KR100767393B1 - A pharmaceutical composition comprising ginseng or lactobacillus-fermented ginseng effective for colitis comprising ulcerative colitis and crohn`s disease - Google Patents

Abstract

The present invention, ginsenosides Ra, Rb1, Rb2, Rc, Rd, Rg3, F2, Re, Rf, Rg1, Rg2, Rh2, Rh1, Rh3, Rh4, Rk1, Rk2, Rk3, Rg5, Protoparanaxadiol, Ginseng extract containing one or more ginseng saponin derivatives selected from the group consisting of protopanaxatriol and compound K (20-0-β-D-glucopyranosyl-20 (S) -protopanaxadiol) and lactic acid bacteria As an invention relating to fermented fermented products, the composition is effective in the prevention or treatment of colitis including ulcerative colitis and Crohn's disease.

Ginseng, Red ginseng, Lactobacillus, Fermentation, Saponin, Ginsenoside, Protoparnaxadiol, Protoparnaxatriol, Compound K

Description

Lactic acid bacteria fermented product composition of ginseng or ginseng having an effect on colitis including ulcerative colitis and Crohn's disease.

Field of technology

The present invention relates to the efficacy on the colitis, including ulcerative colitis and Crohn's disease of lactic acid bacteria fermentation of ginseng prepared by fermenting ginseng with ginseng extract and lactic acid bacteria.

Background

Colitis is referred to including ulcerative colitis (UC) and Crohn's Disease (CD). Crohn's disease is a chronic disease that still has no clear etiology and treatments. It is known to occur in young people as it invades the anterior wall of the gastrointestinal tract and progresses repeatedly with recurrence. There are only a number of hypotheses, including infectious theory, immune dysfunction, genetic factor, environmental factor, and mental factor. Currently, medical treatment is first, but only partially Not only does it respond, but a lot of complications that require surgery, the disorder of nutritional absorption is caused by repeated removal of the small intestine after several operations.

Ulcerative colitis is a disease in which inflammation and ulceration occur in the mucous membrane inside the large intestine (colon, rectum). It usually occurs in the left side of the colon, the sigmoid colon and the rectum, but also in the ileum, the tip of the small intestine that meets the large intestine. Ulcerative colitis specifically does not affect parts of the digestive system other than the large intestine and does not affect the deeper layers of tissues. It usually affects the anus and rectum. Symptoms include squeezing embryonic pain and anal bleeding, thin stools containing several times a day of blood and mucus, diarrhea, and weight loss. The extent of the symptoms depends on the extent of the lesion and the degree of inflammation, often recurring and worsening, usually with one or more symptoms.

The cause of ulcerative colitis has not been clarified so far, but it is generally thought to be related to intestinal motility and intestinal immune function, as well as genetic, intestinal microbial infections, mental factors, and many other circumstances. Multiple factors are believed to be complex. Recent development of several animal models and advances in immunological research techniques have revealed that the mucosal immune system plays an important role in the immune response and chronic inflammation leading to clinical symptoms of ulcerative colitis. In ulcerative colitis, the intestinal immune function is abnormally activated. The immune system consists of immune cells and the proteins they secrete. These cells and proteins are activated by acting as a defense against harmful bacteria, viruses, fungi, and other substances that invade the host. Activation of the immune system causes an inflammatory response in the tissue where the activation occurs. In other words, in case of ulcerative colitis, the intestinal immune system is abnormally and chronically activated.

Ginseng is a perennial root of the genus Ginseng, which belongs to the genus Oga, according to the plant taxonomy. About 11 species of ginseng are known in the world. Excellent ginseng from Panax ginseng CAMeyer; American ginseng (Panax quinquefolium L .; aka Hwagi) grown and grown in the United States and Canada; Panax notoginseng F.H.Chen, wild or cultivated in southwestern Guangxi province from southeastern Yunnan Province of China; And Panax japonicus C.A.Meyer distributed in Japan, southwestern China and Nepal.

