KR20000026393A - Composition for increasing serum high density lipoprotein containing bioflavonoids - Google Patents

Abstract

PURPOSE: A composition for increasing serum high density lipoprotein containing bioflavonoids is provided which is useful for preventing and treating diseases of cardiac circulatory organs. CONSTITUTION: The medical composition for increasing high density lipoprotein consists of(i) an effective amount of bioflavonoids of the following general formula(I) or a plant extract containing thereof, where each R¬1-R¬9 is independently hydrogen, hydroxy, alkoxy having 1-9 carbon atoms(optionally, which is able to include hydroxy, alkoxy having 1-5 carbon atoms, aryloxy or phenyl group which is substituted by one to three substituents selected from hydroxy, alkoxy, aryloxy, halogen, nitro and amido), cycloalkyloxy having 5-9 carbon atoms which is substituted by one to three substituents selected from hydroxy, alkoxy, aryloxy, halogen, nitro and amido, cycloalkylcarbonyloxy having 5-9 carbon atoms which is substituted by one to three substituents selected from hydroxy, alkoxy, aryloxy, halogen, nitro and amido, acyloxy having 2-10 or 16-18 carbon atoms(optionally, which is able to include hydroxy, alkoxy having 1-5 carbon atoms, aryloxy or phenyl group which is substituted by one to three substituents selected from hydroxy, alkoxy, aryloxy, halogen, nitro and amido), or rutinosyl, and X is either a single bond or a double bond; and (ii) a medically acceptable carrier.

Description

Composition for increasing serum high density lipoproteins containing bioflavonoid compounds

The present invention relates to a serum high density lipoprotein (HDL) increasing agent, and more particularly to a composition for increasing serum HDL including bioflavonoids.

Coronary cardiovascular disease currently accounts for more than 30% of all deaths, which is a serious problem in developed countries such as the United States and Europe. In developing countries, heart disease is increasing due to westernization of diet and lack of exercise. These coronary cardiovascular diseases are generally caused by excessive blood cholesterol levels. When the amount of blood cholesterol is high, macrophage and foam cells are formed and deposited on the blood vessel wall, and plaques are formed. Atherosclerosis is known to be easy to form by inhibiting blood circulation (Ross, R., Nature, 362, 801-809 (1993)).

On the other hand, the main culprit of atherosclerosis has been found to be low density lipoprotein (LDL), while the cholesterol contained in HDL has been shown to benefit our bodies. Recent studies have shown that elevated serum HDL correlates with heart disease incidence (Barter P. J., Rye K. A. High density lipoproteins and coronary heart disease.Atheroscleorosis 121: 1-12 (1996)).

Lamarche et al. Have found that polymerization conditions, such as hypertriglyceridemia, low serum HDL and abdominal obesity, pose a significant risk factor for atherosclerosis, leading to atherosclerosis of high concentrations of serum LDL known to date. In addition to effects, low levels of HDL were found to be a major risk factor for atherosclerosis (Lamarche B., Lewis GF.Atherosclerosis prevention for the next decade: risk assessment beyond low density lipoprotein cholesterol.Can.J. Cardiol. 14: 841-851 , 1998).

In addition, Lacko et al confirmed that HDL has anti-inflammatory and anti-arteriosclerosis effects, suggesting that the development of foods, ingredients, or substances that can increase serum HDL could prevent heart disease (Lacko AG). , Miller NE Intenational symposium on the role of HDL in disease prevention: report on a meeting.J. Lipid Research 38: 1267-1273 (1997)).

Recently, pharmaceutical compositions for increasing serum HDL have been developed (US Pat. No. 5,783,600 (1998.7.21)), but these compositions are organic synthetic products and can cause various side effects in terms of toxicity or pharmacological activity.

Accordingly, the present inventors have continued the study of bioflavonoids derived from edible natural products having beneficial effects on the human body, and found that the bioflavonoid compounds increase the concentration of serum HDL and completed the present invention.

An object of the present invention to provide a pharmaceutical composition for increasing HDL comprising a bioflavonoid compound or a plant extract containing the same.

