Composition containing Elaeocarpus longipes for preventing or treating cardiovascular and metabolic diseases

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating cardiovascular and metabolic diseases, comprising as an active ingredient: an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom; and a method for using the same to prevent or treat cardiovascular and metabolic diseases. The composition comprising an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom inhibits the binding of resistin-CAP1 to suppress the production of tumor necrosis factor, thereby having the activity of inhibiting inflammation in the cardiovascular system, and thus can be effectively used for the prevention or treatment of cardiovascular and metabolic diseases.

Description

Technical field

[0001] The present invention relates to a pharmaceutical composition for preventing or treating cardiovascular and metabolic diseases, comprising as an active ingredient: an Elaeocarpus petiolatus extract, a fraction thereof, or a compound separated therefrom; and a method for preventing or treating cardiovascular and metabolic diseases using the pharmaceutical composition. [Background Technology]

[0002] Recent dietary diversity and changes in lifestyle often lead to unbalanced nutritional intake, while modern, mechanized lifestyles contribute to a lack of exercise. Consequently, disease patterns are shifting toward those typical of developed countries, and the incidence of cardiovascular and metabolic diseases is correspondingly increasing. Cardiovascular and metabolic diseases are disorders caused by metabolic imbalances in carbohydrates, lipids, and other substances in the body. Major cardiovascular and metabolic diseases include cardiovascular disease, dyslipidemia, obesity, and diabetes.

[0003] Cardiovascular disease, defined as conditions affecting the heart and major arteries, is the leading cause of death worldwide. Major cardiovascular diseases include hypertension, angina pectoris, myocardial infarction, arteriosclerosis, atherosclerosis, stroke, and arrhythmias. Risk factors associated with cardiovascular disease include age, gender, smoking, lack of exercise, and obesity. However, considering the recent rapid changes in Westernized diet and lifestyle, cholesterol accumulation in lipoproteins may be a prominent cause.

[0004] Atherosclerosis refers to a condition in which increased oil in the blood causes thickening of blood vessel walls, narrowing of the vessel interior, narrowing of the lumen, and decreased arterial elasticity due to thrombosis. Depending on the site of disease, it can be categorized as stroke, angina, myocardial infarction, and peripheral vascular disease (Insull et al., 2009. The American Journal of Medicine 122, S3-S14). Vascular abnormalities caused by atherosclerosis are a major cause of death, with an adult mortality rate of 50% in the United States and Japan and 35% in South Korea.

[0005] Atherosclerosis is the accumulation of fat and fibrous tissue on the inner walls of arteries, causing narrowing or blockage. When arteriosclerosis is mild, normal activities are not affected. However, when more than 50% to 70% of the coronary tissue is blocked by arteriosclerosis, arteriosclerotic heart disease may develop. In severe cases, cerebral or coronary arteries may rupture, leading to the development of cardiovascular diseases such as cerebrovascular disease and heart disease. It is well known that cerebral arteriosclerosis can lead to cerebral softening, while coronary atherosclerosis can cause angina pectoris, myocardial infarction, and other conditions. These conditions can also lead to hypertension, heart disease, and cerebral hemorrhage. Currently, various statin-based drugs, or HMG-CoA reductase inhibitors, have been developed as treatments for arteriosclerosis, but more effective therapies are still needed.

[0006] Dyslipidemia refers to a state in which the blood contains excessive lipids or fat components due to increased biosynthesis or decreased degradation of lipoproteins that transport cholesterol and triglycerides, resulting in increased total cholesterol, low-density lipoprotein cholesterol or triglycerides, or decreased HDL cholesterol in the blood.

[0007] Dyslipidemia can be caused by genetic factors, obesity, diabetes, or alcohol consumption, but a high-fat diet, in particular, can increase blood lipids and, therefore, may lead to dyslipidemia. Recently, alternative therapies have been developed using active ingredients extracted from natural products such as herbs and foods. However, natural pharmaceutical compositions or their raw materials that have superior therapeutic effects and fewer side effects than traditional synthetic pharmaceutical compositions have not yet been fully developed.

[0008] Obesity is known to lead to chronic diseases such as fatty liver disease, hypertension, diabetes, and cardiovascular disease. Xenical, an anti-obesity drug sold both in Korea and abroad, whose main ingredient is orlistat, has been approved by the US FDA. Xenical's lipase inhibition is known to cause gastrointestinal side effects such as fatty stools, gas production, and reduced absorption of fat-soluble vitamins.

[0009] Diabetes is divided into two types: insufficient insulin secretion (Type I) and impaired glucose metabolism due to insulin insensitivity (Type II). Type II diabetes is more common, accounting for 90% of all diabetic patients. Type II diabetes is non-insulin-dependent diabetes mellitus (NIDDM). To date, PPAR-γ activators, GLP-1 derivatives, DPP-IV inhibitors, PTP1B inhibitors, etc. have been developed as drugs to treat NIDDM. Each drug has known side effects, such as toxicity to the liver, kidneys, muscles, and heart, and weight gain.

[0010] In summary, it can be said that lowering blood lipid levels is important for eliminating the main causes of cardiovascular and metabolic diseases, and dietary therapy that suppresses high-fat diets, exercise therapy, and drug therapy are recommended as methods for lowering blood lipid levels. However, strict management and implementation of dietary therapy or exercise therapy are difficult, and the effects are often limited. As lipid-lowering agents that have been developed, drugs that lower cholesterol levels (such as bile acid binding resins, HMG-CoA reductase inhibitors, neomycin, etc.) and drugs that lower triglyceride levels (such as fibric acid derivatives, niacin, and fish oil, etc.) are used as therapeutic agents. However, these drugs have side effects such as hepatotoxicity, gastrointestinal disorders, and the occurrence of cancer.

[0011] Resistin is an inflammatory adipokine (Bokarewa et al., 2005. Journal of immunology 174, 5789-5795; Cho, Y et al., 2011. Journal of the American College of Cardiology 57, 99-109), which is known to induce re-esterification and lipolysis of triglyceride stores and increase cholesterol ester deposition in human macrophages in atherosclerosis (Rae et al., 2007. FEBS Letters 581, 4877-83).