Ginseng is not only stored as a commodity in the Shinnongchocho, but has been used as a valuable medicine since ancient times. Many pharmacological experiments so far have revealed that ginseng enhances the nonspecific resistance of the body to stress and has an acidic action. In addition, hypertension, insulin action, hypoglycemic effect in ALLOXAN diabetic mice, liver RNA synthesis, protein synthesis, sugar and lipid metabolism promoting effect, and anti-cancer effect has been found.

The ginseng has been used for various diseases such as psychiatric diseases, diseases of the nervous system, and diabetes in the form of herbal medicine mainly in Asian countries such as Korea, China, Japan, and saponins, the main components of the ginseng, are tonic, gangjeong, It is known to have an effect on sedation molding and antihypertension.

Currently, ginseng is white ginseng, which is grown and dried at room temperature, red ginseng, which is produced by heat treatment at 98-100 ° C, or high-temperature ginseng produced by heat treatment at 120-180 ° C (eg, sun ginseng). , Black ginseng, etc.).

On the other hand, the root of ginseng contains about 4-10% of ginseng saponins (Korean ginseng is 4-8% and American ginseng is 4-10%), which is a mixture of various ginsenosides. Among them, the content of ginsenosides Rb1, Rc and Rg1 is relatively high in Korea, and the content of ginsenosides Rb1 and Re is relatively high in the US.

The components of ginsenosides and their pharmacological efficacy contained in ginseng are shown in Table 1 below.

Currently known efficacy, anti-cancer effect, the effect on the central nervous system, anti-allergic effect, immune enhancing effect, etc. are known, but the effect on colitis is not known at all until now.

Therefore, ginseng extract and lactic acid bacteria fermented ginseng have excellent new efficacy on colitis and ginsenosides Ra, Rb1, Rb2, Rc, Rd, Rg3, F2, Re, Rf, Rg1 , Rg2, Rh2, Rh1, Rh3, Rh4, Rk1, Rk2, Rk3, Rg5, Protopanaxadiol, Protopanaxatriol, Compound K (20-0-β-D-glucopyranosyl-20 (S)- It was found to be a saponin component of protopanaxadiol).

Accordingly, the present inventors also trace ginsenosides Ra, Rb1, Rb2, Rc, Rd, Rg3, F2 as a result of pursuing ginseng and ginseng fermented products that are effective for colitis, from ginseng. , Re, Rf, Rg1, Rg2, Rh2, Rh1, Rh3, Rh4, Rk1, Rk2, Rk3, Rg5, Protoparnaxadiol, Protoparanatriol, Compound K (20-0-β-D-glucopyranosyl The saponin component of -20 (S) -protopanaxadiol) was found to have significant efficacy in treating colitis and came to complete the present invention.

Therefore, it is an object of the present invention to provide an extract of ginseng that is effective for colitis.

Another object of the present invention is to provide a ginseng alcohol extract that is effective in colitis.

It is another object of the present invention to provide a ginseng fermentation product having an effect on colitis.

In addition, another object of the present invention is to provide a lactic acid bacteria used to obtain the lactic acid bacteria fermented product of the ginseng.

Meanwhile, ginseng raw materials effective for colitis are not particularly limited, and ginseng specifically, Korean ginseng (Panax ginseng CAMeyer), Hwagi (Panax quinquefolium L.), Panax notoginseng FHChen, and Panax ginseng (Panax) japonicus CAMeyer)) itself or a processed product thereof, and more specifically, ginseng, red ginseng, white ginseng, misam and hwagisam (hereinafter referred to as ginseng, including Korean ginseng, hwagisam, jeonchisam, bamboo shoots); One or more of ginseng leaves, ginseng extract and ginseng powder can be used. By processing, ginseng in the dry powder form, acid treated ginseng, high temperature treated ginseng, pressurized ginseng and the like can be preferably used as raw materials for obtaining the lactic acid bacteria fermented product of the ginseng of the present invention.

