Composition for improving insulin resistance

Abstract

The present invention relates to a method and means for improving insulin resistance. Specifically, the present invention relates to a composition for improving insulin resistance, the composition containing turmeric extract as an active ingredient.

Description

Composition for improving insulin resistance

[0001] The present invention relates to a composition for improving insulin resistance. The present invention also relates to a composition for treating, preventing, or improving a disease or disorder associated with insulin resistance.

[0002] Insulin is secreted into the bloodstream from the pancreas after a meal and acts on skeletal muscle cells and fat cells, causing these cells to take up glucose and lower blood sugar levels. When abnormalities in glucose metabolism occur due to aging, overeating, or other irregular lifestyles, the blood sugar-lowering effect of insulin weakens, resulting in an accelerated rise in blood sugar levels after meals and making it difficult for elevated blood sugar levels to return to normal. This state of impaired insulin effectiveness is called insulin resistance. If this condition is left untreated and insulin becomes even less effective, type 2 diabetes can develop. Therefore, in order to prevent type 2 diabetes, it is important to suppress the rise in blood sugar levels after meals.

[0003] It has been reported that blood glucose levels improved in humans who ingested turmeric extract (Patent Document 1). On the other hand, there are reports that in humans who ingested turmeric, an increase in postprandial insulin levels was observed, but no change in blood glucose levels was observed (Non-Patent Document 1), and that no change in postprandial blood glucose or insulin levels was observed (Non-Patent Document 2). There are also reports that in humans who ingested curcumin, a component contained in turmeric, no change in postprandial blood glucose levels was observed (Non-Patent Document 3), and that the increase in postprandial blood glucose levels was suppressed (Non-Patent Document 4).

[0004] Japanese Patent Application Laid-Open No. 2021-8434

[0005] Wickenberg, et al., Nutr J. 9:43, 2010 Lee, et al., Asia Pac J Clin Nutr. 23(4):581-91, 2014 Alwi, et al., Acta Med Indones. 40(4):201-10, 2008 Thota, et al., Sci Rep. 8(1):13679, 2018

[0006] Insulin resistance may be a factor that increases the risk of various diseases other than blood glucose-related diseases. Therefore, an object of the present invention is to provide methods and means for improving insulin resistance. Another object of the present invention is to provide methods and means for preventing, treating, or ameliorating diseases or disorders associated with insulin resistance.

[0007] In the course of intensive research into the effects of turmeric extract, the present inventors discovered that turmeric extract has the effect of improving insulin resistance because it suppresses an increase in blood glucose levels without promoting insulin secretion. They also discovered that turmeric extract can improve insulin resistance and / or improve diseases or disorders associated with insulin resistance, leading to the completion of the present invention.

[0008] Therefore, the present invention encompasses, for example, the following: [1] A composition for improving insulin resistance, comprising a turmeric extract as an active ingredient. [2] A composition for treating, preventing, or improving a disease or disorder associated with insulin resistance, comprising a turmeric extract as an active ingredient. [3] The composition according to [1] or [2], wherein the composition consists solely of a turmeric extract as the active ingredient. [4] The composition according to any of [1] to [3], wherein the turmeric extract comprises a turmeric extract obtained with at least one extraction solvent selected from the group consisting of water and a hydrophilic organic solvent. [5] The composition according to any of [1] to [3], wherein the turmeric extract comprises a mixture of a turmeric extract obtained by extraction with water and a turmeric extract obtained by extraction with supercritical carbon dioxide. [6] The composition according to any of [1] to [5], wherein the turmeric extract contains at least one of turmeronol A, turmeronol B, and bisacron.

[0009] [7] Use of turmeric extract for producing a composition for improving insulin resistance. [8] Use of turmeric extract for producing a composition for treating, preventing, or improving a disease or disorder associated with insulin resistance.

[0010] [9] A method for improving insulin resistance in a subject, comprising administering a turmeric extract to a subject in need thereof, and improving the insulin resistance in the subject.

[10] A method for treating, preventing, or ameliorating a disease or disorder associated with insulin resistance in a subject, comprising administering a turmeric extract to a subject in need thereof, and treating, preventing, or ameliorating the disease or disorder associated with insulin resistance in the subject.

