WO2006135084A1

WO2006135084A1 - Prophylactic or therapeutic agent for steatohepatitis or fatty liver

Info

Publication number: WO2006135084A1
Application number: PCT/JP2006/312209
Authority: WO
Inventors: Hironori Koga
Original assignee: Kurume University
Priority date: 2005-06-14
Filing date: 2006-06-13
Publication date: 2006-12-21
Also published as: JPWO2006135084A1

Abstract

Disclosed are a pharmaceutical for the prevention or treatment of steatohepatitis, particularly non-alcoholic steatohepatitis or fatty liver and a beverage/food for the prevention or amelioration of the disease. A prophylactic or therapeutic agent for steatohepatitis, non-alcoholic steatohepatitis or fatty liver comprising luteolin and/or a glucoside thereof; and a beverage/food for the prevention or amelioration of steatohepatitis, non-alcoholic steatohepatitis or fatty liver comprising luteolin and/or a glucoside thereof, preferably the beverage/food having a label on which the words 'this product is intended to be used for the prevention or amelioration of the disease' are described.

Description

Specification

Technical field for prevention or treatment of steatohepatitis or fatty liver

The present invention relates to a medicament for preventing or treating steatohepatitis, particularly non-alcoholic steatohepatitis, or fatty liver, and a food or drink for preventing or ameliorating these diseases.

Background art

The main causes of fatty liver, a condition in which neutral fat accumulates in the liver, are obesity, excessive consumption of alcohol, and diabetes. The liver synthesizes neutral fats from dietary fats and carbohydrates, and these neutral fats bind to proteins and enter blood vessels from the liver and are mainly used as energy sources. However, there is a limit to the ability of the liver to carry out neutral fat. When neutral fat is synthesized beyond that capacity, neutral fat accumulates in hepatocytes and becomes fatty liver. In fatty liver, there are almost no subjective symptoms, and diagnosis is performed mainly by ultrasonography and partly by CT, triggered by mild abnormal liver function. Long-lived fatty liver with particularly fat accumulation caused liver damage, and some were thought to progress to liver fibrosis, chronic hepatitis, and cirrhosis, but lack of definitive evidence and conventional fatty liver progresses It was considered a benign condition that never happened. Non-alcoholic steatohepati tis (hereinafter referred to as NASH), which is a simple steatosis without inflammation and non-alcoholic steatohepati tis, which is a progressive pathology with inflammation And has attracted attention in recent years. Although NASH has no history of alcohol consumption (less than 20 g in terms of ethanol per day), it shows similar findings to alcoholic liver damage, about half are progressive, and about 20% develop cirrhosis in 10 years. It is a well-developed condition, and it is known that the condition is largely related to obesity, lifestyle-related diseases such as diabetes and hyperlipidemia. In Europe and the United States, it is estimated that 20 to 30% of the population suffers from fatty liver (including nonalcoholic steatohepatitis), and about 3% suffers from nonalcoholic hepatitis. ing. Even in Japan, eating habits With the increase in the obese population and lifestyle-related diseases due to westernization (from 1955 to 1999, obesity population increased about 4 times for men and about 3 times for women), fatty liver patients, nonalcoholic fatty liver disease The number of patients is also expected to increase, and it is estimated that there are patients equivalent to those in the West. For example, there are about 15 million Japanese obese over 15 years old and 10 million women, and overweight (BMI 30 or more) force S 2.5 million. Some estimate that there are 10,000 NASH patients (Adiposcience 1, 305, 200 ⁵ ). In the United States, where the frequency of NASH is extremely high at 3-5%, we consider simple fatty liver as a NASH reserve group, and focus on reducing the first choice of treatment for both NASH and simple fatty liver. Often treated as (non-alcoholic fatty liver disease). Against this background, the development of preventive or therapeutic drugs for fatty liver (including non-alcoholic steatohepatitis) is eagerly desired, but the current situation is that it is not satisfied in clinical practice.

