阅读说明：本技术 含有草绿盐角草提取物的用于预防或治疗肌肉减少症的药物组合物 (Pharmaceutical composition for preventing or treating sarcopenia comprising extract of Salicornia herbacea ) 是由 金贤洙 于 2019-07-19 设计创作，主要内容包括：根据本发明的一实施例,提供一种含有草绿盐角草提取物作为活性成分的用于预防或治疗肌肉减少症的药物组合物,以及含有草绿盐角草提取物作为活性成分的用于预防或改善肌肉减少症的食品组合物。(According to an embodiment of the present invention, there are provided a pharmaceutical composition for preventing or treating sarcopenia comprising an extract of turfgrass as an active ingredient, and a food composition for preventing or improving sarcopenia comprising an extract of turfgrass as an active ingredient.)

1. A pharmaceutical composition for preventing or treating sarcopenia,

the method comprises the following steps:

the extract of Salicornia herbacea is used as active ingredient.

2. The pharmaceutical composition for preventing or treating sarcopenia as claimed in claim 1, wherein the turfgrass salt horn extract comprises laminarin or fucoidan.

3. The pharmaceutical composition for preventing or treating sarcopenia according to claim 1, wherein the expression of myostatin mRNA or protein is inhibited.

4. The pharmaceutical composition for preventing or treating sarcopenia according to claim 3, wherein bleomycin causes the expression of myostatin mRNA or protein.

5. The pharmaceutical composition for preventing or treating sarcopenia according to claim 3, wherein UV causes the expression of myostatin mRNA or protein.

6. The pharmaceutical composition for preventing or treating sarcopenia according to claim 1, wherein the expression of MURF1(Muscle RING-finger protein-1) mRNA or protein is inhibited.

7. A food composition for preventing or improving sarcopenia is characterized in that,

the method comprises the following steps:

the extract of Salicornia herbacea is used as active ingredient.

Technical Field

The present invention relates to a pharmaceutical composition for preventing or treating sarcopenia, comprising an extract of salicornia herbacea as an active ingredient.

Background

The concept of sarcopenia began with the "sarcopenia" proposed by Irwin Rosenberg in 1989, which was derived from greek, being a combination of "sarco" meaning muscle and "penia" meaning reduction. Sarcopenia is associated with aging and refers to a reduction in muscle strength due to a reduction in muscle mass. Here, "muscle (muscle)" refers to skeletal muscle (skeletal muscle), and is not related to smooth muscle (smooth muscle). That is, sarcopenia mainly refers to loss of skeletal muscle mass distributed in four limbs, which is distinguished from muscle atrophy (primary muscle disease) caused by acute diseases such as cachexia (advanced malignant tumor, a significant muscle loss state), influenza, and the like, or primary muscle disease.

With the rapid increase in age groups of older people over 65 years of age, the prevalence of osteoporosis and sarcopenia has also increased rapidly. It is known that a gradual decrease in muscle mass occurs in the 40 year old population until the 70 year old population decreases 8% every 10 years, after which even faster rates of decrease, up to 15% every 10 years, can occur. Many follow-up studies have shown that the physiological changes occurring in the elderly are diverse, and generally, muscle mass and bone density decrease with age.

In addition, there are three main treatments for sarcopenia. First, move. Exercise has been reported to improve the protein synthesis capacity of skeletal muscle in a short period of time, and to increase the muscle strength or activity of the elderly. But this is not suitable for long-term treatment. Second, as a medication, Testosterone (Testosterone) or anabolic steroids (anabolic steroids) can be used, but this leads to virilization in women, while men experience side effects such as prostate symptoms (prostates). Other approved prescriptions include Dehydroepiandrosterone (DHEA) and growth hormone, and studies have shown that DHEA can be used as a therapeutic approach in areas including Selective Androgen Receptor Modulators (SARMs). Furthermore, diet is also considered a treatment, but nutritional assessment indicates that malnutrition or modern dietary habits are not suitable for maintaining adequate total body weight.

