KR20170041997A - Composition comprising extract of Acanthopanax koreanum for preventing or treating of vascular disease - Google Patents
Composition comprising extract of Acanthopanax koreanum for preventing or treating of vascular disease Download PDFInfo
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- KR20170041997A KR20170041997A KR1020150141361A KR20150141361A KR20170041997A KR 20170041997 A KR20170041997 A KR 20170041997A KR 1020150141361 A KR1020150141361 A KR 1020150141361A KR 20150141361 A KR20150141361 A KR 20150141361A KR 20170041997 A KR20170041997 A KR 20170041997A
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- vascular
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/326—Foods, ingredients or supplements having a functional effect on health having effect on cardiovascular health
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
Abstract
The present invention relates to a composition for preventing or treating a vascular disease containing an extract of an aurantium sclerotinus. The extract of an aurantium scutellum has excellent effect of activating endothelial nitric oxide synthase (eNOS) of a vascular endothelial cell, Myocardial infarction, ischemic heart disease, stroke, cerebral infarction, cerebral hemorrhage, and the like. The present invention also relates to a composition for the treatment of various vascular diseases such as peripheral vascular occlusion, vascular restenosis, hypertension, angina pectoris, myocardial infarction,
Description
The present invention relates to a composition for the prevention or treatment of vascular diseases containing an extract of Ischia officinalis.
In modern society, vascular disease is becoming a serious social problem. According to the statistics of death sources released by the National Statistical Office in 2010, vascular diseases including hypertensive diseases, ischemic heart diseases and cerebrovascular diseases were the second leading cause of death in Korea after malignant tumors, , And women who were 65 years or older reported a significant increase in mortality from vascular disease. Age, sex, hypertension, hyperlipidemia, diabetes, smoking, lack of exercise, and obesity are known to be risk factors for arteriosclerosis, which accounts for the largest portion of vascular disease. Patients with vascular disease receive continuous medication to treat the disease but are not easy to cure, and side effects from long-term administration of the medication are present.
Endothelium is the innermost of all blood vessels, including lymphatic and cardiovascular, and is composed of endothelial cells. Vascular endothelium plays a major role in maintaining vascular homeostasis such as vasodilation and contraction, vascular smooth muscle proliferation and migration, thrombogenesis and lysis. When the function of the vascular endothelium is interrupted, the vascular wall is damaged and vascular diseases such as atherosclerosis are induced.
The most important function of vascular endothelium is to secrete nitric oxide (NO). The production of NO is controlled by endothelial nitric oxide synthase (eNOS) present in vascular endothelial cells, and plays a role in producing NO by using L-arginine as a substrate. These eNOS are specifically expressed in vascular endothelial cells (smooth muscle cells), platelets, cardiac muscle cells, osteocytes, neurons and the like, NO generated by the action of eNOS is liberated into blood vessels and induced relaxation of vascular smooth muscle, Low density lipoprotein (LDL) oxidation, leukocyte adsorption, vascular smooth muscle cell proliferation, and platelet aggregation.
(Glueck, CJ 2010), myocardial infarction (Merx, MW et al., 2014), ischemic heart disease (Tratsiakovich, Y. et al., 2013), arterial sclerosis , Hell et al., 2014), hypertension (Na, S. et al., 2014), brain diseases such as stroke, cerebral infarction and cerebral hemorrhage (Li et al., 2014; Vellimana, AK et al., 2011) There have been a variety of attempts to treat various vascular diseases,
As described above, since the degradation of eNOS causes dysfunction of vascular endothelial cells such as atherosclerosis, a substance that promotes eNOS activity can be used as a candidate drug for improving chronic vascular disease. In fact, nebivolol, a third-generation beta blocker, is known to enhance vasodilatory effects through eNOS activation. The activity of eNOS is known to be regulated through various pathways such as calcium accumulation in endothelial cells, regulation of tetrahydrobiopterin coenzyme, phosphorylation, and the like. eNOS has various phosphorylation sites, and Ser-1177 phosphorylation has been reported to play an important role in the change of eNOS activity. Phosphorylation of ser-1177 of eNOS was induced by the estrogen receptor (Simoncini, T. et al., 2002), PI3-kinase / Akt (Hisamoto, K. et al., 1999), MAP kinase (Hisamoto, K. et al. 2001) and AMP kinase (Morrow, VA et al., 2003). In fact, women with postmenopausal women who have weakened estrogen secretion, which is a female hormone, have a significantly higher incidence of cardiovascular disease, which is the main cause of decreased eNOS activity. Therefore, the discovery of natural substances that enhance the enzyme activity by eNOS phosphorylation can be an important strategy for improving the vascular endothelial dysfunction and blood circulation.