In addition, the powdered degree of the ginseng in the dry powder form is not particularly limited, and is not limited to ginseng extracts even in the production of lactic acid bacteria fermented ginseng, and may be powdered enough to penetrate into the ginseng tissue or fiber with high efficiency. Such degree of powdering can be readily appreciated by those skilled in the art, and methods of powdering are also commonly known in the art. On the other hand, high-temperature ginseng and pressurized ginseng may be prepared from ginseng itself, but it is preferable for the ginseng treatment effect and subsequent fermentation efficiency to be obtained from the ginseng in the dry powder form described above. Also in this case, the powdering degree of the ginseng in dry powder form is not specifically limited. Ginseng, ginseng, red ginseng, white ginseng, rice ginseng, hwagi ginseng, ginseng leaf, ginseng extract and ginseng powder (hereinafter referred to as 'ginseng raw material') when using the powder or fermented with lactic acid bacteria in the case of a lactic acid bacterium fermented product has especially active saponin compound of the K component, ginsenoside Rh1 and Rh2 seed, and / or Δ ²⁰ - the content of the seed, such as ginsenoside Rh2 (Rh2 + Rh3) is raised.

On the other hand, the method for obtaining ginseng fermentation is not particularly limited, and fermentation may be carried out under suitable fermentation conditions of lactic acid bacteria used for ginseng fermentation according to the present invention using a method conventional in the art, specifically For example, the raw material of ginseng is suspended in water and then lactic acid bacteria are added, and the bioconversion process of obtaining lactic acid bacteria fermentation product of ginseng by incubating at about 48 hours to 72 hours at an appropriate fermentation temperature of the lactic acid bacteria, and The lactic acid bacteria fermentation may be obtained by a method including centrifugation and concentration of the lactic acid bacteria fermentation product of ginseng by filtering only the supernatant.

On the other hand, as a lactic acid bacterium that can be used for lactic acid bacteria fermentation of ginseng, strains of the genus Lactobacillus, strains of Streptococcus or strains of Bifidobacterium can be used, compounds K, ginsenosides Rh1 and Rh2, of saponin components in ginseng, And a strain having a high production rate of Δ ²⁰ -ginsenoside Rh2. For example, more specifically, Bifidobacterium K-103 (Professor Dong-Hyun Kim, Institute of Pharmacy, Kyung Hee University, Arch. Pharm . Res. , 21, 54-61, 1998), Bifidobacterium K-506 (Medicine University Kyunghee University) Professor Kim Dong - Hyun lab, see Arch. Pharm. Res., 21 , 54-61, 1998), Bifidobacterium Collet Solarium KK-1 (KCCM-10364) , Bifidobacterium mini-drought KK-2 (KCCM-10365) One or more strains of Bifidobacterium H-1 (KCCM-10493) and Bifidobacterium KK-11 (Kim Dong-Hyun, Professor of Pharmacy, Kyung Hee University) can be used.

Among these, Bifidobacterium H-1, Bifidobacterium cholerium KK-1 and Bifidobacterium minimum KK-2 are microorganisms developed by the present inventors to obtain lactic acid bacteria fermentation products of ginseng, The Bifidobacterium KK-1 is deposited as KCCM-10364 (2002.03.22), the Bifidobacterium KK-2 is deposited as KCCM-10365 (2002.03.22), Bifidobacterium H-1 is KCCM-10493 (2003.05.06) has been deposited with the Korean Culture Center of Microorganisms, respectively.

Hereinafter, the present invention will be described in detail with reference to ginseng extract, lactic acid bacteria fermented ginseng, but the present invention is not limited thereto, and modifications apparent to those skilled in the art can be performed. Examples are not limited to Korean ginseng, not limited to white ginseng, Korean red ginseng, high-temperature treated ginseng (eg, ginseng, black ginseng, etc.), not limited to fermentation strains, and not limited to reaction time, reaction temperature, content.

Example

<Example 1>

Fresh ginseng (5 years of Korean ginseng from Kumdong market) is extracted with water (or alcohol) at 4-100 ℃ (appropriately 50-80 ℃) to obtain X or lyophilized to obtain powder.