On the other hand, it is a kind of flavonoid, luteolin ( ³ , 4, 4 ', 5, ⁷ -tetrahydroxy flavone) or its glycoside, which is a natural product contained in celery, peppers, spring chrysanthemum, chamomile, shiso, etc. (3, one-dalk mouth, 6-C-fucoside, 6-C-quinoside, 7-O-rutinoside, etc.) are known to show various medicinal effects. For example, Japanese Patent Application Laid-Open No. 5_4 3 4 6 9 discloses that luteolin 1,3, 1 dalcuronide and the like reduce diarrhea induced by camptothecin, which is an antitumor agent. Japanese Laid-Open Patent Publication No. HEI 7-3 33 7 discloses that luteolin, luteolin and luteolin 1 3′-dalcronide have UDP-dalcronyl transferase inhibitory activity. — 7-Rutinoside and other external preparations are disclosed in Japanese Patent Application Laid-Open No. Hei 10-2 9 8 98 98, in which luteolin or the like obtained from egoma or perilla seeds or defatted seeds has a lipoxygenase inhibitory action, Japanese Patent Application Laid-Open No. 2 00 0-8 6 5 1 0 discloses that seeds of egoma and perilla or the like thereof are effective in preventing or treating allergic diseases, inflammation, circulatory system diseases or cancer metastasis. Obtained from defatted seed Etc. has a histamine release inhibiting activity Teorin, for example, a medicament for the prevention and treatment of allergic diseases, quasi In Japanese Patent Application Laid-Open No. 2000-0 2 3 9 1 3 6, luteolin obtained from perilla and pegoma seeds or leaves against oral bacteria, It has excellent antibacterial activity and can be applied to foods and drinks and oral products as an oral antibacterial agent. JP-A-2001-1 1 46 7 5 discloses that flavonoids such as vitamin K and luteo 5 phosphorus JP-A No. 2000-11075 3 discloses that a composition containing a mixture of aldehydes has an amylase inhibitory action, such as luteolin obtained from an olive leaf, an amylase inhibitor, and a blood sugar level increase inhibitor. Japanese Patent Application Laid-Open No. 20 0-2 2 5 5 7 78 describes that luteolin 7-glycoside and the like can be used in light citral products by light. Citral reduction or 0 for the control of citral-derived odors In fact, Japanese Patent Application Laid-Open No. 2003-34071 discloses that since luteolin itself has an antitumor action, it can be used together with a speridine glycoside agent for antitumor activity. No. 00 3-1 2 8 5 5 8 discloses that luteolin-O-rutinoside can be used as a therapeutic agent for allergic rhinitis and as a food for preventing allergy by adding the therapeutic agent to food. 00 3— 20 1 20 8 publication includes luteolin or glycosides thereof, or plants containing them (Dyer, s Rocket, Weld) Japanese Patent Application Laid-Open No. 2 004-9 1 3 3 8 discloses that flavones such as luteolin can be used as a cosmetic composition because an extract from Synopmoxiso, moxaseiso) exhibits a melanin production inhibitory action. Etc. is 0 urease Japanese Patent Laid-Open No. 2 004-2 1 5 5 5 9 discloses that luteolin is an acrylic from processed foods (including oily foods) that can be used as an odor suppressant or a diaper rash preventer. JP-A 2 0 0 5-7 5 7 6 6 discloses that it is possible to suppress amide formation, as an endothelin-1 production inhibitor containing luteolin and Z or a glycoside thereof as heart disease or As an antihypertensive agent, it is added to various 5 foods and added as a food for specified health use or as a functional food, and it is added to pet food, feed, etc. to improve the heart disease and hypertension of pet animals. Or can be used as a cosmetic for whitening by adding to cosmetics, and Japanese Patent Application Laid-Open No. 2000-589 In Japanese, a lipoxygenase inhibitor comprising a fermented product luteolin content fermented until ^{1 0 0 X 1 0- 5 wt} % or more as a fermented product of Nigana plants, inflammatory and allergic conditions, cardiovascular disease, It also describes that it can be applied to hair growth inhibitory or hair removal regulators or cosmetic compositions.

On the other hand, in Japanese Patent Publication No. 2 0 0 2— 5 4 2 1 9 2, the composition containing isoflavone is hepatic steatosis, steatohepatitis, insulin resistance, impaired glucose tolerance, X syndrome Disclosed are methods for treating or preventing abnormal platelet function or abnormal vascular responsiveness. Here, the isobrabons include genistin derived from soybean, genistin, 6, 1-O-malonyl genistin, 6, 0-acetinoregestin; daidzein, daiddin, 6, 1 O-malonic Noredidodine, 6 ,, 1 O-acetylgenistin; Glycitin, Glycytin, 6 ,, 1 O—Maroninoreglycitin, 6, '1 O-acetylinoreglicity, B iochanin A, or formononetin Yes.

