KR100631073B1 - Composition for preventing and treating alcoholic liver disease and alcoholic hyperlipidemia comprising the extract of codonopsis lanceolata - Google Patents

Abstract

A pharmaceutical composition is provided to decrease the lipid concentration of liver tissue and plasma increased by taking alcohol, and normalize the activity of liver function index enzyme. The pharmaceutical composition for preventing and treating alcoholic liver disease and alcoholic hyperlipidemia comprises an extract of Codonopsis lanceolata, which is prepared by using water or C1-6 alcohol, as an effective ingredient. The extract of Codonopsis lanceolata is used as an effective ingredient of functional food composition for preventing alcoholic liver disease and alcoholic hyperlipidemia.

Description

Composition for preventing and treating alcoholic liver disease and alcoholic hyperlipidemia comprising the extract of Codonopsis lanceolata

1 is a graph showing the weight change over time of the animal model of alcohol intake according to the present invention.

ND: normal group

EC: alcohol intake group

CE: alcohol + deodeok extract intake group

Figure 2 is a microscope observation of the liver tissue of the animal model of alcohol intake according to the present invention.

A: normal group

B: alcohol intake group

C: alcohol + deodeok extract intake group

bar: 500 μm

The present invention relates to a composition for the prevention and treatment of alcoholic liver disease and alcoholic hyperlipidemia comprising a deodeok extract as an active ingredient.

Deodeok ( Codonopsis lanceolata ) is a perennial herb belonging to the genus Campanulaceae, and its root is called larva (Radix Codonopsis lanceolata ). It is distributed in Korea, China, and other countries, and it is effective in Jinhae, expectorant, detoxification, asthma, pulmonary tuberculosis, anti-ulcer, tonsillitis (Han Eun Kyung et al., 1997, Korean Journal of Food and Nutrition Science, 26 (6): 1181-1186). Since ancient times, ginseng has been widely used as a substitute for ginseng (Lee Jong Hwa, 2002, Korean Society of Food Science and Technology, 34 (4): 732-736). The ingredients of deodeok include sterol, N-formylharman, perlolyne, norharman, squalene, squalene, polyacetylene-based substance that is believed to be the main body of cyclone, cycloathenol (cycloartenol), terpenoids and saponins have been identified.

Studies on deodeok conducted in Korea include the effects of increasing the immune activity of deodeok extracts (Jeong-Sook Suh, 1996, Korean Journal of Food and Nutrition, 9 (4): 379-384) and the antioxidant effects of Deodeok ethanol extracts (Meng et al., 1991, Korea Korean Journal of Food Science 23 (3): 311-316). However, there are few systematic studies of liver disease, particularly those related to alcohol-induced liver disease.

On the other hand, an appropriate amount of alcohol is beer mugs for beer, and shochu mugs for soju, about 1 to 2 glasses per day, and alcohol consumption reduces the blood clots and facilitates metabolism through improved blood flow. It is said to reduce the occurrence of chronic metabolic diseases such as hypertension, hyperlipidemia and cardiovascular disease.

However, Korea's alcohol consumption is the fourth largest in the world, so excessive intake of alcohol is a problem. Alcohol absorbed by the human body is mainly converted to acetaldehyde in the cytoplasm by alcohol dehydrogenase (ADH) and then to acetyl-CoA by aldehyde dehydrogenase (ALDH), which is then converted to acetate. In case of excessive intake of alcohol, acetaldehyde, which is a liver toxic substance that damages the liver, is generated in a large amount, which damages the liver. An increase in NADH, which is caused by the metabolism of alcohol, increases the oxygen consumption of the liver and damages liver tissue. Lieber CS, 2003, Alcohol Res Health, 27 (3): 220-231.

In addition, long-term alcohol intake is known to accumulate lipids in liver cells, causing alcoholic fatty liver. Long-term alcohol intake increases oxidative stress and free radical production following the induction of cytochrome P450 2E1 and promotes the production of lipid peroxides. It destroys hepatocytes and blocks microbubbles and blood vessels in the liver, which can worsen hepatitis. In addition, increasing the activity of NFκ-B and increasing the transcription of pre-inflammatory mediators such as TNF-α will lead to fatty liver. In addition, the production of lipopolysaccharide by the activity of acetaldehyde and Kupffer cells produced as a result of alcohol metabolism accelerates damage to liver tissue.