<Example 2>

Red ginseng (5 years of Korean ginseng steamed at 98 ℃ for 2 hours and dried at 65 ℃ for 4 hours) is extracted with water (or alcohol) at 4-100 ℃ (appropriately 50-80 ℃) to obtain or freeze Dry to obtain a powder.

<Example 3>

Hot Ginseng (Korean ginseng steamed under reduced pressure at 120 ° C for 2 hours and dried at 65 ° C) was extracted with water (or alcohol) at 4-100 ° C (preferably 50-80 ° C) to obtain X or lyophilized powder. Get

<Example 4>

Fresh ginseng (5 years old Korean ginseng from Gyeongdong market) was washed well with hot water and dried and finely powdered ginseng powder 0.1-10 g (appropriately 1-2 g) and vitamin C 0.1 g in distilled water 100 After suspension in ml, 1 ml (approximately 10 ⁹ cells / ml) of each of the lactic acid bacteria Bifidobacterium KK-1 strains previously cultured were transplanted, incubated at 37 ° C for 24 hours, and lyophilized.

<Example 5>

Extracted 0.1 g (10 g) (appropriately 1-2 g) and 0.1 g of vitamin C obtained by extracting fresh ginseng or ginseng with water or alcohol and suspending it in 100 ml of milk, followed by pre-cultured lactic acid bacteria Bifidobacterium strain 1 ml (approximately 10 ⁹ cells / ml) of KK-1 are transplanted, respectively, and lyophilized by incubating at 37 ° C for 24 hours.

<Example 6>

0.1 to 10 g (appropriately 1-2 g) of dried ginseng and 0.1 g of vitamin C were added to 100 ml of distilled water and suspended, and then incubated with lactobacillus vulgaris, Streptococcus thermophilus, Or / and Bifidobacterium longgum strains each 1 ml (approximately 10 ⁹ cells / ml), and lyophilized by incubating at 37 ° C. for 12 hours.

<Example 7>

Red ginseng (5 years old Korean Ginseng root steamed for 2 hours at 98 ° C and dried for 4 hours at 65 ° C) was washed well with hot water and dried 0.1 to 10 g (appropriately 1 to 2 g) and powdered powder. 0.1 g was added to 100 ml of milk, suspended and 1 ml (approximately 10 ⁹ cells / ml) of Lactobacillus Bulgaricus, Streptococcus thermophyllus, and / or Bifidobacterium longgum strain, each of which was pre-cultured. Implant and incubate at 37 ° C. for 12 hours to lyophilize.

<Example 8>

Red ginseng (5 years old Korean Ginseng root steamed for 2 hours at 98 ° C and dried for 4 hours at 65 ° C) was washed well with hot water and dried 0.1 to 10 g (appropriately 1 to 2 g) and powdered powder. After 0.1 g is suspended in distilled water, 1 ml (approximately 10 ⁹ cells / ml) of each of the lactic acid bacteria Bifidobacterium strains previously cultured are transplanted, incubated at 37 ° C for 24 hours, and lyophilized.

Example 9

2 g of hot ginseng (Korean ginseng steamed at 120 ° C. under reduced pressure at 120 ° C. and dried at 65 ° C.) and 0.1 g of vitamin C were added to 100 ml of milk, suspended, and then incubated with lactic acid bacteria Bifidobacterium KK-1 strain. 1 ml (approximately 10 ⁹ cells / ml) are respectively transplanted and incubated at 37 ° C. for 24 hours to lyophilize.

<Example 10>

Fresh ginseng or ginseng (5 years of Geumsan ginseng from Gyeongdong Market) washed well with hot water and dried and finely powdered ginseng powder 0.1-10 g (appropriately 1-2 g), yeast extract 0.1-5 g (appropriately 0.5-1 g) and 0.1 g of vitamin C are suspended in 100 ml of distilled water, and then 1 ml (about 10 ⁹ cells / ml) of lactic acid bacteria Bifidobacterium KK-1 strain, respectively ), Incubate at 37 ° C. for 24 hours and lyophilize.

