Composition for improving mitochondrial activity

Abstract

To provide a new material derived from a natural product effective for mitochondrial activation or the like.SOLUTION: Provided is a food composition or a pharmaceutical composition containing any of chlorogenic acid, for improving mitochondrial activity. The chlorogenic acids are preferably any selected from a group consisting of 3-o-caffeoylquinic acid, 5-o-caffeoylquinic acid, and isoorientin. The composition is useful for treatment of any selected from a group consisting of diseases characterized by morphological maturation failure of astrocytes, including Alexander disease; non-disease metabolic disorders including deterioration of sugar and lipid metabolism associated with aging; metabolic diseases including diabetes, high blood pressure, dyslipidemia, fatty liver, metabolic syndrome and obesity; and sarcopenia caused by aging or the metabolic disorders.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a composition for improving mitochondrial activity, which comprises an active ingredient derived from sugarcane tops. [Background technology]

[0002] Mitochondria play a central role in energy metabolism, and their activity is essential for the activity of tissues with high energy demands, such as the brain, liver, and muscles. Therefore, a decrease in mitochondrial activity can lead to the onset of lifestyle-related diseases and aging-related diseases.

[0003] It is known that mitochondrial activity depends on the control of metabolic enzyme gene expression by nuclear transcription factors. One of the energy metabolism control factors is the nuclear receptor coactivator PGC-1α (peroxisome proliferator activated receptor γ coactivator-1α), which is considered to be an important target for mitochondria that promotes energy metabolism (Non-Patent Document 1).

[0004] Skeletal muscle is one of the in vivo tissues in which PGC-1α and mitochondrial energy metabolism are important for its activity. When adapting to load exercise, mitochondria are activated in muscle cells via increased expression of PGC-1α, which improves the production of ATP, which is an energy source for activities such as contraction. It is also known that in order to take in glucose necessary for ATP production from outside the cell, the migration of GLUT4 (glucose transporter 4), a glucose transporter, to the cell surface is promoted, and the uptake of glucose in the blood into the cell is promoted. It is also known that PGC-1α in skeletal muscle increases in a cold environment, and therefore is also involved in the control of heat production. In this way, the activation of mitochondria activates energy consumption, and further activates the metabolism of sugars and lipids, which are energy sources (Non-Patent Document 2).

[0005] Mitochondrial activity is also important in liver metabolism. Disturbances in hepatocyte metabolism induce lipid accumulation in cells, which is believed to be due to a decrease in the catabolism of long-chain fatty acids via mitochondrial β-oxidation. Increased expression of PGC-1α in hepatocytes increases the level of CPT1 (Carnitine palmitoyltransferase I), the rate-limiting enzyme of mitochondrial β-oxidation, promoting mitochondrial fatty acid oxidation and reducing lipid accumulation (Non-Patent Document 3).

[0006] In addition, research into mitochondrial biogenesis and energy production in brain neurons has revealed that PGC-1α expression is closely related to neuronal function. For example, in mice with PGC-1α knockout, degeneration and reduction of neurons resembling neurodegenerative diseases have been observed (Non-Patent Document 4). Furthermore, it has been suggested recently that activation of PGC-1α and the associated shift to mitochondrial biogenesis and oxidative metabolism are crucial for the morphological maturation of brain astrocytes (Non-Patent Document 5).

[0007] As described above, since it is predicted that promoting the expression of PGC-1α and improving mitochondrial activity are highly effective in improving energy metabolism in the living body, for example, a mitochondrial function activator containing a benzimidazole derivative as an active ingredient (Patent Document 1), a mitochondrial function decline inhibitor containing catechins as an active ingredient (Patent Document 2), a mitochondrial function improver containing sphingomyelin as an active ingredient (Patent Document 3), etc. are known as prior art related to promoting PGC-1α expression. In addition, a neurotransmission improver by promoting PGC-1α production containing helipyrone A as an active ingredient (Patent Document 4) is known. In Patent Document 1, it is described that when a target compound is added to a culture system of L6 myoblasts and hPGC1 / L6 cells stably expressing hPGC-1, the transcription activation effect of hPGC-1 is confirmed, and when PGC-1 expression increases, the transcription of the human mitochondrial transcription factor A (hmtTFA) gene is promoted downstream, and when a target compound is added to a culture system of a hmtTFA promoter reporter vector, a cell line stably expressing hmtTFALuc, and an hmtTFA / L6 cell, the transcription activation effect of hmtTFA is confirmed. Patent Document 2 describes that in a group of SAM-P1 male mice (senescence-accelerated model mice) that were given a diet containing catechin in combination with exercise, the expression of COX2-4 and HSP72 genes involved in the electron transport system and mitochondrial differentiation and proliferation associated with aging was significantly higher than that of the control group. Patent Document 3 describes that mice that ingested a test diet containing sphingomyelin had significantly higher PGC-1α gene expression in the gastrocnemius muscle than those that ingested a control diet, and that mice that ingested a test diet containing sphingomyelin had significantly higher oxygen consumption and lipid burning than those that ingested a control diet. Patent Document 4 describes that the addition of Helipyron A to primary neurons obtained from rat fetuses confirmed an increase in the gene expression of PGC1α in neurons.

[0008] The inventors have invented a method for obtaining a composition containing 3-o-caffeoylquinic acid (hereinafter, 3CQA), 5-o-caffeoylquinic acid (hereinafter, 5CQA), 3-o-feruloylquinic acid (hereinafter, 3FQA), and isoorientin (hereinafter, ISO) from sugarcane tops, and have further discovered that this composition has the effect of promoting ATP production in nerve cells and astrocyte development (Patent Document 5, Non-Patent Document 6).

[0009] 3CQA and 5CQA are known to activate lipid metabolism and, in particular, have the effects of preventing and improving obesity, suppressing blood glucose rise or lowering blood glucose, preventing and improving hyperleptinemia, and preventing and improving hyperinsulinemia (Patent Document 6). [Prior art documents] [Patent documents]

[0010] [Patent Document 1] JP 2004-67629 A [Patent Document 2] HYPERLINK "javascript:void(0)" Japanese Patent Application Publication No. 2008-63318 [Patent Document 3] JP 2011-157328 A [Patent Document 4] JP 2017-43566 A [Patent Document 5] International Publication WO2021 / 167012 [Patent Document 6] HYPERLINK "javascript:void(0)" Japanese Patent Application Publication No. 2003-034636 [Non-patent literature]

[0011] [Non-Patent Document 1] Wu et al., Cell 1999, 98, 115-124 [Non-Patent Document 2] Puigsever et al., Cell 1998, 92, 829-839 [Non-Patent Document 3] Kim et al., Nutr Metab(Lond) 2015, 12, 33 [Non-Patent Document 4] Sun et al., Neuroscience 2020, 440, 39-47 [Non-Patent Document 5] Zehnder et al., Cell Reports 2021, 35, 108952 [Non-Patent Document 6] Iwata et al., Front Cell Dev Biol 2020, 8, 573487 Summary of the Invention [Problem to be solved by the invention]

