KR20200042311A - Compositions for for inhibiting of macrophage death by triglycerides comprising extracts of Angelica takeshimana - Google Patents

Abstract

The present invention relates to a composition for suppressing macrophage death by triglycerides, containing an extract of Zanthoxylum piperitum. More specifically, the present invention relates to: a composition and a health functional food composition for suppressing macrophage death by triglycerides all of which contain an extract of Zanthoxylum piperitum or a fraction thereof as an active component; and a method for suppressing macrophage death by triglycerides. The composition containing the extract of Zanthoxylum piperitum of the present invention can maintain a function of macrophages even in a state where the concentration of blood fat is high, thereby being able to be usefully used as a purpose for suppressing macrophage death by triglycerides.

Description

Composition for inhibiting macrophage death by triglycerides, including the extract of Sancho {Compositions for for inhibiting of macrophage death by triglycerides comprising extracts of Angelica takeshimana}

The present invention relates to a composition for inhibiting macrophage death by triglycerides, including a mountain extract, a composition for inhibiting macrophage death by triglycerides, which contains a mountain extract or a fraction thereof as an active ingredient, a health functional food composition, and neutrality It relates to a method for inhibiting the death of macrophages by fat.

Triglycerides are lipids that make up the middle part of lipoproteins, and an increase in concentration due to secondary causes is common. For example, obesity, lack of exercise, smoking, excessive drinking, high intake of carbohydrates, diabetes, chronic kidney failure, nephrotic syndrome and other diseases and beta-blockers, steroids, estrogen, etc. .

The aforementioned triglycerides are also involved in the development of atherosclerosis, and the specific mechanism of development of atherosclerosis is as follows. First, monocytes differentiate into macrophage, and the differentiated macrophages kill HDF / LDL-cholesterol or triglycerides or die or become foam cells. The resulting foam cells continuously induce an inflammatory response. Over time, the foam cells are killed through apoptosis, and the dead cells are removed by newly migrated macrophages. However, some of the killed foam cells remain unremoved, causing secondary necrosis to surrounding cells, which increases the inflammatory response in the plaque and worsens atherosclerosis (Golias C). , In Vivo., 2007, 21 (5): 757-69 .; Thorp E, J Leukoc Biol., 2009, 86 (5): 1089-95 .; Tabas I. Antioxid Redox Signal., 2009, 11 (9 ): 2333-9.).

In addition, when the concentration of triglycerides in the blood increases due to obesity, hyperlipidemia, etc., the rate at which macrophages are converted into foam cells or killed by triglycerides increases. That is, as the macrophages die, their immune function and triglyceride metabolism decreases, and the removal function of the formed foam cells decreases, which increases the likelihood of developing or worsening atherosclerosis. Therefore, in order to prevent the development or exacerbation of arteriosclerosis, it is important to keep macrophages functioning to remove foam cells even when the concentration of triglycerides in the blood is high, or to minimize the death by triglycerides.

Currently, statin-based drugs such as rosuvastatin and simvastatin are mainly used for the treatment of atherosclerosis, but it is known that there is a side effect of reducing the activity of macrophages to remove foam cells. In addition, the statin-based drug is pointed out as a problem that causes side effects such as diabetes, muscular dystrophy, and hyperglycemia, and studies on natural products with fewer side effects are needed.

Accordingly, the composition for the treatment of atherosclerosis containing the extract of oleander (Korea Patent Publication No. 10-2016-0084990), anti-hyperlipidemia and anti-arteriosclerosis composition containing the camphor ginseng fermentation extract (Korea Patent Publication No. 10-2016 -001805), prevention or treatment of arteriosclerosis using natural substances, such as a composition for the prevention or treatment of arteriosclerosis containing the extract of ginseng vine (Korea Patent Publication No. 10-1516764) has been developed.