Conventionally, it is not known that luteolin or its glycoside can prevent or treat steatohepatitis or nonalcoholic steatohepatitis or fatty liver. Disclosure of the invention

An object of the present invention is to provide a medicament for preventing or treating steatohepatitis, particularly non-alcoholic steatohepatitis, or fatty liver, and food and drink for preventing or ameliorating these diseases.

As a result of intensive studies, the present inventor has found a preventive or therapeutic effect of luteolin based on evidence for steatohepatitis and has completed the present invention. The present invention is as follows.

(1) A prophylactic or therapeutic agent for steatohepatitis containing luteolin and / or its glycoside.

(2) A preventive or therapeutic agent for non-alcoholic '! ^ Fatty hepatitis containing luteolin and Z or its glycosides. (3) A prophylactic or therapeutic drug for fatty liver containing luteolin and / or its glycoside.

(4) The preventive or therapeutic agent according to any one of (1) to (3) above, and the prophylactic or therapeutic agent are used for the prevention or treatment of steatohepatitis or nonalcoholic steatohepatitis or fatty liver. A commercial package containing documents stating that it should be obtained or used.

(5) A food or drink containing luteolin and / or its glycoside that prevents or ameliorates steatohepatitis.

(6) A food or drink containing luteolin opino or a glycoside thereof for preventing or improving nonalcoholic steatohepatitis.

(7) A food or drink containing luteolin and / or its glycoside that prevents or improves fatty liver.

(8) The food or drink according to any one of (5) to (7), which is labeled for use in preventing or improving steatohepatitis, non-alcoholic steatohepatitis, or fatty liver.

(9) The food or drink according to any one of (5) to (8), which is a health functional food or a dietary supplement.

(10) The food or drink according to (9), wherein the health functional food is a food for specified health use or a food with a nutritional function.

(1 1) A method for preventing or treating steatohepatitis, non-alcoholic steatohepatitis or fatty liver, comprising administering to a subject an effective amount of luteolin and / or its glycoside.

(1 2) Use of luteolin and Z or a glycoside thereof for the production of a prophylactic or therapeutic agent according to any one of (1) to (3).

(1 3) A fatty liver inhibitor comprising luteolin and / or a glycoside thereof as an active ingredient. ,

(14) The inhibitor according to (13), which is for addition of food and drink. Brief Description of Drawings

Fig. 1 is a graph showing the effects of improving choline deficiency, high fat, and low protein diets on mouse fatty liver and Z or steatohepatitis. In the figure, A shows the liver histology of the group not administered with luteolin, and B shows the liver histology of the group administered with luteolin.

FIG. 2 is a western blot diagram showing the expression of proteins derived from liver tissue in the group not administered with luteolin and in the group administered with luteolin. In the figure, lanes 1 and 2 are phosphorylated (Tyr ⁷⁰⁵ ) STAT3, lanes 3 and 4 are STAT3, lanes 5 and 6 are SREBPlc, lanes 7 and 8 are FAS, odd lanes are not treated with luteolin The even lanes indicate the luteolin administration group.

0

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described in detail. However, the scope of the present invention is not limited to these descriptions, and other than the following exemplifications, the present invention can be appropriately implemented without departing from the spirit of the present invention. -5 As a result of intensive research for the prevention or treatment of steatohepatitis or non-alcoholic steatohepatitis or fatty liver with high efficacy and safety, It has been found that pi or its glycoside has an effect of improving fatty liver and / or steatohepatitis caused by choline deficiency ■ high fat / low protein diet. '

That is, the present invention relates to a preventive or therapeutic agent for steatohepatitis or non-alcoholic steatohepatitis or fatty liver, which contains luteolin and / or its glycoside. The present invention also provides the preventive or therapeutic agent, and the preventive or therapeutic agent for the prevention or treatment of steatohepatitis or nonalcoholic steatohepatitis or fatty liver.

• For commercial packages that contain documents stating that they can be used or should be used.