[0012] On the other hand, at present, there is no mitochondrial activator or PGC-1α expression promoter that uses an active ingredient derived from sugarcane tops. [Means for solving the problem]

[0013] The present invention provides the following: [1] Chlorogenic acids represented by the following formula: [ka] (In the formula, R 1 , R 2 , and R 3 are each independently H, a caffeoyl group, or a feruloyl group, and an active ingredient selected from the group consisting of luteolin and its glycosides, said food composition or pharmaceutical composition being used to improve mitochondrial activity. [2] The composition described in 1, wherein the active ingredient is any one selected from the group consisting of 3-o-caffeoylquinic acid, 5-o-caffeoylquinic acid, and isoorientin. [3] The composition described in 1 or 2, wherein the active ingredient is contained as an extract of sugarcane tops. [4] A food composition or pharmaceutical composition for treating a disease or condition that can be improved through improving mitochondrial activity or promoting the expression of PGC-1α, comprising an active ingredient as defined in 1. [5] The composition of claim 4, wherein the active ingredient is contained as a sugarcane top extract. [6] A food composition or pharmaceutical composition comprising the active ingredient defined in 1 for any one selected from the group consisting of: non-disease metabolic disorders including age-related decline in glucose and lipid metabolism; metabolic diseases including diabetes, hypertension, dyslipidemia, fatty liver, metabolic syndrome, and obesity; and muscle loss (sarcopenia) caused by age or the above-mentioned metabolic disorders; as well as maintenance and improvement of muscle mass or muscle strength, maintenance and improvement of muscle endurance, and maintenance and improvement of walking ability; and diseases characterized by morphological insufficiency of maturation of astrocytes, including Alexander disease. [7] The composition described in 6, wherein the active ingredient is contained as a sugarcane top extract. [8] A method for producing a food material or pharmaceutical material for improving mitochondrial activity, comprising any one selected from the group consisting of 3-o-caffeoylquinic acid, 5-o-caffeoylquinic acid, and isoorientin, the method comprising the steps of: A process for obtaining a fraction containing any one selected from the group consisting of 3-o-caffeoylquinic acid, 5-o-caffeoylquinic acid, and isoorientin from sugarcane tops using an aqueous solvent. Effect of the Invention

[0014] Using active ingredients derived from natural products, compositions for improving mitochondrial activity, compositions for promoting the expression of PGC-1α, and compositions for treating diseases or conditions that can be improved through improving mitochondrial activity or promoting the expression of PGC-1α can be provided.

[0015] Using active ingredients derived from natural products, compositions can be provided for the treatment of metabolic diseases including non-disease metabolic disorders, including age-related decline in sugar and lipid metabolism; diabetes, hypertension, dyslipidemia, fatty liver, metabolic syndrome, and obesity.

[0016] Using an active ingredient derived from a natural product, a composition can be provided for any one selected from the group consisting of maintaining and improving muscle mass or muscle strength, maintaining and improving muscle endurance, and maintaining and improving walking ability.

[0017] Active ingredients derived from natural products can be used to provide compositions for the treatment of diseases characterized by impaired morphological maturation of astrocytes, including Alexander's disease. [Brief description of the drawings]

[0018] [Figure 1] Mitochondrial activity in neural stem cell-derived astrocytes. Top: 24 hrs treatment, (3) 3CQA + 5CQA and (5) 5CQA + ISO treatments showed significant increase (*p value < 0.05). Middle: 48 hrs treatment, (8) 3CQA+5CQA+ISO and All mixed treatments showed increasing tendency (p value < 0.1). Bottom: 72 hrs treatment, (5) 5CQA + ISO, All mixed and STEE treatments showed significant increase (*p value < 0.05), (10) 5CQA+3FQA+ISO treatment showed increasing tendency (p value < 0.1). [Diagram 2] PGC-1α expression in neural stem cell-derived astrocytes *p < 0.05, ****p < 0.0001 Compared to Control cells A significant increase in PGC-1α expression (p<0.0001) was confirmed in (5)5CQA + ISO, (8)3CQA + 5CQA + ISO, the four-mixture (All mixed), and stem cell extract (STEE). [Diagram 3]Mitochondrial activity in myotubes *p < 0.05 Compared to control cells Rh123 fluorescence intensity was significantly increased in treated groups (3), (8), All mixed, and STEE. Fluorescence intensity also tended to increase in treated group (5). [Figure 4] PGC-1α mRNA and TFAM mRNA expression in myotubes *p < 0.05, ***p < 0.001 Compared to Control cells PGC-1α mRNA expression was significantly increased by 6 hours of treatment with 50 μg / mL STEE (p < 0.05, 1.4-fold). It was also significantly increased by 6 hours of treatment with the compound mixture (Mix) (p < 0.05, 1.4-fold), and the expression level was also significantly increased after 24 hours of treatment with the same sample (p < 0.05, 1.5-fold). TFAM mRNA expression showed an increasing tendency by 6 hours of treatment with 50 μg / mL STEE (p = 0.082, 1.25-fold), and the expression level was also significantly increased after 24 hours of treatment with the same sample (p < 0.05, 1.5-fold). In addition, TFAM mRNA expression was significantly increased by 6 hours of treatment with Mix (p < 0.05, approximately 1.25-fold), and the expression level was also significantly increased after 24 hours of treatment with the same sample (p < 0.001, approximately 1.75-fold). [Diagram 5] Mitochondrial activity in hepatocytes Although not statistically significant, Rh123 fluorescence intensity increased by approximately 120% in STEE after 6 hours of treatment, and by approximately 120% in STEE after 24 hours of treatment in treatment groups (7), (8), and STEE. [Figure 6]PGC-1α mRNA and TFAM mRNA expression in hepatocytes *p < 0.05, **p < 0. 01 Compared to Control cells PGC-1α mRNA expression was significantly increased by 24 hours of treatment with 30μg / mL and 50μg / mL STEE (p < 0.01, approximately 1.4-fold), and by 24 hours of treatment with the compound mixture (Mix) (p < 0.01, approximately 1.4-fold). TFAM mRNA expression was significantly increased by 24 hours of treatment with 30μg / mL and 50μg / mL STEE (p < 0.05, approximately 1.2-fold), and by 24 hours of treatment with Mix (p < 0.05, approximately 1.2-fold). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] The present invention relates to a food composition or a pharmaceutical composition comprising an active ingredient selected from the group consisting of chlorogenic acids, and luteolin and its glycosides.

[0020] [Active ingredients, functional ingredients] The composition of the present invention contains, as an active ingredient, any one selected from the group consisting of chlorogenic acids, luteolin and its glycosides. The active ingredient may also be called a functional ingredient or a component associated with functionality.