Another object of the present invention to provide a food and beverage composition for increasing HDL comprising a bioflavonoid compound or a plant extract containing the same.

In accordance with the above object, the present invention provides a pharmaceutical composition for increasing HDL comprising an effective amount of a bioflavonoid compound of formula (I) or a plant extract containing the same as an active ingredient with a pharmaceutically acceptable carrier. The present invention also provides a food and beverage composition for increasing HDL, comprising a bioflavonoid compound of formula (I) or a plant extract containing the same:

Formula 1

Where

R ¹ to R ⁹ are each independently hydrogen, hydroxy, C _1-9 alkoxy (optionally hydroxy, C _1-5 alkoxy, aryloxy, or hydroxy, alkoxy, aryloxy, halogen, nitro and amido groups And a mono- to tri-substituted phenyl group with a substituent selected from the group consisting of: hydroxy, alkoxy, aryloxy, halogen, nitro, and mono- to tri-substituted with a substituent selected from the group consisting of amido groups C _5-9 cycloalkyloxy, hydroxy, alkoxy, aryloxy, halogen, nitro and amino with one substituent selected from the group consisting of ceramic-to tri-substituted C _5-9 cycloalkyl-carbonyl-oxy, C _2-10 or C _16-18 acyloxy (optionally, hydroxy, C _1-5 alkoxy, aryloxy, or a hydroxy, alkoxy, aryloxy, one of the substituents selected from the group consisting of a halogen and a nitro-substituted - to three Carbonyl-containing groups can be), Ruti nosil or la diamino group and;

X is a single bond or a double bond.

Hereinafter, the present invention will be described in detail.

Preferably, the substituent R ¹ in formula (I) of the present invention is hydrogen; R ² is a hydroxy, lutinosyl or laminosyl group; R ³ is hydrogen; R ⁴ is a hydroxy group; R ⁵ is hydrogen, hydroxy or lutinosyl group; R ⁶ is hydrogen; R ⁷ is hydrogen or a hydroxy group; R ⁸ is a hydroxy or methoxy group; R ⁹ is hydrogen; X is a single or double bond.

Particularly preferred examples of the flavonoid compounds corresponding to the general formula (I) of the present invention are shown in Table 1 below.

Chemical structure R ¹ R ² R ³ R ⁴ R ⁵ R ⁶ R ⁷ R ⁸ R ⁹ X Eriodichol H OH H OH H H OH OH H Single bond Hesperidin H ORut H OH H H OH OCH ₃ H " Hesperetin H OH H OH H H OH OCH ₃ H " Narinjin H ORha H OH H H H OH H " Naringenin H OH H OH H H H OH H " Apigenin H OH H OH H H H OH H Double bond Luteolin H OH H OH H H OH OH H " Diosmin H ORut H OH H H OH OCH ₃ H " Camphorol H OH H OH OH H H OH H " Quercetin H OH H OH OH H OH OH H " Routine H OH H OH ORut H OH OH H " ORut: lutinosyl group, ORha: laminosyl group

Bioflavonoid compounds used in the present invention may be extracted from vegetables or various fruits, such as citrus fruits or synthesized by known synthetic methods, citrus fruits refer to tangerines, tangerines, oranges, lemons, citrus fruits, grapefruit or citron, etc. do. For example, rutin and quercetin can be extracted from buckwheat using high temperature (60-121 ° C.) and high pressure water or 20-97% ethanol. In addition, it is possible to obtain a crude routine by recovering the precipitate obtained by alkali treatment of buckwheat leaves or flowers with Ca (OH) ₂ and left at pH 10-12 for overnight. Dry powders such as buckwheat berries, leaves, stems and flowers can also be used.

In addition, the composition of the present invention may include not only the compounds of the general formula (I) but also mixtures thereof or various fruits such as vegetables or citrus fruits containing them.

Generally, various bioflavonoid compounds exist in citrus peels, and representative components present in various citrus fruits are shown in Table 2 (Horowitz, RM and Gentili B., J., Org. Chem., 25, 2183-2187). , 1960).

