KR101807605B1 - Composition for prevention, improvement or treatment of cognitive dysfunction comprising Ficus erecta extract as effective component - Google Patents

Abstract

The present invention relates to a composition for preventing, ameliorating, or treating cognitive dysfunction containing a Ficus erecta Thunb. extract as an active ingredient. More specifically, the Ficus erecta Thunb. extract of the present invention shows anti-oxidative functions, functions of inhibiting amyloid-beta coagulation, neural cell protection effects, and effects of suppressing inflammation in brain cells, thereby being useful as compositions for preventing, ameliorating, or treating cognitive dysfunction.

Description

[0001] The present invention relates to a composition for preventing, improving or treating a cognitive dysfunction which comprises cucumber and tree extract as an active ingredient.

The present invention relates to a method for the treatment of cicadas and trees ( Ficus e recta ) extract as an active ingredient.

Cognition is the whole process of thinking, speaking, remembering, judging, and practicing using the brain as human beings live. Thus, 'cognitive function' includes attention, perception, memory, language ability and executive ability. 'Cognitive dysfunction' is the most prominent phenomenon of brain aging phenomenon. It is characterized by deterioration of learning and memory ability, It is a physiological phenomenon that is erased. In particular, such cognitive dysfunction can be manifested in various ways. Among them, dementia is caused by cognitive dysfunction such as memory capacity, language ability, temporal perception, space-time composition ability and executive function, and remarkable influence on interpersonal relationship, Of the total number of patients. Alzheimer's disease (AD) is a disease that is slowly terminated without any treatment. It is known that Alzheimer's disease (AD) is the most common form of dementia. The disease was reported by German neuropathologist Alois Alzheimer in 1906. In 1960, the number of elderly people was only 2.9% of the total population of 25 million in 1960, but it is expected to increase to 20% of the total population after 2026 since the age of 65 . Experts predict that the number of senile dementia patients will rapidly increase in proportion to the number of senile dementia, which is 10% for those aged 65 and over and 40 to 50% for those aged 85 and over.

Cognitive dysfunction such as loss of memory and learning ability caused by Alzheimer's disease (AD), a kind of senile dementia of the senile dementia, occurs when two proteins insoluble in the hippocampus and cortex are aggregated and deposited, Protein aggregation is the accumulation of neurofibrillary tangles consisting of senile plaques composed of amyloid beta (Aβ) and hyperphosphorylated tau proteins in neurons. Despite numerous efforts, the cause of the Alzheimer's disease and the mechanism of the invention are still not completely understood. As population aging accelerates, demand for more effective drugs (including health-functional food ingredients) for improving cognitive function or memory capacity deterioration is higher than ever. In conclusion, there is a need for research on the development of a new multi-functional effect introducing a neuronal cell mechanism for the onset of dementia.

On the other hand, celestial trees and trees grow at the foot of the beach and are 2 ~ 4m high. The bark is plain, the branches are grayish white, the wasted juice comes out from the wound, the leaves are oval and the eggs are inverted and the edges are flat to be. The lateral veins are 5 to 6 pairs long and 8 to 17 cm long. The surface is green and has hairs and the back side is light brown. Petiole is 1 ~ 4cm long. Flower is bloomed in May-June, is unisex, and one flower ear is attached to the axilla of new branch. At the end of the stem of a flower, a round flower-like flower (囊 囊) runs and there are three bollocks underneath. The cocoon is about 15mm in diameter and contains many flowers inside. Male flower has 5 ~ 6 crustaceans and 3 stamens. Female flower has 3 ~ 5 crusts and 1 pistil. The flower bud grows into fruit, becomes 15 ~ 17mm in diameter, and can be eaten if it is harvested in black color from August to September. Seeds are egg-shaped and about 1.6mm long. It was named for the fruit that the heavenly females eat. It is distributed in Korea, Japan and China.

As an example of a technique related to celestial and tree extracts, Chinese Patent Laid-Open No. 104998174 discloses a method for preventing, improving or treating brain atrophy, which comprises, as an active ingredient, a herbal medicine composition including a root of the root, Korean Patent No. 1042718 discloses a cosmetic composition having skin anti-aging or skin whitening activity, which contains celery root and leaf extract. Korean Patent Registration No. 0694570 discloses a cosmetic composition containing IL-6 and COX- 2 expression inhibition, and a composition for preventing and treating osteoporosis, which comprises an extract and a fraction. However, the composition for prevention and / or improvement of cognitive dysfunction, which comprises the celecoxib and extract of the present invention as an active ingredient, Have not been disclosed for therapeutic compositions.