In recent years, it has been found that the SREBPs (Sterol regulatory element-binding proteins) play an extremely important role in the luteinous synthesis pathway (Jour nal of Clinical Investigation 109, 1125, 2002). That is, SREBP-1 (especially SREBP_lc), one of the SREBPs isofo rms, binds to the promoter region of the FAS (fatty acid synthase) gene and enhances FAS transcription. Since FAS is responsible for the synthesis of free fatty acids and triglycerides, fatty liver is induced via FAS if SREBP-lc expression is enhanced in the liver. More recently, maturation and nuclear translocation of SREBP-lc as a transcription factor depend on phosphorylation (Tyr ⁷ ° ⁵ ) of another transcription factor, STAT3 (signal transducer and activator of transcription). (Journa 1 of Cell Science 117, 1937, 2004). Therefore, suppression of STAT3 phosphorylation may lead to suppression of fatty liver. Previously, a research group, including the present inventor, reported that luteolin extracted and purified from perilla seeds increased ubiquitin-dependent phosphorylation (Tyr ⁷ ° ⁵ ) STAT3 degradation (Proceeding of the American Association for Cancer Research 46, 722, 2005). Then, based on the report, the present inventor considered that luteolin could suppress fatty liver through phosphorylation (Tyr ^7e5 ) STAT3 enhanced degradation, and reached the present knowledge.

In the present invention, luteolin, which is an active ingredient, can use commercially available products. Various plants (for example, celery, peppers, spring chrysanthemum, chamomile, perilla, egoma, pine nuts, etc. where perilla or egoma seeds) And defatted seeds are particularly preferable. It can also be isolated and purified from Dyer's Rocket (D yer, s Rocket, Weld), Synopmox Seiso, Moxeiso, and Kudamonotokeisou (Phytochemistry, 30, 3486, 1991). . Furthermore, it was isolated and purified from a fermented product obtained by fermenting the Japanese algae plant disclosed in Japanese Patent Laid-Open No. 2 0 5-8 8 9 3 8 5 until the luteolin content was 10 0 X 10 0 " ⁵ wt% or more. Can also be used.

The luteolin glycoside, which is an active ingredient that can be used in the present invention, is a naturally occurring glycoside of luteolin and a sugar (eg, glucose, fucose, galactose, 6-deoxydarcos). The sugar binding position is, for example, 6-C, 8-C, 7-0, or 4′_0 of the luteolin molecule, and the preferred luteolin glycoside is luteolin-6-C-darco. Sid. In addition, 3′-dalclonide, 6-C-fucoside, 6-C-quinoside, 7-0-rutinoside and the like can also be used.

Luteolin and luteolin glycosides can be isolated as follows. Isolation from a plant containing luteolin and its glycosides can be done by pulverizing the whole plant or a part of the roots, stems, leaves, flowers, fruits, seeds, etc. with a mixer, etc., followed by water, ethanol, Stir in an extraction solvent such as methanol or ethyl acetate (extraction solvents can be used alone or in combination of two or more), and remove insolubles by centrifugation or filtration. The clear or filtrate is appropriately dried under reduced pressure and can be carried out by a conventional method (such as force chromatography). In the present invention, an extract of any plant can be used as long as it contains luteolin and / or its glycoside, and examples thereof include cerebral family plants such as blue dissociation, red dissociation and egoma, seri and assipac In addition to celery family plants, vegetables such as celery, lettuce, spring chrysanthemum, and peppers, soybean leaves, pinnacle seed coat, yew, honeysuckle, western cherry, chamomile, and peppermint, it is also possible to use extracts such as Kudamono Tokeisou it can.

In general, naturally occurring flavonoids often take the form of glycosides, but perilla seeds contain a large amount of aglycone-like luteolin. Since aglycone is known to have stronger antioxidant activity than glycoside (Biochemical Medicine and Metabolic Biology, 39, 69, 1988), prevention or treatment of steatohepatitis or nonalcoholic steatohepatitis It is desirable to use luteolin that is purified from plant seeds that are rich in aglycone. In particular, extraction from the seeds of Lamiaceae plants such as blue dissociation, red dissociation and sesame is preferred. It is more preferable to use a defatted seed as the seed.

The prophylactic or therapeutic agent for steatohepatitis or nonalcoholic steatohepatitis or fatty liver containing luteolin and / or its glycoside according to the present invention is luteolin and / or its glycoside itself. However, it is formulated into a dosage form such as tablets, powders, emulsions, capsules, injections, drops, external preparations, etc., by a commonly used solid or liquid carrier, emulsion powder, etc. Also good. As the carrier, Water, gelatin, starch, ratatoose, hydroxypropylcellulose, hydroxymethylcellulose, magnesium stearate, talc, vegetable oil, etc., including pharmaceutically acceptable dyes, preservatives, stabilizers, etc. Can be added. The prophylactic or therapeutic drug for steatohepatitis or non-alcoholic steatohepatitis, or fatty liver may contain other active ingredients within a range where contraindications can be avoided, and at the same time or at intervals with other drugs. Can be used.