[0012] Recently, it has been reported that resistin binds to CAP1 protein as its receptor and activates NF-κB, activating the cell signaling system to induce inflammation and promoting the secretion of inflammatory cytokines (such as TNF-α), thereby inducing inflammation (Lee S. et al., Cell Metabolism 2014, 19(3), 484-497). Therefore, compounds that inhibit resistin-CAP1 binding can be used to treat lifestyle diseases such as arteriosclerosis, diabetes, and especially cardiovascular and metabolic diseases.

[0013] In order to develop a drug for the treatment of cardiovascular and metabolic diseases that suppresses inflammation by inhibiting resistin-CAP1 binding, 100 natural materials with confirmed anti-inflammatory activity, which are stored at the Natural Materials Medicine Research Center of the Korea Institute of Biotechnology, were used as the target. Candidate substances with inhibitory effects on resistin-CAP1 binding and the production of tumor necrosis factor α (TNF-α), a resistin-induced inflammatory cytokine, in human monocytes were screened using enzyme immunoassay.

[0014] Elaeocarpus petiolatus, a plant of the family Elaeocarpaceae, which exhibits excellent resistin-CAP1 inhibitory effects, is primarily found in tropical, warm, and temperate zones. Elaeocarpus sphaericus, a species of the same genus, has been reported to improve dry skin and wrinkles with anti-wrinkle agents and topical skin preparations, as well as its anti-inflammatory effects on carrageenan-induced inflammation in rats (Singh H et al., J Pharmacol Toxicol Methods. 2000 May-Jun; 43(3): 219-24). Although the antiviral effects of Elaeocarpus bifidus have been reported in the United States, studies on the effects of this plant on cardiovascular and metabolic diseases have not yet been conducted. [Summary of the invention]

[0015]

Technical Issues

[0016] Therefore, the present researchers confirmed that extracts and fractions of Elaeocarpus petiolatus and single compounds isolated therefrom inhibit resistin-CAP1, thereby reducing inflammatory responses and showing effects on cardiovascular and metabolic diseases, thereby completing the present invention.

[0017]

Technical solution

[0018] An object of the present invention is to provide a pharmaceutical composition for preventing or treating cardiovascular and metabolic diseases, comprising as an active ingredient: an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom.

[0019] Another object of the present invention is to provide a method for preventing or treating cardiovascular and metabolic diseases, which comprises administering the composition to a subject.

[0020]

Beneficial effects

[0021] The composition of the present invention comprising an Elaeocarpus petiolatus extract, its fractions or compounds separated therefrom inhibits the binding of resistin-CAP1 and the production of tumor necrosis factor, thereby having the activity of inhibiting inflammation of the cardiovascular system and can therefore be effectively used for the prevention or treatment of cardiovascular and metabolic diseases.

[0022] [Brief Description of the Figures]

[0023] Figure 1UPLC-QTOF-MS chromatograms of the Elaeocarpus petiolatus leaf extract and solvent fraction.

[0024] Figure 2a Schematic diagram of fractionating butanol and aqueous layers of Elaeocarpus petiolatus leaves using a chromatographic column.

[0025] Figure 2b It is a chromatogram of each fraction obtained by fractionating the butanol and aqueous layers of Elaeocarpus petiolatus leaves using a chromatographic column.

[0026] Figure 3 The chromatograms of each fraction obtained by column fractionation of butanol and aqueous layers of Elaeocarpus petiolatus leaves collected in large quantities.

[0027] Figure 4a Schematic diagram of the isolation of single components from the butanol and aqueous layers of bulk-collected Elaeocarpus petiolatus leaves.

[0028] Figure 4b Chromatograms of single components isolated from the butanol and aqueous layers of bulk-collected Elaeocarpus petiolatus leaves.

[0029] Figure 5a The inhibitory activity of the Elaeocarpus petiolatus leaf extract and solvent fraction on resistin-CAP1 binding is shown.

[0030] Figure 5b Shown are the inhibitory activities of column fractions obtained from butanol and aqueous layers of Elaeocarpus petiolatus leaves on resistin-CAP1 binding.

[0031] Figure 5c The inhibitory activity of single fractions isolated from the butanol and aqueous fractions of bulk-collected Elaeocarpus petiolatus leaves on resistin-CAP1 binding is shown.

[0032] Figure 6a Schematic diagram of the method for determining the inhibitory effect of Elaeocarpus petiolatus in cardiovascular and metabolic disease models using resistin mice.

[0033] Figure 6bThe plaque-inhibiting effect of Elaeocarpus petiolatus in a cardiovascular and metabolic disease model using resistin mice.

[0034] Figure 6c The effect of Elaeocarpus petiolatus on blood lipids was analyzed in a cardiovascular and metabolic disease model using resistin mice.

[0035] Figure 6d Shown are the changes in body weight of the Elaeocarpus petiolatus-treated group in resistin mice.

[0036] Figure 7a These are the chromatograms of Elaeocarpus petiolatus and Elaeocarpus ganitrus samples.

[0037] Figure 7b The inhibitory activities of Elaeocarpus petiolatus and Elaeocarpus ganitrus samples on resistin-induced TNF-α production in THP-1 cells were compared.

[0038] Figure 8 The inhibitory activities of compounds derived from Elaeocarpus petiolatus and their parent compound on TNF-α production were compared.

[0039] [Detailed description of preferred embodiments]

[0040] The present invention will be described in detail below. At the same time, each description and embodiment disclosed herein can be applied to other descriptions and embodiments, respectively. In other words, all combinations of the various elements disclosed herein fall within the scope of the present invention. In addition, the scope of the present invention is not limited by the specific description described below.

[0041] One aspect of the present invention to achieve the above object provides a pharmaceutical composition for preventing or treating cardiovascular and metabolic diseases, which comprises as an active ingredient: an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom.

[0042] In the present invention, the inhibitory effect of the Elaeocarpus petiolatus extract, its fractions or compounds separated therefrom on resistin-CAP1 binding that leads to the onset or aggravation of cardiovascular and metabolic diseases and on the inflammatory response were confirmed, thereby confirming that the Elaeocarpus petiolatus extract, its fractions or compounds separated therefrom can be effectively used to prevent, improve or treat cardiovascular and metabolic diseases.

[0043] As used herein, the term "Elaeocarpus petiolatus" belongs to the genus Elaeocarpus and is an evergreen tree and shrub native to tropical and subtropical regions, widely distributed in India, Malaysia, southern China, Japan, Australia, New Zealand, Fiji, Hawaii, and the like. It is well known that Elaeocarpus petiolatus has antioxidant and anti-inflammatory effects, but its role in cardiovascular and metabolic diseases has been unclear and has been identified for the first time by the present inventors.