[0011]

[11] A turmeric extract for use in improving insulin resistance.

[12] A turmeric extract for use in treating, preventing, or improving a disease or disorder associated with insulin resistance.

[0012] According to one or more embodiments of the present invention, there is provided a composition for improving insulin resistance. According to another one or more embodiments of the present invention, there is provided a composition for preventing, treating, or ameliorating a disease or disorder associated with insulin resistance.

[0013] Graph showing changes in blood glucose levels before a glucose load (0 minutes) and 30, 60, and 120 minutes after a glucose load in a subject group that took turmeric extract and a placebo group. ** indicates a significant difference at p<0.01 compared to the placebo group. Graph showing changes in insulin levels before a glucose load (0 minutes) and 30, 60, and 120 minutes after a glucose load in a subject group that took turmeric extract and a placebo group. ** indicates a significant difference at p<0.01 compared to the placebo group. Graph showing the Cederholm index (an index of insulin sensitivity) calculated from blood glucose and insulin levels in an OGTT test in a subject group that took turmeric extract and a placebo group. * indicates a significant difference at p<0.05 compared to the placebo group.

[0014] This specification includes the disclosure of Japanese Patent Application No. 2023-123395, filed on July 28, 2023, from which this application claims priority.

[0015] The present invention is based on the finding that administration or ingestion of turmeric extract can improve insulin resistance. Specifically, the present invention is based on experimental results showing that ingestion of turmeric extract in humans suppresses postprandial increases in blood glucose levels and, although insulin secretion is not promoted, decreases in insulin levels after a drop in blood glucose levels are observed, indicating that ingestion of turmeric extract improves the effectiveness of insulin (i.e., improves insulin resistance).

[0016] Therefore, in one aspect, the present invention provides a composition for improving insulin resistance, which contains turmeric extract as an active ingredient.

[0017] Insulin resistance refers to a condition in which sensitivity to insulin, a hormone with a blood glucose-lowering effect, is reduced, preventing insulin from exerting its full effect. Specifically, it refers to a condition in which, despite insulin being secreted into the blood from the pancreas, the sensitivity of target organs (skeletal muscle, adipose tissue, and liver) to insulin is reduced, resulting in a blunted effect (glucose uptake in skeletal muscle and adipose tissue, and inhibition of gluconeogenesis in the liver). On the other hand, when insulin production by the pancreas decreases, the amount of insulin secreted decreases, and, as with insulin resistance, blood glucose levels rise and the risk of diabetes increases. However, this condition in which insulin production from the pancreas is reduced is called impaired insulin secretion (decreased insulin secretion), and is distinct from insulin resistance.

[0018] Insulin resistance can be evaluated by measuring blood glucose levels (postprandial blood glucose levels) and insulin levels after a glucose load. Because blood insulin levels increase rapidly after a glucose load, the influence of insulin is greater than that of fasting blood glucose levels (which are controlled not only by insulin but also by glucagon, the liver, etc.), and this can be used as an evaluation index for insulin resistance. Blood glucose concentrations (blood glucose levels) and insulin levels after a glucose load are measured over time, and if insulin secretion is excessively promoted to lower blood glucose levels and insulin levels are higher than normal, or if blood glucose levels are high despite normal insulin levels, insulin resistance can be assessed. The Cederholm index is known as an index of insulin sensitivity (Cederholm, J. and Wibell, L. Diabetes Res Clin Pract. 10(2):167-75, 1990; Radikova, Z. Endocr Regul. 37(3):189-94, 2003). A higher Cederholm index indicates higher insulin sensitivity, and a lower Cederholm index indicates lower insulin sensitivity. A low Cederholm index can be evaluated as having high insulin resistance.

[0019] Improvement of insulin resistance means that, compared to when turmeric extract is not administered or taken, the decrease in insulin action is suppressed, the decreased insulin action is increased or brought closer to normal, the change from increase to decrease in insulin level after glucose loading is normalized or brought closer to normal, or the Cederholm index value is increased or brought closer to normal.

