Control), whereas the mRNA expression of IL1a and IL1b was significantly decreased in the rice germ extract and LGA1 administration group of the present invention (RGE + LGA1) compared to the aging control group.

[0249]

[0250] 6-3-2: Quadriceps

[0251] mRNA expression levels of muscle protein degradation factors (Atrogin-1 and MuRF1), pro-inflammatory cytokines (IL1a, IL1b, IL6, and TNF-α), and muscle protein synthesis and differentiation induction markers (IGF-1, Myogenin, MyoD) were measured in muscle tissue (quadriceps femoris) collected from each experimental group (Figs. 13, 14, and 15).

[0252] Looking at Figure 13, it can be seen that the mRNA expression of MuRF1, a muscle protein degradation factor, was significantly increased in the aging control group (Old Control) compared to the normal group (Young Control), whereas the mRNA expression of MuRF1 was significantly decreased in the rice germ extract and LGA1 administration group of the present invention (RGE + LGA1) compared to the aging control group.

[0253] In addition, looking at Figure 14, it can be seen that the mRNA expression of pro-inflammatory cytokines IL1a, IL1b, IL6, and TNF-α was significantly increased in the aging control group (Old Control) compared to the normal group (Young Control), whereas the mRNA expression of IL1a, IL1b, IL6, and TNF-α was significantly decreased in the rice germ extract and LGA1 administration group of the present invention (RGE + LGA1) compared to the aging control group.

[0254] In addition, looking at Figure 15, it can be seen that the mRNA expression of IGF-1, Myogenin, and MyoD, which are markers for muscle protein synthesis and differentiation induction, was significantly reduced in the aging control group (Old Control) compared to the normal group (Young Control), whereas the mRNA expression of IGF-1, Myogenin, and MyoD was significantly increased in the rice germ extract and LGA1 administration group of the present invention (RGE + LGA1) compared to the aging control group.

[0255]

[0256] conclusion

[0257] Catalytic muscle atrophy occurs due to a decrease in the diameter of muscle fibers caused by the breakdown of muscle cells' proteins [Gilson et al., 2007; Jones et al., 2010; Qin et al., 2013; Kim et al., 2015a]. In the present invention, as a result of catalytic muscle atrophy and / or muscle loss caused by a glucocorticoid (dexamethasone), a decrease in muscle mass was induced in the animal model of muscle atrophy and / or sarcopenia (DEX). Meanwhile, this decrease in muscle mass was effectively inhibited by the administration of the rice germ extract and LGA1 of the present invention. In addition, although a decrease in muscle mass was induced in the aging animal model (Old), this decrease in muscle mass was effectively inhibited by the administration of the rice germ extract and LGA1 of the present invention.

[0258] These results are considered to be direct evidence that the rice germ extract and LGA1 of the present invention exhibit a muscle-protective effect, and furthermore, an inhibitory effect on muscle atrophy and sarcopenia, as well as an effect on increasing muscle mass.

[0259]

[0260] Although the present invention has been described as a preferred embodiment mentioned above, various modifications and variations are possible without departing from the essence and scope of the invention. Furthermore, the appended claims include such modifications and variations that fall within the essence of the invention.

Claims

1. (i) One or more selected from the group consisting of a Lactobacillus gasseri strain, a lysate thereof, a culture solution thereof, an extract of the culture solution, a concentrate of the culture solution, and a dried product of the culture solution; and (ii) A food composition for the prevention or improvement of muscle diseases, comprising rice germ extract as an active ingredient.

2. In Paragraph 1, A food composition characterized by the above strain being a live or dead strain.

3. In Paragraph 1, A food composition characterized in that the above rice germ extract is extracted with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.

4. In Paragraph 3, A food composition characterized in that the above-mentioned mixed solvent is 20 to 80 volume% methanol, ethanol, butanol, or propanol.

5. In Paragraph 1, The above composition is a food composition characterized by reducing the expression of one or more selected from Myostatin, MuRF1, and Atrogin-1, which are factors related to muscle protein degradation.

6. In Paragraph 1, The above composition is a food composition characterized by increasing muscle mass or inhibiting muscle loss.

7. In Paragraph 1, A food composition characterized in that the above-mentioned muscle disease is caused by aging, decreased muscle function, muscle loss, muscle atrophy, muscle wasting, muscle degeneration, disused muscle, or muscle damage.

8. In Paragraph 1, A food composition characterized in that the above-mentioned muscle disease is caused by glucocorticoid side effects.

9. In Paragraph 8, A food composition characterized by the fact that the above-mentioned glucocorticoid side effects are caused by glucocorticoid treatment or an increase in the amount of glucocorticoids in the individual.

10. In Paragraph 8, A food composition characterized in that the above-mentioned glucocorticoid is one or more selected from cortisol, hydrocortin, cortisone, prednisolone, methylprednisolone, triamcinolone, triamcinolone acetonide, paramethasone, dexamethasone, betamethasone, hexastrol, methimazole, fluocinonide, fluocinolone acetonide, fluorometholone, beclomethasone dipropionate, estriol, diflorasone diacetate, diflucortolone valerate, and difluprednate.

11. In Paragraph 1, A food composition characterized by the above-mentioned muscle disease being one or more selected from sarcopenia, muscular atrophy, muscular dystrophy, myopathy, myasthenia, cachexia, muscular injury, myotonia, atony, hypotonia, muscular weakness, myoneural conductive disease, diabetic amyotrophy, amyotrophic lateral sclerosis (ALS), and degenerative muscle diseases.

12. (i) One or more selected from the group consisting of a Lactobacillus gasseri strain, a lysate thereof, a culture solution thereof, an extract of the culture solution, a concentrate of the culture solution, and a dried product of the culture solution; and (ii) A food composition for muscle growth or muscle loss inhibition comprising rice germ extract as an active ingredient.

13. (i) One or more selected from the group consisting of a Lactobacillus gasseri strain, a lysate thereof, a culture solution thereof, an extract of the culture solution, a concentrate of the culture solution, and a dried product of the culture solution; and (ii) A feed composition for the prevention or improvement of muscle diseases, comprising rice germ extract as an active ingredient.

14. (i) One or more selected from the group consisting of a Lactobacillus gasseri strain, a lysate thereof, a culture solution thereof, an extract of the culture solution, a concentrate of the culture solution, and a dried product of the culture solution; and (ii) A pharmaceutical composition for the prevention or treatment of muscle diseases, comprising rice germ extract as an active ingredient.

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