Composition

A wasabi extract with an organic solvent composition addresses liver function decline and fat accumulation by improving enzyme values and reducing liver fat, providing therapeutic benefits for NAFLD.

WO2025159204A1PCT designated stage Publication Date: 2025-07-31EN OTSUKA PHARM CO LTD
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Patent Information

Application Number
PCT/JP2025/002300
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-01-25
Filing Date
2025-01-24
Publication Date
2025-07-31

AI Technical Summary

Technical Problem

Current solutions do not effectively address the decline in liver function and fat accumulation in the liver due to changes in diet and stress, with wasabi extract's potential for improving liver function and preventing fat accumulation being unrecognized.

Method used

A composition containing wasabi extract with an organic solvent, which can be administered orally, is developed to improve liver function, reduce liver fat, and prevent fat accumulation.

Benefits of technology

The composition effectively lowers liver function enzyme values, reduces liver fat, and prevents fat accumulation, offering potential therapeutic benefits for conditions like non-alcoholic fatty liver disease (NAFLD).

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to a composition for improving the function of the liver, said composition containing a Japanese horseradish (wasabi) extract obtained using an organic solvent.
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Description

composition

[0001] The present invention relates to a composition.

[0002] In recent years, various lifestyle-related diseases have become a problem due to changes in eating habits, unbalanced diets, stress, etc. One of these is the decline in liver function and the accumulation of fat in the liver.

[0003] For example, Non-Patent Document 1 discloses that sulforaphane, which is abundant in broccoli sprouts, etc., has the function of lowering ALT, a liver function enzyme level in the blood. Non-Patent Document 2 discloses that curcumin and bisacron derived from autumn turmeric have the function of improving γ-GTP, AST, and ALT, which are liver function enzyme levels.

[0004] Kagome Co., Ltd., "Kagome Mail Order Health Direct Delivery Sulforaphane," [online], accessed November 2, 2023, Internet <URL: https: / / shop.kagome.co.jp / lp2 / sulforaphane / 019r_hk / ?adid=SPlsh0j&argument=Yv9hMnx2&dmai=a639acce7da98b&gad=1&gclid=EAIaIQobChMI2Ian-oaIgAMVmAN7Bx0O1Q9bEAAYASAAEgL3VvD_BwE> House Wellness Foods Co., Ltd., "Curbisa," [online], accessed November 2, 2023, Internet <URL: https: / / curbisa.house-wf.co.jp / >

[0005] However, it was not known that this wasabi extract using an organic solvent had the effect of improving liver function and liver function enzyme levels, preventing fat accumulation in the liver, or reducing liver fat.

[0006] Therefore, one of the objects of the present invention is to provide a novel composition containing the wasabi extract extracted with an organic solvent, which exhibits an effect related to liver function.

[0007] As a result of extensive research, the present inventors have found that a composition containing this wasabi extract extracted with an organic solvent can solve the above problems, and have thus completed the present invention.

[0008] That is, the present invention is as follows. [1] A composition for improving liver function, comprising the present organic solvent-derived wasabi extract. [2] A composition for improving liver function enzyme levels, comprising the present organic solvent-derived wasabi extract. [3] The composition according to [2], wherein the liver function enzyme levels are AST or ALT levels. [4] A composition for preventing fat accumulation in the liver and / or reducing liver fat, comprising the present organic solvent-derived wasabi extract. [5] The composition according to any of [1] to [4], for oral administration.

[0009] The present invention also encompasses the following aspects. [A1] A method for improving liver function, comprising administering to a subject in need thereof a physiologically effective amount of the present wasabi extract dissolved in an organic solvent. [A2] A method for improving liver function enzyme levels, comprising administering to a subject in need thereof a physiologically effective amount of the present wasabi extract dissolved in an organic solvent. [A3] The method described in [A2], wherein the liver function enzyme levels are AST or ALT levels. [A4] A method for preventing fat accumulation in the liver and / or reducing liver fat, comprising administering to a subject in need thereof a physiologically effective amount of the present wasabi extract dissolved in an organic solvent. [A5] The method described in any of [A1] to [A4], wherein the present wasabi extract dissolved in an organic solvent is orally administered.