In addition, excessive intake of alcohol increases the lipid content in the plasma, causing chronic metabolic diseases such as hyperlipidemia, hypertension, and cardiovascular diseases.

Therefore, various attempts have been made to prevent and treat chronic metabolic diseases caused by alcohol consumption. However, most of the currently used therapeutic agents have some degree of side effects, although the degree of chemical agent is different. Therefore, the drug for the treatment and prophylaxis or hangover, lipid reduction and liver damage prevention compositions are developed and sold using natural products having relatively little side effects, but the effect is insufficient.

Accordingly, the present inventors have completed the present invention by elucidating that the extract of Deodeok has an effect of improving alcoholic liver disease and alcoholic hyperlipidemia as a result of research to develop a substance showing an effect on liver disease and hyperlipidemia caused by alcohol.

Therefore, it is an object of the present invention to provide a composition for the prevention or treatment of alcoholic liver disease and alcoholic hyperlipidemia comprising a deodeok extract as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of alcoholic liver disease and alcoholic hyperlipidemia comprising a deodeok extract as an active ingredient.

In order to achieve the another object of the present invention, the present invention provides a food composition for the prevention or improvement of alcoholic liver disease and alcoholic hyperlipidemia comprising a deodeok extract as an active ingredient.

Hereinafter, the content of the present invention will be described in more detail.

The composition of the present invention is characterized in that it contains a deodeok extract as an active ingredient. Codonopsis lanceolata ) can be easily purchased and used in the market, and preferably, the root portion used for food is used in the preparation of the extract. Deodeok used for extraction can be harvested, washed and used as is or dried. Drying can be dry, shade, hot air and natural drying. In addition, in order to increase the extraction efficiency, deodeok or its dry body can be used by grinding the grinder.

Extraction method of Deodeok may use an extraction method known in the art, preferably, can be extracted with water or lower alcohols having 1 to 6 carbon atoms. More preferably, water can be extracted using water, and most preferably hot water can be extracted.

The ratio of deodeok and extraction solvent at the time of extraction is not particularly limited. It can be used 8 to 12 times by weight.

The temperature during extraction may preferably be from 30 to 100 ℃. The extraction time depends on the extraction temperature, but may be 2 to 24 hours, preferably 4 to 24 hours. In addition, when stirring with a stirrer during extraction can further increase the extraction efficiency.

Preferably, the deodeok extract of the present invention is added to 8 ~ 10 times (weight ratio) of hot water in the ground deodeok and 4 to 5 hours at 35 ~ 45 ℃ During heat extraction. The extract is centrifuged to remove the precipitate and recover the supernatant. The recovered supernatant can be concentrated and dried to powder.

The composition of the present invention containing the deodeok extract is characterized in that it has the effect of preventing, treating or improving alcoholic liver disease or alcoholic hyperlipidemia.

In the present invention, "alcoholic liver disease" refers to a disease caused by damage to liver tissue due to excessive ingestion of alcohol, resulting in decreased liver function. More specifically, alcoholic liver disease refers to complications related to cirrhosis and cirrhosis due to acute liver damage caused by drinking and irreversible change. The initial findings of alcoholic liver damage are fatty liver, alcoholic hepatitis caused by repetitive drinking, and it is known to progress to cirrhosis (Hwang, Sung-Kyu, Korean Society of Liver Science , Single Topic Symposium, 2003). Therefore, examples of the alcoholic liver disease include, but are not limited to, alcoholic fatty liver, alcoholic hepatitis, liver fibrosis, cirrhosis of the liver, and the like.

In the present invention, "alcoholic hyperlipidemia" refers to a case in which lipid content such as triglycerides, cholesterol, phospholipids and free fatty acids increased in the plasma due to excessive intake of alcohol, which is angina, myocardial infarction, stroke, arteriosclerosis, fatty liver And various diseases such as pancreatitis.