<Example 11>

0.1-10 g (appropriately 1-2 g) of dried ginseng, yeast x 0.1-5 g (appropriately 0.5-1 g) and 0.1 g of vitamin C are added to 100 ml of distilled water. After suspension, 1 ml (approximately 10 ⁹ cells / ml) of lactic acid bacteria Lactobacillus Bulgaricus, Streptococcus thermophyllus, and / or Bifidobacterium longgum strain, respectively, were transplanted and suspended at 37 ° C for 12 hours. Incubate and lyophilize.

<Example 12>

Red ginseng (5 years old Korean ginseng steamed at 98 ° C for 2 hours and dried at 65 ° C for 4 hours) was washed well with hot water and dried 0.1 to 10 g (appropriately 1 to 2 g), yeast (yeast) ) X 0.1-5 g (appropriately 0.5-1 g) and 0.1 g of vitamin C are suspended in distilled water, and then 1 ml (about 10 ⁹ cells / ml) of each of the previously cultured lactic acid bacteria Bifidobacterium KK-1 strains. ), Incubate at 37 ° C. for 24 hours and lyophilize.

Example 13

Hot ginseng (Korean ginseng steamed at 120 ° C for 2 hours under reduced pressure and dried at 65 ° C) 0.1-10 g (appropriately 1-2 g), yeast x 0.1-5 g (appropriately 0.5-1) g) and 0.1 g of vitamin C were placed in 100 ml of milk, suspended, and then 1 ml (about 10 ⁹ cells / ml) of each of the previously cultured lactic acid bacteria Bifidobacterium KK-1 strains were transplanted. Incubate for hours and lyophilize.

Experimental Example A1: Content Analysis of Saponin Components

Commercial ginseng commercially available (Nonghyup Korea Ginseng Geumsansan 4-6 years old purchased from Gyeongdong Market), and its dry ginseng powder, acid-treated ginseng, high-temperature ginseng and pressurized ginseng (prepared by the same method as the above example), respectively. After adding 0.1 g of vitamin C to 100 ml of milk, 1 g of lactic acid bacteria Bifidobacterium KK-1 and Bifidobacterium KK-2 strains were added.

Cultured at 37 ° C. for 72 hours and concentrated under reduced pressure, ginseng fermented yogurt, high temperature ginseng fermented yoghurt, acid treated ginseng fermented yoghurt, and pressurized ginseng fermented yogurt were obtained. Next, ginseng, and dried ginseng powder, acid treated ginseng, hot ginseng, pressurized ginseng, and each ginseng fermented yogurt obtained above were taken 2 g each, extracted three times with 100 ml of methanol, and concentrated in water. It was suspended and extracted three times with 100 ml of ether. Then, the extract was extracted three times with 100 ml of butanol, and the butanol fraction was concentrated, and the obtained concentrate was dissolved in methanol and analyzed by TLC (CHCl ₃ as solvent. : Lower layer solution of MeOH: H ₂ O = 65: 35: 10; Color reagents include 5% sulfuric acid solution in MeOH; Shimadzu TLC scanner CS-9301PC was used as a detector), and the results shown in Table 2 were obtained. Component content was calculated by the content of each component contained in 100% of the final extraction fraction.

Example  Ginseng in ginseng Fermented product  Saponin content

Colitis Model Animal Production

Colitis Animal Model Induced by Dextran Sulfate-ICR mouse male 4 week old (purchased from Central Animal Laboratory) was used for 1 week in animal laboratory. A group of 6 animals was prepared with 5% aqueous solution of sodium salt of dextran sulfate (molecular weight: 36,000-50,000) to allow the animals to drink instead of water.