[0010] [B1] The wasabi extract dissolved in an organic solvent, for use in a method for improving liver function. [B2] The wasabi extract dissolved in an organic solvent, for use in a method for improving liver function enzyme levels. [B3] The wasabi extract dissolved in an organic solvent according to [B2], wherein the liver function enzyme levels are AST or ALT levels. [B4] The wasabi extract dissolved in an organic solvent, for use in a method for preventing fat accumulation in the liver and / or reducing liver fat. [B5] The wasabi extract dissolved in an organic solvent according to any of [B1] to [B4], for oral administration.

[0011] [C1] Use of the present wasabi extract in an organic solvent for improving liver function. [C2] Use of the present wasabi extract in an organic solvent for improving liver function enzyme levels. [C3] The use according to [C2], wherein the liver function enzyme levels are AST or ALT levels. [C4] Use of the present wasabi extract in an organic solvent for preventing fat accumulation in the liver and / or reducing liver fat. [C5] The method according to any of [C1] to [C4], wherein the present wasabi extract in an organic solvent is orally administered.

[0012] [D1] Use of the present wasabi extract with an organic solvent in the manufacture of a composition for improving liver function. [D2] Use of the present wasabi extract with an organic solvent in the manufacture of a composition for improving liver function enzyme levels. [D3] The use according to [D2], wherein the liver function enzyme levels are AST or ALT levels. [D4] Use of the present wasabi extract with an organic solvent in the manufacture of a composition for preventing fat accumulation in the liver and / or reducing liver fat. [D5] The use according to any of [D1] to [D4], wherein the composition is taken orally.

[0013] [E1] A food for improving liver function, comprising the present organic solvent-derived wasabi extract. [E2] A food for improving liver function enzyme levels, comprising the present organic solvent-derived wasabi extract. [E3] The food according to [E2], wherein the liver function enzyme levels are AST or ALT levels. [E4] A food for preventing fat accumulation in the liver and / or reducing liver fat, comprising the present organic solvent-derived wasabi extract. [E5] The food according to any of [E1] to [E4], for oral administration.

[0014] [F1] A pharmaceutical or quasi-drug for improving liver function, comprising the present organic solvent-derived wasabi extract. [F2] A pharmaceutical or quasi-drug for improving liver function enzyme levels, comprising the present organic solvent-derived wasabi extract. [F3] The pharmaceutical or quasi-drug according to [F2], wherein the liver function enzyme levels are AST or ALT levels. [F4] A pharmaceutical or quasi-drug for preventing fat accumulation in the liver and / or reducing liver fat, comprising the present organic solvent-derived wasabi extract. [F5] A pharmaceutical or quasi-drug according to any of [F1] to [F4], for oral administration.

[0015] In the above [1] to [5] and in each of the above [A1] to [F5] aspects, the present wasabi extract may be an extract prepared using an organic solvent from crushed powder of the present wasabi, an extract prepared using an organic solvent from the roots and / or rhizomes of the present wasabi, or an extract prepared using an organic solvent from fine powder of the roots and / or rhizomes of the present wasabi.

[0016] According to the present invention, a composition for improving liver function containing the present organic solvent-derived wasabi extract can be provided. It is also possible to provide a composition for improving liver function enzyme levels containing the present organic solvent-derived wasabi extract. It is also possible to provide a composition for preventing fat accumulation in the liver and / or reducing liver fat containing the present organic solvent-derived wasabi extract.

[0017] An outline diagram of Study 1 is shown. The results of macroscopic observation of the liver, HE staining of hepatocytes, and Sirius red staining in Study 1 are shown. The measurement results of liver TG, blood ALT, blood AST, hepatic steatosis score, and NAS in Study 1 are shown. The measurement results of average body weight transition, average food intake, average calorie intake, body weight at necropsy, liver weight, and relative liver weight in Study 2 are shown. The measurement results of liver TG, blood ALT, and blood AST in Study 2 are shown. The results of HE staining of hepatocytes, and the measurement results of hepatic steatosis score and NAS in Study 2 are shown. The measurement results of inflammatory markers in Study 3 are shown.