[0021] <Chlorogenic acids> In the present invention, chlorogenic acids refer to compounds represented by the following formula:

[0022] [ka]

[0023] In the formula, R 1 , R 2 , and R 3 are each independently H, a caffeoyl group, or a feruloyl group.

[0024] Specifically, the chlorogenic acids include 3-o-caffeoylquinic acid, 4-o-caffeoylquinic acid, 5-o-caffeoylquinic acid, 3-o-feruloylquinic acid, 4-o-feruloylquinic acid, 5-o-feruloylquinic acid, 3,4-di-o-caffeoylquinic acid, 3,5-di-o-caffeoylquinic acid, and 4,5-di-o-caffeoylquinic acid.

[0025] In one embodiment, the composition contains 3-o-caffeoylquinic acid (R 1 = caffeoyl group, R 2 =R 3 =H), 5-o-caffeoylquinic acid (R 3 = caffeoyl group, R 1 =R 2 =H), and 3-o-feruloylquinic acid (R 1 = phenyl group, R 2 =R 3 =H).

[0026] [ka]

[0027] [ka]

[0028] [ka]

[0029] In one aspect, the composition preferably contains at least one of 3-o-caffeoylquinic acid and 5-o-caffeoylquinic acid selected from the group consisting of the above three compounds as chlorogenic acids, more preferably contains both, and even more preferably contains both and 3-o-feruloylquinic acid.

[0030] <Luteolin and its glycosides> In one embodiment, the composition contains, as an active ingredient, any one selected from the group consisting of luteolin and its glycosides (hereinafter, also referred to as luteolins). The glycoside of luteolin refers to a compound in which a sugar is glycosidically bonded to luteolin (3',4',5,7-tetrahydroxyflavone). Examples of sugars include glucose, galactose, fructose, glucuronic acid, rhamnose, xylose, arabinose, apiose, rutinose, gentiobiose, primeverose, and diglyceryl stearate. Examples of luteolin glycosides include luteolin 4'-o-glucoside, luteolin 4'-o-glucuronide, luteolin 5-glucuronide, luteolin 5-glucoside, luteolin 5-rutinoside, luteolin 5-o-glucuronide, luteolin 6-glucoside (isoorientin), luteolin 6-c-β-d-glucopyranoside, luteolin 8-c-α-l-arabinopyranoside, luteolin 6-c-arabinoside, luteolin 7-(2-o-apiosylglucoside), luteolin 7-(2 Luteolin 7-(2-sulfoglucoside), luteolin 7-o-glucoside, luteolin 7-o-galactoside, luteolin 7-o-glucuronide, luteolin 7,4'-di-o-glucuronide, luteolin 7-[6-o-(2-methylbutyryl)-β-glucoside], luteolin 7-o-[2-o-(4-o-acetyl-α-rhamnopyranosyl)-β-glucuronopyranoside], and luteolin 8-glucoside (orientin).

[0031] In one embodiment, the composition includes, as a luteolin, a compound represented by the following formula:

[0032] [ka]

[0033] In the formula, R 4 , and R 5 are each independently H or a sugar residue.

[0034] In one embodiment, the composition contains isoorientin (R 4=H, R 5 = glucose residue), and orientin (R 4 = glucose residue, R 5 =H).

[0035] In one embodiment, the composition includes isoorientin as the luteolin.

[0036] [ka]

[0037] <Combination of active ingredients> In one embodiment, the composition contains two or more components selected from the group consisting of 3-o-caffeoylquinic acid (3CQA), 5-o-caffeoylquinic acid (5CQA), 3-o-feruloylquinic acid (3FQA), and isoorientin (ISO) from the viewpoint of high target effect. The two or more components are preferably a combination containing at least one selected from 3CQA, 5CQA, and ISO. Particularly preferred examples of such combinations include a combination of 3CQA and ISO, a combination of 5CQA and 3FQA, a combination of 5CQA and ISO, a combination of 3FQA and ISO, a combination of 3CQA, 5CQA, and ISO, and a combination of 5CQA, 3FQA, and ISO. In one embodiment, the composition contains a combination of 3CQA, 5CQA, and ISO, and may further contain 3FQA.

[0038] When the composition contains four types of compounds, 3CQA, 5CQA, 3FQA, and ISO, the ratio thereof is not particularly limited as long as the desired effect is achieved. For example, the molar ratio of 3-o-caffeoylquinic acid:5-o-caffeoylquinic acid:3-o-feruloylquinic acid:isoorientin can be 1:0.10-10:0.15-15:0.080-8.0, 1:0.30-3.0:0.40-4.0:0.20-2.0, or 1:0.60-1.5:0.80-2.0:0.40-1.0.

[0039] <Sugarcane top extract> In one embodiment, the composition may use an extract of sugarcane top as an active ingredient. The sugarcane top refers to the top part of sugarcane (scientific name: Saccharum officinarum L.) above the fifth leaf thickening zone. The extract includes an extract obtained by extracting a raw material with a solvent, as well as a concentrate, a dried product, and a crude product of the extract, unless otherwise specified.

[0040] When extraction is performed under appropriate conditions, an extract containing the four types of 3CQA, 5CQA, 3FQA, and ISO can be obtained in an amount of 100 mg to 170 mg, more specifically 130 mg to 150 mg, on a dry weight basis, from 1 g of dried sugarcane tops (including leaves and bark).

[0041] The amount of 3-o-caffeoylquinic acid contained in the sugarcane top extract can be 0.20 mg or more per 100 g (dry weight) of extract, regardless of the content of other components.By optimizing the extraction conditions, the amount can be 0.30 mg or more, 0.35 mg or more, or 0.40 mg or more, regardless of the content of other components.

[0042] The amount of 5-o-caffeoylquinic acid contained in the sugarcane top extract can be 1.0 mg or more per 100 g (dry weight) of extract, regardless of the contents of other components.By optimizing the extraction conditions, the amount can be 1.5 mg or more, 2.0 mg or more, or 2.5 mg or more, regardless of the contents of other components.

[0043] The amount of 3-o-feruloylquinic acid contained in the sugarcane top extract can be 0.10 mg or more per 100 g (dry weight) of extract, regardless of the content of other components. By optimizing the extraction conditions, the amount can be 0.13 mg or more, 0.16 mg or more, or 0.20 mg or more, regardless of the content of other components.

[0044] The amount of isoorientin contained in the sugarcane top extract can be 0.80 mg or more per 100 g (dry weight) of extract, regardless of the contents of other components. By optimizing the extraction conditions, the amount can be 1.0 mg or more, 1.2 mg or more, or 1.4 mg or more, regardless of the contents of other components.

