KR20210010160A - A new coumarin compound isolated from Fraxinus rhynchophylla, preparation method thereof and anti-wrinkle composition containing the same as an active ingredient - Google Patents

Abstract

The present invention relates to a method for producing Franoside A, which is a novel coumarin-based compound represented by chemical formula, and a cosmetic composition containing the same as an active ingredient. The coumarin-based compound according to the present invention not only effectively inhibits human neutrophil elastase activities but also exhibits excellent skin wrinkle reducing effects by effectively inhibiting production of nitrogen monoxide. Thus, the composition containing the coumarin-based compound as an active ingredient can be useful as a cosmetic composition for reducing wrinkles.

Description

A new coumarin compound isolated from Fraxinus rhynchophylla, preparation method thereof and anti-wrinkle composition containing the same as an active ingredient}

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Technology pertaining to the invention and prior art in the field

The present invention relates to a novel coumarin-based compound obtained from an ash tree extract and an activity of inhibiting the expression of human neutrophil elastase of the present compound, and in detail, after extracting the bark of ash tree with ethanol, Diaion HP-20 column chromatography is again performed. The chemical structure, physicochemical properties, and elastase inhibitory activity of the novel coumarin-based compound obtained from the fraction are related.This compound was first isolated by the present inventors and the chemical structure and biological activity were identified. It may be provided as an improvement cosmetic composition.

The skin is the largest sensory organ in the human body, occupying the outermost part of the body. The skin weight of an adult is about 5 kg, accounting for about 16% of the total body weight, and the surface area is known to be about 2 m ² . In addition, since the skin has nerves that can sense the sense of touch, pressure, and temperature, it functions to protect the human body from external natural environments such as chemical, physical, and mechanical damage. In addition, skin is particularly responsible for various physiological functions such as preventing unnecessary moisture loss inside the human body, preventing leakage of useful ingredients to the outside, regulating body temperature, and preventing the invasion of bacteria. However, in general, as these skin functions gradually weaken with age, skin aging is promoted, the barrier function of the skin decreases, the skin moisture content decreases, and the skin becomes dry and cell aging is promoted, leading to wrinkles and pigmentation. Various skin lesions develop. The skin is mainly composed of collagen fibers (collagen fibers), elastic fibers, fibrous and dermal matrix, all of which are made by fibroblasts and enhance the elasticity of the skin. It plays an important role in maintaining.

Collagen is a fibrous tissue that gives skin flexibility and accounts for 75% of the dermal tissue and provides a barrier (tensile strength) to the skin. The polypeptide chains of collagen fibers are synthesized in the state of having teleepeptides at both ends within the granular reticulum of fibroblasts, and then secreted out of the cell in the form of a procollagen combined in a triple helix structure. The procollagen secreted in this way is cleaved by a specific enzyme to produce tropocollagen, which is combined with each other in the extracellular matrix to synthesize collagen fibers. Synthesis of such collagen fibers rapidly decreases as skin aging progresses, and as the collagen fibers are deformed by the external environment, many wrinkles are generated and deepened in the skin. Collagenase, a collagenase, is involved in the degradation of collagen.

On the other hand, elastin, which accounts for about 4% of the dry weight of the dermis, is a protein that is thinner and shorter than collagen fibers. It has a net shape and crosslinks each molecule. Its main function is the cells responsible for the elasticity of the skin so that the skin deformed by the applied force returns to its original shape, and is deeply involved in the relaxation and wrinkles of the skin. Elastin is degraded by a serine-based degrading enzyme called elastase (Human Neutrophil Elastase, EC 3.4.21.37), and it continues to be produced by fibroblasts until 18-19 years of age, but production ceases after that. It has to be in charge of elasticity, so once elastin is weakened, it is very difficult to restore its elasticity. In other words, deficiency and aggregation of elastin fibers, and a marked increase in the activity of elastase, are the main factors in the creation of skin wrinkles, so inhibition of its expression as the only enzyme capable of decomposing elastin can fundamentally reduce skin wrinkle improvement. have.