[0020] <Composition Containing Turmeric Extract> The composition of the present invention contains turmeric extract. In the present invention, turmeric extract refers to an extract (turmeric extract) of a plant material derived from a plant of the genus Curcuma in the Zingiberaceae family, using an extraction solvent. Turmeric extract is not limited to solvent extracts obtained by extraction with an extraction solvent, but also includes solvent extracts that have been further fractionated and purified by column chromatography or the like. The turmeric extract used in the present invention can be in the form of an extract liquid after the extraction procedure (including fractionation and purification if fractionation and purification is performed), a concentrate obtained by partially removing the solvent from the extract liquid, or a dried product obtained by removing the solvent from the extract liquid. The solvent can be removed from the extract by volatilizing the solvent by heating and / or reducing pressure, etc. The heating and pressure reduction methods are not particularly limited, and for example, conventionally known methods can be used.

[0021] Examples of the plant material include the rhizomes of plants of the genus Curcuma in the Zingiberaceae family, such as Curcuma longa (turmeric), Curcuma aromatica, Curcuma zedoaria, Curcuma phaeocaulis, Curcuma kwangsiensis, Curcuma wenyujin, and / or Curcuma xanthorrhiza. The rhizomes of Curcuma longa are particularly preferred. The rhizomes may be collected from the ground, and an appropriate portion of the rhizome may be used intact, cut to an appropriate size or shape, or pulverized. These plant materials may be appropriately dried.

[0022] The extraction solvent can be at least one selected from the group consisting of water and hydrophilic organic solvents. The at least one extraction solvent selected from the group consisting of water and hydrophilic organic solvents can be water, a hydrophilic organic solvent, or a mixed solvent of water and a hydrophilic organic solvent. The hydrophilic organic solvent can also be a mixed solvent of multiple hydrophilic organic solvents. "Water" also includes hot water. Hot water, for example, can be hot water at 95°C or higher. The hydrophilic organic solvent can include at least one alcohol (or a mixed solvent of multiple alcohols). The alcohol is not particularly limited, but ethanol is preferred. When a mixed solvent of alcohol and water is used as the extraction solvent, the mixing ratio is not particularly limited, but is preferably in the range of 10:90 to 90:10 by weight, and more preferably 20:80 to 50:50 by weight. Supercritical carbon dioxide can also be used as the extraction solvent.

[0023] The method for extracting turmeric extract from plant materials is not particularly limited, and any extraction method commonly used in the art can be employed.

[0024] In the present invention, the turmeric extract may contain one type of turmeric extract, or may contain two or more types of turmeric extracts obtained using different extraction solvents and / or extraction methods. In one embodiment, the turmeric extract comprises a mixture of a turmeric extract obtained using at least one extracting solvent selected from the group consisting of water and a hydrophilic organic solvent, and a turmeric extract obtained using supercritical carbon dioxide, for example, a mixture of a turmeric extract obtained by extraction with water and a turmeric extract obtained by extraction with supercritical carbon dioxide. The ratio of each extract in the mixture is not particularly limited, and may be, for example, a weight ratio of 1:0.01 to 1:1.

[0025] In a preferred embodiment, the turmeric extract comprises at least one of an extract with water, such as hot water, and an extract with supercritical carbon dioxide.

[0026] The turmeric extract used in the present invention contains at least one of turmeronol A, turmeronol B, and bisacronol.

[0027] Turmeronol A and turmeronol B are compounds each having the following planar structure.

[0028]

[0029]

[0030] In the present invention, turmeronol A and turmeronol B each have the above-mentioned planar structure, and may be any optical isomer or a mixture of multiple optical isomers.

[0031] It is known that the configuration of the 6-carbon atom in the partial structure of 2-methyl-2-hepten-4-one in natural products isolated from turmeric extracts, such as turmeronol A and turmeronol B, is S. However, in the present invention, turmeronol A and turmeronol B may have the above-mentioned planar structure, and the configuration may be S, R, or a mixture of S and R.

[0032] In the present invention, bisacron is a compound having the following planar structure: Bisacron has an asymmetric carbon at the position indicated by the * mark in the planar structural formula and may contain multiple optical isomers, but in the present invention, bisacron may be any optical isomer or a mixture of two or more optical isomers.