[0045] In one embodiment, the amount of 3-o-caffeoylquinic acid contained in 100 g (dry weight) of sugarcane top extract is 0.40 mg or more and 0.60 mg or less, the amount of 5-o-caffeoylquinic acid is 2.5 mg or more and 3.5 mg or less, the amount of 3-o-feruloylquinic acid is 0.20 mg or more and 0.30 mg or less, and the amount of isoorientin is 1.4 mg or more and 1.8 mg or less.

[0046] In one embodiment, the sugarcane top may contain 2.1 to 2.6 mg / g (dry weight) of isoorientin. It is also known that isoorientin is contained in rooibos tea. It has been reported that an extract of 10 g of dried green rooibos tea leaves with 500 ml of hot water contains 26 mg of isoorientin (Food Chemistry 128:338-347, 2011).

[0047] <Production method of sugarcane top extract> The sugarcane top extract used as an active ingredient can be produced using sugarcane tops as a raw material. The sugarcane tops used as a raw material may be the whole top of the sugarcane, a part including leaves and bark, or a part excluding leaves and bark. The raw sugarcane tops may be in a raw state or may be dried. Drying may be performed by cold air drying or sun drying. The sugarcane tops may be cut, chopped, or crushed to increase the extraction efficiency.

[0048] The means for extraction from the sugarcane tops is not particularly limited, and extraction may be carried out using a liquid extraction solvent, or supercritical extraction or subcritical extraction may be carried out using a supercritical fluid or subcritical fluid.

[0049] The extraction solvent is preferably a solvent that is effective for extracting luteolin or its glycosides and is also effective for extracting chlorogenic acids. Examples of such solvents include water, methanol, ethanol, isopropanol, butanol, propylene glycol, butylene glycol, glycerin, acetone, ethyl acetate, and methyl ethyl ketone, as well as mixtures of any of these. A preferred example is an aqueous solvent, such as water or a mixture of water and any of the following: methanol, ethanol, isopropanol, butanol, propylene glycol, butylene glycol, and glycerin.

[0050] In one embodiment, water is used as the solvent. In another embodiment, a mixed solvent of water and ethanol is used. The concentration of ethanol can be 5% or more, 10% or more, 20% or more, or 25% or more. The concentration of ethanol can be 95% or less, 90% or less, 85% or less, 70% or less, or 60% or less. From the viewpoint of minimizing the use of ethanol, the concentration of ethanol is preferably 50% or less, more preferably 40% or less, and even more preferably 35% or less. In the present invention, the ethanol concentration of an extraction solvent containing ethanol is a value based on volume (v / v) unless otherwise specified, and ethanol is mixed with water unless otherwise specified.

[0051] The extraction operation may be carried out at room temperature or with heating. When heated under reflux cooling, the components can be extracted efficiently and quickly. The extraction temperature can be 60°C or higher, preferably 70°C or higher, and more preferably 80°C to 100°C. When carried out with heating, the extract can be obtained efficiently and with high purity.

[0052] Extraction can be carried out at normal pressure. Extraction can also be carried out under pressure, at 5 MPa (50 bar) or more, preferably 7.5 MPa (75 bar) or more, and may be 10 MPa (100 bar) or more. In this case, heating may also be carried out in order to efficiently and quickly extract the target component. The temperature can be 25°C or more, preferably 30°C or more, more preferably 35°C or more, and even more preferably 40°C or more. The ratio of raw material to extraction solvent, extraction time, and number of repetitions of the extraction operation can be appropriately determined taking into account the extraction efficiency.

[0053] In one embodiment, the dried sugarcane top is extracted with hot water at room temperature. In another embodiment, a mixture of water and ethanol is used as the extraction solvent, and automatic component extraction is carried out multiple times, for example 2 to 8 times, for 15 to 30 minutes each time, using a high-speed high-pressure extraction device under conditions of a pressure of 100 bar and a temperature of 45°C. The solution obtained by extraction can be concentrated and freeze-dried.

[0054] When performing supercritical extraction or subcritical extraction, the fluid may be, for example, water, carbon dioxide, ethylene, propylene, ethane, propane, dinitrogen monoxide, chlorodifluoromethane, chlorotrifluoromethane, xenon, ammonia, or lower alcohols such as methanol and ethanol. From the viewpoint of safety, it is preferable to use water, ethanol, a mixture thereof, or carbon dioxide. If necessary, insoluble residues may be removed, and the mixture may be concentrated by a conventional method and dried by means of spray drying, freeze drying, or the like.

[0055] [Application] In one embodiment, a composition containing an active ingredient selected from the group consisting of chlorogenic acids, luteolin and its glycosides is used to improve mitochondrial activity. According to the study by the present inventors, it has been found that a composition containing an active ingredient selected from the group consisting of chlorogenic acids, luteolin and its glycosides can activate mitochondria in immature astrocytes, myotubes, and hepatocytes, and is also expected to activate mitochondria in adipocytes and intestinal epithelial cells.

[0056] In one embodiment, a composition containing an active ingredient selected from the group consisting of chlorogenic acids, luteolin and its glycosides is used to promote the expression of PGC-1α (peroxisome proliferator activated receptor gamma coactivator-1α). PGC-1α, a nuclear receptor coactivator, is known as an energy metabolism control factor. PGC-1α is also considered to be an important target for mitochondria, which are responsible for enhancing energy metabolism (Non-Patent Document 1). According to the studies of the present inventors, it has been found that a composition containing an active ingredient selected from the group consisting of chlorogenic acids, luteolin and its glycosides can promote the expression of PGC-1α in immature astrocytes, myotube cells, and hepatocytes, and is also expected to activate mitochondria in adipocytes and intestinal epithelial cells. The expression of PGC-1α refers to the process in which the information of the PGC-1α gene is converted into structure and function, and the promotion of expression includes the promotion of transcription from the gene to mRNA.

[0057] In one aspect, a composition comprising an active ingredient selected from the group consisting of chlorogenic acids and luteolin and its glycosides may be used for the treatment of a disease or condition that may be improved through improved mitochondrial activity.

[0058] In one embodiment, a composition comprising chlorogenic acids and an active ingredient selected from the group consisting of luteolin and its glycosides is used for the treatment of a metabolism-related disease or condition.

[0059] In one aspect, a composition comprising an active ingredient selected from the group consisting of chlorogenic acids and luteolin and its glycosides may be used for the treatment of a disease or condition that can be improved through the promotion of PGC-1α expression.

[0060] In one embodiment, a composition comprising an active ingredient selected from the group consisting of chlorogenic acids, luteolin and its glycosides can be used for the treatment of diseases or conditions associated with muscle loss due to aging or the metabolic disorder. Skeletal muscle is one of the in vivo tissues in which PGC-1α activity and mitochondrial energy metabolism are important for its activity. When adapting to load exercise, mitochondria are activated in muscle cells via increased expression of PGC-1α, improving the production of ATP, which is an energy source for activities such as contraction.