On the other hand, arteriosclerosis refers to a functional impairment in which vascular endothelial cells do not maintain normal homeostasis due to genetic mutations, peroxidation, hypertension, increase in plasma homocysteine concentration, lipid accumulation in the blood vessels, microbial infection and the like. Lipid components such as cholesterol are deposited on the endothelium covering the innermost part of the blood vessel, hypertrophy of vascular endothelial cells occurs, atheroma is formed, blood vessel elasticity weakens or aging progresses, do. (ICAM-1), MCP-1 (monocyte chemoattractant protein-1), and P-selectin (VEGF) in vascular endothelial cells. the expression of adhesion molecules including E-selectin and E-selectin is increased and the expression of low density lipoprotein in blood, the inflow of mononuclear cells and macrophages, The process of activating is repeated to promote plaque formation in the blood vessels.
Adhesive substances such as VCAM-1, ICAM-1 and MCP-1 are known to be activated by reactive oxygen species (ROS) or tumor necrosis factor-α (TNF-α) (Yen, FL et al., 2013; Mackesy, DZ, 2014).
The adherent substance can firmly adhere cells and cells to maintain circularity, and functions to promote adhesion between leukocytes, vascular endothelial cells, white blood cells and extravascular tissues. In addition, leukocytes move through the blood vessels to move to the surrounding tissues, raise the awareness of T lymphocyte antigen, activate lymphocytes and monocytes of peripheral blood, and further enhance the action of activated lymphocytes. Through these functions, adherent substances play an important role in vascular diseases.
Acanthopanax koreanum is a deciduous shrub of the dicotyledonous decidua plant, and is a native species of Jeju native to the sea below 1400m above sea level in Jeju Island, South Korea (Korean Journal of Plant Resources, 1999, 12, 125-132). Branches are much split and fragrant, with broad thorns at the base. Leaves are alternate phyllotaxis. There are 3 ~ 5 small leaves. Egg is inverted or upside down. It has sharp sawtooth on edge and hairy on base of stem. The surface of the leaves is glossy and the back is light green. Flowers bloom from July to August, green, and hang on mountain-shaped inflorescence. The peduncle is 2 ~ 5㎝ long and the flower sack is long. The petals are 5, and calyx is faintly divided into 5 pieces. The fruit is flat with the nucleus and it grows black in October and the style remains. In the private sector, it has been used for back pain, neuralgia, and paralysis, and has traditionally been used as a medicinal product to lighten the body. It has been reported that it has anti-fatigue, anti-stress, central nervous excitement, metabolic stimulation, muscle strengthening, (National Federation of Forestry Cooperatives, 2005, Forest Regions 474, 112-114).
Meanwhile, the inventors of the present invention conducted research on a composition for treating vascular diseases, and confirmed that the extract of Ishigaki japonica had an effect of promoting eNOS activity in vascular endothelial cells. In addition, we confirmed that prior art that PPARγ activates PPARγ, which is the main compound present in the extract of Phellodendus japonicus, is related to arteriosclerosis, and that the content of impression acid As a result, it was confirmed that 0.27 mg (about 0.027%) was present per 1 g of the extract of Ishigaki. In addition, the transcriptional inhibition activity of inflammatory adhesion molecules was examined by treating the extract of Ishigaki japonicus and purified Impress acid, and it was confirmed that the transcriptional repression inhibitory activity was similar even though the amount of Impressic acid in the extract was very low. Thus, the present invention can be completed by confirming that the extract of Ishigaki japonica has excellent effect of preventing or treating vascular diseases.