[0033]

[0034] The turmeric extract may be processed by a conventional method such as drying, powdering, granulation, or solution.

[0035] <Composition of the Present Invention> One aspect of the composition of the present invention relates to a composition for improving insulin resistance, containing the turmeric extract as an active ingredient. By administering the composition of the present invention according to this aspect to a subject such as a human, insulin resistance in the subject can be improved. Here, the active ingredient is ingested or administered in an amount effective for improving insulin resistance. As the route of administration, oral or nasal administration is preferred, oral or nasal administration is more preferred, and oral administration is particularly preferred. The composition of the present invention can improve insulin resistance by suppressing blood glucose level rise in the body (particularly, by suppressing blood glucose level rise without promoting insulin secretion).

[0036] Another aspect of the composition of the present invention relates to a composition for treating, preventing, or ameliorating a disease or disorder associated with insulin resistance, which contains the turmeric extract as an active ingredient. By having a subject, such as a human, ingest or administer the composition of the present invention according to this aspect, the disease or disorder associated with insulin resistance in the subject can be treated, prevented, or ameliorated. Here, the active ingredient is ingested or administered in an amount effective for treating, preventing, or ameliorating a disease or disorder associated with insulin resistance. Oral or nasal administration is preferred as the route of administration, with oral administration being particularly preferred.

[0037] Insulin resistance-related diseases or disorders are diseases or disorders caused by insulin resistance and can be prevented, treated, or ameliorated by improving insulin resistance according to the present invention. Such diseases or disorders include type 2 diabetes, arteriosclerosis, hypertension, heart disease, obesity, metabolically related fatty liver disease, steatosis, steatohepatitis, cirrhosis, energy homeostasis disorders, brain development disorders, Alzheimer's disease, cancer (breast cancer, uterine cancer, cervical cancer, colon cancer, esophageal cancer, pancreatic cancer, kidney cancer, prostate cancer), hyperfiltration, chronic kidney disease, polycystic ovary syndrome, and menstrual disorders and infertility (Li, M. et al. Signal Transduct Target Ther. 6;7(1):216, 2022).

[0038] The composition of the present invention may be in the form of a pharmaceutical, food or drink, feed, food additive, feed additive, etc., and is more preferably a pharmaceutical or food or drink. Food and drink products also include those in the form of functional foods, foods for specified health uses, nutritional supplements, etc. The composition of the present invention is preferably in the form of a composition that is ingested or administered orally or nasally, and more preferably in the form of a composition that is ingested or administered orally.

[0039] The content of the turmeric extract in the composition of the present invention is such that the total amount of turmeronol A and turmeronol B is 100 μg or more per daily intake or administration of the composition of the present invention, preferably per daily intake or administration for one human, particularly one adult, and / or turmeronol A is 17 μg or more, preferably 28 μg or more, more preferably 43 μg or more, even more preferably 57 μg or more, most preferably 80 μg or more, for example 100 μg, and / or turmeronol B is 5 μg or more. In order to effectively improve insulin resistance and treat, prevent, or improve diseases or disorders associated with insulin resistance, it is preferable to contain turmeric extract or its respective components in an amount of 80 μg or more, preferably 133 μg or more, more preferably 200 μg or more, even more preferably 267 μg or more, and most preferably 360 μg or more, for example, 400 μg, and / or bisacron in an amount of 80 μg or more, preferably 133 μg or more, more preferably 200 μg or more, even more preferably 267 μg or more, and most preferably 360 μg or more, for example, 400 μg. The upper limit of the content of turmeric extract or each component is not particularly limited. Here, the "daily intake or administration amount" typically refers to 0.1 g to 500 g of the composition of the present invention when taken or administered orally or nasally, preferably orally. The composition of the present invention may be taken or administered continuously or as needed.

