KR20120066618A - Composition for improvement of fatty liver - Google Patents

Abstract

PURPOSE: A composition containing Citrus sunki fermentation is provided to treat fatty liver and to relieve hangover. CONSTITUTION: A composition for treating fatty liver contains fermentation prepared by adding kelp or ginseng to rice bran, adding Citrus sinki, and naturally fermenting; and hot water extract of the fermentation. A composition for treating hyperlipidemia contains the fermentation or hot water extract as an active ingredient. A composition for relieving hangover contains the fermentation or hot water extract as an active ingredient.

Description

Composition for Improvement of Fatty Liver}

The present invention relates to a fatty liver improver composition, and more particularly, to a fatty liver improver composition comprising an extract or a fermented product derived from the dermis.

Fatty liver is a disease in which fat fear is observed in more than half of hepatocytes due to excessive accumulation of lipids, especially triglyceride, in the liver due to lack of normal fat metabolism.

Clinically, fatty liver is classified as fatty liver when more than 5% of liver weight.

The causes of fatty liver include alcohol, diabetes, obesity, malnutrition (long-term low-protein diet, high-fat diet, hunger and vitamin deficiency, excess sugar intake), drug abuse (Sung Hoon Kim et al., "Cause of fatty liver diagnosed by abdominal ultrasound") Korean Journal of Medicine 175 ('95 .12) pp. 785-794).

Fatty liver is classified into cholesterol fatty liver and triglyceride fatty liver. The most common fatty liver is fatty liver when triglyceride is abnormally accumulated in liver.

Commercially available fatty liver treatments include Legaron ™ (Bugwang Pharm., Korea), Lycaba ™ (Yuhan, Korea), Heparin ™™ (Boryeong Pharm., Korea), Heparmels ™ (Hanhwa Pharmaceutical, Korea), etc. This may be exemplified, and as the prior art, Korean Patent Publication No. 2006-0028561 using Genistein and the like, and Korean Patent No. 0568550 using Rosewood Fragrance Extract may be exemplified.

On the other hand, the dermis is the skin of the citrus sunki (Jeju's native tangerine) has been reported antioxidant activity, antimicrobial activity, anti-inflammatory activity, blood pressure lowering activity (Jeong WS, Park SW, Chung SK. Food Sci. Biotechnol. 6: 292-296 (1997); Kim YC, Koh KS, Koh JS.Food Sci. Biotechnol. 10: 483-487 (2001); Cho C, Park BJ, Chung SH, Kim CB, Cha BS, Byun MW. Food Sci. Biotechnol. 13: 384-386 (2004); Murakami A, et al. Carcinogenesis 21: 1843-1850 (2000)).

The present inventors disclose fatty liver improving activity and the like as other physiological activities of the dermis.

An object of the present invention is to provide a fatty liver improver composition.

Other technical problems of the present invention will be presented below.

In one aspect, the present invention relates to a fatty liver improving composition comprising an dermis-derived extract or fermented product as an active ingredient.

In order to confirm fatty liver inhibitory activity as another physiological activity of the dermis, the present inventors identified a total of nine kinds of dermis-derived extracts or fermentants, that is, ethanol aqueous extract of dermis and ethanol aqueous extract of dermis, as confirmed in the following examples. Water fraction of, water fermentation with lactic acid bacteria and yeast, natural fermentation of dermis, natural fermentation of dermis using rice bran fermentation by lactic acid bacteria and yeast, fermentation of rice bran and kelp mixture by lactic acid bacteria and yeast Natural fermentation of dermis using fermentation of rice bran and ginseng mixture by lactic acid bacteria and yeast, natural fermentation of dermis using fermentation of rice bran, kelp and ginseng mixture by lactic acid bacteria and yeast, And preparing a hydrothermal extract of this fermentation product, and each of the extracts as All results confirmed the fermented product is gajineunga fatty liver inhibitory activity was confirmed by having a fatty liver inhibiting activity.

The fatty liver improver composition of the present invention is provided based on the results of these experiments.

Therefore, the fatty liver improver composition of the present invention is characterized by including any one of the following dermal-derived extracts or fermented products of (I) to (VI) as an active ingredient.

(I) extracts of ethanol, water or mixed solvents of dermis and fractions thereof

(II) fermented product by lactic acid bacteria and yeast of said extract or fraction;

(III) fermented product obtained by fermenting the dermis in a natural state;

(IV) fermented product obtained by sterilizing the fermented product of rice bran by lactic acid bacteria and yeast, adding to the dermis, and fermenting in natural state;

(V) a fermentation product obtained by sterilizing the fermentation product by lactic acid bacteria and yeast of the mixture obtained by adding at least one of kelp and ginseng to rice bran, adding to the dermis and fermenting in a natural state; And

(VI) the water extract of the fermentation of (IV) or the fermentation of (V).

In the present specification, "fatty liver" is meant to include both types of cholesterol fatty liver and triglyceride fatty liver as previously classified, and includes both types according to the cause of fatty liver, that is, alcoholic fatty liver and non-alcoholic fatty liver. I mean. This is because the following Examples and Experimental Examples show that the extract or fermented product derived from the dermis has an activity of lowering the total cholesterol content, triglyceride content, etc. in the liver or blood of the experimental animal. Fatty liver, whether alcoholic or non-alcoholic fatty, appears as an accumulation of cholesterol or triglycerides in the liver.

In addition, in the present specification, the "improvement" is meant to include prevention of symptoms, alleviation of symptoms and removal of symptoms.

In addition, in the present specification, the "extract fraction" means a fraction of each solvent, that is, an ethanol fraction or water fraction obtained by separating these solvents when the extraction solvent is a mixed solvent of ethanol and water, that is, an ethanol aqueous solution. In the following examples and experimental examples, only the fatty liver improving activity of the water fraction is disclosed, it is apparent that the ethanol fraction will also have the fatty liver improving activity in that the following examples and experimental examples disclose the ethanol aqueous solution extract fatty liver improving activity. Therefore, the meaning of the fraction of the extract should be understood to include ethanol fractions as well as water fractions whose activity is directly confirmed in the following examples and experimental examples.

In addition, in the present specification, the "natural state" means a state in which no artificial manipulation is applied in fermentation conditions such as temperature, humidity, concentration of CO ₂ , inoculated microorganisms, presence of oxygen, and the like. Therefore, fermentation in the natural state means that fermentation proceeds under aerobic conditions and at room temperature without artificially inoculating any microorganisms.