Colitis Animal Model Induced with TNBS (2,4,6-Trinitrobenzene sulfonic acid solution) --- ICR mouse males 4 weeks old (purchased from Central Animal Laboratory) were used for 1 week in animal laboratory. The animals were lightly anesthetized in ether, and TNBS 2.5 mg / 50% EtOH was administered 0.1 ml of the large intestine through the anus with a rounded 1 ml syringe and held vertically for 30 seconds. One group was six.

Oxazolone-induced colitis animal model-ICR mouse male 4 weeks old (purchased in a central animal laboratory) was used for 1 week in an animal laboratory. The animals were lightly anesthetized with ether, and a round 1 ml syringe was used to inject 0.1 mg of oxazolone 3.0 mg / 50% EtOH through the anus into the large intestine, held vertically, and maintained for 30 seconds. One group was six.

The colitis model animals were then sacrificed on 7th day under ether anesthesia to collect the colon. The large intestine measures the length from the cecum to the end of the large intestine, dissects the intestine, removes the intestinal contents, and washes with saline to scrape the intestinal mucosa, producing MPO activity, alkaline phosphatase enzyme activity, and the production of cytokines. Was measured by RT-PCR.

The method of measuring MPO (Myeloperoxidase) activity was measured by homogenizing the intestinal mucosa suspended in 0.5% hexa-decyl-trimethyl-ammonium bromide / 10 mM potassium phosphate buffer (pH 7.0) for 30 minutes at 20,000 xg. Centrifugation and the supernatant were used as enzyme solution. 0.1 ml of this enzyme solution, 0.1 ml of 16 mM tetra-methyl-benzidine, and 0.005 ml of 0.1 mM hydrogen peroxide were added and reacted, and the change in absorbance was observed by a time scan method at 650 nm for 5 minutes.

Enzyme and cytokine production was measured by RT-PCR. First, the intestinal mucosa obtained from experimental animals was added with a Tri reagent (Sigma, USA), and left at room temperature for 5 minutes, followed by chloroform and for 10 minutes. Let's do it. Supernatant was taken after centrifugation at 7500 rpm. Isopropyl alcohol was added to the supernatant, centrifuged at 14000 rpm, and the supernatant was removed. Washed with 70% ethanol, the supernatant was removed and dried at room temperature for 20 minutes. DEPC treated water was added thereto and the absorbance was measured at 260 nm. The absorbance 1 was 40 mg / ml of RNA and the amount of RNA was calculated.

Pre-mixture and reverse primer were placed in a sterile tube treated with 0.1% DEPC, reacted at 72 ° C. for 5 minutes, immediately transferred onto ice, and then [AccuPower RT-PCR Premix tube ] Put the forward primer and the distilled shoe treated with 0.1% DEPC, cDNA synthesis reaction at 42 ℃ for 60 minutes, inactivate reverse transcriptase at 94 ℃ for 5 minutes, and then PCR is performed according to PCR conditions. The primer used was 20 pmol and the final concentration was 1 pmol.

PCR products were identified using agarose gel electrophoresis with ethidium bromide (EtBr), and the amount of PCR products was quantified by TLC-scanner-PC9300 (Shimatsu, Japan). Agarose gel is 1.5% gel and buffer was used with 0.5 kPa TBE.

Inflammation-related enzyme alkali in colitis model animals Phosphatase  (alkaline phosphatase ) And Myeloperoxidase  ( myeloperoxidase ) Enzyme inhibitory effect

Myeloperoxidase and alkaline phosphatase enzyme activities were administered to the normal group, colitis model group, white ginseng, red ginseng or red ginseng fermented product and used as an indicator of colitis.

In normal group (N), there was no significant change in the activity of myeloperoxidase enzyme, an inflammation-related enzyme. However, it was significantly increased in colitis model animals treated with DSS. However, when white ginseng, red ginseng or fermented red ginseng was administered to this group, it was significantly inhibited.

There was also a significant increase in colitis model animals administered with TNBS. This group was also significantly inhibited when white ginseng, red ginseng or fermented red ginseng was administered.