[0018] Hereinafter, embodiments of the present invention will be described in detail. Note that the present invention is not limited to the following embodiments, and various modifications can be made within the scope of the present invention.

[0019] (Composition) The composition of the present embodiment contains a present wasabi extract extracted with an organic solvent. In this specification, present wasabi refers to Wasabi japonica (or Eutrema wasabi).

[0020] In this embodiment, the wasabi extract obtained by extracting wasabi with an organic solvent refers to an extract obtained by extracting wasabi with an organic solvent. The part of wasabi used for extraction is not particularly limited, and for example, parts of rootlets, rhizomes, stems, leaves, flower stalks, flowers, etc., or combinations thereof, can be used. From the viewpoint of more effectively and reliably achieving the effects of the present invention, it is preferable to extract wasabi containing roots and / or rhizomes with an organic solvent. The organic solvent may be any solvent containing an organic solvent, and may be, for example, a mixed solvent with water.

[0021] The state of the wasabi used for extraction is not particularly limited, but from the viewpoint of extraction efficiency, it is preferably in a pulverized state by methods such as freeze-pulverization, grating, or mashing. Furthermore, wasabi immediately after harvest or wasabi stored for a certain period after harvest may be used. When storing wasabi for a certain period, the storage temperature is not particularly limited, and it may be stored at, for example, −78°C to 100°C. The wasabi used for extraction may be a pulverized powder of wasabi, or may be a pulverized powder of the root and / or rhizome of wasabi. When pulverized powder of the root and / or rhizome of wasabi is used, the pulverized powder may include parts other than the root and / or rhizome.

[0022] The organic solvent used in the extraction of the present wasabi is not particularly limited, and known organic solvents can be used. Examples of organic solvents include polar solvents and nonpolar solvents. Examples of polar solvents include, but are not limited to, methanol, ethanol, 1-butanol, 2-butanol, 1-propanol, 2-propanol, glycerin, edible oils and fats, acetone, ethyl methyl ketone, diethyl ether, ethyl acetate, methyl acetate, and dichloromethane. Examples of nonpolar solvents include, but are not limited to, cyclohexane, butane, and propane. Among these, polar solvents may be used, such as ethanol, acetone, diethyl ether, or ethyl acetate, from the viewpoint of more effectively and reliably achieving the effects of the present invention. Furthermore, one or more organic solvents may be used in combination. The temperature at which the present wasabi is extracted is not particularly limited, and may be above the melting point and below the boiling point of the organic solvent used. Extraction can be performed under conditions such as room temperature, ice cooling, or heating.

[0023] After extracting wasabi with an organic solvent, the extract may be concentrated to obtain the wasabi extract with an organic solvent. The method for concentrating the extract is not particularly limited, but examples include evaporation, membrane concentration, and freeze concentration. Furthermore, before concentrating the extract, the extract may be dried with a drying agent such as anhydrous sodium sulfate. Furthermore, the extract may be filtered before concentrating it.

[0024] After extracting wasabi with an organic solvent, the extract may be adsorbed or included in a carbohydrate such as dextrin to obtain the organic solvent-based wasabi extract. The carbohydrate such as dextrin is not particularly limited, but for example, cyclodextrin is preferred, and α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin are more preferred. Alternatively, the extract may be concentrated and then adsorbed onto a carbohydrate, or the carbohydrate to which the extract is adsorbed may be dried to obtain the organic solvent-based wasabi extract.

[0025] The components contained in the present wasabi extract with an organic solvent are not particularly limited as long as they are components derived from the present wasabi, and examples thereof include proteins, lipids, carbohydrates, salts, etc. Further, the components contained in the present wasabi extract with an organic solvent also include isothiocyanates derived from the present wasabi, and it is preferable that 6-methylsulfinylhexyl isothiocyanate (hereinafter also referred to as "hexarafan") be included.