The content of luteolin and z or glycoside thereof in the preventive or therapeutic agent for steatohepatitis or non-alcoholic steatohepatitis of the present invention or fatty liver is appropriately changed depending on the purpose of administration, administration route, dosage form For example, it is 0.05 to 1% by weight based on the total weight of the preparation.

The dosage of the prophylactic or therapeutic drug for steatohepatitis or non-alcoholic steatohepatitis or fatty liver of the present invention is not particularly limited. For example, the type of illness, patient age, sex, weight, symptoms It can be determined appropriately according to the degree of administration or the administration method. For example, when orally administered to male adults, the dosage is preferably 0.01 mg / kg to 10,000 mg / kg per day, and can be administered once or divided into several times a day. The dose is more preferably 0.1 mg / kg to 1000 mg / kg, and even more preferably 0.5 mg / kg to 500 mg / kg.

The present invention also relates to a food or drink containing the luteolin and / or glycoside thereof. The food and drink of the present invention is taken for the purpose of preventing or improving steatohepatitis, particularly non-alcoholic steatohepatitis or fatty liver.

The food and drink of the present invention includes foods and beverages, for example, health foods including specified health foods and functional foods, and general foods including so-called health foods such as dietary supplements. Can be given. Forms can be added to milk drinks, juices, sports drinks, Japanese tea, oolong tea, coffee, tea, diet drinks, Japanese confectionery, Western confectionery, bread, ice cream, sorbet, hamburger, pizza and the like. .

When the food or drink of the present invention is used as a health functional food, steatohepatitis, non-alcohol It can be labeled as being used to prevent or ameliorate fatty steatohepatitis or fatty liver. As a display method, preferably, a method described in the packaging material of the food or drink, a method of displaying as an attached document on the food or drink, and the like are given.

The content of luteolin and Z or a glycoside thereof contained in the food or drink of the present invention is not particularly limited. For example, it is desirable to contain about 0.05 to 20% by weight, preferably about 0.01 to 10% by weight, more preferably about 0.05 to 5% by weight.

The amount of the active ingredient ingested from the food or drink of the present invention can be appropriately determined according to the purpose of ingestion, the age, sex, body weight, symptom level, etc. of the subject. For example, in the case of an adult, the intake is preferably 0.01 rag / kg to 10,000 mg / kg per day, and can be taken once or several times a day. The intake is more preferably from 0.5 ltng / kg to 1000 mg / kg, and even more preferably from 0.5 mg / kg to 500 rag / kg. The chemicals and foods and drinks of the present invention can be ingested by animals other than humans, for example, pets such as dogs, cats, hamsters, monkeys, etc. as veterinary medicines or in feeds.

In order to provide the food and drink of the present invention or for the purpose of research on fatty liver, an inhibitor of fatty liver containing luteolin opi Z or a glycoside thereof as an active ingredient is provided.

The fatty liver inhibitor of the present invention can be used as a research reagent or a food or drink additive, but is preferably used for food or drink addition.

The content of luteolin and no or glycoside thereof contained in the fatty liver inhibitor of the present invention is not particularly limited, but is usually from 0.05 to 10% by weight, preferably from 0.001 to 1% by weight, more preferably 0.05 to 100% by weight. It is desirable to contain / ₀ . ..

The inhibitor of fatty liver of the present invention may contain a carrier. As such a carrier Examples include water, gelatin, starch, ratatoose, hydroxypropinolecellulose, hydroxymethylcellulose, magnesium stearate, talc, vegetable oil, etc., which are acceptable for food hygiene, preservatives, Adjuvants such as stabilizers can be added. Example

Hereinafter, the present invention will be described specifically by way of test examples, but these do not limit the scope of the present invention.

Test Example 1 Improvement of fatty liver and Z or steatohepatitis caused by choline deficient 'high fat' and low protein diet of luteolin