Myeloperoxidase enzyme activity was significantly increased in colitis model animals administered oxazolone. However, when white ginseng, red ginseng or fermented red ginseng was administered to this group, it was significantly suppressed.

N (normal group); DSS ( Dextran With sulfate  Induced colitis Model group ); TNBS  ( TNBS Induced colitis Model group ); OXA  ( With oxazolone  Induced colitis Model group ); G50  Colitis model group on  50 mg / kg white ginseng extract); RG50  Colitis model group on  50 mg / kg red ginseng extract); RGf50  (colitis In the model group  50 mg / kg of fermented red ginseng).

In normal group (N), there was no significant change in the activity of alkaline phosphatase enzyme, an inflammation-related enzyme. However, it was significantly increased in colitis model animals treated with DSS. However, this group was significantly inhibited when 25 mg / kg, 50 mg / kg or fermented red ginseng was administered.

There was also a significant increase in colitis model animals treated with TNBS. Red ginseng was also significantly inhibited when 25 mg / kg, 50 mg / kg or fermented red ginseng was administered to this group.

Alkaline phosphatase enzyme activity was significantly increased in colitis model animals treated with oxazolone. However, this group was significantly inhibited when 25 mg / kg, 50 mg / kg or fermented red ginseng was administered.

N (normal group); DSS ( Dextran With sulfate  Induced colitis Model group ); TNBS  ( With TNBS  Induced colitis Model group ); OXA  ( With oxazolone  Induced colitis Model group ); G50  (Group administered 50 mg / kg white ginseng extract to colitis model group); RG50  (colitis In the model group  50 mg / kg red ginseng extract); RGf50  (colitis In the model group  50 mg / kg of fermented red ginseng).

Inflammation-related enzymes in colitis model animals and Cytokine  Inhibitory effect

Inhibitory Effect on DSS-induced Colitis Model Animals

Compared to the normal group, COS-2 (cyclooxygenase-2), iNOS (inducible NO synthetase), IL-1b, TNF-a, and IL-4 were significantly increased in DSS-induced colitis model animals. However, oral administration of 50 mg / kg of white and red ginseng and 50 mg of fermented ginseng (including 5 mg of lactic acid bacteria) significantly improved colitis indices of more than 80% in all inflammatory markers except IL-4. Although cytokine of IL-4 was weakly effective in ginseng, fermented ginseng showed a significant inhibitory effect. In addition, the external colon findings were significantly improved.

COX-2 ( cyclooxygnease ); iNOS  (inducible NO synthetase ); IL-1b (interleukin-1b); TNF -a (tumor necrosis factor-alpha); IL-4 ( interleukin -4); N (normal group); DSS ( Dextran With sulfate  Induced colitis Model group ); DG50  ( Dextran doxy Fate-induced colitis In the model group  Group administered 50 mg / kg of white ginseng); DRG50  ( Dextran  Sulfate-Induced Colitis In the model group  50 mg / kg red ginseng); DRGf50  ( Dex Lan With sulfate  Induced colitis In the model group  50 mg / kg of fermented red ginseng).

TNBS  Effect of Induced Colitis in Model Animals

Compared to the normal group, COX-2 (cyclooxygenase-2), iNOS (inducible NO synthetase), IL-1b, TNF-a and IL-4 were significantly increased in TNBS-induced colitis model animals. However, oral administration of 25 mg / kg, 50 mg / kg, and 50 mg of fermented ginseng (including 5 mg of lactic acid bacteria) significantly inhibited colitis indices. In addition, the external colon findings were significantly improved.

COX-2 ( cyclooxygnease ); iNOS  (inducible NO synthetase ); IL-1b (interleukin-1b); TNF -a (tumor necrosis factor-alpha); IL-4 ( interleukin -4); N (normal group); TNBS  ( With TNBS  Induced colitis Model group ); TG50  ( With TNBS  50 mg / kg of white ginseng in the induced colitis model group); TRG50  ( With TNBS  Induced colitis In the model group  50 mg / kg red ginseng); TRGf50  ( With TNBS  Induced colitis In the model group Fermented Red Ginseng  50 mg / kg group).