[0044] The leaves, stems, flowers, roots or a combination thereof of Elaeocarpus petiolatus may be used, and preferably the leaves of Elaeocarpus petiolatus are used, but the invention is not limited thereto.

[0045] Elaeocarpus petiolatus can be purchased commercially, harvested naturally, or cultivated.

[0046] The origin or growth place of Elaeocarpus petiolatus may be China, Vietnam, Malaysia and other countries, but not limited thereto.

[0047] Furthermore, in one embodiment of the present invention, when comparing the inhibitory effects of Elaeocarpus petiolatus and Elaeocarpus ganitrus, both belonging to the genus Elaeocarpus, on TNF-α production, no inhibitory effect on TNF-α production was observed in the case of treatment with the extract of Elaeocarpus ganitrus, whereas a concentration-dependent inhibitory effect on TNF-α production was confirmed after treatment with the extract of Elaeocarpus petiolatus ( Figure 7bFurthermore, the results of the study confirmed that among the plants of the genus Elaeocarpus, especially Elaeocarpus petiolatus, could be used to treat cardiovascular and metabolic diseases due to its inhibitory activity against resistin-CAP1.

[0048] As used herein, the term "extract" includes an extract obtained by extracting Elaeocarpus petiolatus, a diluted or concentrated extract, a dried product obtained by drying the extract, a crude or purified product of the extract, or a mixture thereof, as well as the extract itself and extracts in all dosage forms that can be formed using the extract.

[0049] The extraction method of Elaeocarpus petiolatus is not particularly limited and can be extracted according to conventional methods in the art. Non-limiting examples of extraction methods include hot water extraction, ultrasonic extraction, filtration, reflux extraction, etc. These methods can be performed alone or in combination with two or more methods.

[0050] In the present invention, the type of extraction solvent used to extract Elaeocarpus petiolatus is not particularly limited, and any solvent known in the art may be used.

[0051] Non-limiting examples of the extraction solvent may include water, alcohols having 1 to 4 carbon atoms, or mixed solvents thereof, which may be used alone or in combination. Specifically, a mixed solvent of ethanol and water may be used, and the ethanol may be 10% to 100% (v / v), but is not limited thereto.

[0052] In the present invention, the Elaeocarpus petiolatus extract may be an ethanol aqueous solution extract of Elaeocarpus petiolatus leaves.

[0053] In a specific embodiment of the present invention, the inhibitory activity of the extract of Elaeocarpus petiolatus on resistin-CAP1 binding was confirmed ( Figure 5a ) and confirmed its inhibitory effect on resistin-induced TNF-α production ( Figure 7b ).

[0054] The above results indicate that the extract of Elaeocarpus petiolatus can be used to treat cardiovascular and metabolic diseases.

[0055] As used herein, the term "fraction" refers to a product obtained by separating a specific component or a specific group of components from a mixture containing various components by performing fractionation.

[0056] In the present invention, the fractionation method for obtaining the fractions of Elaeocarpus petiolatus is not particularly limited and can be performed according to methods commonly used in the art. Non-limiting examples of fractionation methods can include solvent fractionation methods performed by treating various solvents, ultrafiltration fractionation methods performed by passing through an ultrafiltration membrane with a constant molecular weight cutoff value, chromatographic fractionation methods that perform various forms of chromatography (separation based on size, charge, hydrophobicity or affinity), and combinations thereof. Specifically, it can be a method for obtaining fractions from an extract obtained by extracting Elaeocarpus petiolatus by treating it with a predetermined solvent.

[0057] In the present invention, the type of solvent used to obtain the fraction is not particularly limited, and any solvent known in the art can be used.

[0058] Non-limiting examples of fractionation solvents may include polar solvents such as water, alcohols having 1 to 4 carbon atoms, etc.; non-polar solvents such as hexane, ethyl acetate, etc.; or mixed solvents thereof. These may be used alone or in combination of one or more, but are not limited thereto.

[0059] Specifically, the fractionation solvent may be any one or more selected from hexane, chloroform (CHCl 3 ), ethyl acetate (EA), butanol (BuOH) and water (DW), more specifically, butanol and water.

[0060] Furthermore, the extract or fraction may be prepared and used in the form of a dry powder after extraction, but is not limited thereto.

[0061] In one embodiment of the present invention, the inhibitory activity of the solvent fraction of Elaeocarpus petiolatus on resistin-CAP1 binding was confirmed, and in particular, the butanol and aqueous fractions thereof were found to have excellent inhibitory effects on resistin-CAP1 binding ( Figure 5a ). In addition, the inhibitory activity of column fractions 1 to 12 obtained by column fractionation of butanol and the aqueous layer in the solvent fraction on resistin-CAP1 binding was confirmed, and in particular, column fractions 7 to 12 were confirmed to show good effects ( Figure 5b ).

[0062] In a specific embodiment of the present invention, in cardiovascular and metabolic disease models ( Figure 6b) confirmed the plaque inhibitory effect of the butanol and aqueous fractions of Elaeocarpus petiolatus, and confirmed its effect of lowering triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in the blood and increasing high-density lipoprotein cholesterol (HDL-C) in the blood ( Figure 6c ).

[0063] In another embodiment of the present invention, the inhibitory effects of butanol and aqueous fractions of Elaeocarpus petiolatus on resistin-induced TNF-α production were confirmed ( Figure 7b ).

[0064] The above results demonstrate that fractions of Elaeocarpus petiolatus can be used to treat cardiovascular and metabolic diseases.

[0065] As used herein, the term "compound isolated from Elaeocarpus petiolatus" refers to a single compound or substance isolated from Elaeocarpus petiolatus, which can be obtained by conventional methods. Specifically, the single compound can be obtained from an extract or fraction of Elaeocarpus petiolatus, and preferably, can be obtained from a fraction using butanol and water as a fractionation solvent, but is not limited thereto.

[0066] In particular, the extract or fraction of Elaeocarpus petiolatus may be an extract or fraction obtained from the leaves of Elaeocarpus petiolatus.

[0067] The isolated compound may be methyl gallate-O-hexoside, myricetin-3-O-α-L-rhamnoside, ellagic acid, isorhamnetin-3-O-β-D-hexoside or gallic acid, but is not limited thereto.