Meanwhile, Zanthoxylum schinifolium ) is a tree that forms an umbrella with a height of 3m and a water pipe width of 2m. Flowers bloom mainly in September, light green, scentless, fruit greenish brown with black seeds. It is said that oriental medicine uses pericarp (pericarp, except for seeds from fruits) as a treatment for indigestion, vomiting, toothache, dysentery, diarrhea, and roundworms. However, the effect of inhibiting the death of macrophages by triglycerides or the effect of treating arteriosclerosis accordingly has not been known.

Under these backgrounds, the present inventors have studied in earnest efforts to develop a natural substance having an inhibitory effect on macrophage death by triglycerides, which can have a prophylactic or therapeutic effect on arteriosclerosis, and as a result, the extract of wild pepper is caused by triglycerides. The present invention was completed by confirming the effect of suppressing the death of phagocytes.

One object of the present invention is to provide a composition for inhibiting macrophage killing by triglycerides, comprising an extract of wild grass or a fraction thereof as an active ingredient.

Another object of the present invention is to provide a method for inhibiting macrophage death by triglycerides, comprising administering the composition to an individual.

Another object of the present invention is to provide a health functional food composition for inhibiting macrophage killing by triglycerides, comprising an extract of wild grass or a fraction thereof as an active ingredient.

One aspect of the present invention provides a composition for inhibiting macrophage killing by triglycerides, comprising an extract of wild grass or a fraction thereof as an active ingredient.

In the present invention, according to confirming that the pepper extract is effective in inhibiting the death of macrophages by triglycerides, it was confirmed that the pepper extract or its fraction can be usefully used for inhibiting macrophage killing by triglycerides. .

The term "sancho" of the present invention is Zanthoxylum It means a plant with the scientific name of schinifolium . Although it is known to have effects on indigestion, vomiting, toothache, dysentery, diarrhea, etc., the effect of inhibiting macrophage death by triglycerides is unknown, and was first identified by the present inventors.

In the present invention, the sancho may be a seed of sancho, but is not limited thereto. The seed is distinguished from the fruit including the peel, fruit, and the like.

The sancho can be purchased commercially, or can be used that is harvested or cultivated in nature.

The term "extract" of the present invention refers to an extract liquid obtained by extracting the above-mentioned wild grass, a diluent or concentrate of the extract, a dried product obtained by drying the extract, a crude product or a purified product of the extract, or a mixture thereof. And extracts of all formulations that can be formed using the extract.

The method for extracting the sancho is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method may include a hot water extraction method, an ultrasonic extraction method, a filtration method, a reflux extraction method, a compression extraction method, and the like, which may be performed alone or in combination of two or more methods.

In the present invention, the sancho extract may be prepared by compressing sancho.

The term "fraction" of the present invention means a result obtained by performing a fraction to separate a specific component or a specific component group from a mixture containing various various constituents.

In the present invention, the fractionation method for obtaining a fraction of the above-mentioned Sancho extract is not particularly limited, and may be performed according to a method commonly used in the art. Non-limiting examples of the fractionation method include a solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed by passing through an ultrafiltration membrane having a constant molecular weight cut-off value, and various chromatography (size, charge, hydrophobicity) Or a chromatographic fractionation method for performing separation according to affinity), and combinations thereof. Specifically, a method of obtaining a fraction from the extract by treating a predetermined solvent to the extract obtained by extracting the herb of the present invention.

In addition, the extract or fraction may be prepared and used in a dry powder form after extraction, but is not limited.

In the present invention, the Sancho extract may be to inhibit the death of macrophages by triglycerides.

The term "macrophage death by triglyceride" in the present invention means that the function of macrophages is lost or impaired by triglyceride, and macrophages are necrosis, apoptosis, or large This includes the conversion of phagocytes to other cells of different types. Macrophages remove various substances unnecessary to the human body, such as triglycerides or dead cells. When the function of macrophages is lost, an inflammatory reaction is caused by the above-described substances, and diseases such as atherosclerosis may occur. Therefore, the death of macrophages by triglycerides can be useful as a preventive or therapeutic use for diseases caused by the death of macrophages by triglycerides such as atherosclerosis.

