KR20160142430A - A composition comprising fermented extracts of red ginseng and rubus coreanus for preventing, improving or treating vascular disease - Google Patents

Abstract

The present invention relates to a composition for preventing, improving or treating vascular diseases. More particularly, the present invention relates to a composition comprising, as an active ingredient, an extract obtained by fermenting red ginseng and Rubus coreanus separately, mixing the fermented products and extracting them, or by mixing and fermenting red ginseng with Rubus coreanus and extracting the fermented product. The composition comprising a fermented extract of red ginseng and Rubus coreanus as an active ingredient has the effects of decreasing blood pressure, alleviating vascular lesions and reducing expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelin-1 (ET-1), in a high-fructose diet rat model.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for preventing, improving or treating vascular diseases containing red ginseng and bokbunja fermented extract as an effective ingredient.

The present invention relates to a composition for preventing, ameliorating or treating vascular diseases. More particularly, the present invention relates to a composition for fermenting red ginseng and bokbunja, ≪ / RTI >

The composition containing the fermented extract of red ginseng and bokbunja according to the present invention as an active ingredient can be used as an effective ingredient for lowering blood pressure, alleviating vascular lesions and inhibiting the activity of intercellular adhesion molecule-1 (ICAM-1), VCAM- 1 (vascular cell adhesion molecule-1) and ET-1 (endothelin-1).

Recent industrialization and conversion of dietary habits into high-fat and high-protein forms have led to frequent vascular diseases such as hypertension, coronary artery disease, atherosclerosis or hyperlipidemia.

Due to these vascular diseases, simple edema can cause symptoms such as inflammation of blood vessels and lymph vessels, abnormal shrinkage or swelling of blood vessels, bleeding, and clogging due to thrombosis.

When hyperlipidemia or atherosclerosis occurs, blood pressure increases, which can be a cause of cardiovascular disease and cerebrovascular disease. In addition, diabetes mellitus and liver disease are linked to various adult diseases.

In order to prevent this, blood pressure reduction and prevention or treatment of vascular inflammation are important.

However, conventionally used therapeutic agents such as chemical vasoconstrictors cause side effects such as endothelial damage, hemolysis, acute toxicity or fish toxicity, acute nephritis or heart attack in a living body, and the production process is difficult and mass production is easy There was a problem that it was not possible.

Accordingly, the present applicant has discovered the present invention, which is effective for preventing, ameliorating or treating vascular diseases without using side effects by using natural products, having no toxicity even if taken for a long time.

The present invention uses red ginseng and bokbun as a raw material, and briefly describes red ginseng and bokbunja.

Red ginseng (ginseng) ginseng (ginseng, Panax ginseng CA Meyer) refers to dried red ginseng steamed roots.

Important components of red ginseng include glycosides, panacen, polyacetylenic compounds, nitrogenous compounds, flavonoids, vitamins (B group), trace elements, enzymes, antioxidants, organic acids and amino acids .

Red ginseng has sedative and excitatory effects on the central nervous system and acts on the circulatory system to prevent hypertension and arteriosclerosis. In addition, it reduces the blood sugar level (blood sugar level), protects the liver, acts on the endocrine system and indirectly acts on sexual behavior (sexual behavior) and reproductive effect, and anti-inflammatory and anti- Tumor effect), radiation protection, skin protection and softening action.

In addition, red ginseng has been recognized as functional for improvement of blood flow through fatigue recovery, immunity enhancement, and inhibition of platelet aggregation.

As another material, bokbunja (bokbunja) is a berry of Rosaceae ( Rubus coreanus ) is a medicinal product made from unrefined berries. It is named after it is eaten by the urine stem.

It strengthens the kidney function and uses it for the 遗精, 夢 精, 尿 尿, etc. It prevents the weakening of sight, lightens the body and darkens the head. It also makes the skin soft and beautiful.

Bokbunja contains a large amount of polyphenols, and its efficacy has been found to be anti-inflammatory, antioxidant, anti-Helicobacter pylori, anti-cancer, anti-aging, anti-arteriosclerosis, prevention of thrombosis and sterilization.

Meanwhile, Korean Patent Registration No. 10-1517836 discloses a composition for preventing, ameliorating or treating atherosclerosis containing an effective component of a red ginseng complex in the prior art related to the present invention.