First, 6 BALB mice were given a choline-deficient 'high fat' low protein diet (choline-deficient diet, CLEA Japan, Inc.) for 10 weeks to develop fatty liver and Z or steatohepatitis. In these mice, a group treated with luteolin (n = 3) and a group not administered with luteolin (n = 3) were set. Comparison was also made with syngeneic mice (n = 3) fed a normal diet (CE-2; Nippon Claire Co., Ltd.). In the luteolin administration group, 97.2% pure luteolin extracted and purified from perilla seeds was dissolved in dimethyl sulfoxide (DMS0) and adjusted so that the final concentration in the feed water was about 200 ppm ( At this time, some precipitates may be formed). The luteolin-containing water was changed every other day. Ten weeks after the start of the experiment, the body weight and liver weight were measured. The liver tissue was collected and a sample was prepared. The body weight of mice fed choline deficient, high fat, and low protein diets was slightly lighter than the normal diet group (31. 1), but there was no difference in body weight between the luteolin administration group and the luteolin non-administration group. The average was 29.2 g. However, the liver of mice not treated with luteolin was swollen and macroscopically yellowish. The liver weight was 2.23 g in the luteolin non-administered group and 1.86 g in the luteolin-administered group, and the increase in liver weight was suppressed in the luteolin-administered group (the liver weight in the normal diet group was 1.84 g). In the histological examination, fatty degeneration with large lipid droplets was clearly observed in the liver tissue hepatocytes of the group not administered with luteolin, and infiltration of inflammatory cells was also observed. These histological changes were considered to be the cause of hepatomegaly and increased liver weight. In the group not administered with luteolin These histological changes were similar to those of normal human fatty liver and steatohepatitis, and appeared predominantly in the central venous region (Zone 3). On the other hand, the above-mentioned steatosis and inflammation findings were clearly poor in the luteolin administration group, indicating that luteolin significantly suppressed fatty liver and Z or steatohepatitis (Fig. 1).

In order to elucidate the molecular mechanism of macroscopic findings (inhibition of fatty liver in the luteolin-treated group) in this study, Western blot using mouse liver tissue for STAT3 molecule and SREBP-1 molecule that decisively control lipid metabolism We examined by law. As a result, attenuation of STAT3 phosphorylation (Tyr ⁷ ° ⁵ ) was observed in the liver tissue of mice treated with luteolin, and downstream expression of mature SREBP-lc (p68) and further downstream FAS were observed (Fig. 2). ). In other words, luteolin was thought to suppress the development of fatty liver by blocking the STAT3 signal located upstream of SREBP-lc in the fatty liver formation pathway via SREBP-lc cascade. . Industrial applicability

According to the present invention, a safe and effective drug for the prevention or treatment of steatohepatitis or non-alcoholic steatohepatitis or fatty liver is provided. In addition, according to the present invention, food and drink that prevent or ameliorate fatty hepatitis or non-alcoholic steatohepatitis, which is highly safe and effective, is provided. This application is based on Japanese Patent Application No. 2 0 0 5-1 7 3 8 1 3 filed in Japan (filing date: June 14, 2004), the contents of which are incorporated herein by reference. It is included.

Claims

The scope of the claims

1. A prophylactic or therapeutic drug for steatohepatitis containing luteolin and / or its glycoside.

2. A preventive or therapeutic agent for nonalcoholic steatohepatitis 5 containing luteolin and / or its glycoside.

3. A preventive or therapeutic agent for fatty liver containing luteolin and / or its glycoside.

4. Can the prophylactic or therapeutic agent according to any one of claims 1 to 3 and the prophylactic or therapeutic agent be used for the prevention or treatment of steatohepatitis or nonalcoholic steatohepatitis or fatty liver? Or a commercial package containing a document that states that it should be used.

5. A food or drink containing luteolin and / or its glycoside that prevents or ameliorates steatohepatitis.

6. A food or drink containing luteolin and / or its glycoside that prevents or ameliorates nonalcoholic fatty hepatitis.

5 7. Foods and beverages containing luteolin and / or its glycosides that prevent or ameliorate fatty liver.

8. The food or drink according to any one of claims 5 to 7, which is labeled for use in preventing or improving steatohepatitis, non-alcoholic steatohepatitis or fatty liver.

0 9. The food or drink according to any one of claims 5 to 8, which is a health functional food or a dietary supplement.

10. The food or drink according to claim 9, wherein the functional health food is a food for specified health use or a functional food for nutrition.

1 1. A method for the prevention or treatment of steatohepatitis, nonalcoholic steatohepatitis or fatty liver, comprising administering to a subject an effective amount of luteolin opino or a glycoside thereof. ..

1 2. For the manufacture of a prophylactic or therapeutic agent according to any one of claims 1 to 3, Use of theoline and / or its glycosides.

1 3. An inhibitor of fatty liver, comprising luteolin and nose or glycosides thereof as active ingredients.

14. The inhibitor according to claim 13, which is used for food and drink addition.