In particular, human neutrophil elastase (HNE) is a serine protease mainly located in the Hoazur granules of polymorphonuclear leukocytes, and is a water-soluble elastic fiber protein such as elastin, fibronectin, and collagen. , It has a substrate specificity that degrades connective tissue proteins such as cartilage issues. Biologically, it is known that elastase activity increases significantly with age, thereby reducing skin elasticity. Therefore, it is expected that skin wrinkles can be improved by inhibiting the elastase activity (Steinbrecher T. et al., Bioorg. Med. Chem 2008, 16:2385-2390).

The following patents are known as functional substances related to cosmetic compositions and health functional foods produced by ash tree.

Skin whitening composition of fermented ash tree extract (Korean patent registration 10-1820732)

Efficacy in improving skin wrinkles by inhibiting MMP-1 and collagen production (Korean Patent Publication 10-2019-0050415)

Antioxidant and skin inflammation improvement cosmetic composition (Korean patent registration 10-1829892)

Health functional food containing ash tree extract (Korean patent registration 10-1944016)

Effectiveness in preventing depression and anxiety disorders (Korean patent publication 10-2019-0042350)

Mass propagation method using bioreactor (Korean patent registration 10-1179610)

However, all of the patents related to the ash tree and other documents presented as examples above are compositions obtained from the ash tree extract, and there is no study on the chemical and physical substance exhibiting the activity.

Unlike the above patents, this patent is a novel and advanced patent in which the chemical structure and separation and purification of effective substances from ash tree leaves are fully identified.In particular, the coumaran-based compound proposed in this patent is first separated by themselves. It is a new and more advanced patent that investigates the effect of improving skin wrinkles and inhibiting nitrogen monoxide through the manufacturing method, chemical structure, physicochemical properties, and elastase inhibitory activity of the material.

On the other hand, Fraxinus rhynchophylla is a deciduous arboreous tree belonging to the genus Ash tree family, and is a large tree reaching 30 m in height and 50 cm in diameter, and is distributed nationwide in Korea. The leaves are opposite, and the number of the leaves is the upper right biplane. There are 5-7 lobules, ovate, wide ovate, broad lanceolate or lanceolate. The length is 6~15cm, the surface is green, hairless, the back side is gray-green, and the edge has wavy serrations or is flat. The flowers are male and female, but bisexual flowers are sometimes mixed. It blooms in May and runs in a conical inflorescence on the axils of young branches. The male flower has 2 stamens and 2 pieces of calyx, and the female flower has 2~4 pieces of calyx, stamens, and pistils, and the petals are in the shape of a lancet upside down. Fruits are citrus fruits, 2-4 cm long, and ripen in September. The wings of the fruit are lancet shaped or long lancet shaped. It is called an ash tree because the water turns blue when the branches are immersed in water.

In oriental medicine, bark is used as a treatment for rheumatism, gout, uric acidosis, bronchitis, enteritis, and dysentery because bark has the effect of antipyretic, analgesic, blue liver, and anti-inflammatory. In addition, it was used as an adhesive to make food by putting glue in the juice obtained from the skin (Moo Yeon Jo, Primary Color Korean Tree Book, Academy Book, p. 416, 1992).

Previous studies isolated from ash trees include lignan, simple structured phenolic compounds, flavonoids, and secoiridoid glucosides. The presence of compounds such as coumarins has been reported (Si CL et al., Chem. Nat. Comp., 2009, 45:814-816, Kostova I. et. al. , Fitoterapia, 2007, 78:85- 106, Kwon YS et. al ., Kor. J. Pharmacogn. 1996, 27:347-349, Ahn JH et. al ., Nat. Prod. Sci., 2013, 19: 236-241)

The biological efficacy of ash tree extract is also known for various activities such as antioxidant activity, antibacterial activity, and anti-inflammatory activity (Kostova I. et. al ., J. Ethnopharmacol. 1993, 39:205-208, Stefanova Z. et. al. , J. Ethnopharmacol. 1995, 46:101-106, Ivanovska N. et. al. , Meth. Find. Exp. Clin. Pharmacol, 1994, 16:557-562, Marinova EM et. al ., Food Chem. 1994 , 51:125-132)

However, among the compounds isolated from ash trees in the related art, the effect related to the effect of inhibiting expression of human neutrophil elastase is not known at all. In addition, coumarin-based compounds such as Formula 1 presented in the present invention have not yet been reported to the world, and the present invention was completed by revealing the chemical structure, physicochemical properties, and inhibitory efficacy of human neutrophil elastase expression for the first time by the present inventors. I did.