The present invention relates to a composition for preventing, ameliorating or treating cognitive dysfunction which comprises celery root and tree extract as an active ingredient. The present invention relates to a composition for inhibiting amyloid beta aggregation, an antioxidative activity , Neuronal cell protection, and inflammation-suppressing effect of brain cells, thereby completing the present invention.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating cognitive dysfunction, comprising celery root and tree extract as an effective ingredient.

In addition, the present invention provides a health functional food composition for preventing or ameliorating cognitive dysfunction, which contains cucumber and tree extract as active ingredients.

The present invention relates to a composition for preventing, ameliorating or treating cognitive dysfunction which comprises celestial and tree extract as an active ingredient, wherein the celestial and tree extracts inhibit amyloid beta aggregation inhibition, antioxidant activity, nerve cell protection and inflammation suppression of brain cells It can be used for prevention, amelioration or treatment of cognitive dysfunction.

FIG. 1 is a graph showing the inhibitory effect of the celecoxib and extract of the present invention on the amyloid beta agglutination inhibition effect, wherein (A) shows the inhibitory effect on the amyloid beta agglutination of celestial and tree leaf extracts, (B) 100 [mu] M of Morin compound was used as a control.
FIG. 2 shows the antioxidant activity of the extracts of the present invention and (A) the ABTS radical scavenging activity of celestial and tree leaf extracts, and (B) the DPPH radical scavenging activity (C) is the result of ABTS radical scavenging activity of celestial and tree branch extracts, and (D) is the result of DPPH radical scavenging activity of celestial and tree branch extracts. Vitamin C (vit. C) was used as a positive control.
FIG. 3 is a graph showing the neuronal cell protection effect (CCK) of celestial and tree leaf extracts of the present invention. To examine the cytotoxicity against neural hippocampal cell line, (A) (B) shows the result of cytoprotective effect of neurons treated with H ₂ O ₂ and treated with celestial and tree leaf extracts, and (C) And the cell viability was measured by measuring the cell viability. ##, ### indicates a statistically significant difference in cell survival rate or LDH release due to damage of nerve cells due to treatment with H ₂ O ₂ as compared to the normal group. ## is p <0.01, ### means p <0.001. *, ** and *** indicate statistically significant differences in neuronal cell survival or LDH release by treatment with celestial and tree leaf extracts compared to the H ₂ O _2- treated group, p <0.05 ** indicates p < 0.01, and *** indicates p < 0.001.
FIG. 4 shows the result of examining the effect of the present invention on the inhibition of brain cell inflammation according to the treatment of celestial and tree leaf extracts of the present invention, (A) confirming toxicity of microglia, and (B) (C) is the result of PGE ₂ assay after treatment with celecoxib and leaf extract after inducing inflammation in BV-2 cells. ### means that the amount of NO (nitric oxide) or PGE ₂ production was statistically significantly increased by the damage of nerve cells by LPS treatment compared to the normal group, which means that p <0.001. *** means that the amount of NO (nitric oxide) or PGE ₂ production was statistically decreased by treatment of celestial and tree extracts compared to the LPS treatment group, *** means p <0.001.

The present invention relates to a pharmaceutical composition for preventing or treating cognitive dysfunction, which contains celeriac and wood extract as an active ingredient.

The celestial and tree extracts may be prepared by methods including, but not limited to, the following steps:

1) extracting celestial plants and tree plants with an extraction solvent;

2) filtering the extract of step 1); And

3) Concentrating the filtrate obtained in step 2) under reduced pressure and drying to prepare an extract.

In step 1), the extraction solvent is preferably water, a C ₁ -C ₄ lower alcohol or a mixture thereof, more preferably an ethanol extract, more preferably a 70% (v / v) ethanol ultrasonic extract But is not limited thereto.

In the above production method, the conventional methods such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction can be used for extraction of celestial and wood. The extraction solvent is preferably added by 1 to 20 times the volume of the dried celestial sieve and the volume of the wood, more preferably 3 to 10 times. The extraction temperature is preferably 20 to 50 DEG C, but is not limited thereto. The extraction time is preferably 0.5 to 10 hours, more preferably 0.5 to 5 hours, most preferably 1 hour, but not always limited thereto. In the above method, it is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator for the decompression concentration in step 3), but it is not limited thereto. The drying is preferably performed under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, but not always limited thereto.

The celestial and tree extracts may be extensions of outposts, flowers, leaves, branches, roots or seeds, preferably celestial trees and tree leaves or egg plant extracts.