Korean Patent No. 0793204 discloses that a herbal composition containing an augar has the effect of reducing plasma total cholesterol and triglyceride levels and has a therapeutic effect on coronary heart disease or atherosclerosis. In addition, Korean Patent No. 0684436 discloses that a mixed extract of Daphnia magna and G. obtusifolia has antioxidative and antioxidative effects by inhibiting lipid peroxidation. Korean Unexamined Patent Publication No. 2005-0022944 discloses an ethyl acetate fraction of a water extract of Aspergillus oryzae as a composition for the treatment of vascular diseases related to the ability to inhibit vasoconstriction. Korean Patent Registration No. 0372360 discloses that a cosmetic composition comprising an odorless garlic extract or a visa extract having an effect of inhibiting skin aging and Korean Patent No. 0164004 discloses that a herbal composition containing an augar has an antioxidant effect . However, it has not yet been confirmed that the extract of Ismailia japonica can be used as a therapeutic agent for various vascular diseases due to vasodilatory effect through eNOS activity.
It is an object of the present invention to provide a composition for the prevention or treatment of vascular diseases containing an extract of an oak leaf.
The present invention relates to a composition for preventing or treating vascular diseases containing an extract of Acanthopanax koreanum leaf.
The islet leaf extract can be extracted with water, C1 to C4 alcohol or a mixed solution thereof as a solvent.
The extract of Ismailia japonica has an effect of activating eNOS of vascular endothelial cells.
The vascular disease may be selected from atherosclerosis, peripheral vascular occlusion, vascular restenosis, hypertension, angina pectoris, myocardial infarction, ischemic heart disease, stroke, cerebral infarction and cerebral hemorrhage.
In another aspect, the present invention provides a health functional food for preventing or ameliorating a vascular disease that contains an extract of Islet japonica Leaf. The health functional food may be selected from various foods, beverages, gums, tea and vitamin complexes.
Hereinafter, the present invention will be described in detail.
The extract can be obtained by extracting an islet leaf with water, a C1 to C4 alcohol or a mixed solution thereof as a solvent, and the C1 to C4 alcohol is selected from the group consisting of methanol, ethanol, propanol, isopropanol, butanol and isobutanol , Preferably ethanol, more preferably 30% to 90% ethanol may be used.
The water, the C1 to C4 alcohol, or the mixed solution thereof used in the preparation of the islet osmanthus leaf extract may be used in an amount of 1 to 10 times, preferably 5 to 10 times, . The extraction conditions of the islet leaf extract may be 1 to 48 hours at 20 to 100 < 0 > C.
In addition, as an ordinary method in the field of the art, the extract of Ischia officinalis L. can be obtained by dissolving water, C1 to C4 alcohols or a mixed solution thereof in water in water, followed by washing with a solvent such as n-hexane, methylene chloride, acetone, chloroform, ethyl Acetate, n-butanol, and dichloromethane. The solvent may be a solvent or a mixture of two or more solvents.
The production temperature of the extract or its fractions may be 20 ° C to 50 ° C, but is not limited thereto. The extraction time is not particularly limited, but it is preferable to perform extraction within 10 minutes to 1 day. As the extraction apparatus, a conventional extraction apparatus, an ultrasonic pulverization extractor, or a fractionator may be used. The thus prepared island oak leaf extract or fraction can be removed by hot air drying, vacuum drying or freeze drying.
The present invention also provides a pharmaceutical composition for the prevention or treatment of vascular diseases containing an extract of Ischia officinalis. The pharmaceutical composition may contain 0.001 wt% to 100 wt% The pharmaceutical compositions may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to conventional methods. Examples of carriers, excipients and diluents that can be contained in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like. Such solid preparations can be prepared by incorporating at least one excipient, such as starch, calcium carbonate, sucrose, Or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
The dosage of the pharmaceutical composition of the present invention will depend on the age, sex, body weight of the subject to be treated, the particular disease or condition to be treated, the severity of the disease or condition, the route of administration and the judgment of the prescriber. Dosage determinations based on these factors are within the level of ordinary skill in the art and generally the dosage ranges from 0.01 mg / kg / day to approximately 2000 mg / kg / day. A more preferable dosage is 1 mg / kg / day to 500 mg / kg / day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.
The pharmaceutical composition of the present invention can be administered to mammals such as rats, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection. Since the compound of the present invention has little toxicity and side effects, it can be safely used even for long-term administration for preventive purposes.