[0061] More specifically, a composition comprising an active ingredient selected from the group consisting of chlorogenic acids, and luteolin and its glycosides may be used for the following diseases or treatments: Non-disease metabolic disorders, including age-related decline in glucose and lipid metabolism; diabetes, hypertension, dyslipidemia, fatty liver, metabolic syndrome, obesity; sarcopenia, sarcopenia; diseases characterized by morphological maturation defects of astrocytes, including Alexander disease. Alternatively, a composition containing an active ingredient selected from the group consisting of chlorogenic acids, and luteolin and its glycosides can be used for maintaining and improving muscle mass or muscle strength, maintaining and improving muscle endurance, and maintaining and improving walking ability.

[0062] Whether or not a certain component improves mitochondrial activity can be evaluated by, for example, using neural stem cell-derived immature astrocytes (e.g., human fetal neural stem cells), myotube cells (e.g., mouse skeletal muscle-derived myoblasts C2C12), hepatocytes (e.g., human hepatoma-derived cell line HepG2), adipocytes (e.g., mouse preadipocyte cell line 3T3-L1), or intestinal epithelial cells (e.g., human small intestinal epithelial-like cell line Caco-2), and analyzing the amount of rhodamine 123 uptake into mitochondria in the presence or absence of the target component based on the fluorescence intensity. In addition, whether or not a certain component promotes the expression of PGC-1α can be evaluated by, for example, using any of the above-mentioned cells, and analyzing the expression level of PGC-1α mRNA in the presence or absence of the target component. In addition, it can be evaluated by analyzing the expression level of TFAM mRNA, whose transcription is promoted downstream of PGC-1α activity.

[0063] In the present invention, the term "treatment" for a disease or condition includes reducing the risk of onset, delaying onset, prevention, treatment, and stopping or delaying progression. Treatment includes actions performed by doctors with the aim of treating a disease, and non-therapeutic actions performed by people other than doctors, such as nutritionists (including registered dietitians and sports nutritionists), public health nurses, midwives, nurses, clinical laboratory technicians, sports instructors, beauty consultants, estheticians, pharmaceutical manufacturers, pharmaceutical distributors, food manufacturers, and food distributors. Treatment also includes actions performed by veterinarians with the aim of treating a disease in a non-human animal, and non-therapeutic actions performed by people other than veterinarians, such as veterinary nurses, pet animal caretakers, stablemen, breeders, animal drug manufacturers, animal drug distributors, pet food manufacturers, and pet food distributors. In addition, treatment includes the administration or recommendation of the intake of specific foods, dietary guidance, health guidance, nutritional guidance (including nutritional guidance necessary for the recovery of injured or sick persons, and nutritional guidance for maintaining and promoting health), school lunch management, and guidance necessary for nutritional improvement regarding school lunches.

[0064] The subject of the treatment in the present invention includes humans (individuals), and is preferably a human for whom any of the above-mentioned treatments are desirable or necessary. The subject of the treatment in the present invention may be an animal other than a human, and examples of such animals include pets (also called companion animals) such as dogs, cats, rabbits, hamsters, guinea pigs, and squirrels, livestock such as cows and pigs, laboratory animals such as mice and rats, and animals kept in zoos. There is no particular limit to the growth stage of the target non-human animal, and the subject of the treatment in the present invention may be, for example, a puppy, an adult dog, an elderly dog, a puppy, an adult cat, or an elderly cat.

[0065] [Composition, etc.] In one embodiment, the composition may be the sugarcane tops extract itself, or may contain an active ingredient (eg, sugarcane tops extract) and other ingredients.

[0066] In one embodiment, the composition can be a food composition or a pharmaceutical composition. The term "food" refers to not only solids but also liquids, such as soups, beverages, and drinks, unless otherwise specified. In addition, the term "food" refers to not only foods intended for humans, but also foods intended for non-human animals, such as feed and pet food, unless otherwise specified. Furthermore, the term "food" refers to general foods, health foods, supplements, and foods with health claims (foods with specified health uses (commonly known as "FOSHU"), foods with nutrient functions, and foods with functional claims), unless otherwise specified, and also includes therapeutic foods (foods that serve the purpose of treatment. Foods that are prepared based on a menu prepared by a nutritionist or the like according to a doctor's dietary prescription), dietary therapy foods, ingredient-adjusted foods, reduced-salt foods, nursing care foods, reduced-calorie foods, and diet foods.

[0067] In one embodiment, the composition is in the form of an oral medicine, health food, or supplement. In this case, examples of the dosage form include soft capsules, hard capsules, tablets, pills, powders, granules, fine granules, jellies, tubes, and drinks.

[0068] The content of the active ingredient in the composition can be appropriately designed taking into consideration the daily intake / administration amount. In one embodiment, the daily dose for an adult contains 0.2 to 2,000 mg of the active ingredient, preferably 0.5 to 1,000 mg, more preferably 1 to 500 mg, and even more preferably 2 to 200 mg. The daily dose can be ingested / administered multiple times, for example, 2 to 4 times.

[0069] In one embodiment, the composition may contain other ingredients other than the sugarcane top extract, as long as the composition can exhibit the intended effect. The other ingredients may be various additives acceptable for food or various additives acceptable for medicine. Examples of such additives include excipients, antioxidants (antioxidants), flavors, seasonings, sweeteners, colorants, thickening stabilizers, colorants, bleaching agents, fungicides, gum bases, bittering agents, enzymes, gloss agents, acidulants, emulsifiers, strengthening agents, manufacturing agents, binders, tonicity agents (isotonic agents), buffers, solubilizers, preservatives, stabilizers, and coagulants.

[0070] Other ingredients may be functional ingredients. Examples of functional ingredients include amino acids (e.g., branched chain amino acids, ornithine), unsaturated fatty acids (e.g., EPA, DHA), vitamins, trace metals, polyphenols, egg yolk extract, honey processed products, brown sugar, oligosaccharides, dietary fiber, glucosamine, chondroitins, CoQ10, fucoidan, fucoxanthin, astaxanthin, placenta, yeast extract, black vinegar concentrate, plant extracts (garlic extract, ginkgo leaf extract, tea extract, bilberry extract, blueberry extract, various ginseng extracts, maca extract, bean seed coat extract, St. John's wort extract, pine bark extract, acai extract, noni extract), etc.

[0071] In one embodiment, the composition may be ingested or administered with a meal, before or after a meal.

[0072] In one embodiment, the composition can be labeled that it can be used to treat the above-mentioned disease or condition, and can be labeled that its ingestion is recommended for the above-mentioned subject. Labeling can be direct or indirect, and examples of direct labeling include descriptions on tangible objects such as the product itself, packaging, containers, labels, and tags, and examples of indirect labeling include advertising and promotional activities by places or means such as websites, storefronts, exhibitions, signs, bulletin boards, newspapers, magazines, television, radio, mailings, and e-mails.