Preferably, the cognitive dysfunction is selected from dementia, Alzheimer's disease, ischemic stroke, traumatic brain injury, amnesia, Parkinson's disease, pick disease, Kruszfeld-Jacob disease, and mild cognitive dysfunction Do not.

In the present invention, the mild cognitive dysfunction is defined as the pre-dementia phase in which memory and cognitive function are significantly lowered compared to the age and education level, but do not interfere with life.

The composition of the present invention may contain a pharmaceutically acceptable carrier, excipient or diluent in addition to the above-mentioned effective ingredient, and may be various oral or parenteral formulations. 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 capsules, powders, granules, tablets, pills, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid formulations for oral administration include suspensions, emulsions, syrups, aerosols and the like. Various excipients such as wetting agents, sweetening agents, fragrances, preservatives and the like may be included in addition to water and liquid paraffin which are commonly used simple diluents. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like. Intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine, intraperitoneal, or intracerebral injection methods are preferably selected for parenteral administration, and most preferably used for external skin application.

The pharmaceutical composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the level of effective amount depends on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered singly or in multiple doses. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.

The dosage of the composition of the present invention varies depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate and severity of the disease, and the daily dose is the amount , Preferably 30 to 500 mg / kg, more preferably 50 to 300 mg / kg, and may be administered 1 to 6 times a day. The composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

The present invention also relates to a health functional food composition for preventing or ameliorating a cognitive dysfunction which contains cucumber and tree extract as an active ingredient. The composition is characterized by having an antioxidative activity. The composition is preferably prepared by any one of powder, granule, ring, tablet, capsule, candy, syrup and beverage, but is not limited thereto.

When the health functional food composition of the present invention is used as a food additive, the celery and the tree extract may be directly added, used together with other food or food ingredients, and suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). Generally, the composition of the present invention is added in an amount of not more than 15 parts by weight, preferably not more than 10 parts by weight, based on the raw material, when the food or beverage is produced. However, in the case of long-term intake intended for health and hygiene purposes or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range. There is no particular limitation on the kind of the food. Examples of foods to which the extract or its fractions can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, , A drink, an alcoholic beverage, and a vitamin complex, all of which include health functional foods in a conventional sense.

When the composition of the present invention is used as a health drink, various flavors or natural carbohydrates may be added as an additional ingredient such as ordinary beverages. The above-mentioned natural carbohydrates are sugar alcohols such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as texturin and cyclotensitrin, and xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 g of the composition of the present invention. In addition to the above, the composition of the present invention may further comprise various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid concentrating agents, pH adjusting agents, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like. In addition, the composition of the present invention may contain flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of such additives is not critical, the composition of the present invention is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are merely illustrative of the present invention and that the scope of the present invention is not limited thereto.

1. Method for producing extract

The leaves and branches of celestial trees, tree leaves, and branches were distributed from the Department of Life Science and Medicinal Plants Materials, Gachon University. To 500.0 g of each of the dried celestial leaves and branches were added 5 L of 70% (v / v) ethanol and ultrasonically extracted three times for 1 hour using an ultrasonic extractor. The supernatant extract was filtered using Advantec No. 2 (110 mm) filter paper to remove insoluble matter, and then concentrated under reduced pressure at 40 ° C with a condenser equipped with a cooling condenser. In order to completely remove the solvent of the concentrated extract, 500 ml of purified water was added to suspend it and then concentrated using a freeze dryer.

2. Measurement of amyloid beta aggregation inhibitory effect

The amyloid beta aggregation inhibitory activity was measured by fluorescence analysis. The amyloid beta (A [beta] _1-42 ) peptide was stored at -80 [deg.] C and the final concentration used was 100 [mu] g / ml. Thioflavin T used as a fluorescent substance was dissolved in an assay buffer (50 mM Tris / 150 mM NaCl (pH 7.2), 20 mM HEPES / 150 mM NaCl (pH 7.2), 10 mM phosphate / 150 mM NaCl And used at a concentration of 2 mM. Samples were dissolved in assay buffer and used at a final concentration of 100 μg / ml. In order to measure the degree of inhibition of Aβ _1-42 aggregation, 10 μl of thioflavin T and 85 μl of Aβ _1-42 were added to a 96-well microplate and mixed with 5 μl of a sample prepared at a constant concentration, Were measured with a spectrophotometer. The wavelength of the fluorescence spectrometer used was 440 nm / 484 nm (absorbance / light emission), and the measurement was carried out at 37 ° C for 20 minutes in total for 2 hours. Morin compounds were used as positive controls for activity comparisons.