In the present specification, the "lactic acid bacterium" may be understood as a bacterium that breaks down sugars such as glucose to produce lactic acid. Lactobacillus is Lactobacillus sp . ), Streptococcus sp . ), Pediococcus sp . ), Leuconostoc sp . ) And a Bifidobacterium lactic acid bacteria (Bifidobacterium sp . The lactic acid bacteria are meant to include all of these lactic acid bacteria. However, in the following examples, Lactobacillus lactic acid bacteria were used, preferably, the lactic acid bacteria may be understood as Lactobacillus lactic acid bacteria, and in particular may be understood as Lactobacillus plantarum ( Lactobacillus plantarum ).

Also herein, the term “yeast” refers to Saccharomyces spp. Refers to yeast, for example Saccharomyces rouxii), saccharose in my process to the celebrity bicyclic (Sacharomyces cereviciae), access to the MY Ob pole miss Saccharomyces (Saccharomyces oviformis ), Saccharomyces steineri ), etc.

In addition, in the present specification, the "rice bran" is a by-product obtained in the process of refining brown rice with white rice, and refers to rice rice and a whistle layer. It is to be understood that the rice bran is included in the rice bran as long as it includes the rice hull and the whistle layer, even though it additionally includes the outer skins and / or seedlings of the outer skin of brown rice and the endosperm and / or the endosperm.

In the present specification, the "ginseng" is defined as a meaning including all ginseng regardless of the processing method, cultivation method and cultivation area. Ginseng is peeled from fresh ginseng immediately after harvest and white ginseng obtained by natural drying or peeling artificially (for example, heating, humidification, hot air drying, etc.) after peeling from fresh ginseng, depending on processing method. It is divided into red ginseng obtained by steaming and drying without peeling it off. According to the cultivation method, it is divided into cultivated ginseng obtained by artificially cultivating in ginseng field, camphor ginseng obtained by spraying cultivated with ginseng seed in the mountain, and wild ginseng grown in the mountain. Depending on the cultivation region, Korean ginseng produced in the Korean Peninsula, fire ginseng produced in North America such as the United States, Canada, ginseng ginseng produced in China, and bamboo ginseng produced in Japan are classified into all kinds of ginseng. This can be used.

In addition, in the present specification, the "Kashima" is a seaweed of the genus Laminaria ( Laminaria) sp . ), And the meanings include L. japonica , L. ochotensis and L. religiosa .

In the present specification, the "fermented product of (IV) or the extract of the fermented product of (V)" is a solid or liquid fermented product of (IV) or fermented product of (V) regardless of the extraction method regardless of the water (or Refers to an extract obtained by extraction with distilled water). Regardless of the extraction method, any extraction, such as cold soaking, refluxing, heating, or ultrasonic wave, is carried out as long as it is extracted through mixing or immersing the fermented product of (IV) or the fermented product of (V) as extraction solvent with water. Both methods can be applied. However, preferably it is the case of hot water extract.

In addition, in the present specification, the "active ingredient" refers to a component that can exhibit the activity alone or in combination with a carrier having no activity in itself.

Meanwhile, as shown in the following Examples and Experimental Examples, the most active ingredient of the fatty liver improver composition of the present invention is a fermented product of rice bran fermented by lactic acid bacteria and yeast or a mixture of ginseng and / or kelp added to rice bran. Fermented products obtained by sterilization and fermentation in nature and water extracts thereof.

This fermented product and its water extract are much higher in activity than fermented product (III) obtained by fermenting only dermis in nature, and the present inventors have found that rice bran, ginseng and / or kelp When fermented by lactic acid bacteria and yeast, it is presumed that a new substance is produced which promotes the fermentation in the natural state of the dermis in a useful direction (that is, in the direction of increasing the physiological activity of the dermis).

In order to obtain the fermented product, fermentation by lactic acid bacteria and yeast of rice bran or a mixture of ginseng and / or kelp added to rice bran should be preceded. In this case, carbon source such as water, glucose or sucrose is added to promote fermentation. In general, even if there is no addition of water or carbon source, the water or carbon source of rice bran can be used, so adding water or carbon source is essential for fermentation by lactic acid bacteria and yeast of rice bran as long as proper fermentation time is secured. It is not necessary.

And before the fermentation of the rice bran or the fermentation of the mixture of ginseng and / kelp added to the rice bran is added to the dermis, the sterilization should be performed, although this sterilization is performed using a saturated salt solution in the following examples It can be done using any sterilization method known in the art.

And the amount of the fermented product of the rice bran or the mixture of ginseng and / or kelp is added to the dermis powder is preferably 0.5 parts by weight to 10 parts by weight based on 100 parts by weight of the dermis. If it is 0.5 parts by weight or less, the effect of promoting fermentation in a useful direction by the fermentation will be insignificant, and when it is 10 parts by weight or more, fermentation in a natural state is not intended by the inventors (ie, lowers the physiological activity of the dermis). In the direction of

Meanwhile, the fatty liver improver composition of the present invention may include any of the six dermis-derived extracts or fermented products as an active ingredient in an arbitrary amount depending on the use, formulation, and blending purpose, and is generally based on the total weight of the composition. From 0.001% to 20% by weight.

On the other hand, fatty liver may progress to hepatitis, cirrhosis, liver cancer and the like if left untreated.

Therefore, the six dermis-derived extracts or fermented products may be useful for the purpose of preventing hepatitis, liver cirrhosis or liver cancer, which are diseases caused by fatty liver.

Therefore, in another aspect, the present invention can be understood as a composition for the prevention of diseases caused by fatty liver comprising the extract or fermented products of the six dermis derived as an active ingredient.

In another aspect, the present invention relates to an obesity improving composition comprising the six dermis-derived extracts or fermented products as an active ingredient.

In the present specification, "obesity" means a state in which fat tissue is abnormally increased, whether it is caused by genetic factors or obesity due to environmental factors, and obesity according to the division of body mass index (BMI) (BMI of 30.0 or more). Case) and overweight (BMI is 25-30).

In the obesity improver composition of the present invention, with respect to the preferred embodiment of the active ingredient, its content, and the like, the above-described bar is effective as it relates to the fatty liver improver composition of the present invention.

In another aspect, the present invention relates to a diet composition comprising the six dermis-derived extracts or fermented products as an active ingredient.

As used herein, "diet" is defined as a condition in which a weight condition is not obese or overweight, but for which a reduction in weight / body fat is desirable or necessary for cosmetic or health purposes. Usually the composition for a diet of the present invention will be prepared for use for the beauty or health purposes of normal people.

In the diet composition of the present invention, in relation to the preferred embodiment of the active ingredient, its content and the like, the above-described bar is effective as it is with respect to the fatty liver improving composition of the present invention.

In another aspect, the present invention can be understood as a composition for protecting liver cells comprising the extract or fermented product derived from the six dermis as an active ingredient.