Myostatin (myostatin) is a polypeptide growth factor belonging to the TGF- β superfamily. TGF- β has a large number of isoforms (isoforms) known to be associated with cell proliferation (proliferation), apoptosis (apoptosis), differentiation, bone formation and maintenance (Massague & Chen, 2000). Among them, myostatin belongs to Growth Differentiation Factor (GDF) 8, which participates in growth and development of tissues and plays a role by activating Smad signaling system. In addition, it has been reported that the p21 gene inhibits the cell cycle and the proliferation of precursor cells, thereby affecting the formation and regeneration of bone. Myostatin is produced mainly in skeletal muscle cells, causing muscle loss and sarcopenia in an autocrine manner, and is thought to inhibit protein synthesis and cell proliferation in myoblasts by inhibiting the expression of IGF-1 or follistatin associated with muscle hypertrophy.

In addition, the turfgrass grass grows to about 10 to 30cm high with the branches facing each other. The stem is initially dark green or yellow and then turns red in autumn and is as thick and fleshy as a small cactus. Later the leaves degenerate almost invisible and have small film-like scales. Three flowers bloom in the upper segment of the branch in august to september. Plump pistil, 1-2 stamens and 2 flower stipes. The fruit is pomegranate, which is enveloped in the peel and has black seeds. It is an annual herbaceous plant that grows in groups near tidal beaches where seawater flows into inland salt ponds. In the korean medical field, it is considered to eliminate toxins accumulated in the body and constipation and to have excellent therapeutic effects on various incurable diseases such as cancer, hysteromyoma, sinusitis, hypertension, hypotension, back pain, diabetes, bronchial asthma, hypothyroidism, hyperthyroidism, skin diseases, arthritis, etc.

Disclosure of Invention

Technical problem to be solved

Under such circumstances, the present inventors have made an effort to find a substance capable of treating sarcopenia by inhibiting the expression of myostatin, which causes muscle loss and sarcopenia, and found that a component of turfgrass salt can be used for preventing or treating sarcopenia by inhibiting the production of myostatin protein and the increase in mRNA expression, thereby completing the present invention.

The present invention aims to provide a pharmaceutical composition for preventing or treating sarcopenia, comprising an extract of salicornia herbacea as an active ingredient.

Another object of the present invention relates to a food composition for preventing or improving sarcopenia, comprising the extract of salicornia herbacea as an active ingredient.

However, the problems to be solved by the present invention are not limited to the above-mentioned problems, and other problems not mentioned can be clearly understood by those skilled in the art from the following description.

Means for solving the problems

According to an embodiment of the present invention, there is provided a pharmaceutical composition for preventing or treating sarcopenia, comprising an extract of salicornia herbacea as an active ingredient.

According to one aspect, the turfgrass salt horn extract comprises laminarin (laminarin) or fucoidan (fucoidan).

According to one aspect, the pharmaceutical composition may inhibit expression of myostatin (myostatin) mRNA or protein.

According to one side, bleomycin (bleomycin) can cause expression of the myostatin mRNA or protein.

According to one side, UV may cause the expression of myostatin mRNA or protein.

According to one aspect, the pharmaceutical composition can inhibit the expression of MURF1(Muscle RING-finger protein-1) mRNA or protein.

According to another embodiment of the present invention, there may be provided a food composition for preventing or improving sarcopenia, comprising an extract of salicornia herbacea as an active ingredient.

ADVANTAGEOUS EFFECTS OF INVENTION

The pharmaceutical composition for preventing or treating sarcopenia, which contains the turfgrass alternifolia extract as an active ingredient, of the present invention inhibits the production of myostatin protein and the increase of mRNA expression, which directly affect muscle loss and sarcopenia, and can play a more thorough role in preventing or treating sarcopenia.

However, the effects of the present invention are not limited to the above-described effects, and should be understood to include all effects that can be derived from the detailed description of the present invention or the configuration of the present invention described in the claims.

Drawings

FIG. 1 is a graph showing the effect of inhibiting the expression of myostatin by UV when laminarin and fucoidan are used for treatment.