The above red ginseng complex comprises 300 parts by weight of the red ginseng extract, 100 parts by weight of the ginseng extract, 100 parts by weight of the red ginseng extract, And 100 parts by weight of the leaf extract, wherein the composition has an antioxidative effect in the body, an anti-inflammatory effect in the body, an effect of reducing vascular CRP (C reactive protein), a vascular smooth muscle (Vascular cell adhesion molecule), ICAM-1 (intercellular adhesion molecule) and E-selection, and to increase PPAR-γ in the blood vessels Or a pharmaceutically acceptable salt thereof. The present invention also relates to a health functional food composition for preventing or ameliorating atherosclerosis.

In addition, the dissertation (Dong-Seok Medical Dept., Graduate School of East-West Medicine, Kyung Hee University) 'The study on blood vessel changes and hematological indices affecting blood vessels due to administration of red gins' is effective in inhibiting vascular relaxation and vascular relaxation .

However, the above-mentioned prior arts include only red ginseng among the materials of the present invention, and there is a problem that the synergistic effect between the red ginseng and the ginseng by mixing fermentation can not be known.

Korean Patent Registration No. 10-1517836 (Apr. 29, 2015)

A Study on Hematological Indicators Affecting Vascular Changes and Vessels According to Administration of Red Ginseng, Department of East and West Medicine, Graduate School of East and West Medicine, Kyung Hee University, (Ph.D.), 2008.

A problem to be solved by the present invention is to provide a composition for preventing, improving or treating vascular diseases containing fermented red ginseng and bokbun after fermentation, mixing, extracting, To provide.

The present invention has been made to solve the above-mentioned problems, and it is an object of the present invention to provide a method for reducing blood pressure, efficacy for alleviating vascular lesions, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule- It is intended to provide a composition for preventing, ameliorating or treating vascular diseases having an efficacy of decreasing the expression of ET-1 (endothelin-1).

The present invention provides a composition for preventing, improving or treating vascular diseases containing fermented red ginseng and bokbang as an active ingredient after fermenting red ginseng and bokbuni respectively, mixing and extracting them, or mixing red ginseng and bokbun .

The present invention relates to a method for reducing blood pressure and reducing vascular lesions in a high-fructose diet rat model, and a method for inhibiting angiotensin-converting enzyme (ICAM-1), vascular cell adhesion molecule- -1 < / RTI > expression in a mammal, including a mammal, a human, a mammal, and a human.

The composition according to the present invention lowers blood pressure in a hyperfumine diet rat model, alleviates vascular lesions such as hypertrophy of the intravascular smooth muscle and abnormal hypertrophy of endothelial cells, and inhibits intercellular adhesion molecule-1 (ICAM-1), VCAM- 1 (vascular cell adhesion molecule-1) and ET-1 (endothelin-1).

FIG. 1 is a graph showing changes in blood pressure according to a sample treatment in a high-fructose diet rat model.
FIG. 2 is a photograph showing blood vessel atherogenesis of the thoracic aorta according to the sample treatment in a high fructose diet rat model.
FIG. 3 is a graph showing changes in the length of the intima-media of the thoracic aorta according to the sample treatment in a hyperglycemic rat model.
FIG. 4 is a photograph and a graph showing the degree of expression of ICAM-1 according to a sample treatment in a high-fructose diet rat model.
FIG. 5 is a photograph and a graph showing the degree of expression of VCAM-1 according to a sample treatment in a high-fructose diet rat model.
FIG. 6 is a photograph and a graph showing the degree of expression of ET-1 according to the sample treatment in a high-fructose diet rat model.

The terms and words used in the present specification and claims should not be construed as limited to ordinary or dictionary terms and the inventor may properly define the concept of the term in order to best describe its invention It should be construed as meaning and concept consistent with the technical idea of the present invention.

Therefore, the experimental examples and the reference examples described in the present specification are merely the most preferred embodiments of the present invention and are not intended to represent all of the technical ideas of the present invention. Therefore, various equivalents and variations Examples should be understood.

Example  1. Composition containing red ginseng and bokbunja fermented extract as active ingredients

The composition for preventing, ameliorating or treating vascular diseases according to the present invention is a composition containing an extract of fermented red ginseng and bokbunja as an active ingredient.

1) Ferment red ginseng and bokbunja.

Red ginseng and bokbun can be used in the unprocessed state, or can be used in the form of coarsely crushed. Also, before fermentation, red ginseng and bokbun can be sterilized and used.

Here, the red ginseng and the bokbunja may be respectively fermented and then mixed, or the red ginseng and the bokbunja may be first mixed and then fermented.

At this time, the mixing ratio of red ginseng and bokbun may be 1 to 100 parts by weight based on 100 parts by weight of red ginseng.