As confirmed in the following Examples and Experimental Examples, the six dermis-derived extracts or fermented products of glutamic acid pyruvate transaminase (hereinafter referred to as "GPT") and glutamate oxaloacetate transaminase (hereinafter referred to as "GOT") ") And / or lowers the activity of gamma-glutamyl transpeptidase (" GGT ") and in particular has the protective activity of HepG2, an alcohol damaged liver cell. In addition, the six dermis-derived extracts or ferments may be usefully used for liver cell protection.

In the above, GPT, GOT and GGT are enzymes that are used as general indicators of liver dysfunction because the liver is secreted into the blood from the liver when damaged due to obesity, alcohol, and the like.

Also in the composition for liver cell protection of this invention, what was described with respect to the fatty liver improver composition of this invention as mentioned above is effective as it is regarding the preferable aspect of its active ingredient, its content, etc. as it is.

In another aspect, the present invention relates to a hangover relief composition comprising the extract or fermented products derived from the six dermis as an active ingredient.

Hangovers, such as nausea and headaches after drinking too much, are caused by aldehydes in alcohol metabolism. Generally, alcoholase (ADH) and aldehydease (ALDH) are present in the liver, and when alcohol enters the body, it is converted into acetate, which is harmless to the body.

As identified in the following examples, the six dermis-derived extracts or fermented products may be usefully used for hangover relief in that they promote ADH activity and ALDH activity.

In the hangover-relieving composition of the present invention, as described above with respect to the fatty liver improving composition of the present invention as described above in relation to the preferred embodiment of the active ingredient, its content and the like, it is effective as it is.

In another aspect, the present invention relates to a hyperlipidemic improver composition comprising the extract or fermented product derived from the six dermis as an active ingredient.

Hyperlipidemia refers to a condition in which triglyceride, LDL cholesterol, and phospholipids are increased in the blood because fat metabolism is not smoothly performed.

Since hyperlipidemia does not show any symptoms by itself but is a problem as a cause of cardiovascular diseases such as atherosclerosis and hypertension, the hyperlipidemic composition of the present invention may be usefully used as an agent for improving the disease caused by hyperlipidemia. have.

Also in the hyperlipidemic improver composition of the present invention, as described above with respect to the fatty liver improver composition of the present invention as described above in relation to the preferred embodiment of the active ingredient, its content and the like is effective as it is.

Meanwhile, the fatty liver improving composition of the present invention, the composition for preventing diseases caused by fatty liver, obesity improving composition, diet composition, hangover relieving composition, and hyperlipidemic improving composition (hereinafter collectively referred to as "composition of the present invention") In a specific embodiment, can be understood as a pharmaceutical composition.

The pharmaceutical composition of the present invention may include pharmaceutically acceptable conventional ingredients in addition to the six dermis-derived extracts or fermented ingredients, which are the active ingredients. As commonly used, lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup , Methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, and the like.

The pharmaceutical compositions of the present invention may also further comprise lubricants, wetting agents, sweetening agents, flavoring agents, emulsifying agents, suspending agents, preservatives and the like as additives. Components suitable for each use such as lubricants, wetting agents, etc. are already known in the art, so those skilled in the art can select and use appropriate components.

Such ingredients may be included in the pharmaceutical composition of the present invention in an amount of from 85% to about 99.99% by weight, preferably from about 90% to about 99.99% by weight, based on the total weight thereof.

On the other hand, the pharmaceutical composition of the present invention can be administered by various routes, for example, orally or rectally, or by injection into veins, muscles, subcutaneous, intrauterine dura, and the like.

The pharmaceutical compositions of the invention may be prepared in unit dose form or may be prepared by incorporation into a multidose container. In this case, the formulation may be in the form of a solution, suspension, or emulsion, or may be in the form of an exerciser, extract, powder, granule, tablet, or the like.

The pharmaceutical composition of the present invention is usually in the range of 0.001 to 150 mg / kg body weight within a range that does not toxic to the human body, it can be administered once or divided into several times. However, since the dosage of the pharmaceutical composition of the present invention is determined in view of various related factors such as the route of administration, the age, sex, weight of the patient, the severity of the patient and the like, the dosage may limit the scope of the present invention in any aspect. It should not be understood as.

The composition of the present invention may be regarded as a food composition in specific embodiments.

The food composition of the present invention may be prepared from gums, vitamin complexes, dietary supplements, special nutritional supplements, functional drinks (particularly in the case of the fatty liver improving composition, hangover relieving composition or hyperlipidemic improving composition).

In addition to the six dermal-derived extracts or fermented products, the food composition of the present invention may be added with monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, or polysaccharides such as dextrin and cyclodextrin. Sugar alcohols such as xylitol, sorbitol, erythritol and the like may also be added, sweeteners such as taurine, stevia extract and the like may also be added, and other food additives may also be added.

As mentioned above, according to the present invention there is provided a fatty liver improver composition. In addition, according to the present invention there is also provided a diet composition, fatty liver improver composition, liver cell protective composition, hangover composition and the like.

1 is a result of evaluating the GOT (AST) activity of the blood of the experimental animals after the end of the test, the positive control group (methformin administration group) GOT average value 177.375 IU / L, experimental group GOT average value 160.5 IU / L, obesity control group Compared with the average value of 321.375 IU / L, it was low and significantly decreased (P value 0.011, 0.002).
2 is a result of evaluating the GPT (ALT) activity of the blood of the experimental animals after the end of the test, the positive control group (methformin administration group) showed a low ALT average value of 62.75 IU / L, but it is not significant, the experimental group ALT The mean value was 32.875 IU / L, which was very low compared to the 124.875 IU / L, which was significantly lower than the control group (P value 0.005).
3 is a result of evaluating the GGT activity of the blood of the experimental animals after the end of the test, the mean GGT of the experimental group of the group except the normal group was 0.750, which is low compared to the average of the obese control group 2.75 and significantly decreased. (P value 0.024).
4 is a result of measuring the total cholesterol content of the blood of the experimental animals after the end of the test, the positive control group of the group receiving the drug except the normal group has a total cholesterol average value of 84 mg / dL and an average value of the total cholesterol of the experimental group 73.75 mg / dL was lower than that of the obese control group (180.75 mg / dL) and decreased significantly (P value 0.0015,0.0004).
5 is a result of measuring the HDL cholesterol content of the blood of the experimental animals after the end of the test, the mean value of HDL cholesterol in the positive control group (24.75 mg / dL) and the experimental group (23 mg / dL) of the group to which the drug was administered the average value of the obese control group Phosphorus increased to 20.25 mg / dL but was not significant.
Figure 6 is the result of measuring the LDL cholesterol content of the blood of the experimental animals after the end of the test, the positive control group of the group receiving the drug except the normal group LDL cholesterol average value 43.95 mg / dL, experimental group LDL cholesterol average value 33.525 mg / dL was significantly lower than that of the control group (136.825 mg / dL) and significantly decreased (P value 0.001, 0.0003).
* Figure 7 is a result of measuring the triglyceride content of the blood of the experimental animals after the end of the test, the average of the triglyceride average of 76.50 mg / dL in the positive control group of the group except the normal group, the triglyceride in the experimental group The mean value was 86.125 mg / dL, which was lower than the control group's average value of 118.375 mg / dL and decreased significantly (P value 0.0002, 0.0071).
8 is a result of measuring the phospholipid content of the blood of the experimental animals after the end of the test, the experimental group of the drug administration group was 212.5 mg / dL, the average value of the phospholipids compared to the average value of the obese control group 247.875 mg / dL It was measured and significantly decreased (P value 0.03).
9 shows the results of histological examination of liver tissues of experimental animals after the end of the test.