In a specific embodiment of the present invention, it was confirmed that the Sancho extract can increase the survival rate of macrophages by inhibiting the death of macrophages by triglycerides (FIG. 1).

This, because the pepper extract is a high level of fat in the blood to maintain the function of macrophages, the composition of the present invention comprising the extract can be usefully used for inhibiting macrophage death by triglycerides It is suggestive.

The composition of the present invention may include the extract of the herb or a fraction thereof in an amount of 0.001 to 80, specifically 0.001 to 70, and more specifically 0.001 to 60% by weight based on the total weight of the composition, but is not limited thereto.

Another aspect provides a method of inhibiting macrophage death by triglycerides, comprising administering the composition to a subject.

At this time, the definition of the "macrophage death by triglycerides" is as described above.

The term "administration" of the present invention means introducing the composition to the individual in an appropriate manner.

The term "individual" of the present invention means all animals, such as mice, mice, livestock, including humans, which may or may have caused macrophage death by triglycerides. The animals may be mammals such as cows, horses, sheep, pigs, goats, camels, antelopes, dogs, cats, etc., which have similar symptoms as humans, but are not limited thereto.

The composition may be administered orally or parenterally (eg, intravenously, subcutaneously, intraperitoneally, or topically) depending on the desired method. At this time, the dosage varies depending on the condition and weight of the individual, the degree of the disease, the drug form, the administration route and time, but can be appropriately selected by those skilled in the art. As a specific example, the composition may be administered by dividing the amount of 0.001 to 1000 mg / kg, more specifically 0.05 to 200 mg / kg, and most specifically 0.1 to 100 mg / kg, once or several times a day, The preferred dosage may be appropriately selected by a person skilled in the art depending on the condition and weight of the individual, the degree of disease, the drug form, the route and duration of administration.

Another aspect provides a health functional food composition for inhibiting macrophage killing by triglycerides, comprising an extract of wild grass or a fraction thereof as an active ingredient.

At this time, the definitions of "wild grass", "extract", "fraction", and "macrophage death by triglycerides" are as described above.

The health functional food composition of the present invention can be consumed on a daily basis, and unlike other medicines, it has the advantage that there is no side effect that can occur when taking medicines for a long time by using natural substances as raw materials, and thus inhibits macrophage death by triglycerides. It can be very useful for purposes.

The term “health functional food” in the present invention is the same term as food for special health use (FoSHU), and medicine and medical treatment processed to efficiently exhibit bioregulatory functions in addition to nutrition. It means food with high effectiveness. Here, the term 'function' means to obtain a useful effect for health use such as adjusting nutrients or physiological effects on the structure and function of the human body. In some cases, the terms health functional food, health food, and health supplement may be used interchangeably.

Specifically, the health functional food is a food prepared by adding the herbal extract or fractions thereof of the present invention to food materials such as beverages, teas, spices, gums, confectionery, or by encapsulation, powdering, suspension, etc. In this case, it means that it has a certain effect on health, but unlike general medicines, it has the advantage that there is no side effect that can occur when taking medicines for a long time using food as a raw material.

The health functional food of the present invention can be prepared by a method conventionally used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art. In addition, the health functional food composition may be prepared without limitation as various types of formulations as long as the formulation is recognized as food.

In addition, the health functional food composition may further include a physiologically acceptable carrier, and the type of the carrier is not particularly limited, and any carrier commonly used in the art may be used.

In addition, the health functional food composition is commonly used in food composition may include an additional component that can improve the smell, taste, vision, and the like. For example, vitamin A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantotenic acid, and the like. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chromium (Cr); And amino acids such as lysine, tryptophan, cysteine, and valine.