In addition, the present invention provides a health functional food for preventing or improving vascular diseases, which comprises an islet oak leaf extract and a pharmaceutically acceptable food-aid additive. The islet leaf extract may be added to the health functional food of the present invention in an amount of 0.001% by weight to 100% by weight. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamins .
The present invention relates to a composition for the prevention or treatment of vascular diseases, which comprises an extract of Ismailia japonica. The extract of Ismailia japonica is excellent in the effect of activating eNOS of vascular endothelial cells, and is useful as a therapeutic agent for atherosclerosis, peripheral vascular occlusion, And can be easily used as a composition for treating various vascular diseases such as stenosis, hypertension, angina pectoris, myocardial infarction, ischemic heart disease, stroke, cerebral infarction, cerebral hemorrhage and the like.
1 shows the MTT assay results (FIG. 1A) and the LDH assay results (FIG. 1B) confirming the cytotoxicity of islet leaf extract on HUVEC.
FIG. 2 is a Western blotting result confirming that the phosphorylation (p-eNOS) of eNOS in HUVEC is increased in a concentration-dependent manner on the extract of aphids.
FIG. 3 shows fluorescence analysis photographs of NO produced by the treatment of anthocyanin extracts in HUVEC.
FIG. 4 is a fluorescence image showing that the increase of monocyte adhesion due to TNF-.alpha. Treatment in HUVEC is reduced in a concentration-dependent manner by treatment with an extract of Ishigaki japonica.
Figure 5 shows that the transcriptional activity of ICAM-1 (Figure 5A) and VCAM-1 (Figure 5B) increased due to TNF- [alpha] treatment in HUVEC was decreased in a dose- This is the result of the assay.
Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, the intention is to provide an exhaustive, complete, and complete disclosure of the principles of the invention to those skilled in the art.
≪ Example 1 > Preparation of an extract of Ishigaki japonica leaf &
20 ℓ of 50% ethanol was added to 10 ㎏ of leaves of Acanthopanax koreanum and refluxed for 5 hours. New ethanol was added to the leaves of the islets and the same procedure was repeated two more times. The liquid phase was removed from the extract obtained by reflux extraction, and the liquid phase was distilled under reduced pressure to obtain 960 g of 50% ethanol extract of islet oak leaf.
≪ Comparative Example 1 > Preparation of Comparative Extracts >
Comparative Example 1-1. Preparation of 100% Ethanol Extract of Island Ogarie Leaf
The extract was prepared in the same manner as in Example 1-1 except that 100% ethanol was used instead of 50% ethanol.
Comparative Example 1-2. Manufacture of Water Extract of Ishigaki-japonica Island
10 kg of the leaves of an augar ispang were placed in 100 liters of water, and the extract was subjected to hot-water extraction at 90 ° C. for 10 hours. The extract was freeze-dried to obtain an extract of aquaticus.
<Experimental Example 1> Culture of vascular endothelial cells>
HUVEC (Human umbilical vein endothelial cell, supplied by Inoparma Screen Co., Ltd.) was used to confirm the effect of eNOS activity, NO production ability, and cell adhesion substance expression in vascular endothelial cells. Cell culture medium for HUVEC culture contained 2% fetal bovine serum, 0.1% ascorbic acid, 0.1% recombinant human epidermal growth factor (rhEGF), 0.1% hydrocortisone, BBE (bovine brain (Endothelial basal medium, Lonza) containing 0.1% of GA-1000 (gentamicin sulfate amphotericin) was used. HUVEC was cultured in a culture dish coated with 1% gelatin (Sigma) and cultured in a humidified chamber at 37 ° C and 5% CO 2. The HUVEC was incubated with 80% to 90% Were treated with trypsin-EDTA (Welgene) and subcultured.
<Experimental Example 2> Cytotoxicity>
In order to confirm that the extract of Ischia japonica L. prepared in Example 1 was a compound having no cytotoxicity, 5 μg / ㎖ to 50 μg / ml of an extract of Ismailia japonica was added to the vascular endothelial cell culture and cultured for 24 hours, (Lactate dehydronase assay kit, Roche Applied Science, Indianapolis, Ind.) Was used as an assay reagent, and 3- (4,5-dimethylthiazol-2-yl) -2,5- diphenyltetrazolium bromide assay kit , IN, USA) was used to measure cell viability.