[Technical task to be achieved]

Therefore, the technical problem to be achieved by the present invention is to inhibit the expression of human neutrophil elastase from the ash tree extract and at the same time provide a method for preparing a novel coumarin compound with excellent safety when applied to the skin, chemical structure, physicochemical properties and efficacy. will be.

[Composition of the invention]

In order to achieve the above technical problem, the present invention provides a coumarin-based compound extracted from the bark of the ash tree ( Fraxinus rhynchophylla ) represented by the following Chemical Formula 1, and a method for preparing the same.

[Formula 1]

In addition, the present invention provides a pharmaceutical composition for preventing and improving skin wrinkles by inhibiting the expression of human neutrophil elastase containing the coumarin-based compound represented by Formula 1 as an active ingredient.

Furthermore, the present invention provides a composition for preventing and improving wrinkles containing the coumarin-based compound represented by Formula 1 as an active ingredient.

Since the coumarin-based compound according to the present invention effectively inhibits human neutrophil elastase activity and exhibits excellent skin wrinkle improvement effect, a composition containing them as an active ingredient can be usefully used in cosmetics for wrinkle improvement.

1 is a ¹³ C-NMR spectrum and ¹ H-NMR spectrum data of Example 1 according to the present invention.

The present invention provides a coumarin-based compound represented by the following formula (1).

[Formula 1]

Formula 1 is referred to as Furanoside A.

In addition, the present invention includes not only the furanoside A compound of Formula 1 or a pharmaceutically acceptable salt thereof, but also all possible solvates or hydrates that can be prepared therefrom.

Furthermore, the present invention provides a method for preparing a furanoside A compound represented by Chemical Formula 1.

The coumarin-based compound of Formula 1 according to the present invention is obtained by adding water, an organic solvent or a mixed solvent thereof to an ash tree to obtain an ash tree extract (step 1);

Next, the step 2 is a step of dispersing the ash tree extract obtained in step 1 in water, and then sequentially fractionating with a solvent having a different polarity to obtain a fraction (step 2); And

The ash tree fraction obtained in step 2 may be prepared by a manufacturing method comprising the step of performing Diaion HP-20 column chromatography (step 3).

Hereinafter, the manufacturing method according to the present invention will be described in more detail step by step.

First, step 1 according to the present invention is a step of obtaining an ash tree extract as an extraction solvent.

It can be obtained by extracting from the ash tree or a dried product thereof, and the ash tree may be used without limitation, such as harvested or commercially available.

The extract is a method using an extraction device such as supercritical extraction, subcritical extraction, high temperature extraction, high pressure extraction, or ultrasonic extraction method, or a method using an adsorption resin including XAD and HP-20. It may be prepared, preferably heated and prepared by reflux extraction or extraction at room temperature, but is not limited thereto. The number of extractions is preferably 1 to 5 times, and more preferably, extraction is repeated 3 times, but is not limited thereto.

The extract may be extracted using water, an organic solvent, or a mixed solvent thereof as an extraction solvent. The organic solvent is preferably any one selected from the group consisting of C1 to C4 alcohol, ethyl acetate, methylene chloride and chloroform, or a mixed solvent thereof, more preferably a C1 to C4 alcohol, and extracted with ethanol. It is most preferred. The extraction solvent is preferably added in an amount of 2 to 10 times the weight of the ash tree to extract, and it is more preferable to extract it in an amount of 3 to 5 times, but is not limited thereto.

For example, the ash tree extract according to the present invention can be obtained by pulverizing the dried ash tree into an appropriate size, putting it in an extraction container, adding an extraction solvent, leaving it for a certain period of time, and then filtering it with filter paper, etc. to obtain an alcohol extract. The extraction time is preferably 1 to 5 days, more preferably 2 to 4 days. After that, a method such as vacuum concentration or freeze drying may be additionally performed.