[0068] In one embodiment of the present invention, the inhibitory effect of compounds isolated from the butanol and aqueous layers of a large number of Elaeocarpus petiolatus leaves on resistin-CAP1 binding was confirmed ( Figure 5c ).

[0069] Based on the above results, it was confirmed that the compounds isolated from Elaeocarpus petiolatus can be used to treat cardiovascular and metabolic diseases.

[0070] The term "cardiovascular and metabolic diseases" as used herein refers to diseases caused by metabolic imbalances of carbohydrates, lipids, etc. in the body, and may include but are not limited to cardiovascular diseases and metabolic diseases.

[0071] Cardiovascular disease refers to conditions that affect the heart and major arteries. Major cardiovascular diseases include hypertension, angina pectoris, myocardial infarction, arteriosclerosis, atherosclerosis, stroke, and arrhythmias. Cholesterol accumulation in blood vessels (increases in total cholesterol, low-density lipoprotein cholesterol, and triglycerides, and decreases in high-density lipoprotein cholesterol) is one of the main causes of cardiovascular disease.

[0072] The term "metabolic disease" is not particularly limited, but may include metabolic diseases caused by abnormal glucose metabolism or abnormal lipid metabolism. Specifically, as used herein, "metabolic diseases caused by abnormal carbohydrate metabolism" refers to diseases caused by an imbalance in the body's carbohydrate metabolism process, and is not particularly limited thereto, but may include diabetes, prediabetes, type II diabetes, etc. Specifically, metabolic diseases caused by abnormal lipid metabolism refer to diseases caused by an imbalance in the body's lipid metabolism process, and are not particularly limited thereto, and may also include cardiovascular disease, dyslipidemia, obesity, etc.

[0073] The term "atherosclerosis" as used herein refers to a disease in which blood vessels are narrowed or occluded, resulting in poor peripheral blood circulation. Arteriosclerosis may include, but is not limited to, coronary atherosclerosis and arteriosclerosis. Resistin is an adipose factor that induces inflammation. In arteriosclerosis, it induces the storage of triglycerides and increases the deposition of cholesterol esters through re-esterification and lipolysis in human macrophages. In addition, it has recently been known that inflammation is caused by activating the cell signaling system by binding to the CAP1 protein (the receptor for resistin) and activating NF-κB, thereby promoting the secretion of inflammatory cytokines (such as TNF-α). Therefore, inhibiting resistin-CAP1 binding may play an important role in the prevention or treatment of atherosclerosis.

[0074] In a specific embodiment of the present invention, the effect on cardiovascular and metabolic diseases (such as arteriosclerosis) is confirmed by reducing atherosclerotic plaques, and the therapeutic effect on cardiovascular and metabolic diseases is confirmed by confirming the effects of lowering triglycerides and low-density lipoprotein cholesterol and increasing high-density lipoprotein-cholesterol.

[0075] As used herein, the term "dyslipidemia" refers to a state in which total cholesterol, LDL cholesterol, or triglycerides in the blood are elevated, or a state in which HDL cholesterol is decreased. Specific examples include, but are not limited to, hyperlipidemia, hypercholesterolemia, or hypertriglyceridemia.

[0076] In a specific embodiment of the present invention, the pharmaceutical composition is confirmed to have an effect on dyslipidemia by demonstrating the effects of reducing triglycerides, low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol.

[0077] In addition, a weight loss effect has been demonstrated, thereby also demonstrating a preventive effect on obesity caused by cardiovascular and metabolic diseases.

[0078] In the present invention, a composition comprising an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom as an active ingredient can be a composition that inhibits resistin-CAP1 binding. The Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom has the effect of inhibiting resistin-CAP1 binding, which can induce the onset or aggravation of cardiovascular and metabolic diseases, and exhibits the effects of inhibiting NF-κB activity and TNF-α production, and thus can be used to prevent or treat cardiovascular and metabolic diseases.

[0079] As used herein, the term "treatment" refers to any action of administering a composition comprising an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom to inhibit or delay the onset of cardiovascular and metabolic diseases.

[0080] As used herein, the term "prevention" refers to any action of administering a composition comprising an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom to improve or beneficially alter symptoms caused by cardiovascular and metabolic diseases.

[0081] In one embodiment of the present invention, it was confirmed that the extract, fraction or compound isolated therefrom of Elaeocarpus petiolatus can inhibit the binding of resistin-CAP1 ( Figure 5c ), and its inhibitory effect on the production of cytokine TNF-α was also confirmed (Table 3).

[0082] Furthermore, by confirming the inhibitory effect of a sample showing resistin-CAP1 inhibitory activity on resistin-induced TNF-α, it can be confirmed that the inhibition of TNF-α production is due to the inhibition of resistin-CAP1 binding.

[0083] In addition, in another embodiment, the inhibitory effect on cardiovascular and metabolic diseases was confirmed by confirming that the TG and LDL levels in the blood were reduced and the HDL level was increased in a cardiovascular and metabolic disease mouse model (resistin mouse). Figure 6c ).

[0084] That is, by confirming the effect of the Elaeocarpus petiolatus extract, its fractions or compounds separated therefrom in inhibiting the secretion of inflammatory cytokines (such as TNF-α) by inhibiting the binding of resistin CAP, it is suggested that the composition of the present invention comprising the Elaeocarpus petiolatus extract, its fractions or compounds separated therefrom can be effectively used to prevent or treat cardiovascular and metabolic diseases.

[0085] The pharmaceutical composition of the present invention may contain 0.1 μg / mL to 1000 μg / mL, specifically 0.1 μg / mL to 200 μg / mL, 0.1 μg / mL to 100 μg / mL of the Elaeocarpus petiolatus extract and fraction, based on the total weight of the composition, but is not limited thereto.

[0086] The pharmaceutical composition of the present invention may contain 0.1 μg / mL to 1000 μg / mL, specifically 0.1 μg / mL to 20 μg / mL of the compound isolated from Elaeocarpus petiolatus, based on the total weight of the composition, but is not limited thereto.

[0087] In addition, the pharmaceutical composition may further contain pharmaceutically acceptable carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions, and the carrier may include a non-naturally occurring carrier. Specific examples of carriers, excipients and diluents include lactose, glucose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum arabic, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, talc, magnesium stearate or mineral oil, but are not limited thereto.