For this, HUVEC was divided into 48 well plates (1 × 10 4 cells / well) and cultured for 24 hours. The cell extract (500 μl) Lt; / RTI > Then, the treated medium was collected, and 50 μl of each sample was dispensed into a 96-well plate. After 50 μl of the LDH assay kit was reacted within 10 minutes, a microplate reader ) Was measured at 490 nm. In addition, 500 쨉 l of an MTT solution at a concentration of 0.2 mg / ml was added to each well and incubated for 30 minutes. After completion of the reaction, the supernatant was removed and 100 μl of DMSO (dimethyl sulfoxide) was added to dissolve the generated formazan crystals, and the absorbance was measured at 550 nm with a microplate analyzer.
As shown in FIG. 1, the 50% ethanol extract of P. japonicus from Example 1 was found to be cytotoxic at the concentrations tested through MTT assay (FIG. 1A) and LDH assay (FIG. 1B).
< Experimental Example 3. Islet Leaf Extract eNOS Identification of phosphorylation activity>
The total cell lysates were obtained by treating the 50% ethanol extract of P. japonicus leaf of Example 1 with 5 μg / ml to 20 μg / ml of HUVEC for 30 minutes, and Western blot analysis was performed using the extract To confirm the phosphorylation of eNOS (Ser-1177) in the cell lysate.
For this, HUVEC was divided into 1 × 10 5 cells on a 60 mm cell culture plate. After 24 hours, 5 μg / ml to 20 μg / ml of the 50% ethanol extract of islet leaf of Example 1 was replaced with 30 Min and centrifuged to collect the treated cells of each sample. The collected cells were treated with 100 쨉 l of cell lysis buffer (120 mM NaCl, 40 mM Tris [pH 8], 0.1% NP40 [Nonidet P-40]) and centrifuged at 12,000 rpm. The supernatant was collected, ≪ / RTI > Subsequently, the cell lysate was subjected to 10% SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) electrophoresis, and the protein was fixed on a nitrocellulose transfer membrane using a transfer kit. The membrane was blocked at 5% skim milk for 1 hour at room temperature, reacted with primary antibody against phosphorylated eNOS and secondary antibody thereto, and then the amount of phosphorylated eNOS expressed , Which is shown in Fig.
2, it can be seen that the 50% ethanol extract of Ishigaki japonica leaf increases the phosphorylation (p-eNOS) of eNOS in a concentration-dependent manner. Thus, the 50% ethanol extract of Ishigaki japonica has an excellent eNOS phosphorylation activity .
<Experimental Example 4> Determination of NO production ability of an extract of Ishigaki japonica leaf
To determine the NO production ability of the 50% ethanol extract of Ogaki leaf, the degree of fluorescence was measured using DAF-FM diacetate (Molecular Probe, OR) (DAF-FM diacetate: matter).
For this, HUVEC was dispensed into 96-well plates at 5 × 10 4 cells / well and cultured in cell culture medium for 12 hours. Thereafter, the cells were cultured in a medium without FBS at 37 ° C for 3 hours. The cells were treated with L-NAME (LN G- nitroarginine methyl ester, NOS [nitiric oxide synthase] Lt; / RTI > for 30 minutes. After the L-NAME pretreatment, a 50% ethanol extract of islet oak leaf of Example 1, a 100% ethanol extract of islet oak from Comparative Example 1-1 and an oak extract water extract of Comparative Example 1-2 were mixed at a concentration of 5 / / The cells were treated with L-NAME and untreated groups for 30 minutes, washed twice with PBS, and treated with 10 μM of DAF-FM diacetate for 20 minutes. Next, the cell culture medium was removed, and the cells were fixed with a cell fixative (4% paraformaldehyde) for 5 minutes. Then, the medium was replaced with a medium without FBS to measure the fluorescence intensity of DAF-FM diacetate in each cell to 488 nm And the results are shown in Table 1 and FIG. 3.
(占 퐂 / ml)
50% ethanol extract
100% ethanol extract
Water extract
As shown in Table 1, it was found that the 50% ethanol extract of P. ogalis leaf of Example 1 had a higher NO production ability than the extracts of Comparative Example 1-1 and Comparative Example 1-2. From further experiments, it was confirmed that the NO production ability of the extract of Ischia japonica L., extracted with 30% to 90% ethanol, was similar to that of the extract of P. japonicus extracted with 50% ethanol.