[0073] Examples of functional claims on compositions include the following: Maintaining muscle strength necessary for independent daily living and preventing its decline, Maintaining necessary muscle strength (muscle strength required for standing, walking, etc.), Maintaining muscle mass and strength, Maintaining walking ability, Improving walking function, Maintaining muscle that decreases with age, Supporting the synthesis of muscle that weakens with age, Making it easier to burn fat, Reducing abdominal fat. Maintaining healthy liver function. EXAMPLES

[0074] Production examples and test examples are shown below, but the present invention is not limited to the following examples in any way.

[0075] [Production Example 1] -Production of ethanol extract from sugarcane tops- Automatic component extraction was carried out four times for about 20 minutes each from 1 g of dried sugarcane tops (including leaves and bark) using 80% ethanol as the extraction solvent and a high-speed, high-pressure extraction apparatus E-916 (AG Buchi) under conditions of a pressure of 100 bar and a temperature of 45°C. The solution after extraction was concentrated using a rotary evaporator and then freeze-dried to obtain 140 mg of a sample. The contents of 3CQA, 5CQA, 3FQA, and ISO in 1 g of the extract, quantified by component analysis using high-performance liquid chromatography (HPLC), are equal to the analytical values ​​described in Patent Document 5 (Example [Component Analysis of Sugarcane Tops Extract]) and Non-Patent Document 6 (Chemical Analysis).

[0076] [Test Example 1] - Mitochondrial activity evaluation test in immature astrocytes derived from neural stem cells - It has been shown that mitochondrial biogenesis is required for the morphogenesis and maturation of astrocytes. It has been suggested that sugarcane top extract promotes the development and maturation of astrocytes. Therefore, we evaluated the effects of sugarcane top extract and its polyphenolic compounds on mitochondrial activity in immature astrocytes.

[0077] First, human fetal neural stem cells (hNSCs; Cell Applications) were cultured at 10,000 cells / cm 2 hNSCs were seeded at a concentration of 1000 mM NaCl onto a 96-well plate and then incubated for 48 hours in astrocyte differentiation medium consisting of Dulbecco's modified Eagle's medium (DMEM), 1% N-2 supplement (Gibco), 1% fetal bovine serum (FBS), and 1% penicillin / streptomycin to induce astrocytes. The differentiated astrocytes were then switched to astrocyte differentiation medium containing the samples, i.e., sugarcane top extract or polyphenolic compounds (including their combinations), and further incubated for 24, 48, and 72 hours.

[0078] The sugarcane top extract used was the extract obtained in Production Example 1. The final concentration of the extract in the medium was set to 50 μg / mL. The concentration of each compound was set to the content contained in the 50 μg / mL extract, calculated from the analytical quantitative values ​​described in Patent Document 5 and Non-Patent Document 6. That is, the concentrations of 3CQA, 5CQA, 3FQA, and ISO in the medium were 0.50 μM, 0.70 μM, 0.85 μM, and 0.48 μM, respectively. In addition to the combination of four types of compounds, six groups of two-type combinations and four groups of three-type combinations were set as treatment groups. The numbering of the two- and three-type combination treatment groups is shown in the table below.

[0079] After incubation, mitochondrial activity (content) was evaluated using rhodamine 123 (Rh123). Rh123 is easily incorporated into intracellular mitochondria, and mitochondrial activity can be evaluated by measuring its fluorescence intensity. After washing the cells with PBS, 10 μg / mL Rh123 solution was added to each well and incubated at 37°C for 20 minutes. After washing the cells again, 1% Triton-X solution was added to each well and incubated at room temperature in the dark for 30 minutes to lyse the cells. The cell lysate was transferred to a black clear-bottom 96-well plate, and the fluorescence intensity was measured under the conditions of λex = 507 nm and λem = 529 nm using a plate reader (Varioskan LUX, Thermo Fisher Scientific). The obtained values ​​were subjected to a significance test (*P<0.05) using the One-way ANOVA method.

[0080] [Table 1]

[0081] --Test Results-- After 24 hours of treatment, the mitochondrial Rh123 fluorescence intensity was significantly increased in treatment groups (3) and (5). After 48 hours of treatment, the fluorescence intensity tended to increase in treatment group (8) and the four-compound mixture (All mixed) (p = 0.097, p = 0.082, respectively). After 72 hours of treatment, the fluorescence intensity was significantly increased in treatment groups (5), (8), and the sugarcane top head extract (STEE) (Figure 1). These results suggest that the sugarcane top head extract activates mitochondria in immature astrocytes derived from hNSCs. It was also suggested that 3CQA, 5CQA, and ISO, among the polyphenolic components in the extract, contribute to this activity by the extract.

[0082] [Test Example 2] -Examination of PGC-1α mRNA expression in immature astrocytes derived from neural stem cells- Mitochondrial activity depends on the control of metabolic enzyme gene expression by nuclear transcription factors, among which the transcription factor PGC-1α plays an important role. It is known that activation of PGC-1α is essential for the maturation of astrocytes as a master regulator of mitochondrial biogenesis. Since the sugarcane top head extract was found to have a mitochondrial activation effect in [Test Example 1], we next evaluated the effect of sugarcane top head extract on PGC-1α mRNA expression in immature astrocytes.

[0083] First, astrocytes were induced from hNSCs in a 24-well plate using the same method as in Test Example 1. The medium for the differentiated astrocytes was switched to an astrocyte differentiation-inducing medium containing sugarcane top extract or polyphenol compounds (including combinations thereof), and further incubated for 48 hours.

[0084] The concentrations of the sugarcane top extract and each compound in the medium were the same as in [Test Example 1]. The combinations of each compound used as treatment groups were the same as in [Test Example 1].

[0085] After incubation, total RNA was isolated from the cells using an RNeasy micro kit (Qiagen). The total RNA was used as a template for quantitative real-time polymerase chain reaction (qRT-PCR) on a 7500 Fast Real-Time PCR System (Applied Biosystems) to measure mRNA expression levels. TaqMan primers (Applied Biosystems) for GAPDH (Hs02786624_g1) and PPARGC1 (Hs00173304_m1) were used, and GAPDH was used as an internal control to determine the relative expression levels of the transcripts. The obtained values ​​were subjected to a one-way ANOVA test for significance ( *P<0.05, ****<0.001).

[0086] --Test Results-- Figure 2 shows the expression level of PGC-1α mRNA in immature astrocytes derived from hNSCs. The expression level of PGC-1α mRNA was significantly increased by 48 hours of STEE treatment (p < 0.0001, approximately 2.5-fold). In the compound treatment groups (5), (8), and All Mix, the expression level of PGC-1α mRNA was significantly increased at the same level as the STEE treatment group (p < 0.0001).