The composition containing the deodeok extract of the present invention has the activity to prevent, treat or improve the alcoholic liver disease as described above. That is, the composition of the present invention can improve the alcoholic liver disease to maintain the morphological, structural, and physiological functions of the liver to inhibit the progression of liver disease, to treat liver disease, and to prevent the occurrence of alcoholic liver disease. There is also. In addition, the composition of the present invention has the activity of preventing, treating or improving alcoholic hyperlipidemia by reducing the lipid content present in the plasma, and also has the effect of preventing the development of the disease caused by hyperlipidemia, suppressing the progression and improving the disease state. have.

In one embodiment of the present invention to prepare an alcohol intake animal model of continuous intake of alcohol (see Experimental Example 1), administration of the deodeok extract of the present invention effects on alcoholic liver disease (see Experimental Example 2) and alcoholic hyperlipidemia Was examined (see Experimental Example 3). As a result, the deodeok extract lowers the lipid concentration of liver tissue, reduces liver damage, and has the effect of preventing, treating or improving alcoholic liver disease (see Tables 3 to 5 and FIG. 2). It was confirmed that there is an effect to prevent, treat or improve hyperlipidemia (see Table 6).

Therefore, the composition containing the deodeok extract of the present invention as an active ingredient may be provided in the form of a pharmaceutical composition for the prevention or treatment of alcoholic liver disease and alcoholic hyperlipidemia.

The pharmaceutical composition according to the present invention may include a pharmaceutically effective amount of Deodeok extract alone or may further comprise one or more pharmaceutically acceptable carriers. As used herein, the term “pharmaceutically effective amount” refers to an amount that exhibits a higher response than a negative control, and preferably refers to an amount sufficient to treat or prevent alcoholic liver disease or alcoholic hyperlipidemia. A pharmaceutically effective amount of the deodeok extract according to the present invention is 100 to 500 mg / day / kg body weight, preferably 100 to 350 mg / day / weight kg. However, the pharmaceutically effective amount may be appropriately changed depending on various factors such as the disease and its severity, the patient's age, weight, health condition, sex, route of administration and duration of treatment.

As used herein, "pharmaceutically acceptable" is a non-toxic composition that, when administered physiologically to humans, does not inhibit the action of the active ingredient and typically does not cause an allergic reaction such as gastrointestinal disorders, dizziness, or the like. Say The composition of the present invention may be formulated in various ways according to the route of administration by a method known in the art together with the pharmaceutically acceptable carrier. Routes of administration may be administered orally or parenterally, but not limited to these. Parenteral routes of administration include, for example, several routes such as transdermal, nasal, abdominal, muscle, subcutaneous or intravenous.

In the case of oral administration of the pharmaceutical composition of the present invention, the pharmaceutical composition of the present invention is prepared in powder, granule, tablet, pill, dragee, capsule, liquid, gel, according to methods known in the art together with a suitable oral carrier. , Syrups, suspensions, wafers and the like. Examples of suitable carriers include sugars, including lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol and maltitol and starch, cellulose, starch including corn starch, wheat starch, rice starch and potato starch, and the like. Fillers such as cellulose, gelatin, polyvinylpyrrolidone, and the like, including methyl cellulose, sodium carboxymethylcellulose, hydroxypropylmethyl-cellulose, and the like. In addition, crosslinked polyvinylpyrrolidone, agar, alginic acid or sodium alginate and the like may optionally be added as a disintegrant. Furthermore, the pharmaceutical composition may further include an anticoagulant, a lubricant, a humectant, a perfume, an emulsifier, a preservative, and the like.

In addition, when administered parenterally, the pharmaceutical compositions of the present invention may be formulated according to methods known in the art in the form of injections, transdermal and nasal inhalants together with suitable parenteral carriers. Such injections must be sterilized and protected from contamination of microorganisms such as bacteria and fungi. Examples of suitable carriers for injections include, but are not limited to, solvents or dispersion media comprising water, ethanol, polyols (e.g., glycerol, propylene glycol and liquid polyethylene glycols, etc.), mixtures thereof and / or vegetable oils Can be. More preferably, suitable carriers are Hanks solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanol amine or sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose Etc. can be used. In order to protect the injection from microbial contamination, various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal, and the like may be further included. In addition, the injection may in most cases further comprise an isotonic agent such as sugar or sodium chloride. In the case of transdermal administrations, ointments, creams, lotions, gels, external preparations, pasta preparations, linen preparations, air rolls and the like are included. As used herein, "transdermal administration" means the topical administration of the pharmaceutical composition to the skin to deliver an effective amount of the active ingredient contained in the pharmaceutical composition into the skin. These formulations are described in Remington's Pharmaceutical Science , 15th Edition, 1975, Mack Publishing Company, Easton, Pennsylvania, a prescription generally known in pharmaceutical chemistry. In the case of inhaled dosages, the compounds used according to the invention may be pressurized packs or by means of suitable propellants, for example dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. It can be delivered conveniently from the nebulizer in the form of an aerosol spray. In the case of a pressurized aerosol, the dosage unit can be determined by providing a valve to deliver a metered amount. For example, gelatin capsules and cartridges for use in inhalers or blowers can be formulated to contain a mixture of the compound and a suitable powder base such as lactose or starch.