[0088] In addition, the pharmaceutical composition of the present invention can be formulated into any one of the following preparations according to conventional methods: tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized agents, and suppositories, and can be in the form of various oral or parenteral preparations. In the case of formulation, the preparation is prepared using diluents or excipients, such as commonly used fillers, bulking agents, binders, wetting agents, disintegrants, and surfactants. Oral solid preparations include tablets, pills, powders, granules, capsules, etc., which are prepared using at least one or more excipients (such as starch, calcium carbonate, sucrose, lactose, or gelatin). In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Oral liquid preparations include suspensions, internal solutions, emulsions, syrups, etc., and in addition to water and liquid paraffin as commonly used simple diluents, they may also contain various excipients such as wetting agents, sweeteners, spices, and preservatives. Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, or suppositories. Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils (e.g., olive oil), injectable esters (e.g., ethyl oleate), and the like. Suppository bases include, but are not limited to, Witepsol, Macrogol, Tween 61, cocoa butter, laurel fat, and glycerin gelatin.

[0089] Another aspect of the present invention provides a method for preventing or treating cardiovascular and metabolic diseases, comprising administering the composition to a subject.

[0090] At this time, the definitions of “cardiovascular and metabolic diseases,” “prevention,” and “treatment” remain the same as above.

[0091] As used herein, the term "administering" refers to introducing a pharmaceutical composition into a subject by an appropriate method.

[0092] As used herein, the term "subject" refers to all animals that have developed or may develop cardiovascular and metabolic diseases, including humans, rats, mice, livestock, etc. Animals include not only humans, but also mammals that need to treat similar symptoms, such as cattle, horses, sheep, pigs, goats, camels, antelopes, dogs, cats, etc., but are not limited thereto.

[0093] The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount.

[0094] The term "pharmaceutically effective amount" refers to an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to any medical treatment. The effective dose can be determined based on factors including the type and severity of the condition, age, sex, drug activity, drug sensitivity, time of administration, route of administration and excretion rate, duration of treatment, other drugs used concurrently, and other factors well known in the medical field.

[0095] The pharmaceutical composition can be administered as a single therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents. In addition, the pharmaceutical composition can be administered once or multiple times. Taking all of the above factors into account, it is important that the dosage be such that the maximum effect is achieved with the minimum amount without side effects, which can be easily determined by those skilled in the art.

[0096] In addition, oral or parenteral administration (e.g., intravenous administration, subcutaneous administration, intraperitoneal administration or topical administration) can be performed according to the desired method. The dosage can be varied according to the patient's condition and body weight, the severity of the disease, the pharmaceutical form, and the route and time of administration, but can be appropriately selected by those skilled in the art. In a specific embodiment, the pharmaceutical composition can be administered once a day or several times, and those skilled in the art can appropriately select the preferred dosage according to the subject's condition and body weight, the severity of the disease, the pharmaceutical form, and the route and duration of administration.

[0097] At this time, the definitions of "Elaeocarpus petiolatus", "extract", "fraction", "isolated compound", "cardiovascular and metabolic diseases" and "prevention" are as described above.

[0098] As used herein, the term "ameliorate" may refer to all actions that reduce a parameter associated with the condition to be treated, for example, reducing the extent of symptoms.

[0099] As used herein, the term "food" includes meat, sausage, bread, chocolate, candy, snacks, candy, pizza, ramen, other noodles, chewing gum, dairy products (including ice cream), various soups, beverages, tea, beverages, alcoholic beverages, vitamin complexes, health functional foods, health foods, etc., and includes all foods in the traditional sense.

[0100] Health functional foods and foods for special health purposes (FoSHU) are the same term, which refers to foods that have been processed and can effectively play a biological regulatory function in addition to providing nutrition, and have high medical and therapeutic effects.

[0101] Here, "functionality" refers to achieving a useful effect for health purposes, such as regulating the physiological effects of nutrients or the structure and function of the human body. Health foods are foods that have a positive health or promoting effect compared to conventional foods, while health supplement foods are foods intended for health. In some cases, the terms health functional foods, health foods, and health supplement foods are used interchangeably.

[0102] Specifically, health functional foods refer to foods produced by adding Elaeocarpus petiolatus extracts, fractions thereof, or compounds isolated therefrom to food ingredients such as beverages, teas, spices, chewing gum, and candies, or by encapsulating, powdering, or suspending them, which have specific effects on health when ingested, and because foods are used as raw materials, unlike ordinary drugs, they have the advantage of being free of side effects that may occur during long-term drug use.

[0103] Another aspect of the present invention to achieve these objects provides a quasi-drug for preventing or improving cardiovascular and metabolic diseases, comprising as an active ingredient: an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom.

[0104] The definitions of "Elaeocarpus petiolatus", "extract", "fraction", "isolated compound", "cardiovascular and metabolic diseases" and "prevention" are as described above.

[0105] As used herein, the term "quasi-drug" may be defined as products other than apparatus, machines, and devices intended for use in the diagnosis, medical care, mitigation, treatment, or prevention of disease in humans or animals, and products other than apparatus for use in machines or devices intended to produce a pharmacological effect on the structure or function of humans or animals.

[0106] In the present invention, the quasi-drug composition may have the effect of preventing or improving cardiovascular diseases, but is not limited thereto.

[0107] In addition to the aforementioned ingredients, the quasi-drug composition of the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent, if necessary. The pharmaceutically acceptable carrier, excipient, or diluent is not limited, as long as it does not impair the effects of the present invention, and may include, for example, fillers, extenders, binders, wetting agents, disintegrants, surfactants, lubricants, sweeteners, flavorings, preservatives, and the like.

[0108] As used herein, the term "pharmaceutically acceptable carrier" refers to a carrier, excipient, or diluent that does not cause irritation to an organism and does not abrogate the biological activity and properties of the administered compound, and specifically may be a non-natural carrier. The types of carriers that can be used in the present invention are not particularly limited, and any carriers and pharmaceutically acceptable carriers commonly used in the art can be used. Non-limiting examples of carriers include saline solutions, sterile water, Ringer's solution, buffered saline solutions, albumin injection solutions, glucose solutions, maltodextrin solutions, glycerol, ethanol, and the like, which can be used alone or in mixtures of two or more thereof.