[0087] These results suggest that the sugarcane top head extract induces an increase in PGC-1α mRNA expression in immature astrocytes derived from hNSCs, and that 3CQA, 5CQA, and ISO, among the polyphenolic components in the extract, contribute to this activity.

[0088] The mitochondrial activity and PGC-1α mRNA expression by the sugarcane top-derived composition can also be evaluated by carrying out the tests described below.

[0089] [Test Example 3] - Mitochondrial activity evaluation test in myotube cells - In order to enhance energy production for muscle contraction and other activities, it is necessary to improve intracellular mitochondrial activity. We evaluated the effects of sugarcane top extract and its polyphenol compounds on mitochondrial activity in myotube cells.

[0090] First, mouse skeletal muscle-derived myoblasts, C2C12, were cultured at 30,000 cells / cm 2 The cells were seeded on a 96-well plate at a concentration of 100 mM sodium phosphate phosphate (pH 7.0) and then cultured in a medium consisting of DMEM, 10% FBS, and 1% penicillin / streptomycin to grow as myoblasts. When the cells reached confluence, the medium was replaced with a medium consisting of DMEM and 2% Horse Serum (HS) to induce differentiation into myotubes. The myotubes differentiated after 6 days of culture were added with dissolved test samples, i.e., sugarcane top extract or polyphenol compounds (including combinations thereof), and further incubated for 6 and 24 hours.

[0091] The test samples were the same as those used in [Test Example 1]. That is, the extract obtained in Production Example 1, each polyphenol compound, and the compounds in Table 1 were combined. The final concentration of the extract in the medium was set to 50 μg / mL, and the concentrations of each compound were set to 0.50 μM for 3CQA, 0.70 μM for 5CQA, 0.85 μM for 3FQA, and 0.48 μM for ISO. The concentrations of these compounds were also the same when they were combined.

[0092] After incubation, mitochondrial activity (content) was evaluated using Rh123. The test method was the same as that described in [Test Example 1]. The obtained values ​​were subjected to a significance test (*P<0.05) using the One-way ANOVA method.

[0093] --Test Results-- After 6 hours of treatment, Rh123 fluorescence intensity was significantly increased in treatment groups (3), (8), All mixed, and STEE. Furthermore, the fluorescence intensity tended to increase in treatment group (5). After 24 hours of treatment, no significant change in fluorescence intensity was observed in any of the treatment groups (Figure 3). These results suggest that the exposure of sugarcane top extract for 6 hours induces mitochondrial activation in myotube cells. It was also suggested that 3CQA, 5CQA, and ISO, among the polyphenolic components in the extract, contribute to this activity of the extract.

[0094] [Test Example 4] -Examination of PGC-1α mRNA and TFAM mRNA expression in myotube cells- The transcription factor PGC-1α plays an important role in regulating mitochondrial activity, and downstream of PGC-1α expression, the transcription of mitochondrial transcription factor A (TFAM) gene is promoted, enhancing mitochondrial biogenesis. We evaluated the effects of sugarcane top extract and its polyphenolic compounds on PGC-1α mRNA and TFAM mRNA expression in myotube cells.

[0095] First, differentiation of C2C12 into myotubes was induced in a 6-well plate using the same method as in [Test Example 3]. After 6 days, the test samples, i.e., sugarcane top extract or polyphenol compound mixture, were added to the differentiated myotubes, and the cells were further incubated for 6 or 24 hours.

[0096] The sugarcane top extract used was the extract obtained in Production Example 1. The final concentrations of the extract in the medium were set to 15 μg / mL, 30 μg / mL, and 50 μg / mL. A combination of four compounds was used as a test sample (Mix), and the concentrations of each compound in the medium were set to the content contained in the 50 μg / mL extract, i.e., 0.50 μM for 3CQA, 0.70 μM for 5CQA, 0.85 μM for 3FQA, and 0.48 μM for ISO.

[0097] After incubation, qRT-PCR was performed as in [Test Example 2] to measure the mRNA expression level. The TaqMan primers used were Gapdh (Mm99999915_g1), Ppargc1 (Mm01208835_m1), and Tfam (Mm00447485_m1), and Gapdh was used as an internal standard to determine the relative expression levels of the transcripts. The obtained values ​​were subjected to a significance test (*P<0.05, ***<0.001) using the One-way ANOVA method.

[0098] --Test Results-- The expression levels of PGC-1α mRNA and TFAM mRNA in myotubes are shown in Figure 4. The expression level of PGC-1α mRNA was significantly increased by 6 hours of treatment with 50 μg / mL STEE (p < 0.05, approximately 1.4-fold), and no change was observed after 24 hours of treatment with the same sample. The expression level of PGC-1α mRNA was significantly increased by 6 hours of treatment with the compound mixture (Mix) (p < 0.05, approximately 1.4-fold), and the expression level was also significantly increased after 24 hours of treatment with the same sample (p < 0.05, approximately 1.5-fold). The expression level of TFAM mRNA showed an increasing tendency by 6 hours of treatment with 50 μg / mL STEE (p = 0.082, approximately 1.25-fold), and the expression level was also significantly increased after 24 hours of treatment with the same sample (p < 0.05, approximately 1.5-fold). In addition, TFAM mRNA expression was significantly increased by 6 hours of treatment with Mix (p < 0.05, approximately 1.25-fold), and the expression level was also significantly increased after 24 hours of treatment with the same sample (p < 0.001, approximately 1.75-fold).

[0099] These results suggest that the sugarcane top extract induces an increase in PGC-1α mRNA and TFAM mRNA expression in myotubes, and that 3CQA, 5CQA, 3FQA, or ISO in the extract contributes to this activity.

[0100] [Test Example 5] - Mitochondrial activity evaluation test in hepatocytes - In the liver, which is the center of metabolism in the body, intracellular mitochondria play an important role in improving the activity of the liver. We evaluated the effects of sugarcane top extract and its polyphenol compounds on mitochondrial activity in hepatocytes.

[0101] First, human hepatoma-derived cells, HepG2, were cultured at 30,000 cells / cm 2 The cells were seeded in a 96-well plate at a concentration of 100 μg / ml and cultured in a medium consisting of DMEM, 10% FBS, and 1% penicillin / streptomycin. After 24 hours of culture, the medium was replaced with a low-serum medium (Opti-MEM®) containing 1% penicillin / streptomycin and the test sample, i.e., sugarcane top extract or polyphenolic compound (including combinations thereof), and incubated for another 6 and 24 hours.

[0102] The concentrations of the sugarcane top extract and each compound in the medium were the same as in [Test Example 3]. The combinations of each compound used as treatment groups were the same as in [Test Example 3].

[0103] After incubation, mitochondrial activity (content) was evaluated using Rh123. The test method was the same as that described in [Test Example 1]. The obtained values ​​were subjected to a significance test using the One-way ANOVA method.