It will be described below with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.

* <Example> dermis extract, fermented and fermented dermal preparation of the dermal extract

Example 1 Preparation of Dermis Extract

1L of 80% ethanol aqueous solution was added to 100 g of the dermis powder obtained by drying and pulverizing the dermis at room temperature, and extracted at room temperature for 7 days, followed by filtration (Whatman GF / C Fiter), and the filtered extract was concentrated under reduced pressure and lyophilized. Was prepared. This extract was stored at −20 ° C. and used in the experiments below.

Example 2 Preparation of Dermis Extract

1L of 80% ethanol aqueous solution was added to 100 g of dermis powder, and extracted at room temperature for 7 days. Dried to prepare a dermis extract. This extract was stored at −20 ° C. and used in the experiments below.

<Example 3> Preparation of fermented extract dermis

The dermis extract obtained in <Example 2> was autoclaved, and the sterilized dermis extract 50% (w / w), sucrose 5% (w / w) and 5% (w / w) in a mixture of water w) inoculated with Lactobacillus plantarum (ATCC 8014) (3X10 ⁶ cells / mL) and 5% (w / w) Saccharomyces cerevises (IFO 0203) 8014) (4X10 ⁶ cells / mL) Fermented anaerobicly at 38 ° C. for 7 days and lyophilized to obtain fermented product of dermis extract. This fermentation was stored at -20 ° C and used for the experiments below.

<Example 4> The dermis fermentation preparation of

0.1 L of water was added to 1 kg of dermis powder and fermented in a natural state for about 2 weeks to obtain a fermented product having a water content of 15%. This fermentation was stored at -20 ° C and used for the experiments below.

<Example 5> The dermis fermentation preparation of

5% (w / w) Lactobacillus plantarum (ATCC 8014) (3X10 ⁶ cells / mL) and 5% (w / w) Saccharomyces cerevisiae (IFO 0203) 8014) in rice bran powder (4X10) ⁶ cells / mL) inoculated anaerobic fermentation for 7 days at 38 ℃ and mixed with a saturated salt solution 1:50 weight ratio (fermentation: saturated salt solution) and sterilized by salt and filtered (Whatman GF / C Fiter). Next, 0.1L of water was added to 1 kg of dermis powder, and 1% (w / w) of the filtrate was added thereto, followed by natural fermentation for about 2 weeks at room temperature, thereby finally obtaining a fermentation product having a water content of 15%. This fermentation was stored at -20 ° C and used for the experiments below.

<Example 6> The dermis fermentation preparation of

5% (w / w) Lactobacillus plantarum (ATCC 8014) (3X10 ⁶ cells / mL) and 5% (w / w) Saccharomyces in 1:10 mixture medium of kelp powder and rice bran powder Inoculated with Seth cerevise (IFO 0203) 8014) (4X10 ⁶ cells / mL) anaerobic fermentation for 7 days at 38 ℃ and mixed with a saturated salt solution 1:50 weight ratio (fermentation: saturated salt solution) After sterilization with salt and filtered (Whatman GF / C Fiter). Next, 0.1L of water was added to 1 kg of dermis powder, and 1% (w / w) of the filtrate was added thereto, followed by natural fermentation for about 2 weeks at room temperature, thereby finally obtaining a fermentation product having a water content of 15%. This fermentation was stored at -20 ° C and used for the experiments below.

<Example 7> The dermis fermentation preparation of

5% (w / w) Lactobacillus plantarum (ATCC 8014) (3X10 ⁶ cells / mL) and 5% (w / w) Saccharomyces in a 1:20 mixture medium of ginseng powder and rice bran powder Inoculated with Seth cerevise (IFO 0203) 8014) (4X10 ⁶ cells / mL) anaerobic fermentation for 7 days at 38 ℃ and mixed with a saturated salt solution 1:50 weight ratio (fermentation: saturated salt solution) After sterilization with salt and filtered (Whatman GF / C Fiter). Next, 0.1L of water was added to 1 kg of dermis powder, and 1% (w / w) of the filtrate was added thereto, followed by natural fermentation for about 2 weeks at room temperature, thereby finally obtaining a fermentation product having a water content of 15%. This fermentation was stored at -20 ° C and used for the experiments below.

<Example 8> dermis fermentation preparation of

5% (w / w) Lactobacillus plantarum (ATCC 8014) (3X10 ⁶ cells / mL) and 5% (w / w) in a 1: 2: 20 mixture medium of ginseng powder, kelp powder and rice bran powder ) Was inoculated anaerobic fermented with Saccharomyces cerevisiae (IFO 0203) 8014) (4X10 ⁶ cells / mL) for 7 days at 38 ℃ and a saturated salt solution 1:50 weight ratio (fermented solution: salt) Saturated solution) and filtered after sterilization with salt (Whatman GF / C Fiter). Next, 0.1L of water was added to 1 kg of dermis powder, and 1% (w / w) of the filtrate was added thereto, followed by natural fermentation for about 2 weeks at room temperature, thereby finally obtaining a fermentation product having a water content of 15%. This fermentation was stored at -20 ° C and used for the experiments below.

Example 9 Preparation of Extract of Dermal Fermentation

250L of water was added to 12.43 kg of the dermis fermented product obtained in <Example 8>, followed by hot water extraction at a temperature of 100 ° C. for 2 hours, and the extract was filtered through a 1 μm filter and lyophilized to obtain an extract in powder form. This extract was stored at −20 ° C. and used in the experiments below.