Other pharmaceutically acceptable carriers may be referred to those described in the following documents (Remington's Pharmaceutical Sciences, 19th ed., Mack Publishing Company, Easton, PA, 1995).

Furthermore, the pharmaceutical composition of the present invention may be administered in parallel with a known compound having the effect of preventing or treating alcoholic liver disease or alcoholic hyperlipidemia.

In addition, the deodeok extract according to the present invention may be provided in the form of a food composition for the purpose of improving alcoholic liver disease or alcoholic hyperlipidemia. The food composition of the present invention includes all forms such as functional foods, nutritional supplements, health foods and food additives. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.

For example, as a health food, the deodeok extract of the present invention may be prepared in the form of tea, juice and drink for drinking, or may be ingested by granulation, encapsulation and powdering. In addition, it may be prepared in the form of a composition by mixing with the deodeok extract of the present invention and known substances or active ingredients known to improve the liver disease or hyperlipidemia.

In addition, functional foods include beverages (including alcoholic beverages), fruits and processed foods (e.g. canned fruit, canned foods, jams, marmalade, etc.), fish, meat and processed foods (e.g. ham, sausage cornebipe) Breads and noodles (e.g. udon, soba noodles, ramen, spaghetti, macaroni, etc.), fruit juices, various drinks, cookies, syrups, dairy products (e.g. butter, cheese), edible vegetable oils, margarine, vegetable protein , Retort food, frozen food, various seasonings (eg, miso, soy sauce, sauce, etc.) can be prepared by adding the deodeok extract of the present invention.

In addition, in order to use the deodeok extract of the present invention in the form of food additives can be prepared in powder or concentrate form.

Below. The present invention is explained in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

<Example 1>

Preparation of Deodeok Extract

The raw materials of Deodeok were of good quality and unchanged, and had no off-flavor. Furthermore, 5 kg of surface was washed and cut to a constant length to facilitate extraction. The selected deodeok was placed in the extractor, and placed in 8 times hot water relative to the weight of the deodeok to continue heating at 40 ℃ for 4 hours to extract the ingredients in the deodeok.

The extract was cooled to room temperature and then filtered to 10 microns using a filter machine to remove the deodeok body, and concentrated under reduced pressure so that the solid content was 50% or more. Deodeok concentrate was freeze-dried to prepare a deodeok extract.

Experimental Example 1

Preparation of Alcohol Intake Animal Model

<1-1> Experimental Animal Design and Experimental Composition

50 male rats (5 weeks old, 110-120 g in weight, Sprague-Dawley strains) were orientated to normal solid feed for 3 days, followed by a purified liquid diet (control diet). Re-adapted for 1 week. Each rat was divided into three groups by the compactly randomized design, and each rat was divided into a normal group (ND), an ethanol intake group (EC), and an ethanol + detox extract intake group (CE) for 8 weeks. Animal environment was controlled to maintain a temperature of 23 ± 1 ℃, humidity 50 ± 5% and a light cycle of 12 hours, and the experimental diet was prepared and supplied between 10 and 11 am every day.

The experimental diet used a liquid diet containing ethanol capable of inducing fatty liver, which is known method (De Carli et al., J Nutr ., 91: 331-336, 1967 and Yamada et al., J Nutr . , 115 (10): 1285-1290, 1985). That is, in the normal group (ND), 18% of the total calories were provided as protein, 35% as fat, and the remaining 47% as sugar, and the ethanol intake group (EC) and ethanol + deodeok extract intake group (CE) For 18% of the total calories in protein, 35% in fat, 11% in sugar and the remaining 36% in ethanol. The components of the diet for each group during the breeding period are shown in Table 1 below.