[0104] --Test Results-- No significant changes in fluorescence intensity were observed in any of the treatment groups after 6 and 24 hours of treatment (Figure 5). Although not statistically significant, Rh123 fluorescence intensity increased by approximately 120% in STEE after 6 hours of treatment, and Rh123 fluorescence intensity increased by approximately 120% in treatment groups (7), (8), and STEE after 24 hours of treatment (Figure 5).

[0105] [Test Example 6] -Examination of PGC-1α mRNA and TFAM mRNA expression in hepatocytes- As mentioned above, the transcription factor PGC-1α and TFAM, whose transcription is promoted downstream of its activity, play an important role in regulating mitochondrial activity. We evaluated the effects of sugarcane top extract and its polyphenolic compounds on PGC-1α mRNA and TFAM mRNA expression in hepatocytes.

[0106] First, HepG2 cells were cultured in a 6-well plate using the same method as in Test Example 5. After 24 hours of culture from seeding the cells, the test samples, i.e., sugarcane top extract or polyphenol compound mixture, were added and incubated for another 6 or 24 hours.

[0107] The test sample was the same as in [Test Example 5]. The concentration of the test sample in the medium was the same as in [Test Example 5].

[0108] After incubation, qRT-PCR was performed as in [Test Example 2] to measure the mRNA expression level. The TaqMan primers used were GAPDH (Hs02786624_g1), PPARGC1 (Hs00173304_m1), and TFAM (Hs00273372_s1), and GAPDH was used as an internal standard to determine the relative expression levels of the transcripts. The obtained values ​​were subjected to a significance test (*P<0.05, **<0.01) using the One-way ANOVA method.

[0109] --Test Results-- The expression levels of PGC-1α mRNA and TFAM mRNA in hepatocytes are shown in Figure 6. The expression levels of PGC-1α mRNA were significantly increased by 24-hour treatment with 30 μg / mL and 50 μg / mL STEE (p < 0.01, approximately 1.4-fold), and by 24-hour treatment with the compound mixture (Mix) (p < 0.01, approximately 1.4-fold). The expression levels of TFAM mRNA were significantly increased by 24-hour treatment with 30 μg / mL and 50 μg / mL STEE (p < 0.05, approximately 1.2-fold), and by 24-hour treatment with Mix (p < 0.05, approximately 1.2-fold). There was no significant change in the expression levels of PGC-1α mRNA and TFAM mRNA by 6-hour treatment with any sample.

[0110] These results suggest that the sugarcane top extract induces an increase in PGC-1α mRNA and TFAM mRNA expression in hepatocytes, and that 3CQA, 5CQA, 3FQA, or ISO in the extract contributes to this activity.

[0111] The mitochondrial activity and PGC-1α mRNA expression due to the components derived from sugarcane tops can also be evaluated by carrying out the tests described below.

[0112] [Example 1] --Evaluation test of mitochondrial activity and PGC-1α mRNA expression in adipocytes-- First, 3T3-L1, a mouse-derived preadipocyte cell line, is grown as preadipocytes in a medium consisting of DMEM, 10% FBS, and 1% penicillin / streptomycin. Two days after the cells reach confluence (post-confluence), a differentiation inducer consisting of isobutylmethylxanthine (IBMX), insulin, and dexamethasone (DEX) is added to the medium to induce differentiation into adipocyte-like cells. Simultaneously with the addition of the differentiation inducer, test samples (sugarcane top extract and polyphenol compounds) are added to an appropriate medium concentration. After the addition of the differentiation inducer, the cells are incubated for 2 to 3 days, and differentiation into adipocytes is generally completed.

[0113] For differentiated adipocytes, mitochondrial activity can be evaluated using the above-mentioned Rh123, and the amount of PGC-1α mRNA expression can be evaluated using the above-mentioned qRT-PCR.

[0114] [Example 2] --Evaluation of mitochondrial activity and PGC-1α mRNA expression in intestinal epithelial cells-- First, Caco-2, a human small intestinal epithelial cell line, is cultured in a medium consisting of DMEM, 10% FBS, and 1% penicillin / streptomycin. After the culture reaches confluence, the cells are further cultured for 14 days to differentiate into intestinal epithelial cells. Dissolved test samples (sugarcane top extract and polyphenol compounds) are added to the differentiated intestinal epithelial cells to achieve appropriate concentrations in the medium.

[0115] After the addition of the sample, the intestinal epithelial cells can be incubated for an appropriate period of time, and then the mitochondrial activity can be evaluated using the above-mentioned Rh123, and the PGC-1α mRNA expression level can be evaluated using the above-mentioned qRT-PCR.

Claims

1. A food composition or pharmaceutical composition for improving mitochondrial activity in the treatment of a subject in which promotion of expression of the PGC-1α gene is desired via promotion of expression of the PGC-1α gene in myotube cells or in skeletal muscle, comprising isoorientin and at least one of 3-o-caffeoylquinic acid and 5-o-caffeoylquinic acid.

2. 2. The composition of claim 1, comprising 3-o-caffeoylquinic acid, 5-o-caffeoylquinic acid, and isoorientin.

3. 3. The composition according to claim 1 or 2, wherein the active ingredient is contained as an extract of the tops of sugarcane (which may include any one selected from the group consisting of leaves and bark).

4. 3. A food composition or pharmaceutical composition as described in claim 1 or 2, for supporting any of the following selected from the maintenance and prevention of decline of muscle strength necessary for living an independent daily life, maintenance of muscle strength necessary for standing and walking, maintenance of muscle mass and muscle strength, maintenance of walking ability, improvement of walking function, maintenance of muscle that decreases with age, and synthesis of muscle that weakens with age.

5. 5. The composition according to claim 4, wherein the active ingredient is contained as an extract of the tops of sugarcane (which may include any one selected from the group consisting of leaves and bark).

6. The food composition or pharmaceutical composition according to claim 1 or 2, for any one selected from the group consisting of muscle loss (sarcopenia) caused by aging, as well as maintaining or improving muscle mass or muscle strength, maintaining or improving muscle endurance, and maintaining or improving walking ability.

7. 7. The composition according to claim 6, wherein the active ingredient is contained as an extract of the tops of sugarcane (which may include any one selected from the group consisting of leaves and bark).

8. A method for producing a food material or pharmaceutical material for improving mitochondrial activity in the treatment of a subject for which promotion of PGC-1α gene expression is desired via promotion of PGC-1α gene expression in myotubes or in skeletal muscles, the method comprising the steps of: A process for obtaining a fraction containing isoorientin and at least one of 3-o-caffeoylquinic acid and 5-o-caffeoylquinic acid from a top portion of sugarcane (which may include a portion selected from leaves and bark) using an aqueous solvent.

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