< Experimental Example > Experiments such as obesity improvement activity

Experimental Example 1 Obesity Improvement Activity Experiment

Three-week-old ICR male rats purchased from Daehan Biolink Co., Ltd. (Seoul, South Korea) were acclimated for one week with solid feed and water, and randomly divided mice of similar weight into eight groups of 13 rats. The normal group (I) is a normal diet, the obesity control group (II) is a high fat diet, and the experimental group (III) is a high fat diet and an extract or a mixture of fermented products (the high fat diet is 100 parts by weight of each example extract) Or 0.2 parts by weight of the fermentation product was dissolved in water and mixed), and fed one by one for 97 days. The breeding environment was maintained at a temperature of 23 ± 2 ° C., a humidity of 50 ± 5%, and a night and day cycle for 12 hours.

In the above diet, Laboratory Rodent Diet 5001 (PMI Nutrition International, United States) diet was used, and the high-fat diet was Dyets # 101556 (> 17.7% protein, 40% fat, 31.4% carbohydrate) (Dyets Inc., United States). ) Feed was used.

Body weight was measured using an animal weight scale at the beginning of the experiment and after 97 days of breeding. The results are shown in <Table 1> to <Table 9>.

When the extract of <Example 1> is administered division Initial weight (g) Final weight (g) Normal group (Ⅰ)
28.32 ± 2.13
46.86 ± 2.56 Obesity control group (Ⅱ) 52.63 ± 7.47 Experimental group (Ⅲ) 50.47 ± 5.46

* Is p <0.05 and ** is p <0.01.

When the extract of <Example 2> is administered division Initial weight Final weight Normal group (Ⅰ)
26.59 ± 3.25
45.46 ± 3.21 Obesity control group (Ⅱ) 52.57 ± 5.63 Experimental group (Ⅲ) 49.42 ± 5.76

* Is p <0.05 and ** is p <0.01.

When the fermentation product of <Example 3> is administered division Initial weight Final weight Normal group (Ⅰ)
26.45 ± 3.32
46.98 ± 2.78 Obesity control group (Ⅱ) 55.45 ± 8.28 Experimental group (Ⅲ) 51.52 ± 5.37 *

* Is p <0.05 and ** is p <0.01.

When the fermentation product of <Example 4> is administered division Initial weight Final weight Normal group (Ⅰ)
27.48 ± 2.52
47.59 ± 2.47 Obesity control group (Ⅱ) 59.27 ± 4.42 Experimental group (Ⅲ) 52.21 ± 2.31 **

* Is p <0.05 and ** is p <0.01.

When the fermentation product of <Example 5> is administered division Initial weight Final weight Normal group (Ⅰ)
28.32 ± 3.92
46.27 ± 2.43 Obesity control group (Ⅱ) 58.92 ± 3.25 Experimental group (Ⅲ) 47.82 ± 3.56 **

* Is p <0.05 and ** is p <0.01.

When the fermentation product of <Example 6> is administered division Initial weight Final weight Normal group (Ⅰ)
27.21 ± 2.14
47.21 ± 1.43 Obesity control group (Ⅱ) 57.57 ± 2.52 Experimental group (Ⅲ) 47.69 ± 2.24 **

* Is p <0.05 and ** is p <0.01.

When the fermentation product of <Example 7> is administered division Initial weight Final weight Normal group (Ⅰ)
27.65 ± 2.94
48.56 ± 1.75 Obesity control group (Ⅱ) 59.35 ± 4.24 Experimental group (Ⅲ) 46.32 ± 2.93 **

* Is p <0.05 and ** is p <0.01.

When the fermentation product of <Example 8> is administered division Initial weight Final weight Normal group (Ⅰ)
27.53 ± 2.85
47.73 ± 3.32 Obesity control group (Ⅱ) 58.32 ± 3.21 Experimental group (Ⅲ) 45.92 ± 2.43 **

* Is p <0.05 and ** is p <0.01.

When the fermentation product of <Example 9> is administered division Initial weight Final weight Normal group (Ⅰ)
29.32 ± 2.89
49.94 ± 2.54 Obesity control group (Ⅱ) 59.65 ± 2.96 Experimental group (Ⅲ) 51.37 ± 3.57 **

* Is p <0.05 and ** is p <0.01.

When the extracts of Examples 1 and 2 were fed, the weight of the experimental group was lowered as compared to the weight of the obese control group, but there was no significant difference. When the fermented products of Examples 3 to 9 were fed, the weight of the experimental group was This obesity was significantly reduced compared to the body weight of the control group. In particular, when the fermentation product or the extract of <Examples 5 to 9> was administered, the weight loss effect was the highest.

Experimental Example 2 Hangover Relief Activity Experiment

Whether the extract or fermented product of each example had hangover-relieving activity was measured through alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity.

The activity of ADH and ALDH was performed with a slight modification of Bostian et al. (Bostian KA, et al. Biochem. J. 173: 787-798 (1978)).

The ADH fraction and the ALDH fraction were first obtained from S9 rat liver homogenate (Moltox Co., Boone, Nc, USA), and the reaction mixture for ADH activity analysis was 1.4 ml of distilled water, 0.75 ml of 1M Tris-HCl (pH 8.8). , 0.3 ml 20 mM NAD +, 0.3 ml ethanol, 0.15 ml ADH fraction, and 0.3 ml sample, the reaction mixture for ALDH activity analysis was 2.1 ml distilled water, 0.3 ml 1M Tris-HCl (pH 8.8) , 0.1 ml 20 mM NAD +, 0.1 ml 3M KCl, 0.1 ml 0.33 M 2-mercaptoethanol, 0.1 ml ALDH fraction, and 0.3 ml sample.

The activity was measured for 5 minutes at 30 ° C., and then the production rate of NADH from NAD + was measured using absorbance at 340 nm. The results are shown in Table 10 below.

Relative units of ADH and ALDH division ADH activity ALDH activity CTL 1 ± 0.18 1 ± 0.13 Extract of <Example 1> 1.5 ± 0.12 ** 1.3 ± 0.07 ** Extract of <Example 2> 1.7 ± 0.11 ** 1.3 ± 0.10 ** Fermented product of <Example 3> 2.3 ± 0.09 ** 1.8 ± 0.04 ** Fermented product of <Example 4> 2.4 ± 0.08 ** 2.0 ± 0.07 ** Fermented product of <Example 5> 3.1 ± 0.11 ** 2.7 ± 0.09 ** Fermented product of <Example 6> 2.9 ± 0.07 ** 2.8 ± 0.13 ** Fermented product of <Example 7> 3.0 ± 0.06 ** 2.8 ± 0.08 ** Fermented product of <Example 8> 3.3 ± 0.12 ** 3.1 ± 0.06 ** Extract of Example 9 3.4 ± 0.10 ** 3.1 ± 0.07 **

CTL is untreated group, negative control, * is p <0.05 and ** is p <0.01.