[0040] The composition of the present invention containing the turmeric extract as an active ingredient may be the turmeric extract itself, or it may be a composition containing the turmeric extract and at least one other ingredient. When the composition of the present invention contains the turmeric extract and at least one other ingredient, it may be a composition obtained by mixing the turmeric extract and at least one other ingredient, a composition obtained by formulating the turmeric extract and at least one other ingredient by an appropriate means, or a composition obtained by mixing a composition obtained by formulating the turmeric extract and at least one other ingredient with other ingredients. In one embodiment, the composition of the present invention is a composition consisting solely of turmeric extract as an active ingredient. "Consisting solely of turmeric extract as an active ingredient" means that the active ingredient exhibiting the desired activity (improvement of insulin resistance) is turmeric extract alone, and no other active ingredients are present. However, components other than the active ingredient, such as carriers and excipients, may also be contained in the composition of the present invention.

[0041] The form of the composition of the present invention is not particularly limited, and may be, for example, any of liquid, fluid, gel, semi-solid, and solid forms.

[0042] The at least one other component that may be contained in the composition of the present invention is not particularly limited, but preferably includes a component that is acceptable in the final form of a pharmaceutical, food or drink, nutritional supplement, supplement, feed, food additive, feed additive, etc., and that can be orally ingested.

[0043] Such other ingredients include, for example, sweeteners, acidulants, vitamins, minerals, thickeners, emulsifiers, antioxidants, water, etc. Furthermore, colorants, flavorings, preservatives, antiseptics, fungicides, and other physiologically active substances may also be added as necessary.

[0044] Examples of sweeteners include monosaccharides and disaccharides such as glucose, fructose, sucrose, lactose, maltose, palatinose, trehalose, and xylose, isomerized sugars (glucose-fructose corn syrup, fructose-glucose corn syrup, mixed sugar isomerized sugars, etc.), sugar alcohols (erythritol, xylitol, lactitol, palatinit, sorbitol, reduced starch syrup, etc.), honey, and high-intensity sweeteners (sucralose, acesulfame potassium, thaumatin, stevia, aspartame, etc.).

[0045] The acidulant may be citric acid, malic acid, gluconic acid, tartaric acid, lactic acid, phosphoric acid, or salts thereof, and one or more of these may be used.

[0046] Vitamins include vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin E, niacin, inositol, etc.

[0047] Examples of minerals include calcium, magnesium, zinc, and iron.

[0048] Examples of thickeners include carrageenan, gellan gum, xanthan gum, gum arabic, tamarind gum, guar gum, locust bean gum, karaya gum, agar, gelatin, pectin, soybean polysaccharides, and carboxymethylcellulose (CMC).

[0049] Examples of emulsifiers include glycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, lecithin, plant sterols, and saponin.

[0050] Examples of antioxidants include vitamin C, tocopherol (vitamin E), enzyme-treated rutin, etc. The other components can be appropriately blended in amounts within the ranges that would normally be used by those skilled in the art in compositions such as foods and beverages, pharmaceuticals, etc.

[0051] The form of a composition prepared by appropriate means from the composition of the present invention and at least one other ingredient may be in the form of a solid composition such as powder, granules, capsules, tablets (including coated tablets such as sugar-coated tablets or multi-layer tablets, orally disintegrating tablets, chewable tablets, etc.), or in the form of a liquid composition such as a solution.

[0052] Furthermore, the composition of the present invention is relatively safe and can be easily taken continuously over a long period of time. Therefore, the composition of the present invention can be preferably used in foods and beverages, nutritional supplements, dietary supplements, and feed. The composition of the present invention has the above-mentioned functions or activities, and also contains a turmeric extract that has been conventionally taken, making it relatively safe. Furthermore, it can be added to various foods and beverages and taken continuously, and is expected to exert the desired functions or effects.

[0053] The composition of the present invention is preferably a composition to be taken continuously, specifically, a composition to be taken continuously once or twice a day, preferably for 4 weeks or more, more preferably for 8 weeks or more, and most preferably for 12 weeks or more.

[0054] <Method for improving insulin resistance> A further aspect of the present invention relates to a method for improving insulin resistance, comprising: administering the turmeric extract to a subject in need of improvement of insulin resistance; and improving the insulin resistance in the subject.

[0055] The turmeric extract used in the method according to this embodiment may be in the form of the composition of the present invention as described above.