[0026] The content of each component contained in the organic solvent-derived wasabi extract is not particularly limited, but examples are as follows: Per 100% by mass of the organic solvent-derived wasabi extract, the protein content is preferably 2.5 to 3.5% by mass, and more preferably 2.7 to 3.2% by mass. Per 100% by mass of the organic solvent-derived wasabi extract, the lipid content is preferably 0.3 to 1.5% by mass, and more preferably 0.5 to 1.2% by mass. Per 100% by mass of the organic solvent-derived wasabi extract, the hexarafan content is preferably 0.5% by mass or more, and more preferably 0.7% by mass or more. Per 100% by mass of the organic solvent-derived wasabi extract, the carbohydrate content is preferably 85 to 96% by mass, and more preferably 87 to 94% by mass. Note that, when the organic solvent-derived wasabi extract is obtained by extracting wasabi with an organic solvent and then adsorbing or inclusion-forming the extract on a carbohydrate such as dextrin, the carbohydrate used for adsorption or inclusion is also included in the carbohydrate content. The sodium salt content is preferably 0.0015 to 0.0035% by mass, and more preferably 0.0020 to 0.0030% by mass, per 100% by mass of the organic solvent-derived wasabi extract. The sugar content is preferably 1.0 to 3.0% by mass, and more preferably 1.5 to 2.5% by mass, per 100% by mass of the organic solvent-derived wasabi extract. In this specification, the sodium salt content may be understood as the sodium equivalent content of the sodium salt content. Alternatively, the sodium salt content may be understood as the sodium ion content. The content of each of the above components may be the content per 100% by mass of the wasabi extract obtained by extracting wasabi with an organic solvent and then adsorbing or including the extract onto a carbohydrate such as dextrin.As an example, the wasabi extract prepared using an organic solvent preferably contains 2.5 to 3.5% by mass of protein, and more preferably 2.7 to 3.2% by mass of protein, preferably 0.3 to 1.5% by mass of lipids, and more preferably 0.5 to 1.2% by mass of lipids, preferably 0.5% by mass or more, and more preferably 0.7% by mass or more of hexaraphane, preferably 85 to 96% by mass of carbohydrates, and more preferably 87 to 94% by mass of carbohydrates, and preferably 0.0015 to 0.0035% by mass of sodium as a salt, and more preferably 0.0020 to 0.0030% by mass of sodium. The content of each component, as an example, may be any combination of a preferred amount and a more preferred amount. Furthermore, as part of the carbohydrate content, sugars may be contained in an amount of 1.0 to 3.0% by mass, or 1.5 to 2.5% by mass, per 100% by mass of the wasabi extract obtained with an organic solvent.

[0027] The form of the present wasabi extract obtained with an organic solvent is not particularly limited, but examples include liquid, solid, powder, etc., with powder being preferred.

[0028] (Improvement of Liver Function) The composition of this embodiment has the effect of improving liver function. In this embodiment, improving liver function is not particularly limited, but examples thereof include improving liver function enzyme levels. Improving liver function enzyme levels means that liver function enzyme levels are reduced compared to before taking the composition of this embodiment. It may also mean reducing liver function enzyme levels that are high in the healthy range. Examples of liver function enzyme levels include AST (GOT), ALT (GPT), γ-GTP, etc. The composition of this embodiment preferably improves AST and ALT levels.

[0029] (Preventing Fat Accumulation in the Liver, Reducing Liver Fat) The composition of this embodiment has the effect of preventing fat accumulation in the liver and / or reducing liver fat. In this embodiment, preventing fat accumulation in the liver means, but is not limited to, for example, that the liver weight does not increase or the number of fat droplets does not increase after ingesting the composition of this embodiment compared to before ingesting the composition of this embodiment. Furthermore, reducing liver fat in this embodiment means, but is not limited to, for example, that the liver weight does not decrease or the number of fat droplets does not decrease after ingesting the composition of this embodiment compared to before ingesting the composition of this embodiment. Furthermore, preventing fat accumulation in the liver and / or reducing liver fat means, but is not limited to, for example, that the triglyceride (TG) level, which is also an indicator of liver function, is improved. Generally, an increase in TG in the liver can cause fatty liver.