Naringin, one of the flavonoid compounds of Table 1, may be modified to produce neohesperidine dihydrochalcone of the following general formula (II), which has a structural formula of C ₂₈ H ₃₆ O ₅ (molecular weight 612.60) and is higher than sugar. It was identified as an HDL enhancer with a sweetness between 1000 and 1500 times, 20 times stronger than saccharin:

The bioflavonoid compounds or plant extracts containing the same may be used in the pharmaceutical and food compositions because they are useful for the prevention and treatment of cardiovascular diseases such as hypertension, arteriosclerosis, and stroke due to an increase in serum HDL when administered to animals. .

Most of the bioflavonoid compounds present in citrus fruits are known to be non-toxic, and the results of the toxicity studies studied so far include naringin, naringenin, hesperidin, hesperetin, diosmin, neohesperidin dihydrochalcone, rutin and quercetin. When administered orally to rats at a dose of mg / kg, little toxicity was found. In addition, these substances show no adverse effects on the function of organs, including the liver.

According to the present invention, in order to increase serum HDL, the compound of formula (I) or a plant extract containing the same may be mixed with a pharmaceutically acceptable carrier as an active ingredient to prepare a composition for increasing serum HDL. The pharmaceutical composition may further include conventionally used excipients, disintegrants, sweeteners, suspending agents, flavoring agents and the like, and may be prepared by tablets, capsules, powders, granules, and suspensions, emulsions or syrups by conventional methods. It may be formulated in unit dosage form or in multiple dosage form pharmaceutical preparations, such as formulations for parenteral or parenteral administration.

In addition, the composition for increasing HDL containing the compound of formula (I) of the present invention as an active ingredient can be parenterally or orally administered as desired, and 0.1 to 500 mg per kg of body weight per day, preferably May be administered in one to several portions to be administered in an amount of 0.5 to 100 mg. Dosages for a particular patient may vary depending on the patient's weight, age, sex, health condition, diet, time of administration, method of administration, rate of excretion, severity of the disease, and the like.

In addition, the compound of formula (I) of the present invention or a plant extract containing the same may be added to food or beverage for the purpose of increasing serum HDL. In this case, the compound of general formula (I) may be added in an amount of 0.01 to 50% by weight, preferably 0.05 to 10% by weight based on the raw materials in the preparation of the food or beverage. Foods to which the above substances can be added for the development of dietary supplements include, for example, meat, beverages, chocolate, snacks, confectionary, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups. , Tomato paste, tea, alcoholic beverages, and vitamin complexes.

Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the following Examples are only for illustrating the present invention, and the scope of the present invention is not limited to these.

Example 1: Acute Toxicity Test of Rutin

The purpose of this study was to determine the extent of acute toxicity in oral administration of rutin, to provide information on available drug dosages in general pharmacology and efficacy tests, and to derive basic data on toxicity.

Specific pathogens free of 7-8 weeks of age, 6 females weighing 25-29 g and 6 males weighing 34-38 g, temperature 22 ± 1 ° C, humidity 55 ± 5%, illumination 12L It was bred in the / 12D animal room. Mice were allowed to acclimate for about a week before being used in the experiment. Feed for experimental animals (Jeil Jedang Co., Ltd., mice and rats) and drinking water were supplied after sterilization and freely ingested.

Rutin purchased from Aldrich-Sigma Co., St. Louis, Missouri, was prepared at a concentration of 100 mg / ml with 0.5% Tween 80 as a solvent and then orally in an amount of 0.2 ml per 20 g of mouse weight. Administered. Samples were administered orally once and observed for side effects or lethality for 10 days after administration. That is, on the day of dosing, the change of general symptoms and the presence or absence of dead animals were observed at least once in the morning, at least once every afternoon from 1 hour, 4 hours, 8 hours, 12 hours after the administration and from the next day until the 10th. In addition, the animals were killed and dissected at 10 days of administration, and the internal organs were visually examined. The change in body weight was measured at daily intervals from the day of administration to observe the weight loss phenomenon of the animals by routine.