[0056] The subject in the method according to this embodiment is typically a human, but may also be a mammal other than a human.

[0057] In the method according to this embodiment, the route of administration is preferably oral or nasal administration, with oral administration being particularly preferred.

[0058] In the method according to this embodiment, the dose of the turmeric extract administered to a subject is not particularly limited as long as it is an amount effective for improving insulin resistance. For example, if the subject is an adult, the turmeric extract is preferably administered to an adult per day, based on the components contained therein, so that the total amount of turmeronol A and turmeronol B is 100 μg or more, and / or turmeronol A is 17 μg or more, preferably 28 μg or more, more preferably 43 μg or more, even more preferably 57 μg or more, most preferably 80 μg or more, for example 100 μg, and / or turmeronol B is 5 μg or more, preferably 8 μg or more, more preferably 12 μg or more, even more preferably 16 μg or more, most preferably 20 μg or more, for example 100 μg, and / or bisacrolone is 80 μg or more, preferably 133 μg or more, more preferably 200 μg or more, even more preferably 267 μg or more, most preferably 360 μg or more, for example 400 μg.

[0059] The amount of administration or intake of the composition of the present invention varies depending on the age and weight of the subject, the route of administration / intake, the number of administrations / intakes, and the purpose of administration (e.g., improvement of insulin resistance, prevention, treatment, or improvement of diseases or symptoms related to insulin resistance), and can be varied widely at the discretion of those skilled in the art so as to achieve the desired effect. The proportion of turmeric extract in the composition is not particularly limited and may be adjusted appropriately depending on factors such as ease of production and the desired daily dose. Because turmeric extract is relatively safe, the intake amount can be further increased. The daily intake amount may be taken in a single dose or in several divided doses. The frequency of administration or intake is also not particularly limited and can be appropriately selected depending on various conditions such as the route of administration / intake, the age and weight of the subject, and the desired effect.

[0060] <Method for treating, preventing, or ameliorating a disease or disorder associated with insulin resistance> A further aspect of the present invention relates to a method for treating, preventing, or ameliorating a disease or disorder associated with insulin resistance, comprising administering the turmeric extract to a subject in need thereof, and treating, preventing, or ameliorating the disease or disorder associated with insulin resistance in the subject.

[0061] The turmeric extract used in the method according to this embodiment may be in the form of the composition of the present invention as described above.

[0062] The subject in the method according to this embodiment is typically a human, but may also be a mammal other than a human.

[0063] In the method according to this embodiment, the route of administration is preferably oral or nasal administration, with oral administration being particularly preferred.

[0064] In the method according to this embodiment, the dose of the turmeric extract administered to a subject is not particularly limited, as long as it is an amount effective for treating, preventing, or ameliorating a disease or disorder associated with insulin resistance. For example, if the subject is an adult, the turmeric extract is preferably administered to an adult per day, based on the components contained therein, so that the total amount of turmeronol A and turmeronol B is 100 μg or more, and / or turmeronol A is 17 μg or more, preferably 28 μg or more, more preferably 43 μg or more, even more preferably 57 μg or more, most preferably 80 μg or more, for example 100 μg, and / or turmeronol B is 5 μg or more, preferably 8 μg or more, more preferably 12 μg or more, even more preferably 16 μg or more, most preferably 20 μg or more, for example 100 μg, and / or bisacrolone is 80 μg or more, preferably 133 μg or more, more preferably 200 μg or more, even more preferably 267 μg or more, most preferably 360 μg or more, for example 400 μg.

[0065] [Reference Examples] (1) Methods for Preparing Turmeric Extracts Turmeric extracts were prepared by water extraction and supercritical gas extraction. In the water extraction method, turmeric rhizome parts were extracted with water (including hot water), and the resulting extract was then dried under reduced pressure to remove moisture. In the supercritical gas extraction method, turmeric rhizome parts were contacted with supercritical carbon dioxide, and the extracted components were mixed with vegetable oil. In the following examples, turmeric extracts prepared by each extraction method were mixed at a weight ratio of 8:1.