[0030] Furthermore, the effect of improving liver function and the effect of preventing liver fat accumulation and / or reducing liver fat may be related to each other. That is, the effect of preventing liver fat accumulation and / or reducing liver fat may be exerted by improving liver function, and the effect of preventing liver fat accumulation and / or reducing liver fat may be exerted by improving liver function.

[0031] Furthermore, the effects of improving liver function, preventing fat accumulation in the liver, and reducing liver fat are more effective when this wasabi extract is administered using an organic solvent than when hexarafan is administered alone.

[0032] The composition of the present embodiment can improve, alleviate, treat, and / or prevent, for example, fatty liver, NAFLD (non-alcoholic fatty liver disease), etc. Generally, the etiology and progression mechanism of NAFLD are complex. However, for example, a pathway is known in which oxidative stress is caused by fatty liver or metabolic abnormalities in the liver, resulting in increased inflammatory signals (e.g., inflammatory markers, etc.) and increased levels of liver function enzymes in the blood, leading to the progression of NAFLD (e.g., Reference Material 1: Kenichi Ikeshima, Journal of the Japanese Society of Internal Medicine, Vol. 105 (2016), No. 1, pp. 15-24; Reference Material 2: Tomomi Ogiso, Journal of the Japanese Society of Internal Medicine, Vol. 105 (2016), No. 1, pp. 31-37). Here, the composition of the present embodiment can, for example, reduce liver fat, thereby preventing the production of oxidative stress and improving, alleviating, treating, and / or preventing NAFLD. Furthermore, the effect of improving, alleviating, treating, and preventing fatty liver, NAFLD, etc. may be exerted by an effect of improving liver function, an effect of preventing fat accumulation in the liver, and / or an effect of reducing liver fat. NAFLD may be a disease called metabolic dysfunction associated steatotic liver disease (MASLD).

[0033] The composition of the present embodiment is not particularly limited, but is preferably taken orally or parenterally, and more preferably taken orally. The composition of the present embodiment is not particularly limited, but is preferably for human use, for example.

[0034] (Foods and Pharmaceuticals) The composition of this embodiment may be used as a food or food additive, a pharmaceutical, or a quasi-drug. In this embodiment, the dosage or intake of the composition is not particularly limited, and may be determined depending on, for example, the age and weight of the patient or user, symptoms, administration time, dosage form, administration method, drug combination, etc. When ingested as a food, the total amount of the composition is not particularly limited, but is preferably 10 to 1000 mg per adult per day, more preferably 20 to 800 mg, even more preferably 30 to 700 mg, and even more preferably 40 to 200 mg / day. When orally administered as a pharmaceutical, the total amount of the composition is not particularly limited, but is preferably 10 to 1000 mg per adult per day, more preferably 20 to 800 mg, even more preferably 30 to 700 mg, and even more preferably 40 to 200 mg / day. It may be administered once a day or in divided doses (2 to 5 times a day).

[0035] The wasabi extract obtained with an organic solvent according to this embodiment can be used as a food or food additive. Examples of such foods include, but are not limited to, general foods, health foods, functional foods, nutritional supplements, health-related foods (e.g., foods for specified health uses, foods with functional claims, and foods with nutrient functions), and foods for special dietary uses (e.g., foods for infants, foods for pregnant women, and foods for the sick). The wasabi extract obtained with an organic solvent according to this embodiment may also be provided or sold as a food labeled with uses related to improving liver function, improving liver function enzyme levels, improving AST or ALT levels, preventing liver fat accumulation, reducing liver fat, etc. Such "labeling" includes all acts intended to inform consumers of the intended uses. As long as the expression can evoke or infer the intended uses, it is considered a "labeling" act in this embodiment, regardless of the purpose, content, or medium of the labeling.

[0036] The labeling is not particularly limited, but is preferably labeling that claims, for example, that it improves liver function, improves liver function enzyme values, improves AST or ALT values, prevents fat accumulation in the liver, reduces liver fat, etc. in healthy individuals, and more preferably labeling as a food that has been approved or notified as necessary (health functional foods such as specified health foods, functional food with functional claims and nutrient functional foods, foods for special dietary uses, etc.). Foods that have been approved or notified as having functional claims can be distinguished from general foods.