Next, step 2 is a step of dispersing the ash tree extract obtained in step 1 in water, and then sequentially fractionating with a solvent having a different polarity to obtain a fraction.

Next, step 3 is a step of performing column chromatography on the fraction obtained in step 2.

A column filled with Diaion HP-20 may be used as the column for chromatography of the column chromatography.

The fraction obtained in step 2 was subjected to concentration gradient Diaion HP-20 column chromatography using a mixed solvent of methanol and water. At this time, the concentration gradient of the mixed solvent of methanol and water is preferably 1:100 to 100:1, the flow rate is preferably 4.0 to 5.0 ml/min, and the execution time is preferably 20 to 25 hours.

The fraction obtained by performing the Diaion HP-20 column chromatography may be subjected to chromatography using a concentration gradient reversed phase C-18 column using a mixed solvent of methanol and water. At this time, the concentration gradient of the mixed solvent of methanol and water is preferably 2:8 to 100:1.

After performing the Diaion HP-20 column chromatography and reverse phase C-18 column chromatography, high performance liquid chromatography may be performed to separate the furanoside A compound of Formula 1. The high performance liquid chromatography may be performed using a mixed solvent (3:7) of methanol and distilled water as a developing solvent. At this time, the flow rate of the mobile phase is preferably 3.0 to 5.0 ml/min, and the execution time is preferably 20 to 50 hours.

In addition, the present invention provides a pharmaceutical composition for preventing and treating wrinkles containing furanoside A, a coumarin-based compound represented by Chemical Formula 1, or a pharmaceutically acceptable salt thereof as an active ingredient.

The furanoside A compound of Formula 1 according to the present invention can be used for preventing and treating wrinkles by inhibiting human neutrophil elastase activity. Their use for preventing and treating wrinkles will be described based on specific experimental results.

The coumarin-based compound of Formula 1 according to the present invention inhibits elastase activity in a concentration-dependent manner in a human neutrophil elastase inhibitory effect measurement experiment, and exhibits an IC ₅₀ value of 3.6 ± 0.2 μM, which is very good at inhibiting elastase activity. By showing the effect, it can be seen that an excellent skin wrinkle improvement effect is exhibited (see Example 2 and Table 1).

Therefore, since the furanoside A compound of Formula 1 according to the present invention effectively inhibits human neutrophil elastase activity and exhibits excellent skin wrinkle improvement effect, a composition containing them as an active ingredient is usefully used in cosmetics for wrinkle improvement. I can.

Further, the present invention provides a cosmetic composition for preventing and improving wrinkles containing the furanoside A compound represented by Chemical Formula 1 or a cosmetically acceptable salt thereof as an active ingredient.

The cosmetic composition for preventing and improving wrinkles containing the furanoside A compound represented by Formula 1 or a cosmetically acceptable salt thereof according to the present invention as an active ingredient is a basic cosmetic composition (toilet water, Face wash such as cream, lotion, essence, cleansing foam and cleansing water, pack, body oil), color cosmetic composition (foundation, lipstick, mascara, makeup base), hair product composition (shampoo, conditioner, hair conditioner, hair gel), It can be manufactured in the form of soap or the like.

The excipients may include emollients, skin penetration enhancers, colorants, fragrances, emulsifiers, thickeners, and solvents, but are not limited thereto. In addition, flavoring, coloring, disinfecting agents, antioxidants, preservatives, moisturizing agents, etc. may be additionally included, and thickeners, inorganic salts, synthetic polymer materials, etc. may be included for the purpose of improving physical properties. For example, in the case of preparing a face wash and soap with the cosmetic composition of the present invention, a megastigman derivative compound of Formula 1 or Formula 2 or a cosmetically acceptable salt thereof may be added to a conventional face wash and soap base. Can be manufactured. When preparing a cream, it can be prepared by adding a coumarin-based compound represented by Formula 1 or a cosmetically acceptable salt thereof to a general oil-in-water (O/W) cream base. Synthetic or natural materials such as proteins, minerals, vitamins, etc. for the purpose of improving physical properties, such as fragrances, chelating agents, coloring agents, antioxidants, preservatives, etc., may be additionally added.