Fermentation of red ginseng and bokbang can be carried out at 30 ~ 50 ℃ for 12 ~ 72 hours and may be fermented with stirring.

Depending on the design conditions, the fermentation temperature and fermentation time can be controlled and an environment suitable for the fermentation of the fermentation strain is sufficient.

The fermentation product may be selected from bifidobacteria, lactic acid bacteria, yeast, bacillus, and photosynthetic bacteria, and the fermented product fermented by the fermentation product may be easily extracted from the body and easily absorbed in the body It becomes.

2) Extract the fermented product.

The fermentation product is extracted to prepare a composition according to the present invention.

Various extraction methods such as a solvent extraction method, a steam distillation method, a carbon dioxide supercritical extraction method, a steam distillation method, a microwave process extraction method and a percolation extraction method may be used as the extraction method, and a solvent extraction method may be preferably used.

In solvent extraction, extraction solvents and various solvents may be used.

Extractable solvents include water, ethanol, methanol, fatty oil, glycerin, mayo, propylene glycol, ether, chloroform, petroleum ether, hexane, benzene, methylene chloride, ethyl acetate, acetone, butanol and isopropanol. Depending on the extraction temperature, the extraction time, the amount of the solvent, and the method of treating the residual components, the treatment can be performed.

In the composition according to the present invention, the concentration of the fermented extract of red ginseng and bokbunja may be 10 to 200 mg / kg per day on the basis of a high fructose diet rat model, preferably 125 mg / kg per day.

In addition to the processes described above, filtration, concentration, extraction, and the like may be repeatedly performed in accordance with design conditions, and other processes such as fermentation and freezing may be performed before and after each process.

Reference Example  1. Preparation of experimental model

1) High fructose diet rat model

A high fructose diet rat model was used to induce vascular disease.

A high fructose diet rat model was constructed by administering Research Diets high fructose diet for about 9 weeks, and the feed contained 60% fructos.

2) Sample administration

Red ginseng and bokbunja fermented extracts were prepared according to the above Example 1, and administered at a dose of 125 mg / kg per day. As a comparative group, red ginseng extract was prepared and administered at a dose of 250 mg / kg per day.

Were administered to the rats simultaneously with the high fructose diet for 9 weeks each.

Hypertension is seen in most people with metabolic syndrome, which is one of the most dangerous factors in heart disease and cerebrovascular disease.

Therefore, the drug used as a positive control was the AT type II receptor antagonist Losartan, which is used in clinical practice as an angiotensin receptor blocker (ARB), and was administered at a dose of 30 mg / kg per day for 9 weeks to the high fructose diet At the same time, they were administered to the rats.

Experimental Example  1. Measurement of blood pressure change

1-1. Experimental course

Systolic mean blood pressure was measured in rat tail artery using automatic sphygmotonography (Mutomachi Kikai, Tokyo, Japan). Blood pressure was measured at least 8 times for each subject, and 5 measurements within 5 mmHg were used as mean values.

1-2. Experiment result

FIG. 1 is a graph showing changes in blood pressure according to a sample treatment in a high-fructose diet rat model.

There was no significant difference between the groups in terms of blood pressure before and after high fructose diet and drug administration.

However, blood pressure was measured after the initiation of high fructose diet and drug administration (3 weeks). As a result, blood pressure was increased in the rest of the control group.

In the control group and the high fructose group, there was a significant difference in blood pressure at 6 and 9 weeks. In the group treated with red ginseng extract and red ginseng and bokbunja fermented extract, blood pressure was significantly decreased .

Experimental Example  2. Check for vascular lesions

2-1. Experimental course

The extracted thoracic aortic tissue was fixed in 10% formalin (pH 7.4) for 3 days, and the remaining formalin was removed.

Dehydrated in the order of increasing concentration from 50% alcohol to 100% alcohol, substituted with xylen, embedded in paraffin, and embedded.

The prepared paraffin blocks were attached to the slides after 4-5 μm separation using a microtome (Thermo Electron Corporation, Pittsburg, Pa.).

Hematoxylin-eosin staining was performed to observe the morphologic changes of the thoracic aorta, and the thoracic aorta was photographed after observing the thoracic aorta at 400-fold visual field under an optical microscope.

2-2. Experiment result

FIG. 2 is a photograph showing blood vessel atherogenesis of the thoracic aorta according to the sample treatment in a hyperglycemic-type rat model, and FIG. 3 is a graph showing changes in the intima-media thickness of the thoracic aorta according to the sample treatment in a hyperglycemic- to be.