3. Antioxidant activity analysis

(A) ABTS free radical scavenging ability measurement

The antioxidant activity of ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)) was measured by ABTS + cation decolorization assay. 7 mM ABTS and 2.45 mM potassium persulfate were mixed at a final concentration and incubated in a dark place at room temperature for 24 hours to form ABTS + 占 and diluted with PBS to an absorbance value of 0.7 at 743 nm. The ABTS + solution and the sample were mixed in a 96-well plate, reacted at room temperature for 30 minutes, and then absorbance was measured at 743 nm using an Epoch microplate spectrophotometer. The radical scavenging activity of each sample was expressed as a percentage of the radical scavenging activity relative to the control group using PBS as a control. Vitamin C (vit. C) was used as a positive control for activity comparison.

(B) Measurement of DPPH free radical scavenging ability

DPPH (1-1-diphenyl-2-picrylhydrazyl) radical was used to measure the antioxidant efficacy using a 96-well plate. 0.15 mM DPPH solution and sample were mixed in a 96-well plate, and reacted at room temperature for 30 minutes, and absorbance was measured at 517 nm. The antioxidative activity of each extract was expressed as a percentage of the radical scavenging activity of the control group using DMSO as a control. Vitamin C (vit. C) was used as a positive control for activity comparison.

4. Measurement of nerve cell protection efficacy

(A) Cytotoxicity measurement for neuronal hippocampal cell line

Cell Counting Kit-8 (CCK-8) was used according to manufacturer's instructions to determine the cytotoxicity of the samples. The HT22 cell line (5 × 10 ³ cells / well), which had been divided into 96-well plates, was treated with the samples at different concentrations and cultured for 24 hours. 10 μl of CCK-8 solution was added and cultured for 4 hours. Absorbance was measured at 450 nm and relative cell viability (% of control) was calculated by comparison with the control group.

(B) Measurement of nerve cell protection efficacy

HT22 cells were treated with 250 μM hydrogen peroxide (H ₂ O ₂ ) for 6 hours to induce neuronal damage. Through the CCK assay, H ₂ O ₂ The cell protection efficacy was evaluated by comparing changes in cell survival rate of the single treatment group and samples and simultaneous treatment group of H ₂ O ₂ . Carvedilol was used as a positive control.

(C) LDH assay

Cell viability was measured by measuring LDH efflux due to cell membrane damage. HT22 cells were treated with 250 μM hydrogen peroxide (H ₂ O ₂ ) for 6 hours to induce neuronal damage. The culture supernatant was collected, mixed with the LDH substrate solution in the same amount, and reacted at room temperature for 30 minutes. Then, the reaction was stopped by addition of 1N HCl and the absorbance was measured at 490 nm (experimental LDH release).

After removing the supernatant, the lysis solution was added to the remaining cells, followed by reaction at 37 ° C for 45 minutes, followed by centrifugation at 250 g for 4 minutes. The supernatant was collected and the LDH reaction was performed in the same manner as described above to measure the absorbance at 490 nm (Maximum LDH release). The cell viability was calculated by the following formula (1).

Equation (1)

Cell survival rate (%) = {[experimental LDH release (OD ₄₉₀ )] / [maximum LDH release (OD ₄₉₀ )]}

5. Measurement of inhibitory effect on brain cell inflammation

(A) Measurement of microglial cell toxicity

The BV-2 cell line (1 x 10 ⁴ cells / well) dispensed into 96-well plates was treated with each sample for each concentration and cultured for 24 hours. 10 μl of CCK-8 solution was added and cultured for 4 hours. Absorbance was measured at 450 nm and relative cell viability (% of control) was calculated by comparison with the control group.

(B) NO (nitric oxide) assay

BV-2 cells were pretreated for 2 hours and then treated with LPS (lipopolysaccharide, 1 μg / ml) to induce an inflammatory reaction. After culturing for 24 hours, the supernatant was recovered. The supernatant was mixed with the same amount of Griess reagent (sulfanilamide: N- 1-napthylethylenediamine dihydrochloride = 1: 1) for 5 to 10 minutes, absorbance was measured at 540 nm, and the amount of NO (nitric oxide) was calculated based on the standard curve . Ibuprofen was used as a positive control.