[0037] The form of the food or food additive is not particularly limited, but examples include orally ingestible forms such as solutions, suspensions, powders, and solid moldings. Examples of such forms include, but are not limited to, supplements (powders, granules, soft capsules, hard capsules, tablets, chewable tablets, rapidly disintegrating tablets, syrups, liquids, etc.), beverages (carbonated drinks, lactic acid drinks, sports drinks, fruit juice drinks, vegetable drinks, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, nutritional drinks, alcoholic drinks, etc.), sweets (gummy candies, jellies, gum, chocolate, cookies, candy, caramel, Japanese sweets, snacks, etc.), instant foods (instant noodles, retort foods, canned foods, microwave foods, instant soups, miso soups, freeze-dried foods, etc.), oils, oily foods (mayonnaise, dressings, butter, cream, margarine, etc.), flour products (bread, pasta, noodles, cake mixes, breadcrumbs, etc.), seasonings (sauces, tomato-processed seasonings, flavor seasonings, cooking mixes, soups, etc.), and processed livestock products (livestock hams, sausages, etc.).

[0038] The food may contain, but is not limited to, various nutrients, various vitamins (vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, vitamin K, etc.), various minerals (magnesium, zinc, iron, sodium, potassium, selenium, etc.), dietary fiber, stabilizers such as dispersants and emulsifiers, sweeteners, taste components (citric acid, malic acid, etc.), flavors, royal jelly, propolis, agaricus, etc.

[0039] The composition of the present embodiment can be used as a pharmaceutical or quasi-drug. The dosage form of the pharmaceutical or quasi-drug is not particularly limited, but examples thereof include powders, granules, pills, soft capsules, hard capsules, tablets, chewable tablets, rapidly disintegrating tablets, syrups, liquids, suspensions, etc. Furthermore, the pharmaceutical or quasi-drug may be administered orally or parenterally, but is preferably administered orally.

[0040] Pharmaceutical or quasi-drug preparations can be prepared in the desired dosage form using conventional methods. In preparing the preparations, additives may be used in addition to the active ingredient. Examples of additives include, but are not limited to, animal and vegetable oils such as soybean oil, safflower oil, olive oil, germ oil, sunflower oil, beef tallow, and sardine oil; polyhydric alcohols such as polyethylene glycol, propylene glycol, glycerin, and sorbitol; surfactants such as sorbitan fatty acid esters, sucrose fatty acid esters, glycerin fatty acid esters, and polyglycerin fatty acid esters; excipients such as purified water, lactose, starch, crystalline cellulose, D-mannitol, lecithin, gum arabic, sorbitol solution, and sugar solution; sweeteners, colorants, pH adjusters, flavorings, binders, disintegrants, stabilizers, and lubricants. Liquid preparations may be dissolved or suspended in water or other suitable media at the time of administration. Tablets and granules may be coated using well-known methods.

[0041] The present embodiment will be described in more detail below with reference to examples and comparative examples, but the present embodiment is not limited to these examples.

[0042] <Study 1> A study was conducted to determine the mouse model to be used in the study. [Test Method] Approximately 1-year-old mice (C57BL / 6J, male, purchased from Jackson Laboratory Japan) were divided into an LFD group fed a normal diet and an HFD group fed a high-fat diet on day 0 of the study. Each group consisted of five mice. The normal diet contained soybean oil as fat, with approximately 12% of the calories derived from fat. On the other hand, the high-fat diet contained soybean oil and lard as fat, with approximately 60% of the calories derived from fat. From day 0 to day 62 of the study, mice were fed approximately 5g of normal or high-fat diet once a day and allowed to eat ad libitum. They were fasted from the evening of day 62 and necropsied on day 63. The test method was based on Ishizuka, J. Gastroenterol. Hepatol. 2020.