It can be seen that the extract or fermented product of each of the above examples significantly increased the activity of ADH and ALDH. In particular, similar to the above results it can be seen that the fermentation or extracts of Examples 5 to 9 significantly increased the activity of ADH and ALDH.

Experimental Example 3 Protective Activity of HepG2 Hepatocytes

Hepatocellular HepG2 protective activity of the extracts or fermentations of the above examples was measured by MTT assay.

HepG2 cells were purchased from Daehan Biolink Co., Ltd. (Seoul, South Korea), and the cells were used in the experiment while culturing in a humidified incubator maintained at 5% CO ₂ using DMEM medium containing 10% FBS.

Experiments were carried out according to the method of Parrizas et al. (Parrizas M, et al. J. Biol. Chem. 272: 154-161 (1997)), first inoculating cells in a 24-well culture dish and extract or fermentation of each of the above examples. Water (untreated, 0.125 mg / mL, 0.5 mg / mL, and 1.0 mg / mL) was treated for 30 minutes by concentration, then treated with 5% ethanol and incubated for 48 hours. Next, the culture solution was removed and treated with 200 ml of MTT reagent (Sigma, St. Louis, MO, USA) for 1 hour at 37 ° C., and the same amount of 2-propanol as the MTT reagent was added to lyse the cells. After inducing the reaction, the absorbance at 570 nm was measured.

The results are shown in Tables 11 to 19 below.

MTT activity when the extract of Example 1 was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.063 ± 0.021 0.5 mg / mL + 5% ethanol 0.065 ± 0.013 1 mg / mL + 5% ethanol 0.175 ± 0.021 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

MTT activity when the extract of Example 2 was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.064 ± 0.014 0.5 mg / mL + 5% ethanol 0.064 ± 0.043 1 mg / mL + 5% ethanol 0.194 ± 0.051 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

MTT activity when the fermented product of <Example 3> was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.069 ± 0.011 0.5 mg / mL + 5% ethanol 0.109 ± 0.012 1 mg / mL + 5% ethanol 0.362 ± 0.015 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

MTT activity when the fermented product of <Example 4> was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.113 ± 0.014 * 0.5 mg / mL + 5% ethanol 0.141 ± 0.032 ** 1 mg / mL + 5% ethanol 0.374 ± 0.012 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

MTT activity when the fermented product of <Example 5> was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.156 ± 0.014 ** 0.5 mg / mL + 5% ethanol 0.172 ± 0.052 ** 1 mg / mL + 5% ethanol 0.453 ± 0.017 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

MTT activity when the fermented product of <Example 6> was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.152 ± 0.021 ** 0.5 mg / mL + 5% ethanol 0.169 ± 0.023 ** 1 mg / mL + 5% ethanol 0.427 ± 0.025 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

MTT activity when the fermented product of Example 7 was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.149 ± 0.031 ** 0.5 mg / mL + 5% ethanol 0.182 ± 0.035 ** 1 mg / mL + 5% ethanol 0.437 ± 0.024 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

MTT activity when the fermented product of <Example 8> was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.163 ± 0.032 ** 0.5 mg / mL + 5% ethanol 0.195 ± 0.032 ** 1 mg / mL + 5% ethanol 0.483 ± 0.021 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

MTT activity when the extract of Example 9 was treated division MTT activity (A ₅₇₀ ) CTL 0.261 ± 0.052 0 mg / mL + 5% ethanol 0.062 ± 0.041 0.125 mg / mL + 5% ethanol 0.141 ± 0.044 ** 0.5 mg / mL + 5% ethanol 0.223 ± 0.056 ** 1 mg / mL + 5% ethanol 0.476 ± 0.036 **

CTL is untreated group, * is p <0.05 and ** is p <0.01.

When the extracts or fermented products of each of the above examples were treated, it can be seen that significant differences were recognized at all at least 1 mg / mL. Herein, the fermented products or extracts of Examples 5 to 9 had the highest hepatocellular protective activity.

Experimental Example 4 Fatty Liver Improvement Activity Experiment

The extract or fermented product of each example was divided into two groups to confirm fatty liver improvement activity.

First, the extracts or fermented products of <Examples 1 to 8> were slaughtered in the experimentally terminated mice in <Experimental Example 1> to measure the lipid concentration of liver tissue and the activity of the indicator of liver damage indicator, <Example 9 For extracts of>, other laboratory animals were used for the activity of liver damage indicator enzymes, blood fat content and liver histology.

<Experimental Example 4-1> <Examples 1 to 8> of the extract or fermentation water liver improved activity test

<1> Lipid concentration analysis of liver tissue

In order to investigate the change in the lipid concentration of the liver according to the administration of the test substance, the rats of each experimental group whose experiments were terminated in <Experimental Example 1> were extracted from the liver, and the washed liver was washed with physiological saline, and then (Folch J. et al., J. Biol. Chem., 226: 497-509, 1957), grind the liver finely, place it in a homogeneous tube, destroy the cell membrane with an ultrasonic cell membrane grinder, and remove chloroform and methanol ( Lipids were extracted with a mixture of chloroform: methanol = 2: 1). The extract was then centrifuged at 2000 rpm to obtain a supernatant and the supernatant as a sample to measure the total cholesterol and triglyceride levels in the liver. The total cholesterol content was analyzed using a commercial kit (AM202-K, Asan Pharmaceutical Co., Ltd.). The absorbance was measured at 500 nm and the content was expressed in mg / dl according to the calibration curve. The triglyceride content was also analyzed using a commercial kit (AM 157S-K, Asan Pharmaceutical Co., Ltd.). The absorbance was measured at 550 nm and the content was expressed in mg / dl according to the calibration curve.

The experimental results are shown in Tables 20 to 28 below.

Triglyceride and Cholesterol Concentrations in Liver Tissues of the Extract Administration Group of Example 1 division Triglyceride (mg / ㎗) Total Cholesterol Concentration (mg / dl) Normal group (Ⅰ) 39.78 ± 3.24 3.1 ± 0.9 Obesity control group (Ⅱ) 74.62 ± 1.17 8.2 ± 0.6 Experimental group (Ⅲ) 63.21 ± 2.35 ** 7.1 ± 0.4

* Is p <0.05 and ** is p <0.01.

Triglyceride and Cholesterol Concentrations in Liver Tissue of the Extract-administered Group of Example 2 division Triglyceride ㎎ / ㎗ Total cholesterol concentration mg / dl Normal group (Ⅰ) 38.57 ± 3.68 3.2 ± 0.8 Obesity control group (Ⅱ) 72.75 ± 3.43 7.9 ± 0.7 Experimental group (Ⅲ) 64.41 ± 3.23 ** 6.8 ± 0.7

* Is p <0.05 and ** is p <0.01.