For acute oral toxicity, no lethal animals were observed for 10 days at a routine dose of 1000 mg / kg. An autopsy of the surviving animals was performed 10 days later, and there were no gross lesions, and normal body weight gain was observed without any weight loss for 10 days from the day after the administration.

In conclusion, no toxicity was observed when rutin was orally administered at the above concentrations.

Example 2 Dietary Composition of Experimental Animals and Animal Administration of Bioflavonoid Compounds of the Present Invention- (1)

1) Animal Experiment

Forty Sprague Dawley rats, 3 weeks old, were purchased from the Korean Experimental Animal Center in Eumseong-gun, Chungbuk, Korea, and were bred for one week in experimental animal feed and fed at 4 weeks of age (weight: 90-110 g). It was divided into four groups by randomized block design. Four groups of rats each had four different high cholesterol diets: a diet containing 1% cholesterol in the normal diet (AIN-76 experimental animal diet), 1% cholesterol and 0.1% hesperetin, 1 A diet containing% cholesterol and 0.1% naringin, and 1% cholesterol and 16.7% citrus peel extract (equivalent to 0.1% hesperidin) was consumed. The composition of the diet ingested in four groups of rats is shown in Table 3 below.

Dietary group Control Hesperetin group Naringin administration group Citrus peel extract group Casein 20 20 20 20 D, L-methionine 0.3 0.3 0.3 0.3 Corn starch 15 15 15 15 Sucrose 49 48.90 48.90 32.3 Cellulose powder 5 5 5 5 Mineral mixtures 3.5 3.5 3.5 3.5 Vitamin mixtures One One One One Byartic Acid Choline 0.2 0.2 0.2 0.2 Corn oil 5 5 5 5 cholesterol One One One One Hesperetin - 0.1 - - Narinjin - - 0.1 - Citrus Peel Extract - - - 16.7 gun 100 (%) 100 (%) 100 (%) 100 (%)

All diets correspond to high cholesterol diet (1%, wt / wt), hesperetine and naringin were purchased from Sigma Chemical Company, St. Louis, Mo. Citrus peel extracts from grapefruit peel Extracted in 30% ethanol for 3 hours and then concentrated under reduced pressure. Cellulose, mineral mixtures and vitamin mixture components of the laboratory rat AIN-76 dietary composition were obtained from Teklad premier, Madison, Wisconsin, USA.

Rats in all diets were given free intake of water with water for 8 weeks, and their dietary intake was recorded daily and weighed every 7 days. Analysis of the data in the breeding journal after animal breeding was completed showed no significant differences between the four groups in terms of dietary intake and weight gain and showed normal growth.

Eight weeks after the animal experiment, four groups of mice were sacrificed and blood was analyzed.

2) blood analysis

The blood collected from the sacrificed rats was allowed to stand for about 2 hours, and then centrifuged at 3,000 rpm for 15 minutes to separate serum from the upper layer and stored in a cryogenic freezer before being used for blood analysis.

Total cholesterol (TC) content was measured directly from the serum of each experimental group using a blood chemistry analyzer (CIBA Corning 550 Express, USA). In addition, in the case of HDL-cholesterol (HDL), dextran sulfate and magnesium sulfate are added to the serum of each experimental group to precipitate LDL and VLDL and then measure HDL in the supernatant (Stein, EA, et al. , Clin. Chem., 24: 1112-1115 (1978); Finley, PR, et al., Clin. Chem., 24: 931-933 (1978); Warnick, GR, et al., Clin. Chem. , 28: 1379-1388 (1982)]) and the reagent for measuring HDL (Chiron Diagnostics Co., USA) was mixed with the serum of each experimental group in a ratio of 1:10 and in an incubator at 20-25 ° C. After reacting for 5 minutes, the supernatant obtained by centrifugation at 2,500 rpm for 10 minutes was transferred to a blood chemistry analyzer for measurement. The measured total cholesterol and HDL-cholesterol concentrations are shown in Table 4 below.