[0109] The composition containing a pharmaceutically acceptable carrier can be various oral or parenteral preparations, preferably oral preparations, but not limited thereto. When formulated, a diluent or excipient is used to formulate the pharmaceutical composition, which includes fillers, fillers, adhesives, wetting agents, disintegrants, surfactants, etc. commonly used in the art. Specifically, solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations can be prepared by mixing at least one compound with one or more excipients (such as starch, calcium carbonate, sucrose, lactose, gelatin, etc.). In addition to simple excipients, lubricants such as magnesium stearate and talc can also be used. Oral liquid preparations include suspensions, inner solutions, emulsions, syrups, etc., and in addition to water and liquid paraffin as commonly used simple diluents, they may also contain various excipients such as wetting agents, sweeteners, spices, and preservatives. Parenteral preparations include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. As non-aqueous solvents and suspending agents, propylene glycol, polyethylene glycol, vegetable oils (such as olive oil), injectable esters (such as ethyl oleate), etc. can be used. As the base of suppositories, Witepsol, Macrogol, Tween 61, cocoa butter, laurel fat, glycerin gelatin, etc. can be used.

[0110] Examples of the quasi-drug composition of the present invention include, but are not limited to, disinfectant detergents, shower foams, ointments, wet wipes, coatings, etc. The formulation method, dosage, method of use, quasi-drug ingredients, etc. can be appropriately selected from conventional techniques known in the art.

[0111] Another aspect of the present invention to achieve the above object provides a composition for preventing, improving or treating cardiovascular and metabolic diseases, wherein the composition comprises as an active ingredient: an Elaeocarpus petiolatus extract, a fraction thereof or a compound isolated therefrom.

[0112] The definitions of "Elaeocarpus petiolatus", "extract", "fraction", "isolated compound", "cardiovascular and metabolic diseases" and "prevention" are as described above.

[0113] Another aspect of the present invention to achieve the above object provides use of a composition for preparing a medicament for preventing or treating cardiovascular and metabolic diseases, wherein the composition comprises as an active ingredient: an Elaeocarpus petiolatus extract, a fraction thereof, or a compound isolated therefrom.

[0114] Another aspect of the present invention to achieve these objectives provides use of a composition for preparing a quasi-drug for improving, preventing or treating cardiovascular disease, the composition comprising as an active ingredient: an Elaeocarpus petiolatus extract, a fraction thereof or a compound isolated therefrom.

[0115] [Implementation Methods of the Invention]

[0116] The following will describe the composition and effects of the present invention in detail through embodiments and experimental examples. However, these embodiments and experimental examples are given only for illustrative purposes, and the scope of the present invention is not limited by these embodiments and experimental examples.

[0117] Example 1: Preparation and UPLC Analysis of Solvent Fractions from Elaeocarpus petiolatus

[0118] 234.1 g of an ethanol-water extract from the leaves of Elaeocarpus petiolatus was fractionated using a bioactivity fractionation method into a hexane (40.3 g) layer, a chloroform (CHCl3, 11.9 g) layer, an ethyl acetate (EA, 18.9 g) layer, a butanol (BuOH, 45.9 g) layer, and a water (DW, 95.0 g) layer, yielding a total of five fractions. Qualitative analysis of the active index substances in the Elaeocarpus petiolatus leaf extract (extraction solvent: 95% ethanol) was performed using an ACQUITY UPLC Ultra Performance instrument equipped with a BEHC18 (2.1 mm × 100 mm, 1.7 mm) column and a PDA detector (200-600 nm, max plot) at a flow rate of 0.4 mL / min using distilled water containing 0.1% formic acid and acetonitrile (see Tables 1 and 2). Figure 1 ).

[0119] Table 1: UPLC-PDA-QTOF-MS conditions for Elaeocarpus petiolatus leaf extract

[0120]

[0121] Example 2: Isolation and Analysis of Pure Substances from Elaeocarpus petiolatus Leaf Extract Using UPLC

[0122] MPLC was used to prepare the active fractions (BuOH and water layers) from the fractions obtained in Example 1, and then bioassay-guided fractionation was performed to isolate the substance exhibiting physiological activity. The butanol and water (DW) layers were loaded into a 2 cm × 25 cm column tube filled with 10 nM YMC Pack ODS AQ-HG in a SPOTPREP II 250 (MPLC, Armen) instrument. Column chromatography was performed using a MeOH-H2O mixed solvent (0-100% for 0-60 min; 100% for 60-90 min) as the mobile phase while gradually increasing the MeOH ratio and using a UV detector (254 nM). A total of 12 bioactive column fractions (Fr. 1 to 12) were obtained by bioassay-guided fractionation ( Figure 2a and 2b ).

[0123] In addition, in order to isolate a single substance, a large amount of Elaeocarpus petiolatus leaves were collected to obtain a butanol layer (BuOH) and a water layer (DW), which were then separated into 7 fractions by chromatography columns and analyzed by HPLC ( Figure 3 ). Based on this, through Figure 4a The single substances separated were 6 types of compounds. The names of the compounds were determined by spectral data (Table 2). The chromatograms of the separated compounds are shown in Table 2. Figure 4b shown.

[0124] Table 2: Spectral data of six compounds isolated from the BuOH and DW layers of Elaeocarpus petiolatus collected in large quantities

[0125]

[0126] [Example 3: Resistin-CAP1 binding inhibitory activity (Resistin-CAP1 competitive binding assay)]

[0127] To determine whether Elaeocarpus petiolatus leaf extracts and fractions directly inhibit resistin-CAP1 binding, extract and fraction samples were validated using an enzyme immunoassay.

[0128] Recombinant CAP-1 protein is attached to the plate overnight for immunoassays. After washing, the attachment of other proteins is blocked with a 1% BSA / PBS solution, and recombinant resistin attached to the mouse Fc is pre-reacted with the sample for one hour. The solution is then dispensed onto the plate and allowed to react at room temperature for two hours. After washing the plate, HRP attached to the mFc of resistin bound to CAP-1 is dispensed and allowed to react for one hour. After washing, substrate is dispensed and allowed to react with HRP for 30 minutes. The absorbance at 450 nm is measured using a microplate reader.

[0129] The absorbance of the group in which mFc-resistin bound to CAP-1 was set as 100%, and the inhibition rate of the compound on resistin-CAP1 binding was calculated.