Ingredient and Content of Dietary Composition (g / L) Ingredient (g / L) Normal group (ND) Ethanol Intake Group (EC) Ethanol + Deodeok Extract Intake Group (CE) casein 41.40 41.40 41.40 L-cystine 0.50 0.50 0.50 DL-Methionine 0.30 0.30 0.30 Corn oil 8.50 8.50 8.50 Olive oil 28.40 28.40 28.40 Safflower oil 2.70 2.70 2.70 Dextrin-Maltose (4: 1) 115.20 25.60 25.60 Vitamin Mixture (AIN-76G) ¹⁾ 2.50 2.50 2.50 Mineral mixture (AIN-76G) ²⁾ 8.75 8.75 8.75 Choline bitartrate 0.53 0.53 0.53 Fibrin (carboxymethyl cellulose sodium salt) 10.00 10.00 10.00 Sodium carrageenate 2.00 2.00 2.00 ethanol - 50.00 50.00 Codonopsis lanceolata - - 5.00

1) vitamin mixture (g / kg of mix): thiamin.HCl 0.6; Riboflavin 0.6; Nicotinamide 2.5%; Pyridoxine-HCl 0.7; Nicotinic acid 3; D-calcium pantothenate 1.6; Folic acid 0.2; D-biotin 0.02; Cyanocobalamin (Vitamin B ₁₂ ) 0.001; Retinyl palmitate (250,000 IU / gm) 1.6; DL-α-tocopherol acetate (250 IU / gm) 20; Cholecalciferol (Vitamin D ₃ ) 0.25; Menaquinone (Vitamin K ₂ ) 0.05; Sugar powder 972.9.

2) mineral mixture (g / kg of mix): CaHPO ₄ 500; NaCl 74; K ₂ H ₆ O ₇ H ₂ O 220; K ₂ SO ₄ 52; MgO 24; MnCO ₃ 3.57; Fe (C ₆ H ₅ O ₇ ) .6H ₂ O 6; ZnCO ₃ 1.6; CuCO ₃ 0.3; KIO ₃ 0.01; Na ₂ SeO ₃ .5H ₂ O 0.01; CrK (SO ₄ ) ₂ 0.55; Sugar powder 118.00.

<1-2> Weight gain, dietary efficiency and tissue weight of experimental animals

The cumulative weight gain, dietary efficiency, and tissue weight were examined for each experimental animal of Experimental Example <1-1> during the experimental period. In addition, the animals were autopsied after the end of the experiment and the organ weight was measured to calculate tissue weight per weight unit. The body weight of the test animals was measured every week before feeding.

As a result, in the case of body weight, the cumulative weight gain of the ethanol intake group (EC) was significantly lower than that of the normal group (ND), and the cumulative weight increase of the ethanol + detox extract intake group (CE) was normal (ND group). There was no difference from that (FIG. 1).

The dietary efficiency was significantly lower in the EC group than in the ND group, and the CE group was significantly higher than the EC group.

The weight of liver tissue per body weight was significantly heavier in the EC group than in the ND group, and the spleen and kidney weights were also heavier in the EC group than in the ND group. In the CE group, liver tissue and kidney weights were significantly lower than those in the EC group. The spleen weight was significantly lower in the CE group than in the EC group (Table 2).

Weight gain, dietary efficiency, and tissue weight per unit of weight (mean ± SEM) division Weight gain (g / 8 weeks) Dietary efficiency ^{1 )} Tissue weight (g / 100g body weight) liver spleen kidney Normal group (ND) 135.7 ± 4.8 ^a 2.62 ± 0.18 ^a 5.59 ± 0.45 ^a 0.36 ± 0.03 ^a 1.25 ± 0.08 ^a Ethanol Intake Group (EC) 68.3 ± 7.6 ^b 1.30 ± 0.15 ^b 9.83 ± 1.17 ^b 0.50 ± 0.05 ^b 2.40 ± 0.27 ^b Ethanol + Deodeok Extract Intake Group (CE) 120.6 ± 7.7 ^a 2.25 ± 0.15 ^a 5.80 ± 0.32 ^a 0.36 ± 0.02 ^a 1.45 ± 0.09 ^a