COX-2 ( cyclooxygnease ); iNOS  (inducible NO synthetase ); IL-1b (interleukin-1b); TNF -a (tumor necrosis factor-alpha); IL-4 ( interleukin -4); N (normal group); OXA  ( With oxazolone  Induced colitis Model group ); OG50  ( With oxazolone  Induced colitis In the model group  50 mg / kg white ginseng Administered ); ORG50  ( With oxazolone  50 mg / kg red ginseng in induced colitis model group Administered ); ORGf50  ( With oxazolone  Induced colitis model group Fermented Red Ginseng  50 mg / kg Administered ).

Ginseng saponin Oxazolone  Inflammation-related enzyme alkali in colitis model animals Phosphatase  And Myeloperoxidase  Enzyme activity inhibitory effect

Experiments were carried out in the same manner as in the previous experimental method, but one group of experimental animals was determined to be five and three days later. Ginsenosides Ra, Rb1, Rb2, Rc, Rd, Rg3, F2, Re, Rf, Rg1, Rg2, Rh2, Rh1, Rh3, Rh4, Rk1, in normal and oxazolone colitis model groups and this colitis model animal. Rk2, Rk3, Rg5, Protoparnaxadiol, Protopanaxatriol, Compound K (20-0-β-D-glucopyranosyl-20 (S) -Protofanaxadiol) is administered and used as an indicator of colitis Myeloma peroxidase enzyme activity was measured.

Oxazolone  Effect of Induced Colitis in Model Animals

Compared to the normal group, COX-2 (cyclooxygenase-2), iNOS (inducible NO synthetase), IL-1b, TNF-a, and IL-4 were significantly increased in oxazolone-induced colitis model animals. However, oral administration of 25 mg / kg, 50 mg / kg, and 50 mg of fermented ginseng (including 5 mg of lactic acid bacteria) significantly inhibited colitis indices. In addition, the external colon findings were significantly improved.

Example  Saponin fraction is 10 times the weight of dry matter Suspending  Extract the same amount of butanol Dry  Fractions were taken as saponin fractions.

As described above, the composition of the present invention is effective in the prevention or treatment of colitis including ulcerative colitis and Crohn's disease.

Claims (8)

A pharmaceutical composition for treating colitis, comprising ginseng saponin as an active ingredient. The composition of claim 1, further comprising lactic acid bacteria. Ginseng fermentation obtained by culturing by adding lactic acid bacteria or enterobacteriaceae to ginseng selected from ginseng, red ginseng, white ginseng, rice ginseng, red ginseng, ginseng leaf, hot ginseng, acid ginseng, pressurized ginseng and extracts and powders thereof A pharmaceutical composition for treating colitis, containing water as an active ingredient. The composition according to claim 2 or 3, wherein the lactic acid bacteria is a strain belonging to the genus Lactobacillus, Streptococcus, or Bifidobacterium. The method according to claim 2 or 3, wherein the lactic acid bacteria, Bifidobacterium K-103, Bifidobacterium K-506, Bifidobacterium cholrium KK-1, Bifidobacterium minimum KK-2, Bifidobacterium H-1, and Bifidobacterium KK-11 is a strain belonging to the genus Bifidobacterium selected from the group consisting of. delete Ginsenosides Ra, Rb1, Rb2, Rc, Rd, Rg3, F2, Re, Rf, Rg1, Rg2, Rh2, Rh1, Rh3, Rh4, Rk1, Rk2, Rk3, Rg5, Protopanaxadiol, Protopananatriol A composition for the prophylaxis or treatment of colitis containing ol g and one or more ginseng saponin derivatives selected from the group consisting of Compound K (20-0-β-D-glucopyranosyl-20 (S) -protopanaxadiol). 8. The composition according to any one of claims 1 to 3 or 7, wherein the colitis is ulcerative colitis or Crohn's disease.