The content of the coumarin-based compound represented by Formula 1 or a cosmetically acceptable salt thereof contained in the cosmetic composition of the present invention is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight based on the total weight of the composition. However, it is not limited thereto. When the content is less than 0.001% by weight, the desired wrinkle improvement effect cannot be expected, and when the content is more than 10% by weight, safety or formulation may be difficult to manufacture.

In addition, the cosmetic composition of the present invention includes a fatty substance, an organic solvent, a solubilizing agent, a thickening agent, a gelling agent, an emollient, and an antioxidant in addition to the furanoside A compound or a cosmetically acceptable salt thereof, which is a coumarin-based compound represented by Formula 1 above. Agents, suspending agents, stabilizers, foaming agents, fragrances, surfactants, water, ionic or nonionic emulsifiers, fillers, sequestering agents and chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils , Dyes, pigments, hydrophilic or lipophilic actives, lipid vesicles or any other ingredients commonly used in cosmetics, such as adjuvants commonly used in the field of cosmetics or dermatology. And the above ingredients may be introduced in an amount generally used in the field of dermatology.

Hereinafter, the present invention will be described in detail by examples and experimental examples.

However, the following examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following examples.

Example 1. Preparation of Furanoside A

Step 1: Preparation of ethanol extract of ash tree

1 kg of ash tree trunks collected in Namyangju, Gyeonggi-do was placed in an extraction container, and 10 ℓ of 70% ethanol was added to extract for 3 days at room temperature, and then filtered through filter paper to obtain an extract. The extraction process was repeated three times, and then the solvent was concentrated under reduced pressure and dried to obtain 106 g of an ethanol extract.

Step 2: Preparation of ash tree extract fraction

In order to fractionate the ethanol extract obtained in Preparation Example 1 according to polarity, systemic fractionation using an organic solvent was performed. Specifically, the ethanol extract was subjected to Diaion HP-20 column chromatography. At this time, four fractions were obtained by sequentially fractionating from 100% water to 100% methanol.

Step 3: Preparation of Furanoside A

The ethanol fraction obtained in step 2 of Preparation Example 1 was purified by chromatography using a concentration gradient reversed phase C-18 column using a mixed solvent of methanol and water (20-100%), and then high-performance liquid chromatography was performed. To obtain purely purified furanoside A. At this time, a peak appearing at 20 minutes was obtained using a mixed solvent of methanol and water (3:7) as a mobile phase. The flow rate was 4 ml/min, and a YMC-Pack ODS (20×250 mm) column was used.

Physicochemical properties of Furanoside A

IUPAC Name: Fraxetin 8-O-(6'-O-galloyl)-β-D-glucopyranoside

Appearance: white powder;

: +30.0 (c 0.1, MeOH)

: +30.0 ( c 0.1, MeOH)

UV (MeOH) λ _max (log ε ): 225 (3.4), 280 (2.8), 340 (1.2) nm

IR (KBr) ν _max : 3255, 1699, 1603, 1447, 1391, 1307 cm ^-1

HR-ESI Ms m/z: 559.1065 [M+Na] ⁺ (calc. for C ₁₅ H ₂₂ O ₃ ,Na, 559.1064)

Molecular formula: C ₂₄ H ₂₄ O ₁₄

Molecular weight: 536.44

NMR was measured using a Bruker DRX-400 spectrometer, ¹³ C-NMR (100 MHz) and ¹ H-NMR (400 MHz), and 2D-NMR (HMQC and HMBC) was measured with a Bruker Avence 500 NMR spectrometer. Tetramethylsilane (TMS) was used as an internal standard.

^{The data of the 13} C-NMR spectrum, ¹ H-NMR spectrum, and HMBC spectrum are as follows.