1) Dietary efficiency = [weight gained during the experiment (g / day)] / [the amount of food consumed during the experiment (g / day)]

* Different characters in the same column mean that there is a significant difference (p <0.05)

From the experimental results, it was found that the weight of liver and kidney is increased when ingesting alcohol. This may be related to the accumulation of toxic substances in the liver and kidney with the intake of chronic alcohol (Brzoska MM et al., Alcohol & Alcoholism , 38 (1): 2-10, 2003). On the other hand, administration of the deodeok extract was found to be able to suppress the weight gain of liver and kidney due to alcohol intake. Meanwhile, the spleen weight of the object that is associated with immune function in alcohol-fed groups (paper, etc. ryuhyesuk Korea Nutrition Society, 37 (9): 780-785, 2004), the increase is to protect the individual from tissue damage due to ethanol It is considered to be a protective effect, and deodeok extract was found to have an activity of regulating immune function to normal.

Experimental Example 2

Determination of Liver Disease Amelioration Effect of Deodeok Extract

To determine whether the deodeok extract has an effect on improving liver disease caused by alcohol, the lipid concentration, liver activity index enzyme activity, and lipid peroxide concentration of liver tissue of the alcohol ingested animal model in which the deodeok extract was ingested in Experimental Example 1 Was measured and pathological examination of liver tissue was performed. All experimental results were statistically analyzed using SAS (Statistical Analysis System, SAS version 8.01, SAS Institure Inc, Cary, NC) PC package, and the analysis values are expressed as mean ± SEM. Significant differences between the experimental groups were verified by one-way ANOVA. If significance was observed at the p <0.05 level, the significance of the difference between the mean values of each experimental group was determined by Duncan's multiple test. It evaluated using.

<2-1> Lipid Concentration Analysis of Liver Tissue

After 8 weeks from the start of the experiment, the rats of each group of <Experimental Example 1> were opened and the livers were extracted. The extracted liver was washed with PBS (phosphate buffer saline) and placed on a filter paper to remove excess water. Lipid components of liver tissue were extracted according to a method known by Folch et al. (Folch et al., 1957, J Biol Chem , 226: 497-509). That is, 2 ml of distilled water was added to 0.5 g of liver tissue, followed by uniform homogenization using a polytron homogenizer (IKA-WERKE GmbH & Co., Germany). 5 ml of a chloroform: methanol solution (2: 1, v / v) was added to the homogeneous solution, mixed for 1 minute, and centrifuged at 1000 × g for 10 minutes to separate only the lower layer solution. The remaining supernatant and pellets were mixed again with 2 ml of chloroform: methanol solution (2: 1, v / v), followed by centrifugation at 1000 × g for 10 minutes, and only the lower layer was separated to completely separate the lipid components of the liver. The separated lower layers were mixed, and then 3 ml of a chloroform: methanol: 0.05% CaCl ₂ (3:48:47, v / v / v) solution was added thereto, mixed for 1 minute, and centrifuged at 1000 × g for 10 minutes. Only the lower layer solution was taken and completely dried with nitrogen gas, and then dissolved in 1 ml of ethanol (95%) and used for lipid analysis.

The triglyceride and cholesterol concentrations of hepatic lipid extracts were colorimetrically determined using Triglycerides kit (BCS, Korea) and Cholesterol kit (BCS, Korea), respectively.

As a result, in the ethanol intake group (EC), the triglyceride and cholesterol concentration of liver tissue did not differ significantly from the normal group (ND) group. On the other hand, in the ethanol + deodeok extract group (CE), triglyceride and cholesterol concentrations were reduced compared to the ethanol group (EC) (Table 3).