[0130] The results showed that the extract of Elaeocarpus petiolatus had an excellent inhibitory effect on resistin-CAP1 binding ( Figure 5a ).

[0131] Furthermore, it was confirmed that among the solvent fractions of Elaeocarpus petiolatus, butanol and water layers had the best inhibitory effects on resistin-CAP1 binding ( Figure 5a ).

[0132] When the bioactive column fractions of the butanol and aqueous layers were used as samples, it was confirmed that the column fractions corresponding to the 7th to 12th column fractions among the 13 column fractions showed a strong resistin-CAP1 binding inhibitory effect ( Figure 5b ).

[0133] Furthermore, single compounds isolated from the butanol and aqueous fractions by collecting a large amount of Elaeocarpus petiolatus leaves also showed resistin-CAP1 binding inhibitory activity, and it was confirmed that concentration-dependent resistin-CAP1 binding inhibitory effects were observed in all single compounds of methyl gallate-O-hexoside (2C, 2D), myricetin-3-O-α-L-rhamnoside (5E2), ellagic acid (6D), or isorhamnetin-3-O-β-D-hexoside (6E) ( Figure 5c ).

[0134] Thus, the resistin-CAP1 binding inhibitory effects of Elaeocarpus petiolatus extracts, fractions and single compounds isolated therefrom were confirmed.

[0135] [Example 4: Cytokine production inhibitory activity]

[0136] To examine the inhibitory effects of extracts, fractions, and single compounds isolated from Elaeocarpus petiolatus on inflammation induced by resistin-CAP1 binding, a TNF-α assay was performed.

[0137] THP-1 cells (human monocytes) were cultured in RPMI (Welgene, Korea) medium supplemented with 10% fetal bovine serum (FBS), and the inhibitory rate of the samples on resistin-induced TNF-α production was determined. THP-1 cells were plated at 5×10 5 The cells were suspended at a concentration of 100 cells / mL and inoculated in a 96-well plate at 100 μL, and each sample was then treated at a concentration of 5 μM. After 1 hour of culture, 2 μg / mL of human recombinant resistin (Biovision) was treated and further cultured for 6 hours. Thereafter, the supernatant was recovered and stored at -70°C.

[0138] For TNF-α detection, analysis was performed using a human TNF-α ELISA kit (BD bioscience) according to the manufacturer's protocol.

[0139] The results of Example 3 were determined. Figure 5b Among the 12 butanol and aqueous column fractions of Elaeocarpus petiolatus that showed inhibitory activity against resistin-CAP1 binding, fractions 7 to 12 showed particularly superior inhibitory activity against resistin-induced TNF-α (Table 3).

[0140] Therefore, as shown in Table 3, when treated at a concentration of 10 μg / mL, all fractions showed an inhibitory effect of 50% or more.

[0141] In addition, the inhibitory effects of single compounds isolated from the butanol and aqueous layers of Elaeocarpus petiolatus collected in large quantities on resistin-induced TNF-α were confirmed. All three compounds (myricetin-3-O-α-L-rhamnoside, ellagic acid, and isorhamnetin-3-O-β-D-hexoside) were shown to inhibit TNF-α production (Table 4).

[0142] These results demonstrate that extracts, fractions, and single compounds isolated from Elaeocarpus petiolatus inhibit TNF-α activity by inhibiting resistin-CAP1 binding.

[0143] Table 3: Inhibitory effects of butanol and aqueous column fractions of Elaeocarpus petiolatus on TNF-α

[0144] Sample name μg / mL RETN TNF-α inhibition rate (%, mean ± standard deviation) Butanol + water layer 10 + 61.52±4.40 Fr.7 10 + 76.48±1.98 Fr.8 10 + 83.85±4.01 Fr.9 10 + 84.23±2.60 Fr.10 10 + 73.76±6.84 Fr.11 10 + 79.20±0.51 Fr.12 10 + 70.19±1.51

[0145] Table 4: Inhibitory effects of compounds isolated from Elaeocarpus petiolatus on TNF-α

[0146]

[0147]

[0148] [Example 5: Cell viability study]

[0149] In order to confirm the effects of Elaeocarpus petiolatus extracts and compound samples isolated therefrom on cell viability, THP-1 cells were cultured at a rate of 1×10 5 Cells were suspended at a concentration of 100 cells / mL and inoculated into 96-well plates at 100 μL each. After 1 hour, each sample was treated with a concentration of 5 μM. After 24 hours of incubation, 5 μL of CytoX (Korean LPS solution) solution was added to each well and incubated for a further 4 hours. Then, the absorbance at 450 nm was measured. The value of the negative control group treated with DMSO was set to 100%, and the cell survival rate was calculated according to the following mathematical formula.

[0150] The results confirmed that when used at a concentration of 10 μg / mL, the butanol and aqueous layer fractions of Elaeocarpus petiolatus and column fractions 7 to 12 of the 12 column fractions of butanol and aqueous layers, which had excellent resistin-CAP1 binding inhibition effects, did not affect cell viability (Table 5).

[0151] Table 5: Effects of butanol and aqueous column fractions on cell viability of Elaeocarpus petiolatus

[0152] Sample name μg / mL Survival rate (%, mean ± standard deviation) comparison 0 100.00±3.86 BuOH+DW 10 101.62±3.15 Fr.7 10 104.17±6.51 Fr.8 10 106.07±7.45 Fr.9 10 102.85±6.06 Fr.10 10 99.36±3.27 Fr.11 10 101.70±3.67 Fr.12 10 99.33±3.08

[0153] In addition, by examining the effects of single compounds isolated from the butanol and aqueous layers of a large amount of Elaeocarpus petiolatus collected on the viability of THP-1 cells, as shown in Table 6, it was confirmed that when used at a concentration of 2.5 to 20 μg / mL, they did not significantly affect cell viability (Table 6).

[0154] Table 6: Effects of compounds isolated from Elaeocarpus petiolatus on cell viability

[0155]

[0156]

[0157] [Example 6: Inhibitory Effects of Elaeocarpus petiolatus on Cardiovascular and Metabolic Diseases in a Resistin Mouse Model]

[0158] [Example 6-1: Preparation of Cardiovascular and Metabolic Disease Model Mice (Resistin Mice)]

[0159] To prepare cardiovascular and metabolic disease model mice, mechanical stress was induced by ligating the carotid artery of 6- to 8-week-old resistin-induced mice, thereby inducing inflammation, thrombosis, oxidative stress, and shear stress, and creating an atherosclerosis model by altering the function and structure of the external carotid artery (EC) (Cho et al., 2011).