3, fluorescence expression of DAF-FM diacetate was greatly increased in cells treated with the extract of Ischia japonica leaf extract, but only the control (L-NAME) (NOS inhibitors) NO production was not observed in one group.
EXPERIMENTAL EXAMPLE 5. Confirmation of monocyte adhesion inhibition effect [
It was confirmed that 50% ethanol extract of Ishigaki leaves inhibits the adhesion of monocyte which is involved in the early stage of atherosclerosis in vascular endothelial cells.
To this end, HUVEC cells were seeded at 5 × 10 4 cells per well on a 48-well plate to attach the cells to the plate. Then, 5 μg / ml to 20 μg / ml of 50% Ml < / RTI > for 12 hours. Subsequently, 10 ng / ml of TNF-alpha was treated with HUVEC for 12 hours, monocytes (U937 cells) labeled with a fluorescent substance (Calcein green) were attached to a 48 well plate with the HUVEC and co-cultured for 1 hour. After co-cultivation, the cell culture medium was removed, and the cells were washed with PBS (phosphatized buffered saline) and fixed with 1% paraformaldehyde. The cells were fixed with fluorescence microscope, and monocytes The degree of adhesion was confirmed, and the results are shown in FIG.
4, the increase in monocyte adhesion in the TNF-a treated group compared with the control (control) group, whereas the treatment with 50% ethanol extract of Ishigaki japonica markedly decreased the adherence of mononuclear cells in a concentration-dependent manner . Therefore, it is expected that the extract of Ishigaki japonica inhibits the adherence of mononuclear cells in vascular endothelial cells, and thus it is expected to exert an excellent effect of inhibiting vascular diseases such as arteriosclerosis.
<Experimental Example 6: Inhibitory effect of ICAM-1 and VCAM-1 on the expression of islet oak leaf extract>
A luciferase promoter assay was used to confirm that 50% of the extract of Ogakiri leaf inhibited ICAM-1 and VCAM-1 protein expression in vascular endothelial cells.
The promoter activities of ICAM-1 and VCAM-1 were confirmed by luciferase assays using the luciferase assay system kit (Promega). To this end, HUVEC cells were seeded on a plate at a density of 5 × 10 4 cells / well in a 48-well plate, and then 1 μg of ICAM-1 or VCAM-1 promoter-luciferase (VCAM-1 promoter luciferase and 0.2 μg of pCMV-β-galactosidase were transfected with Lipofectamine ™ 2000 (Lipofectamine ™ 2000). After 4 hours, the cell culture broth was replaced with FBS-free medium, and the 50% ethanol extract of the osmanthus leaf of Example 1, the 100% ethanol extract of the
(占 퐂 / ml)
50% ethanol extract
100% ethanol extract
Water extract
As shown in Table 2, the inhibitory activity of ICAM-1 expression was found to be superior to that of Comparative Example 1-1 and Comparative Example 1-2 in that the 50% ethanol extract of the oak leaf of Example 1 was superior to the extract of Comparative Example 1-1 and Comparative Example 1-2. In addition, it was confirmed that ICAM-1 expression inhibitory activity of islet leaf extract from 30% to 90% ethanol was similar to that of 50% ethanol extract.
5, it can be seen that the activity of ICAM-1 (FIG. 5A) and VCAM-1 (FIG. 5B) increased due to TNF-α treatment was decreased in a concentration- have.
≪ Formulation Example 1 >
Formulation Example 1-1. Manufacture of tablets
200 g of the extract of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. To this mixture was added a 10% gelatin solution, which was pulverized and passed through a 14-mesh sieve. This was dried, and a mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into tablets.
Formulation Example 1-2. Injection preparation
1 g of the extract of the present invention, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was placed in a bottle and sterilized by heating at 20 DEG C for 30 minutes.
<Formulation Example 2: Food Preparation>
Formulation Example 2-1. Manufacture of cooking seasonings
The safflower leaf extract of Example 1 of the present invention was added to the cooking seasoning at 1 wt% to prepare a cooking sauce for health promotion.