FIG. 2 is a graph showing the effect of bleomycin-induced inhibition of myostatin expression when treated with laminarin and fucoidan.

FIG. 3 is a graph showing the effect of UV-induced inhibition of the expression of MURF1(Muscle RING-finger protein-1) protein in the treatment with laminarin and fucoidan.

Detailed Description

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. Various modifications may be made to the following examples, and thus the scope of the claims of the present application is not limited or restricted by the following examples. All modifications, equivalents and alternatives to all embodiments are intended to be included within the scope of the claims.

The terminology used in the embodiments is for the purpose of describing particular embodiments only and is not intended to be limiting of the embodiments. Where not otherwise stated in the context, singular expressions include plural meanings. In the present specification, the terms "comprising" or "having" are used to express that there are the features, numerals, steps, operations, constituent elements, components or combinations thereof described in the specification, and do not exclude that there are one or more other features, numerals, steps, operations, constituent elements, components or combinations thereof, or additional functions.

All terms used herein, including technical or scientific terms, have the ordinary meaning as understood by one of ordinary skill in the art without further definition. The terms commonly used in the art, which are commonly defined as dictionary definitions, should be understood as meanings consistent with the common contents of the related art, and should not be over-idealized or formally construed without explicit mention in this application.

In the description with reference to the drawings, the same constituent elements are denoted by the same reference numerals regardless of the reference numerals, and redundant description thereof will be omitted. In describing the embodiments, when it is judged that a detailed description of the related well-known art may unnecessarily obscure the embodiments, a detailed description thereof will be omitted.

According to an embodiment of the present invention, there is provided a pharmaceutical composition for preventing or treating sarcopenia, comprising an extract of salicornia herbacea as an active ingredient.

In the present invention, the term "Salicornia herbacea extract (Salicornia herbacea)" is a medicinal name of Korean medicine, and refers to halophytes (halophytes) belonging to the family Chenopodiaceae of the order Dianthus.

In the present invention, the term "extract" includes an extract obtained by extracting a plant, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, a preparation or a purified product of the extract or a mixture thereof, an extract itself, and extracts of all preparations that can be formed using the extract. The turfgrass salt carex extract of the present invention can be preferably prepared and used in the form of dry powder after extraction. In addition, the turfgrass salt carex extract may be extracted from natural, hybrid or variety plants of green tea, and may be extracted from plant tissue cultures, and includes extracts extracted from parts of leaves, stems, roots, flowers and fruits, etc.

The Salicornia herbacea extract may include laminarin (laminarin) or fucoidan (fucoidan).

In the present invention, the term "laminarin" refers to a carbohydrate contained in the cell wall of brown algae, and is a hypotonic polysaccharide corresponding to starch of higher plants.

In the present invention, the term "fucoidan (fucoidan)" refers to a viscous polysaccharide contained in brown algae, which is a substance that binds basic sugar called Fucose (Fucose) and a sulfate group.

In the present invention, the term "prevention" refers to any action that inhibits or delays the onset of sarcopenia by administering a composition.

In the present invention, the term "treatment" refers to the amelioration or beneficial alteration of all behaviors of sarcopenia symptoms by administration of a composition.

Laminarin and fucoidan included in the pharmaceutical composition of the present invention can inhibit myostatin (myostatin) mRNA or protein expression and MURF1(Muscle RING-finger protein-1) protein expression, and particularly can reduce an increase in myostatin expression caused by bleomycin treatment or UV stimulation (see fig. 1 to 3). The bleomycin (bleomycin) is an antitumor antibiotic which is used as an effective anticancer agent for squamous cell carcinoma or malignant lymphoma, etc., or is called an aging factor.

The pharmaceutical composition of the present invention can be prepared by a method known in the field of medicine to be used as a medicament, and mixed with a pharmaceutically acceptable carrier, excipient, diluent, stabilizer, preservative, etc., to be prepared and used in the form of powder, granules, tablets, capsules, injection, etc. Also, the composition may be prepared as a sustained-release preparation such that the release of the active ingredient (including a matrix for sustained-release purposes in addition to the active ingredient) occurs slowly.