In addition, the health functional food composition is a preservative (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), fungicides (bleached and highly bleached, sodium hypochlorite, etc.), antioxidants (butyl hydroxyanisole (BHA), Butyl hydroxytoluene (BHT, etc.), colorants (such as tar color), colorants (sodium nitrite, sodium nitrite, etc.), bleach (sodium sulfite), seasonings (such as MSG sodium glutamate), sweeteners (dulcin, cyclate) , Saccharin, sodium, etc.), fragrances (vanillin, lactones, etc.), swelling agents (alum, D-potassium hydrogen sulphate, etc.), strengthening agents, emulsifiers, thickeners (foaming agents), coating agents, gum starting agents, foam inhibitors, solvents, improvers, etc. May include food additives. The additive may be selected according to the type of food and used in an appropriate amount.

Since the composition comprising the extract of the herb of the present invention can maintain the function of macrophages even in a state where the concentration of fat in the blood is high, it can be usefully used for the purpose of inhibiting macrophage death by triglycerides.

1 is a graph prepared according to an embodiment of the present invention, showing the effect of inhibiting the killing of macrophages by triglycerides of the pepper extract. Cell viability was shown to be relative to a normal control. At this time, TG means triglyceride.

Hereinafter, the present invention will be described in more detail by the following examples and experimental examples. However, the following examples and experimental examples are intended to illustrate the present invention, and the scope of the present invention is not limited thereto.

Manufacturing example  1. Preparation of Sancho Extract

After coarsely pulverizing the shaded sancho seeds, they were put in a steamer preheated to 92 to 98 ° C and steamed for 5 minutes. Subsequently, the extract was prepared by squeezing for 15 minutes at a pressure of 600 kg / cm ^{2 in} a milking machine.

Example  1. Confirmation of anti-atherosclerotic effect of Sancho extract

In order to confirm the anti-atherosclerotic effect of the Sancho extract prepared according to Preparation Example 1, the effect of inhibiting the death of macrophages by triglycerides was confirmed.

Specifically, the human mononuclear cell line THP-1 was inoculated into a 96-well plate at a number of 1.5 × 10 ⁴ cells / well, and then treated with 200 nM PMA (phorbol-12-myristate-13-acetate) for 24 hours to macrophages. Differentiation was induced. Differentiated macrophages were maintained using RPMI medium containing 1% penicillin-streptomycin, 10% fetal bovine serum at 37 ° C and 5% carbon dioxide conditions, and treated with 0.2-2 µl / mL concentration of pepper extract for 24 hours. Did. Then, the cells were washed twice with DPBS, and triglyceride (TG) at a concentration of 1 mg / ml was treated for 24 hours. Cell viability was measured using Ez-Cytox (Dojin Bio) for macrophages after the above process.

As a result, as can be seen in Figure 1, when processing the extract, it was confirmed that the survival rate of macrophages reduced by triglycerides increased, it was confirmed that this increase effect is similar to the normal control.

Through the above results, the Sancho extract effectively suppresses the death of macrophages caused by triglycerides, thereby suppressing the immune function decrease due to the death of macrophages, the deterioration of triglyceride metabolism, the formation of foam cells, and the reduction of the removal function of the formed foam cells. Therefore, it was found that it can be usefully used for the prevention or treatment of arteriosclerosis.

From the above description, those skilled in the art to which the present invention pertains will understand that the present invention may be implemented in other specific forms without changing its technical spirit or essential characteristics. In this regard, it should be understood that the embodiments described above are illustrative in all respects and not restrictive. The scope of the present invention should be construed as including all changes or modifications derived from the meaning and scope of the following claims rather than the above detailed description and equivalent concepts thereof.

Claims (5)

A composition for inhibiting macrophage killing due to triglycerides, comprising an extract of Sancho or its fraction as an active ingredient.
The composition according to claim 1, wherein the wild grass is a seed of wild grass.
The composition of claim 1, wherein the extract is prepared by squeezing wild pepper.
A method of inhibiting macrophage death by triglycerides, comprising administering the composition of any one of claims 1 to 3 to an individual other than a human.
A health functional food composition for inhibiting macrophage killing by triglycerides, comprising an extract of wild grass or a fraction thereof as an active ingredient.

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