[0160] Specifically, mice fed a high-fat diet for one week underwent carotid artery ligation, and the left common carotid artery (LCA) was ligated after abdominal anesthesia. Three branches of the LCA, the external carotid artery (ECA), the internal carotid artery (ICA), and two or three branches of the occipital artery (OA) were partially ligated. At this time, the ICA and OA were ligated, and the ECA was ligated separately. In the ligated mice, the amount of blood flowing to the heart was reduced and the flow direction was changed, thus creating an atherosclerosis model ( Figure 6a ).

[0161] [Example 6-2: Confirmation of the inhibitory effect of Elaeocarpus petiolatus on cardiovascular and metabolic diseases in cardiovascular and metabolic disease model mice]

[0162] After the AAV-PCSK9 virus (1×10 11 Ifu / mL) and Elaeocarpus petiolatus (30μg / g / day) were injected into the cardiovascular and metabolic disease model mice prepared as above for 1 week, and then the carotid artery was ligated. Four weeks after ligation, the model was confirmed to be complete, and gross plaque imaging, plasma lipid profile in serum, and body weight changes were measured. The experimental results showed that, as can be seen from the gross plaque imaging results, the atherosclerotic plaques in the group treated with Elaeocarpus petiolatus were reduced ( Figure 6bIn addition, the plasma lipid profile results showed that in the Elaeocarpus petiolatus treated group, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) decreased, and high-density lipoprotein cholesterol (HDL-C) increased ( Figure 6c In addition, when comparing the changes in body weight after 7 weeks, the body weight of the Elaeocarpus petiolatus treated group decreased by about 10% ( Figure 6d ).

[0163] The above results confirmed that it is effective for cardiovascular and metabolic diseases such as arteriosclerosis by reducing atherosclerotic plaques, and since it was confirmed that it has the effects of lowering triglycerides, low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol, it was shown that it is effective not only for arteriosclerosis but also for cardiovascular and metabolic diseases such as dyslipidemia.

[0164] In addition, since its weight-reducing effect has been demonstrated, it is suggested that it also has the effect of preventing obesity caused by cardiovascular and metabolic diseases.

[0165] Example 7: Comparison of Chromatograms of Elaeocarpus petiolatus and Elaeocarpus ganitrus

[0166] The active index substances (Table 1 and Table 2 ) of the leaf extracts of Elaeocarpus petiolatus (EP) and Elaeocarpus ganitrus (EP) were qualitatively analyzed using an ACQUITY UPLC Ultra Performance column equipped with a BEH C18 (2.1 mm × 100 mm, 1.7 mm) column and a PDA detector (200-600 nm, maxplot) at a flow rate of 0.4 mL / min using distilled water and acetonitrile containing 0.1% formic acid. Figure 7a ).

[0167] Example 8: Comparison of the inhibitory activity of Elaeocarpus petiolatus and Elaeocarpus ganitrus on resistin-induced TNF-α

[0168] The therapeutic effects of Elaeocarpus plants on cardiovascular and metabolic diseases were compared in THP cells. The inhibitory effects of each extract of Elaeocarpus petiolatus and Elaeocarpus ganitrus, as well as butanol and aqueous fractions as effective fractions, on resistin-induced TNF-α production were compared. Figure 7b It was confirmed that no cytotoxicity was observed in all three samples of extracts and fractions from Elaeocarpus petiolatus and Elaeocarpus ganitrus when used at concentrations ranging from 0.6 μg / mL to 20 μg / mL.

[0169] Furthermore, when samples were treated at concentrations of 0.6 μg / mL to 20 μg / mL, the extract and effective fraction of Elaeocarpus petiolatus (EP) inhibited resistin-induced TNF-α production in THP-1 cells in a concentration-dependent manner. In contrast, no inhibitory effect of the extract of Elaeocarpus ganitrus (EG) on resistin-induced TNF-α production was observed ( Figure 7b ).

[0170] Therefore, it can be seen from the above results that the extract and effective fraction of Elaeocarpus petiolatus have more significant inhibitory effects on resistin-induced TNF-α than the extract of Elaeocarpus ganitrus.

[0171] Furthermore, the findings suggest that not all Elaeocarpus species exhibit the same efficacy, but rather that Elaeocarpus petiolatus in particular possesses inhibitory activity against resistin-induced TNF-α, suggesting its potential use in the treatment of cardiovascular and metabolic diseases.

[0172] Example 9: Comparison of the resistin-CAP1 binding inhibitory activity of a compound derived from Elaeocarpus petiolatus and myricetin

[0173] Myricetin (Sigma, M6760) (as the parent of EP_5E2 (myricetin 3-O-α-L-Rha) of the compound isolated from Elaeocarpus petiolatus) was purchased, and its resistin-CAP1 binding inhibitory activity was measured. As a result, when each sample was treated at concentrations of 25 μM, 50 μM, and 100 μM, the EP_5E2 compound inhibited resistin-CAP1 binding in a concentration-dependent manner, while myricetin did not show inhibitory activity on resistin-CAP1 binding ( Figure 8 ).

[0174] The results confirmed that the compound isolated from Elaeocarpus petiolatus of the present invention has different effects from its parent compound, thus once again confirming that Elaeocarpus petiolatus can be used to treat cardiovascular and metabolic diseases because of its inhibitory activity against resistin-induced TNF-α.

[0175] Based on the foregoing, those skilled in the art to which the present invention pertains will be able to understand that the present invention may be embodied in other specific forms without modifying the technical concepts or basic features of the present invention. In this regard, the exemplary embodiments disclosed herein are for illustrative purposes only and should not be construed as limiting the scope of the present invention. On the contrary, the present invention is intended to encompass not only exemplary embodiments, but also various alternatives, modifications, equivalents, and other embodiments that may be included within the spirit and scope of the present invention as defined by the appended claims.

Claims

1. Use of fractions of an extract of Elaeocarpus petiolatus in the manufacture of a pharmaceutical composition for preventing or treating cardiovascular and metabolic diseases, wherein the cardiovascular and metabolic disease is atherosclerosis, and The fractions are obtained by separating an aqueous ethanol extract of leaves of Elaeocarpus petiolatus using n-butanol and water.

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