[0066] (2) Test Food Containing Turmeric Extract The test food is a soft capsule containing the turmeric extract prepared in Example 1 at 100 μg of turmeronol A (TA), 100 μg of turmeronol B (TB), and 400 μg of bisacronol per two capsules. The test food is a soft capsule made from vegetable oil, gelatin, glycerin, an emulsifier (soybean-derived), and beeswax as raw materials. The placebo food is a soft capsule of the above test food that does not contain turmeric extract.

[0067] (3) Amounts of Turmeronol A, Turmeronol B, and Bisacron in Turmeric Extract The amounts of turmeronol A, turmeronol B, and bisacron in the turmeric extract were measured using HPLC as follows. The amounts of turmeronol A, turmeronol B, and bisacron per gram of turmeric extract were confirmed to be 724 μg, 578 μg, and 2182 μg, respectively.

[0068] Turmeronol A analysis: Turmeric extract was weighed, water and ethyl acetate were added, and the mixture was centrifuged. The ethyl acetate was removed from the resulting supernatant by vacuum distillation, and then the mixture was dissolved in acetonitrile. The resulting liquid was used as the measurement sample and subjected to HPLC. HPLC was performed under the following conditions: Column: L-column ODS 5 μm (4.6 mm φ × 250 mm) Mobile phase: 48% acetonitrile (20 min) ⇒ 100% acetonitrile (5 min) ⇒ 48% acetonitrile (10 min) Flow rate: 1.0 mL / min Column temperature: 40°C Detection wavelength: 238 nm

[0069] Analysis of Turmeronol B Turmeric extract was weighed, water and ethyl acetate were added, and the mixture was centrifuged. The ethyl acetate was removed from the resulting supernatant by vacuum distillation, and the resulting solution was dissolved in acetonitrile. The resulting solution was used as the measurement sample and subjected to HPLC. HPLC was performed under the following conditions: Column: COSMOSIL 5PYE Packed Column (4.6 mm φ x 150 mm) Mobile phase: 57% methanol (30 min) ⇒ 100% methanol (5 min) ⇒ 57% methanol (15 min) Flow rate: 1.0 mL / min Column temperature: 40°C Detection wavelength: 238 nm

[0070] Analysis of Bisacron The turmeric extract was weighed, water and ethyl acetate were added, and the mixture was centrifuged to obtain a supernatant. The ethyl acetate was then removed under reduced pressure from the resulting supernatant, and the mixture was dissolved in acetonitrile. The resulting liquid was used as a measurement sample and subjected to HPLC. HPLC was performed under the following conditions: Column: Wakopak Navi C18-5 (4.6 mm φ x 250 mm) Mobile phase: 30% acetonitrile (20 minutes) ⇒ 20% acetonitrile (5 minutes) ⇒ 80% acetonitrile (10 minutes) Flow rate: 0.7 mL / min Column temperature: 50°C Detection wavelength: 240 nm

[0071] [Example 1] Oral glucose tolerance test (OGTT) Male and female subjects aged 40 to 69 were randomly assigned to two groups and, under double-blind conditions, had the subjects take two tablets of a test food containing turmeric extract or a placebo food not containing the extract once daily before dinner for 12 weeks (placebo group: n=42, turmeric extract group: n=39). After 12 weeks of taking the test food, an OGTT was performed and blood glucose and insulin levels were measured.

[0072] The specific method for the OGTT is as follows: Subjects fasted from the night before the test, and on the day of the test, blood was drawn immediately before glucose loading (0 minutes). Subjects then ingested 75 g of Trelan G solution (a partial starch hydrolysate solution), and blood was drawn 30, 60, and 120 minutes later, and blood glucose and insulin levels were measured. The results were shown as the change from immediately before glucose loading (0 minutes).

[0073] In addition, the Cederholm index (ISI), an index of insulin sensitivity, was calculated. The Cederholm index was proposed as an index of insulin sensitivity by Cederholm and Wibell (Cederholm, J. and Wibell, L. Diabetes Res Clin Pract. 10(2):167-75, 1990; Radikova, Z. Endocr Regul. 37(3):189-94, 2003). The ISI, which is the Cederholm index, was calculated. Cederholm is calculated according to the following formula: The higher this value, the higher the insulin sensitivity, and the lower this value, the lower the insulin sensitivity.