NMR spectrum of Furanoside A

¹ H-NMR (400 MHz, CD ₃ OD) δ _H

7.66 (1H, d, J = 9.6 Hz, H-4), 6.78 (2H, s, H-2 " , 6 " ), 6.70 (1H, s, H-5), 6.30 (1H, d, J = 9.6 Hz, H-3), 5.21 (1H, d, J = 5.2 Hz, H-1 ' ), 4.51 (1H, dd, J = 11.6, 7.6 Hz, H-6 ' a), 4.30 (1H, dd , J = 11.6, 2.0 Hz, H-6 ' b), 3.92 (3H, s, OC H ₃ -7),3.81(3H,s,OC H ₃ -6),3.55(1H,m,H-2 ' ), 3.52 (1H, m, H-4 ' ), 3.48 (1H, m, H-3 ' ), 3.41 (1H, m, H-5 ' );

¹³ C-NMR (100 MHz, CD ₃ OD) δ _C

167.9 (C-7 " ), 163.0 (C-2), 151.6 (C-6), 146.4 (C-3 " , 5 " ), 145.9 (C-4), 143.7 (C-9), 142.7 (C -8), 142.4 (C-7), 139.7 (C-4 " ), 121.4 (C-1 " ), 116.8 (C-10), 115.6 (C-3), 110.1 (C-2 " , 6 " ), 105.9 (C-5), 103.5 (C-1 ' ), 78.1 (C-3 ' ), 75.9 (C-4 ' ), 75.7 (C-2 ' ), 72.4 (C-5 ' ), 64.4 (C-6 ' ), 62.5 (7-O C H ₃ ), 57.0 (6-O C H ₃ );

Example 2. Elastase inhibitory activity of Furanoside A

When human neutrophil elastase, an enzyme that decomposes elastin, exhibits activity, elastin, an elastic fiber, is decomposed, thereby accelerating the formation of skin wrinkles. In order to measure the inhibitory effect of the compound according to the present invention on the activity of human neutrophil elastase, an experiment was performed as follows.

Furanoside A, the compound of Example 1, was dissolved in 500 µl of DMSO at concentrations of 1, 3, 10, 30, and 100 µM, and then Tris-HCl buffer was added to prepare an experimental solution. 60 µl of the above test solution and N-methoxysuccinyl-ala-ala-pro-val-p-nitroanilide, a substrate of elastase, N-methoxysuccinyl-alanine-alanine-proline-valine-p-nitroanilide 125 µl and 390 µl of Tris-HCl buffer were mixed, and 25 µl of human neutrophil elastase (0.18 units) was added, followed by incubation at 37°C for 1 hour. After 1 hour, the reaction was stopped by adding a soybean trypsin inhibitor. When decomposed, N-methoxysuccinyl-alanine-alanine-proline-valine-p-nitroanilide, the substrate of elastase, becomes yellow p-nitroaniline, and the degree of color development of p-nitroaniline is determined by a spectrometer. The elastase activity inhibition rate was measured by measuring the absorbance at 405 nm. EGCG was used as a positive control. The elastase activity inhibition rate was calculated by the following equation (1), and the IC ₅₀ value was calculated by measuring the elastase activity inhibitory effect for each concentration of the compound. The results are shown in Table 1 below.

A: Absorbance in the absence of an elastase activity inhibitor

B: absorbance in the presence of an elastase activity inhibitor

Referring to Table 1, it can be seen that the compound according to the present invention inhibits elastase activity in a concentration-dependent manner. Particularly, it can be seen that the furanoside A compound of Example 1 exhibits an IC ₅₀ value of 3.6 ± 0.2 μM, thereby exhibiting a strong elastase activity inhibitory effect similar to that of EGCG used as a control.

Example 3. Atopic Anti-inflammatory Inhibitory Activity of Furanoside A

Various mediators are involved in the mechanism of expression of inflammation, and the causes of the disease are also diverse. When macrophages are treated with lipopolysacharide (LPS) known as endotoxin, NO biosynthesis is increased by the expression of iNOS (inducible NOS) and an inflammatory response is induced. NO is a pathological secondary signaling material secreted by many cells, regulates the activity of COX, and acts synergistically in the inflammatory response. By measuring NO produced by NOS induced by LPS in Raw264.7 cells, the effect of inhibiting atopic inflammatory reaction of furanoside A according to the present invention can be determined.