Triglyceride and Cholesterol Concentrations of Liver Tissues from Fermented Fertilizers of Example 3 division Triglyceride ㎎ / ㎗ Total cholesterol concentration mg / dl Normal group (Ⅰ) 37.57 ± 4.15 2.9 ± 0.9 Obesity control group (Ⅱ) 73.73 ± 2.76 8.3 ± 0.4 Experimental group (Ⅲ) 55.84 ± 1.24 ** 5.7 ± 0.9 **

* Is p <0.05 and ** is p <0.01.

Triglyceride and Cholesterol Concentrations of Liver Tissues from Fermented Fertilizers of Example 4 division Triglyceride ㎎ / ㎗ Total cholesterol concentration mg / dl Normal group (Ⅰ) 39.53 ± 2.57 3.0 ± 0.6 Obesity control group (Ⅱ) 71.72 ± 4.02 8.2 ± 0.7 Experimental group (Ⅲ) 52.31 ± 3.27 ** 5.5 ± 0.8 **

* Is p <0.05 and ** is p <0.01.

Neutral Fatty Acid and Cholesterol Concentrations of Liver Tissues of the Fermented Fermented Group of Example 5 division Triglyceride ㎎ / ㎗ Total cholesterol concentration mg / dl Normal group (Ⅰ) 35.05 ± 5.17 2.8 ± 1.1 Obesity control group (Ⅱ) 75.04 ± 1.27 8.4 ± 0.6 Experimental group (Ⅲ) 41.35 ± 1.29 ** 3.7 ± 0.9 **

* Is p <0.05 and ** is p <0.01.

Triglyceride and Cholesterol Concentrations of Liver Tissue in the Fermented Fermented Group of Example 6 division Triglyceride ㎎ / ㎗ Total cholesterol concentration mg / dl Normal group (Ⅰ) 35.05 ± 5.17 2.8 ± 1.1 Obesity control group (Ⅱ) 72.02 ± 2.32 8.4 ± 0.9 Experimental group (Ⅲ) 42.43 ± 2.35 ** 3.9 ± 0.4 **

* Is p <0.05 and ** is p <0.01.

Neutral Fatty Acid and Cholesterol Concentrations of Liver Tissues of the Fermented Fermented Group of Example 7 division Triglyceride ㎎ / ㎗ Total cholesterol concentration mg / dl Normal group (Ⅰ) 35.05 ± 5.17 2.8 ± 1.1 Obesity control group (Ⅱ) 73.02 ± 2.43 8.2 ± 0.3 Experimental group (Ⅲ) 43.21 ± 2.31 ** 3.8 ± 0.4 **

* Is p <0.05 and ** is p <0.01.

Neutral Fatty Acid and Cholesterol Concentrations of Liver Tissues of the Fermented Fermented Group of Example 8 division Triglyceride ㎎ / ㎗ Total cholesterol concentration mg / dl Normal group (Ⅰ) 35.05 ± 5.17 2.8 ± 1.1 Obesity control group (Ⅱ) 76.02 ± 1.35 8.7 ± 0.4 Experimental group (Ⅲ) 39.26 ± 1.29 ** 3.5 ± 0.5 **

* Is p <0.05 and ** is p <0.01.

Although no significant difference was recognized, all of the extracts or fermented products of the above examples had activity of lowering the concentration of triglyceride and cholesterol in liver tissue. Here, the highest activity is the fermented product or extract of <Examples 5 to 8>.

<2> Activity analysis of liver function indicator enzyme

GPT and GOT levels used as indicator enzymes of liver tissue damage were measured using an analysis kit (Asan Pharmaceutical, Korea) after separation of plasma after 97 days of experiment. > To <Table 35>.

Activity of liver function indicator enzyme of extract administration group of <Example 1> division GPT (IU / L) GOT (IU / L) Normal group (Ⅰ) 37.84 ± 4.23 67.45 ± 3.27 Obesity control group (Ⅱ) 63.74 ± 2.34 113.46 ± 1.55 Experimental group (Ⅲ) 57.56 ± 1.32 90.37 ± 3.21 *

* Is p <0.05 and ** is p <0.01.

Activity of liver function indicator enzyme of extract administration group of <Example 2> division GPT (IU / L) GOT (IU / L) Normal group (Ⅰ) 36.26 ± 2.54 65.64 ± 4.54 Obesity control group (Ⅱ) 65.21 ± 1.67 116.56 ± 5.21 Experimental group (Ⅲ) 57.05 ± 3.35 * 84.57 ± 5.32 *

* Is p <0.05 and ** is p <0.01.

Activity of liver function indicator enzyme of fermented product administration group of <Example 3> division GPT (IU / L) GOT (IU / L) Normal group (Ⅰ) 37.54 ± 3.15 68.94 ± 5.23 Obesity control group (Ⅱ) 62.42 ± 3.17 113.65 ± 4.87 Experimental group (Ⅲ) 52.21 ± 2.23 ** 80.65 ± 1.21 **

* Is p <0.05 and ** is p <0.01.

Activity of liver function indicator enzyme of fermented product administration group of <Example 4> division GPT (IU / L) GOT (IU / L) Normal group (Ⅰ) 39.27 ± 1.53 69.42 ± 2.32 Obesity control group (Ⅱ) 65.21 ± 1.34 116.45 ± 6.64 Experimental group (Ⅲ) 53.34 ± 2.37 ** 81.75 ± 5.67 **

* Is p <0.05 and ** is p <0.01.

Neutral Fatty Acid and Cholesterol Concentrations of Liver Tissues of the Fermented Fermented Group of Example 5 division GPT (IU / L) GOT (IU / L) Normal group (Ⅰ) 37.94 ± 2.75 65.54 ± 3.56 Obesity control group (Ⅱ) 62.31 ± 3.52 119.76 ± 2.43 Experimental group (Ⅲ) 38.87 ± 4.25 ** 69.43 ± 1.69 **

* Is p <0.05 and ** is p <0.01.

Triglyceride and Cholesterol Concentrations of Liver Tissue in the Fermented Fermented Group of Example 6 division GPT (IU / L) GOT (IU / L) Normal group (Ⅰ) 37.94 ± 2.75 65.54 ± 3.56 Obesity control group (Ⅱ) 64.63 ± 3.73 108.54 ± 4.63 Experimental group (Ⅲ) 41.75 ± 2.43 ** 73.42 ± 3.22 **

* Is p <0.05 and ** is p <0.01.