The pharmaceutically acceptable carrier may further include, for example, a carrier for oral administration or a carrier for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, and the like. Also, it may include various drug delivery substances for oral peptide formulation. In addition, the carrier for parenteral administration may include water, suitable oil, saline, aqueous glucose, ethylene glycol, etc., and may further include a stabilizer and a preservative. Suitable stabilizers include antioxidants such as sodium bisulfite, sodium sulfite, ascorbic acid, or the like. Suitable preservatives may be benzalkonium chloride, methyl or propyl p-hydroxybenzoates and chlorobutanol. In addition to the above ingredients, the pharmaceutical composition of the present invention may further include lubricating agents, wetting agents, sweetening agents, flavoring agents, emulsifying agents, suspending agents and the like.

The diluent may be a non-aqueous solvent such as propylene glycol, polyethylene glycol, olive oil, vegetable oil such as peanut oil, or saline (preferably, 0.8% saline), or an aqueous solvent such as water containing a buffer medium (preferably, 0.05M phosphate buffer), but is not limited thereto.

The excipient may be starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, anhydrous skim milk, glycerol, propylene, glycol, water, ethanol, etc., but is not limited thereto.

The stabilizer may be a carbohydrate such as sorbitol, mannitol, starch, sucrose, dextran, glutamic acid, or glucose, or a protein such as milk powder, animal, plant, or microbial protein such as serum albumin or casein, but is not limited thereto.

The preservative may be thimerosal, merthiolate (mercuritate), gentamicin, neomycin, nystatin, amphotericin B, tetracycline, penicillin, streptomycin, and polymyxin B, but is not limited thereto.

The pharmaceutical compositions of the present invention may be administered to mammals, including humans, by any method, such as oral administration or parenteral administration. The parenteral administration method may be intravenous injection, intramuscular injection, intraarterial administration, intramedullary administration, intrathecal administration, transdermal administration, subcutaneous administration, intraperitoneal administration, intranasal administration, intestinal administration, topical administration, sublingual administration or rectal administration, but is not limited thereto.

The pharmaceutical composition of the present invention may be formulated for oral administration or parenteral administration according to the administration route as described above.

The total effective amount of the pharmaceutical composition of the present invention may be administered to a patient in a single dose (single dose) and may be administered by a split treatment regimen of multiple dose (multiple dose) long-term administration. The pharmaceutical composition of the present invention may vary the content of the active ingredient according to the severity of the disease. This can be determined in consideration of various factors such as formulation method, administration route and treatment frequency, and age, body weight, health condition, disease symptoms, administration time and method of the patient, etc. In view of these points, one skilled in the art will be able to determine an appropriate effective dose of the composition of the present invention. The pharmaceutical composition according to the present invention is not particularly limited in its dosage form, administration route and administration method as long as it exhibits the effects of the present invention.

According to another embodiment of the present invention, there is provided a food composition for preventing or improving sarcopenia, comprising an extract of salicornia herbacea as an active ingredient.

In the present invention, the term "improvement" refers to a parameter related to the treatment situation, for example, to all actions that at least reduce the extent of symptoms.

Further, when the food composition of the present invention is used as a food additive, the composition may be added as it is or may be used together with other foods or food ingredients, and may be suitably used according to a conventional method. Generally, when preparing a food or beverage, the composition of the present invention is added in an amount of 15% by weight or less, preferably 10% by weight or less, based on the raw materials. However, if it is ingested for a long period of time for health and hygiene or for the purpose of health control, it may be lower than the above range and there is no problem in safety, so the amount of active ingredient used may be higher than the above range.

The kind of the food is not particularly limited. Examples of foods to which the substance can be added include meats, sausages, breads, chocolates, candies, snacks, cookies, pizza, ramen, other noodles, chewing gums, dairy products including ice cream, various soups, beverages, teas, drinks, alcoholic beverages, vitamin complexes, and the like, and include all health foods in a general sense.

Hereinafter, the present invention will be described in more detail by way of examples. The following examples are merely illustrative of the present invention and the scope of the present invention is not limited thereto.