In order to confirm the anti-inflammatory effect of the compound of Formula 1, nitrix oxide (NO) inhibitory activity was performed by the Griess method using the RAW264.7 cell line.

In detail, RAW264.7 cells, which are macrophages, were subcultured several times, put into a 24-well plate so as to enter each of 5×10 ⁴ cells in each well, and cultured for 24 hours. Subsequently, it was replaced with a cell medium diluted with the compound of Formula 1 at a final concentration of 1, 2, 5, 10, and 20 μM. At this time, the NO-production inhibitor L-NMMA (L-NG-Monomethyl arginine) was treated together as a positive control and incubated for 30 minutes, and LPS (Lipopolysaccharide) was treated with 1 μg each and cultured for 24 hours. Take 100 μl of the supernatant, transfer it to a 96-well plate, add 100 μl of Griess solution, react at room temperature for 10 minutes, and measure the absorbance at 540 nm to investigate the NO inhibitory effect of the compound of Formula 1, and the results are as follows. Shown in Figure 1

Figure 1. Effect of Formula 1 Furanoside A on Nitric Oxide Inhibitory Activity

Referring to the above figure, it can be seen that the furanoside A compound according to the present invention inhibits nitrix oxide activity in a concentration-dependent manner. In particular, it can be seen that the compound of Example 1, the furanoside A compound, exhibits an IC ₅₀ value of 3.6 ± 0.2 μM, thereby exhibiting a better inhibitory effect on nitrix oxide activity than the control.

Figure 2. iNOS and COX-2 inhibitory activity of Furanoside A

Referring to the above figure, it can be seen that the furanoside A compound according to the present invention is an excellent compound that inhibits iNOS and COX-2 activity in a concentration-dependent manner.

Formulation Example 1: Manufacture of cosmetics

Formulation Example 1-1: Preparation of lotion

When the lotion was prepared with all the ingredients presented in Formulation Example 1-1, it was confirmed that lotion production was possible effectively.

Formulation Example 1-2: Preparation of lotion

It was confirmed that when a cream was prepared with all the ingredients presented in Formulation Example 1-2, it was possible to effectively prepare a cream.

Formulation Example 1-3: Preparation of atopic lotion

It was confirmed that when an atopy lotion was prepared with all the ingredients presented in Formulation Example 1-3, it was possible to effectively produce a lotion for atopy.

Effects of the Invention

As described in detail above, the furanoside A compound, a coumarin-based compound derived from an ash tree extract according to the present invention, is the first new compound having a chemical structure that has not yet been reported, and has an excellent effect of inhibiting the activity of human neutrophil elastase. By inhibiting the activity of nitrogen monoxide and consequently inhibiting the activity of iNOS and COX-2, it has the advantage of exhibiting excellent skin wrinkle improvement effect without skin irritation, so it can be used as a novel cosmetic composition.

Claims (7)

Coumarin-based compound represented by the following formula (1).
[Formula 1]

The compound of claim 1, wherein the coumarin-based compound represented by Formula 1 is isolated from an extract of Fraxinus rhynchophylla . Obtaining an extract of Fraxinus rhynchophylla (Step 1); And
Separating the coumarin-based compound from the ash tree extract obtained in step 1 (step 2); a method for producing a coumarin-based compound represented by Formula 1 of claim 1, comprising. A cosmetic composition for preventing or improving skin wrinkles containing a coumarin-based compound represented by Formula 1 of claim 1 as an active ingredient The cosmetic composition of claim 4, wherein the cosmetic composition for preventing or improving skin wrinkles inhibits the expression of human neutrophil elastase. A cosmetic composition for preventing or improving inflammation containing the coumarin-based compound represented by Formula 1 of claim 1 as an active ingredient The cosmetic composition according to claim 6, wherein the cosmetic composition for preventing or improving inflammation inhibits the expression of nitrogen monoxide.

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