Lipid concentration in liver tissue (mean ± SEM) division Triglycerides (mg / g) Cholesterol (mg / g) Normal group (ND) 14.95 ± 0.49 ^a 5.07 ± 0.35 ^ab Ethanol Intake Group (EC) 13.40 ± 2.72 ^a 5.79 ± 0.85 ^a Ethanol + Deodeok Extract Intake Group (CE) 9.77 ± 2.06 ^a 3.12 ± 0.96 ^bc

* Different characters in the same column mean that there is a significant difference (p <0.05)

<2-2> Activity analysis of liver function indicator enzyme

Increasing the activity of glutamate oxaloacetate transferase (GOT) and glutamate pyruvate transferase (GPT), which are indicators of hepatic impairment, leads to impairment of fat metabolism due to high fat diet or excessive ingestion of alcohol, resulting in impaired hepatic parenchymal cells and increased release into the blood. (Him Sook Kim, et al., Korean Journal of Food and Nutrition , 11 (3): 312-318, 1998). The present inventors investigated the effect of the deodeok extract on GOT and GPT activity.

Eight weeks after the start of the experiment, each rat of <Experimental Example 1> was fasted for 12 hours, opened in anesthesia with ethyl ether, and blood was collected from the abdominal aorta. The collected blood was centrifuged at 4 ° C. and 3,000 rpm for 15 minutes to separate plasma.

GOT and GPT activity of plasma isolated from rats was measured by an automated hematology analyzer (Express Plus, Chiron Diagnostics Co., USA) using reagents for automated analysis (Bayer, Co., USA).

As a result, the ethanol intake group (EC) showed a 33% and 40% increase in GOT and GPT levels, respectively, compared to the normal group (ND). On the other hand, the ethanol + deodeok extract intake group (CE) was shown to decrease the GOT value compared to the ethanol intake group (EC) (Table 4). It can be seen from the above test results that the administration of Deodeok extract from rats ingesting alcohol has an effect of improving liver tissue damage due to decreased GOT activity.

Activity of liver function indicator enzyme (mean ± SEM) division GOT (Unit / L) GPT (Unit / L) Normal group (ND) 90.76 ± 6.59 ^b 39.00 ± 2.14 ^c Ethanol Intake Group (EC) 120.37 ± 4.09 ^a 54.67 ± 4.30 ^b Ethanol + Deodeok Extract Intake Group (CE) 107.23 ± 2.09 ^a 66.90 ± 4.57 ^a

* Different characters in the same column mean that there is a significant difference (p <0.05).

<2-3> Measurement of lipid peroxide concentration

The concentration of lipid peroxide in plasma obtained in Experimental Example <2-2> was measured according to a known method (Buege et al., 1978, Methods Enzymol ., 52: 302-310, 1978). Add 0.4 ml of serum to 0.8 ml of 15% (w / v) trichloroacetic acid, 0.375% (w / v) thiobarbituric acid (TBA), and 0.25N hydrochloric acid, and mix well The mixture was then heated at 95 ° C. for 15 minutes and then cooled on ice. After centrifugation at 1000 × g for 10 minutes, the supernatant was taken, and the absorbance was measured at 535 nm and colorimetrically determined by comparing with a standard solution of malondialdehyde.

The concentration of lipid peroxide in liver tissue obtained in Experimental Example <2-1> is also known (Ohkawa et al., 1979, Anal Biochem , 95: 351-358). 0.2 ml of liver homogenate was added to 0.2 ml of SDS (8.1%) and 0.6 ml of distilled water, followed by mixing at room temperature for 5 minutes to settle the foam. 1.5 ml of 20% acetic acid (pH 3.5) and 1.5 ml of 0.8% TBA solution were added thereto and mixed. This mixed solution was heated in a 95 ° C shaking water bath for 60 minutes, and then cooled in ice for 3 minutes. 1 ml of distilled water and 5 ml of n-butanol: pyridine (15: 1) mixed solution were mixed well, and the mixture was shaken well, and the supernatant was separated by centrifugation at 1000 × g for 15 minutes. The absorbance of the supernatant was measured at 532 nm and colorimetrically determined in comparison with the malondialdehyde standard solution.

As a result, the concentration of lipid peroxides in plasma and liver tissues was increased in the ethanol intake group (EC) compared to the normal group (ND), but decreased in the ethanol + deodorant extract intake group (CE) supplemented with the extract. The level was similar to that of the normal group (Table 5).