Dietary group lipid content Control Hesperetin group Naringin administration group Citrus peel extract group Total cholesterol (mg / dl) 147.11 ± 11 125.1 ± 16.1 100.8 ± 16.1 94.5 ± 12 HDL-cholesterol (mg / dl) 22.2 ± 2.1 25.7 ± 1.5 24.0 ± 1.5 24.8 ± 1.0 HDL / Total Cholesterol (%) 15.7 ± 1.6 20.0 ± 1.9 23.9 ± 3.1 26.2 ± 7.5

As can be seen from Table 4, compared with the control group, the hesperetin group, naringin group and citrus peel extract group significantly increased the HDL / total cholesterol ratios by 27, 52 and 67%, respectively. This suggests that bioflavonoids increase the animal's serum HDL and at the same time contribute to the suppression of cardiovascular disease.

Example 3: Dietary Composition of Experimental Animals and Animal Administration of Bioflavonoid Compounds of the Present Invention- (2)

1) Animal Experiment

As experimental animals, 34 male rats of 4 weeks old Sprague Dawley, weighing about 110-130 g, were distributed from the Korean Center for Experimental Animals and used for the experiment. The experiments were conducted while animals were housed in an animal breeding environment controlled at a temperature of 22 ± 2 ° C., a humidity of 55 ± 10% and a light / dark cycle of 12 hours.

The experimental group fed diosmin, neohesperidine dehydrochalcone and rutin, respectively, including a control group fed with cholesterol powder feed (test diet 5799M-B, PMI, USA) supplemented with 1% cholesterol and high fat lard. It was divided into a total of four experimental groups of the test group administered by mixing to. Eight or nine rats were used in one group of experiments, and each experimental group and the 5799M-B dietary composition are shown in Table 5 below.

Experimental group Marisu Furtherance One 8 5799M-B (1% Cholesterol) Diet (Control) 2 9 5799M-B (1% Cholesterol) Diet + 0.1% Diosmin 3 9 5799M-B (1% Cholesterol) Diet + 0.05% Neohesperidin Dihydrochalcone 4 8 5799M-B (1% Cholesterol) Diet + 0.1% Routine 5799M-B Dietary composition: 21% casein (vitamin free), 15% sucrose, 3% cellulose, 2% vitamin mixture, 5% mineral mixture, 0.15% D, L-methionine, 0.5% sodium cholate, dextrin 32.15 %, Lard 20%, choline chloride 0.2% and cholesterol 1%

The diets of all experimental groups correspond to high cholesterol (1%, wt / wt) and high fat lard (20%, wt / wt) diets, and test substances, diosmin, neohesperidine dihydrochalcone and rutin, were tested by Sigma, USA. Purchased from

All dietary rats were given free diet with water for six weeks. Six weeks after the animal experiment, four groups of mice were sacrificed and blood was analyzed.

2) blood analysis

The blood collected from the sacrificed rats was allowed to stand for about 2 hours, and then centrifuged at 3,000 rpm for 15 minutes to separate serum from the upper layer and stored in a cryogenic freezer before being used for blood analysis. Using a blood chemistry analyzer, the concentration of total cholesterol and HDL-cholesterol was measured in the same manner as in Example 2, and is shown in Table 6 below:

Dietary group lipid content Control Diosmin administration group Neohesperidin dihydrocalcon administration group Routine administration group Total cholesterol (mg / dl) 690 503 336 373 HDL-cholesterol (mg / dl) 70 ± 19 131 ± 59 180 ± 90 216 ± 11 HDL / Total Cholesterol (%) 10 26 53 58

It can be seen from Table 6 that the bioflavonoids of the present invention increase the serum HDL of the animal and at the same time contribute to the suppression of cardiovascular disease.

Example 4 Human Administration of Bioflavonoid Compounds of the Invention

Hesperidin and naringin capsules, respectively, were administered orally to two men in their mid-fifties for 2 months in an amount of 10 mg / kg body weight per day. After 2 months, the change in human serum HDL was measured.In the case of naringin administration, serum HDL was averaged at 51mg / dA and 60mg / dA, and hesperidin was averaged 47mg / dA and 56mg / dA, respectively. And 19%.