[0074] where 75000 is the oral glucose load in mg in the OGTT, G is the fasting blood glucose level (mmol / L), and G 120 is the blood glucose level (mmol / L) at 120 minutes of the OGTT, 1.15 is the factor for converting total venous glucose to plasma values ​​(not required if blood glucose is assessed in plasma), 180 is the factor for converting plasma glucose from mmol / L to mg / L, 0.19 is the volume of distribution of glucose per kg of body weight, m ​​is body weight (kg), 120 is the time of the OGTT (minutes), and I mean is the mean plasma insulin concentration during the OGTT (mU / L), and G mean is the mean plasma glucose concentration (mmol / L) during the OGTT.

[0075] Figures 1 and 2 show the changes in blood glucose (mg / dL) and insulin levels (μU / mL) from before (0 minutes) to 30, 60, and 120 minutes after ingestion of Trelan G solution. The data shown in Figures 1 and 2 are the mean ± SEM for the turmeric extract intake group (n = 39) or the placebo group (n = 42), and ** indicates p < 0.01 vs. the placebo group. As can be seen from Figures 1 and 2, ingestion of Trelan G solution caused a rapid increase in both blood glucose and insulin levels from 0 minutes (baseline).

[0076] As shown in Figure 1, blood glucose levels in the turmeric extract group were significantly lower at both 60 and 120 minutes after glucose loading compared to the placebo group. This suggests that turmeric extract intake suppresses the rise in blood glucose levels after meals (or accelerates the disappearance of blood glucose levels (i.e., accelerates the return to baseline)). Furthermore, as shown in Figure 2, insulin levels were significantly lower in the turmeric extract group at 120 minutes compared to the placebo group. After a meal, insulin is secreted in large amounts from the pancreas to lower blood glucose levels, but as blood glucose levels fall, insulin becomes unnecessary and insulin levels return to normal. Therefore, as shown in Figure 2, blood glucose levels in the turmeric extract group were significantly lower than those in the placebo group, and it is thought that insulin levels also decreased accordingly. Furthermore, as shown in Figure 3, the change from week 0 to week 12 in the Cederholm index (ΔCederholm index), an index of insulin sensitivity, in the turmeric extract group was significantly higher than in the placebo group (p < 0.05), suggesting that turmeric extract improves insulin sensitivity.

[0077] There are various mechanisms that control postprandial blood glucose levels, including glucagon and hepatic gluconeogenesis. However, because insulin levels rise rapidly, insulin has a much greater influence than other control factors. Therefore, the improvement in blood glucose levels due to turmeric extract intake is likely due to the promotion of insulin secretion or the improvement of insulin resistance. In this study, although an increase in insulin levels (promoting insulin secretion) was not observed in the turmeric extract group, an improvement in blood glucose levels was observed (Figures 1 and 2). Furthermore, improved insulin sensitivity was also observed in the turmeric extract group (Figure 3). This can be interpreted as an improvement in insulin effectiveness, i.e., an improvement in insulin resistance.

[0078] These results demonstrate that turmeric extract intake improves insulin resistance.

[0079] All patents, patent applications and publications cited herein are hereby incorporated by reference in their entirety.

Claims

1. A composition for improving insulin resistance, comprising turmeric extract as an active ingredient.

2. A composition for treating, preventing or ameliorating a disease or disorder associated with insulin resistance, comprising turmeric extract as an active ingredient.

3. The composition according to claim 1 or 2, wherein the composition consists solely of turmeric extract as an active ingredient.

4. The composition according to claim 1 or 2, wherein the turmeric extract comprises a turmeric extract with at least one extraction solvent selected from the group consisting of water and hydrophilic organic solvents.

5. The composition according to claim 1 or 2, wherein the turmeric extract comprises a mixture of a turmeric extract obtained by extraction with water and a turmeric extract obtained by extraction with supercritical carbon dioxide.

6. The composition according to claim 1 or 2, wherein the turmeric extract contains at least one of turmeronol A, turmeronol B and bisacron.

Images