As a result, vascular atheromatosis was not observed in the thoracic aorta of the vascular lesion metabolic syndrome model using a high fructose diet rat model, but the endothelial tissue was damaged by the length of the intima-media, indicating that the thickening of smooth muscle and abnormal endothelial cells Hypertrophy, that is, early atherosclerosis.

In the group treated with red ginseng extract and red ginseng and bokbunja fermented extract, the degree of vascular injury was decreased.

Experimental Example  3. Expression of vascular disease-related factors

3-1. Experimental course

1) Expression of vascular inflammatory factor

Immunohistochemistry staining was performed to measure the expression levels of ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1), which are vascular inflammatory factors, Were photographed after observing at 400x field of view.

Plasma was also centrifuged at 3000 rpm for 20 minutes and then measured using an ELISA kit.

2) Measurement of expression of vasoconstrictor

The expression level of ET-1 (endothelin-1), a vasoconstrictor, was measured in order to investigate the changes in vasoconstriction in the thoracic aorta. The experimental procedure was the same as that in 1) of 3-1.

3-2. Experiment result

FIG. 4 is a photograph and a graph showing the degree of expression of ICAM-1 according to a sample treatment in a high-fructose diet rat model, and FIG. 5 is a graph showing the degree of expression of VCAM-1 in the high- And graphs.

ICAM-1 (intercellular adhesion molecule-1), also called CD (antigen), is a transmembrane protein with a molecular weight of 90,000. (IgSF), which is widely distributed in vascular endothelial cells, epithelial cells, hematopoietic cells, and the like, and mainly binds to leucocyte β2 integrin LFA-1 in a divalent metal cation-dependent manner.

Expression of ICAM-1 plays an important role in the inflammatory state by inducing stimulation of inflammatory cytokines such as TNF-α, active oxygen, leukocyte extravasation and activation of T cells by antigen presenting cells do.

In addition, VCAM-1 (vascular cell adhesion molecule-1) is a cell adhesion molecule that induces expression at the peak of 24 to 48 hours by inflammatory cytokinins or lipopolysaccharides such as interleukin 1, tumor necrosis factor α, interferon γ, As molecules, they belong to the immunoglobulin superfamily family, and there are three kinds of isoforms.

In vivo, activated vascular endothelial cells appear in inflamed areas, and are expressed in stromal cells of the thymus and bone marrow, dendritic cells in the center of the spleen (embryo), and skeletal muscle. It also binds to integrin α4β1, is involved in lymphocyte infiltration into inflammatory sites, adhesion of stem cells and stromal cells, and root canal formation.

The expression of ICAM-1 and VCAM-1 was increased in the high fructose group compared to the control group. This suggests that the high fructose diet promotes vascular inflammation damage.

However, the levels of ICAM-1 and VCAM-1 were significantly decreased in the Losartan group, the red ginseng extract group, and the red ginseng and bokbunja fermented extract groups, compared to the high fructose group.

FIG. 6 is a photograph and a graph showing the degree of expression of ET-1 according to the sample treatment in a high-fructose diet rat model.

ET-1 (endothelin-1) is a vasoconstrictor, a protein that contracts blood vessels, increases blood pressure, and reduces oxygen supply to the heart.

Increased ET-1 increases the risk of heart disease (Psychosomatic Medicine 2002; 64: 707-713).

As a result, ET-1 expression was significantly increased in the high fructose group compared to the control group, but the expression level of ET-1 was higher in the group treated with the red ginseng extract and the red ginseng and bokbunja fermented extract than in the high fructose group Was significantly decreased.

Claims (5)

A composition for preventing, improving or treating vascular diseases containing red ginseng and bokbunja fermented extract as an active ingredient.
The method according to claim 1,
The composition for preventing, ameliorating or treating vascular diseases according to claim 10, wherein the concentration of the red ginseng and the bergamot fermented extract is 10 to 200 mg / kg per day on the basis of a high fructose diet rat model.
The method according to claim 1,
Wherein the vascular disease is hypertension, coronary artery disease, atherosclerosis, and hyperlipidemia.
The method according to claim 1,
The composition reduces the blood pressure in the hyperglycemic rat model and alleviates vascular lesions such as hypertrophy of the intravascular smooth muscle and abnormal hypertrophy of the endothelial cells and inhibits vascular lesions such as intercellular adhesion molecule-1 (ICAM-1), vascular cell 1, and endothelin-1 in a mammal, comprising administering to the mammal an effective amount of a compound of the present invention.
A health functional food for preventing or improving vascular diseases containing red ginseng and bokbunja fermented extract as active ingredients.

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