Therefore, it can be seen that the bioflavonoid compound of the present invention is useful for suppressing human cardiovascular disease by increasing human serum HDL.

The pharmaceutical composition and food composition for increasing serum HDL of the present invention may be prepared as follows.

Formulation Example 1 Preparation of HDL Increasing Agent

The following ingredients were mixed to prepare hard gelatin capsules by conventional methods.

Bioflavonoids (eg hesperidin, naringin, rutin) 200 mg

Vitamin C 50 mg

Lactose 150 mg

Total 400 mg / capsule

Formulation Example 2: Preparation of Functional Food

(1) Preparation of Tomato Ketchup, Sauce and Juice

Functional ketchup, sauces and juices were prepared by adding naringin to 0.01-50% by weight in conventional tomato ketchup, sauce and juice.

(2) Manufacture of flour foods such as ramen, noodles, bread, cakes, cookies, and crackers

In order to prepare the flour food, a functional food was prepared after adding rutin to 0.01-50% by weight of flour as a raw material.

(3) Preparation of soups and gravy

The functional food was prepared after adding quercetin to 0.01-50 wt% to the raw material of soup or gravy.

(4) Manufacture of Ground Beef

Functional food was prepared after adding diosmin to 0.01-50 weight% to the ground beef raw material.

(5) Manufacture of dairy products (milk, ice cream, cheese, yogurt, etc.)

Functional foods were prepared after adding rutin or quercetin to the milk at 0.01-50% by weight.

At this time, in particular, during the manufacture of cheese, the milk protein was coagulated and recovered, and then the active ingredient was added.

(6) Preparation of Carbonated Drinks

A functional carbonated beverage was prepared by adding hesperidine to 0.01 to 50% by weight to a conventional carbonated beverage.

Formulation Example 3 Preparation of Health Supplement

3-1) The following ingredients were mixed to prepare a health supplement by a conventional method.

Ginseng Powder or Extract 20%

Naringin, hesperidin or extract containing them 1-10%

70-80% of other sweetening and flavoring agents

100% total

3-2) Preparation of health supplements containing rutin derived from buckwheat

Buckwheat berries, leaves, stems and flowers were dried and powdered at room temperature. In addition, 200 ml of 70% ethanol was added to 100 g of buckwheat leaves and flowers, respectively, and extracted twice at 40 ° C. for 5 hours, and then the extract was filtered. The extract obtained from the buckwheat leaf contained about 1.8%, and the extract obtained from the buckwheat flower contained about 4% rutin. In addition, the leaves or flowers of buckwheat were alkali treated with Ca (OH) ₂ and left at pH 12 overnight, and then the precipitate obtained by neutralizing the mixture to pH 6-7 was recovered to obtain a crude having purity of 40-50%. ) Routines.

By a conventional method, a pharmaceutical or health food comprising the rutin powder or extract obtained by the method as described above can be produced.

3-3) A mixture containing the following components was prepared.

Onion Powder 40%

Garlic Powder 10%

Jujube Powder 30%

Buckwheat Flower Powder 5%

Raisin Powder 15%

100% total

When the mixture of the above composition was mixed with 5% of the feed and administered to the rats for 2 months, the serum HDL concentration of the rat was increased by about 30% compared to just before administration.

The composition of the present invention comprising a bioflavonoid compound of general formula (I) is useful for the prevention and treatment of cardiovascular diseases such as hypertension, atherosclerosis, and stroke due to increased serum HDL in humans and animals. It can be used in addition to.