Formulation Example 2-2. Manufacture of flour food products
The oyster leaf extract of Example 1 of the present invention was added to wheat flour in an amount of 0.1 wt%, and bread, cake, cookies, crackers and noodles were prepared using the mixture to prepare a food for health promotion.
Preparation Example 2-3. Manufacture of soups and gravies
The health enhancing soup and the juice were prepared by adding 0.1% by weight to the soup and the juice of the eel of the present invention in Example 1.
Formulation Example 2-4. Manufacture of dairy products
The oyster leaf extract of Example 1 of the present invention was added to milk in an amount of 0.1 wt%, and various dairy products such as butter and ice cream were prepared using the milk.
Formulation Example 2-5. Vegetable juice manufacturing
The vegetable juice for health promotion was prepared by adding 0.5 g of the extract of the osmanthus sinensis extract of Example 1 of the present invention to 1,000 ml of tomato juice or carrot juice.
Formulation Example 2-6. Manufacture of fruit juice
The fruit juice for health promotion was prepared by adding 0.1 g of the extract of the oak leaf of Example 1 of the present invention to 1,000 ml of apple juice or grape juice.
Claims (12)
The composition for preventing or treating vascular diseases according to claim 1, wherein the extract is obtained by extracting an islet leaf with water, C1 to C4 alcohol or a mixed solution thereof.
Wherein the extract is obtained by extracting ethanol with ethanol, preferably 30% to 90% ethanol as a solvent.
The composition for preventing or treating vascular diseases according to any one of claims 1 to 3, wherein the extract of Ismailia japonica has an effect of activating endothelial nitric oxide synthase (eNOS) of vascular endothelial cells.
Wherein the vascular disease is a disease selected from atherosclerosis, peripheral vascular occlusion, vascular restenosis, hypertension, angina pectoris, myocardial infarction, ischemic heart disease, stroke, cerebral infarction and cerebral hemorrhage.
The pharmaceutical composition for preventing or treating vascular diseases according to any one of claims 1 to 3, wherein the extract of Ismailia japonica has an effect of activating endothelial nitric oxide synthase (eNOS) of vascular endothelial cells.
Wherein the vascular disease is a disease selected from atherosclerosis, peripheral vascular occlusion, vascular restenosis, hypertension, angina pectoris, myocardial infarction, ischemic heart disease, stroke, cerebral infarction and cerebral hemorrhage.
Wherein said extract is obtained by extracting islet leaves with water, C1 to C4 alcohol, or a mixed solution thereof as a solvent.
Wherein the vascular disease is a disease selected from atherosclerosis, peripheral vascular occlusion, vascular restenosis, hypertension, angina pectoris, myocardial infarction, ischemic heart disease, stroke, cerebral infarction and cerebral hemorrhage. .
Wherein the health functional food is selected from various foods, beverages, gums, tea and vitamin complex.
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| KR20210104974A (en) * | 2020-02-18 | 2021-08-26 | 삼육대학교산학협력단 | Composition Comprising the Extract of Acanthopanax koreanum for the Prevention or Treatment of Nicotine Addiction and Withdrawl Symptoms |
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| KR100684436B1 (en) | 2005-09-08 | 2007-02-16 | 주식회사 다원 | Composition comprising the extract of dioscorea quinqueloba and acanthopanax senticosus showing anti-oxidative, anti-aging by anti-lipidperoxidative, anti-inflammatory and discharge of phlegm activity |
| KR100793204B1 (en) | 2006-05-18 | 2008-01-10 | 동아대학교 산학협력단 | Pharmaceutical Composition for Treating or Preventing Coronary Heart Diseases or Arteriosclerosis Containing an Extract of Chinese Herb as an Effective Ingredient |
| KR20130009206A (en) * | 2011-07-14 | 2013-01-23 | 연세대학교 원주산학협력단 | Composition comprising the diethylstilbestrol for the prevention and treatment of cardiovascular disease |
| KR20130046115A (en) * | 2011-10-27 | 2013-05-07 | (주)아모레퍼시픽 | Composition for inhibition of vascular aging comprising syringaresinol |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20210104974A (en) * | 2020-02-18 | 2021-08-26 | 삼육대학교산학협력단 | Composition Comprising the Extract of Acanthopanax koreanum for the Prevention or Treatment of Nicotine Addiction and Withdrawl Symptoms |
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