[0043] [Test Results] Visual observation of the liver revealed that the HFD group had larger livers and more accumulated fat than the LFD group. Furthermore, hematoxylin-eosin (HE) staining of hepatocytes revealed that the HFD group had a greater number of white lipid droplets than the LFD group. Sirius red staining of hepatocytes revealed no staining in either the HFD or LFD groups, indicating no progression of fibrosis (Figure 2). Measurement of liver triglycerides (TG) revealed increased TG levels in the HFD group compared to the LFD group. Furthermore, blood ALT and AST measurements revealed increased ALT and AST levels in the HFD group compared to the LFD group, indicating elevated blood liver function enzyme levels. Furthermore, Hepatology. 2005 Jun;41(6):1313-21, and according to the table below, the hepatic steatosis score and NAS (NAFLD Activity Score) were evaluated. The HFD group was found to have a higher score than the LFD group (Figure 3).

[0044]

[0045] Based on the above, it was determined that the model used in <Test 1> was appropriate as an animal model for evaluating liver function and liver function enzyme values, and it was decided to use the same model as in <Test 1> in <Tests 2 and 3>.

[0046] <Test 2> A test was conducted to confirm the inhibitory effect of organic solvent-based wasabi extract on hepatic fat deposition and the suppression of increases in blood liver function enzyme levels. [Test Method] As in <Test 1>, a 55-week-old mouse model was used. Each group was fed approximately 5 g of normal or high-fat diet ad libitum once daily from Day 0 to Day 64 or 65 of the test, according to the table below. Kinjirushi Wasabi Sulfinyl (registered trademark), sold by Kinjirushi Wasabi Co., Ltd., was used as the organic solvent-based wasabi extract. Kinjirushi Wasabi Sulfinyl (registered trademark) is the wasabi extract, and per 100 g of Kinjirushi Wasabi Sulfinyl (registered trademark), contains 2.9 g of protein, 0.7 g of lipids, 93.8 g of carbohydrates, 25.0 mg of sodium, and 1.8 g of sugars. In addition, Kinjirushi Wasabi Sulfinyl (registered trademark) contains more than 0.8% hexaraphane and cyclic oligosaccharides as carbohydrates.

[0047] [Test Results] The mean body weight transition, mean food intake, mean calorie intake, body weight at necropsy, liver weight, and relative liver weight were measured for each group (Figure 4). No differences were observed in mean food intake, calorie intake, or body weight at necropsy between the high-fat diet groups. On the other hand, liver weight was low in the LW and MW groups, especially in the MW group. Next, liver TG, blood ALT, and blood AST were measured (Figure 5). As a result, high-fat diet intake was observed to increase liver TG and blood liver function enzyme levels. On the other hand, liver TG, blood ALT, and blood AST were low in the LW and MW groups, especially in the MW group. Next, liver steatosis score and NAS (NAFLD Activity Score) were evaluated as in <Test 1> (Figure 6). The scores were calculated using the HE staining results of hepatocytes shown in Figure 6. As a result, the LW group and the MW group had lower hepatic steatosis scores and NAS values ​​compared to the HFD group.

[0048] <Test 3> A test was conducted to confirm the effect of organic solvent-based wasabi extract on inflammatory gene expression. [Test Method] For the mice used in <Test 2>, RNA was extracted from livers collected at autopsy according to the ISOGEN II protocol. Real-time PCR using the intercalator method was performed to measure the gene expression levels of inflammatory markers IL-6, TNF, Ccl2, and Ccr2 in the liver. TATA binding protein (Tbp) was used as an endogenous control, and the expression level ratio was calculated (Figure 7). As a result, an increase in inflammatory markers was observed in the HFD group ingesting a high-fat diet. On the other hand, the LW and MW groups showed a suppressed increase in inflammatory markers compared to the HFD group, indicating that oxidative stress was prevented and suppressed. Therefore, it was found that organic solvent-based wasabi extract can suppress liver inflammation, which is involved in the progression of NAFLD, and is effective in the treatment and prevention of NAFLD.

Claims

1. A composition for improving liver function, containing the wasabi extract with an organic solvent.

2. A composition for improving liver function enzyme values, containing the wasabi extract with an organic solvent.

3. The composition according to claim 2, wherein the liver function enzyme value is the value of AST or ALT.

4. A composition for preventing fat accumulation in the liver and / or reducing liver fat, containing the wasabi extract with an organic solvent.

5. The composition according to any one of claims 1 to 4, for oral ingestion.

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