Neutral Fatty Acid and Cholesterol Concentrations of Liver Tissues of the Fermented Fermented Group of Example 7 division GPT (IU / L) GOT (IU / L) Normal group (Ⅰ) 37.94 ± 2.75 65.54 ± 3.56 Obesity control group (Ⅱ) 64.67 ± 2.65 122.42 ± 3.51 Experimental group (Ⅲ) 42.49 ± 3.56 ** 68.59 ± 4.93 **

* Is p <0.05 and ** is p <0.01.

Neutral Fatty Acid and Cholesterol Concentrations of Liver Tissues of the Fermented Fermented Group of Example 8 division GPT (IU / L) GOT (IU / L) Normal group (Ⅰ) 37.94 ± 2.75 65.54 ± 3.56 Obesity control group (Ⅱ) 65.93 ± 4.69 124.39 ± 3.06 Experimental group (Ⅲ) 38.21 ± 4.89 ** 66.53 ± 4.64 **

* Is p <0.05 and ** is p <0.01.

It can be seen that all of the extracts or fermentations of the above examples lower GPT and GOT activity. In particular, the fermented products of Examples 5 to 8 have the highest effect.

<Example 4-2> Experiment of fatty liver improvement activity of the extract of < Example 9>

<1> Measurement of the activity of liver damage indicator enzymes through blood analysis

A five-week-old SD rat was purchased from Orient Bio Co., Ltd. (Gyeonggi-do, South Korea), and then purified for 7 days and used for the experiment. The test animals were divided into 4 groups of 8 animals each, and the normal group (Ⅰ) was a normal diet (FORMULA-M07, Seoul, Gyeonggi-do), and the obese control group (II) was a high-fat diet (DYET # 101836 (Modified AIN-). 76A purified rodent dirt with 2% Cholesterol & 0.5% Cholic acid), Feedlab Co., Ltd., Seoul, Gyeonggi-do, Korea (Experimental group Ⅲ), high fat diet (DYET # 101836) and the extract of <Example 9> 2g / kg The positive control group (IV) was divided into three to four animals fed with high-fat diet (DYET # 101836) and metformin (350 mg / kg) of metformin for 8 weeks with water. Here, water and feed were freely ingested, and the test substance extract and metformin were administered orally once a day, and the breeding environment was 23 ± 3 ° C., 55 ± 15% humidity, night and day. It was kept in a 12 hour cycle.

Eight weeks after the start of the experiment, plasma was isolated from the test animals to obtain GOT (AST, aspartate amino-transferase) activity, GPT (ALT, alanine amino-transferase) activity, GGT activity, total cholesterol content, HDL cholesterol content, triglyceride content, lipid Content was used toshiba TBA-30R plasma analyzer, the assay reagent was HamLap product, LDL cholesterol content was Fridwald equation ([LDL-C = [Total C]-{[HDL-C] + [TG / 5] ]}) And the results are shown in FIGS. 1 to 8.

Referring to Figures 1 to 8, it can be seen that the GOT, GPT and GGT activities of liver toxicity indicator enzymes were significantly reduced in the experimental group as compared to the obese control group, and the total cholesterol content, LDL cholesterol content and triglyceride content And phospholipid content was also significantly decreased (HDL cholesterol was increased compared to the obese control group, but was not significant). Compared with the positive control group (methformin-administered group), the experimental group is excellent overall except for triglyceride.

<2> liver biopsy

After the end of the 8-week experiment, the abdomen of the experimental animal was incised, the liver was extracted, put in 10% formalin and fixed for at least 24 hours, washed with running water sufficiently, dehydrated with ethanol, and passed through paraffin. Embedded. Tissue sections were fabricated into thin sections with a thickness of about 4 μm, and then stained with HE (Hematoxylin & eosin) stained and examined under a microscope. The percentage of macrotropes that might appear in the accumulation of triglycerides was measured. 0 according to Brunt et al. (Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR.Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94: 2467-2474) (None), 1 (0 to 33%), 2 (33 to 66%) and 3 (66 to 100%), the scores were calculated and averaged, and the results are shown in FIG. 9.

Referring to FIG. 9, it can be seen that the experimental group has a weak phobia compared to the obese control group, and the degree of phobia is lower than that of the metformin administration group, which is a relatively positive control group.

Statistical processing

All experimental results are expressed as Mean ± SD values. ANOVA analysis was performed on all the experiments except for Experimental Example 4-2, and the significant difference was verified by Duncan test, and the experimental difference was verified using Student's t- test for Experimental Example 4-2. It was.

Claims (12)

Fatty liver improver composition comprising any of the following (I) to (II) as an active ingredient;
(I) a fermentation product obtained by sterilizing the fermentation product by lactic acid bacteria and yeast of the mixture obtained by adding at least one of kelp and ginseng to rice bran, adding to the dermis and fermenting in a natural state; And
(II) The water extract of the fermentation product of the above (I).
The method of claim 1,
The lactic acid bacteria is a fatty liver improver composition, characterized in that Lactobacillus genus lactic acid bacteria.
The method of claim 1,
The yeast is genus Saccharomyces Fatty liver improver composition, characterized in that it is yeast.
The method of claim 1,
Fatty liver improver composition, characterized in that the extract of (II) is a hot water extract.
Hyperlipidemic improver composition comprising any one of the following (I) to (II)) as an active ingredient;
(I) a fermentation product obtained by sterilizing the fermentation product by lactic acid bacteria and yeast of the mixture obtained by adding at least one of kelp and ginseng to rice bran, adding to the dermis and fermenting in a natural state; And
(II) The water extract of the fermentation product of the above (I).
The method of claim 5,
The lactic acid bacteria is Lactobacillus genus lactic acid bacteria, characterized in that hyperlipidemic improver composition.
The method of claim 5,
The yeast is genus Saccharomyces Hyperlipidemic improver composition, characterized in that the yeast.
The method of claim 5,
Hyperlipidemic improver composition, characterized in that the extract of (II) is a hot water extract.
Hangover relief composition comprising any of the following (I) to (II)) as an active ingredient;
(I) a fermentation product obtained by sterilizing the fermentation product by lactic acid bacteria and yeast of the mixture obtained by adding at least one of kelp and ginseng to rice bran, adding to the dermis and fermenting in a natural state; And
(II) The water extract of the fermentation product of the above (I).
10. The method of claim 9,
The lactic acid bacterium is lactobacillus genus lactic acid bacteria, characterized in that hangover relief.
10. The method of claim 9,
The yeast is genus Saccharomyces Hangover elimination composition characterized in that it is yeast.
10. The method of claim 9,
The extract of (II) is hangover relief composition, characterized in that the hot water extract.

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