(C) PGE ₂ (Prostaglandin E ₂ ) assay

BV-2 cells were pretreated for 2 hours and then treated with LPS (lipopolysaccharide, 1 μg / ml) to induce an inflammatory reaction. After 24 hours of culture, the supernatant was recovered. Experiments were performed using an enzyme-linked immunosorbent assay (ELISA) kit to measure the amount of PGE _{2 in} the cell culture. The supernatant was added to each well of a 96-well plate coated with goat anti-mouse IgG, and 50 μl of the primary antibody solution and 50 μl of PGE ₂ conjugate were added thereto, followed by reaction at 4 ° C for 18 hours. After washing 5 times with washing buffer solution and treating 200 μl of the substrate solution for 90 minutes, the absorbance was measured at 412 nm.

Example  1. Confirmation of amyloid beta agglutination inhibition efficacy of celestial and tree extracts

6.25, 12.5, 25, 50, and 100 ㎍ / ㎖ of celery, tree leaves and eggplant extracts were treated to inhibit aggregation of amyloid beta. As a result, as shown in FIG. 1, celestial and tree leaf extracts inhibited amyloid beta aggregation in a concentration-dependent manner. When 50 μg / ml of celestial and tree leaf extracts were treated, the inhibition of amyloid beta aggregation was about 60% , And 100 .mu.g / ml of celestial and tree leaf extracts showed that the inhibition of amyloid beta aggregation was about 60% or more. On the other hand, 100 ㎍ / ㎖ of celestial stem and tree branch extract showed 35 ~ 40% inhibition of amyloid beta aggregation.

Example  2. Identification of Antioxidant Activity of Celestial and Tree Extracts

In Example 2, the ABTS radical scavenging activity and the DPPH radical scavenging activity were confirmed in order to examine antioxidative activities of celestial, tree and branch extracts. As shown in Fig. 2, Radical scavenging activity and DPPH radical scavenging activity were shown. The ABTS radical scavenging activity of celestial and tree branch extracts were similar to those of celestial and tree leaf extracts, but DPPH radical scavenging activity showed little.

Example  3. Confirmation of nerve cell protection efficacy of celestial and tree extracts

In Example 3, it was confirmed that celecoxib and tree extracts showed almost no cytotoxicity to normal neurons (Fig. 3 (A)), cell viability was reduced due to H ₂ O ₂ -induced neuronal cell damage, and H ₂ &lt; / _RTI &gt; ₂ inhibited the decrease in cell viability by treating celestial and tree leaf extracts (Fig. 3 (B)).

In addition, the cell membrane of H ₂ O ₂ -adrenergic neurons was damaged and the LDH release was increased. However, the treatment of celestial and tree leaf extracts alleviated the increase of LDH release (FIG. 3C).

Example  4. Confirmation of brain cell inflammation inhibitory efficacy

As shown in FIG. 4, the celecoxib and leaf extracts of the present invention showed almost no toxicity to brain cells and maintained cell survival rate of 100% . The production of NO (nitric oxide) was increased by inducing inflammation in brain cells by treating with LPS. However, when treated with the celery root and leaf extract of the present invention, the production of NO (nitric oxide) was remarkably reduced, Ug / ㎖ of celestial stem and tree leaf extract did not produce nitric oxide (NO).

In addition, the results of measuring the PGE ₂ content in cell culture, if the inflammation is induced on the other hand, the amount of PGE ₂ increased processing group cheonseon and tree leaf extract was found that decreased PGE ₂ quantity compared to the LPS-treated group.

Claims (10)

A pharmaceutical composition for the prevention or treatment of dementia or Alzheimer which contains the extract of Ficus e recta as an active ingredient. delete The pharmaceutical composition for preventing or treating dementia or Alzheimer's disease according to claim 1, wherein the solvent of the cucumber and tree leaf extract is water, a C ₁ -C ₄ lower alcohol or a mixture thereof. delete The pharmaceutical composition for preventing or treating dementia or Alzheimer's disease according to claim 1, which further comprises a pharmaceutically acceptable carrier, excipient or diluent in addition to the active ingredient. The pharmaceutical composition for preventing or treating dementia or Alzheimer's disease according to claim 1, wherein the composition is prepared from any one of a capsule, a powder, a granule, a tablet, a suspension, an emulsion, a syrup and an aerosol. A health functional food composition for preventing or ameliorating dementia or Alzheimer which contains celestial and tree leaf extract as an active ingredient. The health functional food composition according to claim 7, wherein the solvent of the cucumber and tree leaf extract is water, a C ₁ - C ₄ lower alcohol or a mixture thereof. The health functional food composition according to claim 7, wherein the composition has antioxidative activity. The health functional food composition according to claim 7, wherein the composition is prepared from one of powder, granule, ring, tablet, capsule, candy, syrup and beverage.

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