Claims (8)

A pharmaceutical composition for increasing high-density lipoprotein (HDL) comprising an effective amount of a bioflavonoid compound of formula (I) or a plant extract containing the same as an active ingredient with a pharmaceutically acceptable carrier: Formula 1 Where R ¹ to R ⁹ are each independently hydrogen, hydroxy, C _1-9 alkoxy (optionally hydroxy, C _1-5 alkoxy, aryloxy, or hydroxy, alkoxy, aryloxy, halogen, nitro and amido groups And a mono- to tri-substituted phenyl group with a substituent selected from the group consisting of: hydroxy, alkoxy, aryloxy, halogen, nitro, and mono- to tri-substituted with a substituent selected from the group consisting of amido groups C _5-9 cycloalkyloxy, hydroxy, alkoxy, aryloxy, halogen, nitro and amino with one substituent selected from the group consisting of ceramic-to tri-substituted C _5-9 cycloalkyl-carbonyl-oxy, C _2-10 or C _16-18 acyloxy (optionally, hydroxy, C _1-5 alkoxy, aryloxy, or a hydroxy, alkoxy, aryloxy, one of the substituents selected from the group consisting of a halogen and a nitro-substituted - to three Carbonyl-containing groups can be), Ruti nosil or la diamino group and; X is a single bond or a double bond. The method of claim 1, A composition according to claim 1, wherein the compound of formula (I) is hesperidin, hesperetin, naringin, naringenin, diosmin, rutin, quercetin or mixtures thereof. The method of claim 1, The plant extract containing the compound of general formula (I) is a composition characterized in that the vegetable or fruit extract. The method of claim 3, wherein A composition characterized in that the plant extract is extracted from buckwheat fruit, leaves, stems or flowers. The method of claim 1, A composition characterized in that the effective amount of the compound of formula (I) is 0.5 mg to 100 mg / kg body weight / day. A food composition for increasing serum high density lipoprotein (HDL), comprising 0.01 to 50% by weight of a bioflavonoid compound of formula (I) or a plant extract containing the same: Formula 1 Where R ¹ to R ⁹ are each independently hydrogen, hydroxy, C _1-9 alkoxy (optionally hydroxy, C _1-5 alkoxy, aryloxy, or hydroxy, alkoxy, aryloxy, halogen, nitro and amido groups And a mono- to tri-substituted phenyl group with a substituent selected from the group consisting of: hydroxy, alkoxy, aryloxy, halogen, nitro, and mono- to tri-substituted with a substituent selected from the group consisting of amido groups C _5-9 cycloalkyloxy, hydroxy, alkoxy, aryloxy, halogen, nitro and amino with one substituent selected from the group consisting of ceramic-to tri-substituted C _5-9 cycloalkyl-carbonyl-oxy, C _2-10 or C _16-18 acyloxy (optionally, hydroxy, C _1-5 alkoxy, aryloxy, or a hydroxy, alkoxy, aryloxy, one of the substituents selected from the group consisting of a halogen and a nitro-substituted - to three Carbonyl-containing groups can be), Ruti nosil or la diamino group and; X is a single bond or a double bond. A beverage composition for increasing serum high density lipoprotein (HDL), comprising 0.01 to 50% by weight of a bioflavonoid compound of formula (I) or a plant extract containing the same: Formula 1 Where R ¹ to R ⁹ are each independently hydrogen, hydroxy, C _1-9 alkoxy (optionally hydroxy, C _1-5 alkoxy, aryloxy, or hydroxy, alkoxy, aryloxy, halogen, nitro and amido groups And a mono- to tri-substituted phenyl group with a substituent selected from the group consisting of: hydroxy, alkoxy, aryloxy, halogen, nitro, and mono- to tri-substituted with a substituent selected from the group consisting of amido groups C _5-9 cycloalkyloxy, hydroxy, alkoxy, aryloxy, halogen, nitro and amino with one substituent selected from the group consisting of ceramic-to tri-substituted C _5-9 cycloalkyl-carbonyl-oxy, C _2-10 or C _16-18 acyloxy (optionally, hydroxy, C _1-5 alkoxy, aryloxy, or a hydroxy, alkoxy, aryloxy, one of the substituents selected from the group consisting of a halogen and a nitro-substituted - to three Carbonyl-containing groups can be), Ruti nosil or la diamino group and; X is a single bond or a double bond. A pharmaceutical composition for increasing high-density lipoprotein (HDL), comprising as an active ingredient an effective amount of neohesperidine dihydrochalcone of formula (II) Formula 2