Plasma and liver lipid peroxide concentrations (mean ± SEM) division Plasma (nmol MDA / mL) Liver (nmol MDA / g liver) Normal group (ND) 0.31 ± 0.07 ^a 45.19 ± 2.32 ^b Ethanol Intake Group (EC) 0.52 ± 0.14 ^a 51.98 ± 1.76 ^a Ethanol + Deodeok Extract Intake Group (CE) 0.37 ± 0.08 ^a 47.82 ± 2.30 ^ab

* Different characters in the same column mean that there is a significant difference (p <0.05).

<2-4> Pathological examination of liver tissue

The liver tissue obtained in Experimental Example <2-1> was fixed with 10% formalin, then embedded in paraffin and prepared into sections having a thickness of 3 μm. After staining with hematoxylin and eosin, it was examined under a microscope (DP70, Olympus Optical Co., LTD, Japan).

As a result, there was no abnormality in the normal group (ND), but fatty liver lesion was confirmed in the ethanol intake group (EC). On the other hand, in the alcohol + deodeok extract intake group (CE) it was observed that the amount of fat accumulation in hepatocytes was significantly reduced (Fig. 2). From the results of the experiment, it was found that the deodeok extract has the effect of preventing or improving the occurrence of lesions and fat accumulation in liver tissue in the rats ingested alcohol.

Experimental Example 3

Determination of Efficacy Improvement of Deodeok Extract

Plasma lipid concentrations were analyzed to determine the effect of the extract on hyperlipidemia. Total cholesterol, HDL-cholesterol and triglyceride concentrations in plasma isolated in Experimental Example <2-2> were measured using Triglycerides kit (BCS, Korea), Cholesterol kit (BCS, Korea) and HDL-cholesterol kit ( HDL-cholesterol kit; BCS, Seoul, Korea) was repeated twice. Plasma HDL-C / Total-C (%) concentrations and atherosclerotic index were calculated using total cholesterol and HDL-cholesterol concentrations. Statistical processing of the experimental results was carried out in the same manner as in Experiment 2.

As a result, the ethanol intake group (EC) was significantly higher plasma total cholesterol and HDL-cholesterol concentration than the normal group (ND) (p <0.05). On the other hand, in the ethanol + detox extract intake group (CE) fed the deodeok extract with ethanol, plasma total cholesterol and HDL cholesterol concentrations were 13% and 26% lower than the ethanol intake group (EC), respectively. 6). Plasma triglyceride levels were not significantly different in all groups.

Lipid concentration in plasma (mean ± SEM) division Triglycerides (mg / dl) Total cholesterol (mg / dl) HDL-cholesterol (mg / dl) HDL-Cholesterol / Total Cholesterol (%) ¹⁾ Normal group (ND) 44.49 ± 5.82 ^a 61.56 ± 3.31 ^c 29.06 ± 1.51 ^b 46.1 ± 2.2 ^a Ethanol Intake Group (EC) 48.37 ± 3.71 ^a 88.70 ± 4.92 ^a 39.95 ± 2.89 ^a 45.0 ± 2.1 ^a Ethanol + Deodeok Extract Intake Group (CE) 42.71 ± 3.94 ^a 76.96 ± 3.61 ^b 29.69 ± 1.19 ^b 38.1 ± 1.4 ^b

1) [HDL cholesterol (mg / dl) / total cholesterol (mg / dl)] * 100

* Different characters in the same column mean that there are significant differences (p <0.05)

As described above, the composition comprising the deodeok extract of the present invention as an active ingredient has an effect of reducing the concentration of lipids, lipid peroxides and increased liver tissue and plasma concentrations due to alcohol intake and normalizes the activity of liver function indicator enzymes. Since it can be useful for the purpose of prevention, alleviation and treatment of alcoholic liver disease and alcoholic hyperlipidemia.

Claims (8)

A pharmaceutical composition for preventing or treating alcoholic fatty liver or alcoholic hyperlipidemia, which comprises an extract of Codonopsis lanceolata with water or a lower alcohol having 1 to 6 carbon atoms as an active ingredient. delete delete delete Food composition for the prevention or improvement of alcoholic fatty liver or alcoholic hyperlipidemia comprising the extract of Codonopsis lanceolata with water or a lower alcohol having 1 to 6 carbon atoms as an active ingredient. delete delete delete

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