Example 1 verification of inhibitory Effect against sarcopenia caused by UV irradiation

C2C12 muscle precursor cells (ATCC, US) were cultured in DMEM containing 10% FBS. At this time, 3x10⁵Cells were seeded in a 60-pie culture dish. The next day after sowing, laminarin and fucoidan were treated separately and left for 1 hour. After 1 hour, growth medium (growth media) (10% FBS DMEM) was removed and washed with PBS. After removal of PBS, the plate cover was removed from the UV cross-linker (UVP CL-1000) and the process was carried out at 3J/m²UV irradiation (0 days). After 24 hours of culture in a CO2 Incubator (Incubator), the growth medium was removed in the same manner and PBS was washed, followed by 3J/m²UV irradiation (1 day).

The next day, harvesting was performed at the same time (2 days) and western blotting was used to detect changes in expression of myostatin and MURF1 proteins as target proteins in cell lysates that modulate muscle mass. Comparative analyses were performed using anti-GDF 8(Genetex, GTX32624) as myostatin, anti-MURF 1 antibody (Abcam, ab172479) as MURF1, and β -actin antibody (ENOGene E12-041-4) as a protein loading control.

RNA was isolated using RNeasy-Mini kit (Qiagen, US), and after cDNA was synthesized using AMV Reverse Transcriptase (Promega, US), the degree of myostatin mRNA expression was confirmed by cDNA using PCR. The PCR conditions were performed in the following order: initial denaturation at 95 ℃ for 5 minutes, i) denaturation at 95 ℃ for 5 seconds, ii) annealing at 62.8 ℃ for 10 seconds, and iii) final extension at 72 ℃ for 10 minutes. The following primers were used to detect mRNA expression.

[ Table 1]

As a result, as shown in fig. 1 to 3, it was confirmed that the expression of myostatin and MURF1 increased by UV irradiation was decreased with the treatment of laminarin and fucoidan.

Example 2 verification of inhibitory Effect against sarcopenia caused by bleomycin

C2C12 muscle precursor cells (ATCC, US) were cultured in DMEM containing 10% FBS. At this time, 3x10⁵Cells were seeded in a 60-cake dish, and after seeding, bleomycin (bleomycin) was treated and left for 1 hour.

Next, laminarin and fucoidan were treated separately and left for 1 hour, and then growth medium (growth media) (10% FBS DMEM) was removed and washed with PBS. After washing, western blotting was used to detect changes in expression of myostatin and MURF1 proteins as target proteins in cell lysates that modulate muscle mass. A comparative analysis was performed using anti-GDF 8(Genetex, GTX32624) as myostatin and β -actin antibody (ENOGene E12-041-4) as protein loading controls.

RNA was isolated using RNeasy-Mini kit (Qiagen, US), and after cDNA was synthesized using AMV Reverse Transcriptase (Promega, US), the degree of myostatin mRNA expression was confirmed by cDNA using PCR. The PCR conditions were performed in the following order: initial denaturation at 95 ℃ for 5 minutes, i) denaturation at 95 ℃ for 5 seconds, ii) annealing at 62.8 ℃ for 10 seconds, and iii) final extension at 72 ℃ for 10 minutes. The same primers as described in example 1 were used to detect mRNA expression.

As a result, as shown in fig. 1 and 2, it was confirmed that the expression of myostatin increased by bleomycin was decreased by the treatment of laminarin and fucoidan.

From the results of the examples, it can be seen that laminarin and fucoidan components in the carex niveus extract can inhibit the expression of the indicative proteins myostatin and MURF1 associated with muscle mass regulation, thereby effectively preventing or treating sarcopenia.

In summary, the embodiments have been described with respect to a limited number of embodiments and drawings, and those skilled in the art will be able to make numerous modifications and variations to the above description. For example, the techniques described may be performed in a different order from the methods described, or the components described may be combined or combined in a different form from the methods described, or may be replaced or substituted with other components or equivalents, thereby obtaining the same effects.

Accordingly, other embodiments, examples, and equivalents to the scope of the claims are all within the scope of the claims.