KR20160019006A - Pharmaceutical composition comprising Astragali radix derivative for preventing or treating arthritis - Google Patents

Abstract

The present invention relates to a pharmaceutical composition comprising a substance derived from Astragali Radix for preventing or treating arthritis and, more specifically, to a pharmaceutical composition comprising a substance derived from Astragali Radix having preventive or therapeutic activities for arthritis by inhibiting the activities of matrix metalloprotease (MMP)-1, MMP-2, MMP-3, MMP-9, and MMP-13, and to a health functional food composition for preventing or alleviating arthritis.

Description

[0001] The present invention relates to a pharmaceutical composition for preventing or treating arthritis,

The present invention relates to a pharmaceutical composition for preventing or treating arthritis, which comprises a material derived from a stem cell. More particularly, the present invention relates to a pharmaceutical composition for preventing or treating arthritis comprising matrix metalloprotease (MMP) -1, MMP-2, MMP- And MMP-13, thereby to prevent or treat arthritis, and a health functional food composition for preventing or ameliorating arthritis.

Arthritis is a disease caused by inflammatory changes in the joints caused by various causes such as bacteria and trauma. The incidence of arthritis is estimated to be about 30% of the population over 60 years old. According to foreign statistics, It is known as a disease that is. In addition, recent research by the Korea Institute for Health and Social Affairs has reported that, in Korea, arthritis has the highest incidence of diabetes and hypertension after 50 years of age. Therefore, many researchers expect arthritis to arise as the most important disease that can interfere with the quality of life of mankind in the 21st century along with cancer and cardiovascular disease.

On the other hand, arthritis can be classified into non-inflammatory arthritis and inflammatory arthritis. Non-inflammatory arthritis is an osteoarthritis, and inflammatory arthritis is rheumatoid arthritis.

Degenerative arthritis is caused by degeneration of chondrocytes constituting the joints, which inhibits the synthesis of type 2 collagen (type II collagen) and proteoglycan, which are matrix materials of joints in chondrocytes, and inhibits interleukin- The synthesis and activity of matix metalloproteinase (hereinafter referred to as "MMP"), which degrades the matrix of the joint due to the production of inflammatory cytokines such as 1? And tumor necrosis factor, It is a disease caused by destruction. In addition, inflammatory cytokines increase the production of prostaglandin E2 (hereinafter referred to as "PGE2 "), a lipid metabolite, resulting in an inflammatory response in the joints. Rheumatoid arthritis is a systemic inflammatory reaction that affects many tissues and organs (skin, blood vessels, heart, lungs, muscles) in the body and especially affects the joints causing irreversible proliferative synovitis, And the stiffness of the joint. Major symptoms include fatigue, weakness, pain, arthritis, fever and weakness. In addition, muscle atrophy and muscle spasm appear near the inflamed joints, affecting movement of the joints.

Therefore, the purpose of treating arthritis is to reduce the pain and inflammation of the joints, not only to prevent joint deformation, but also to fundamentally elucidate the mechanism of intracellular action that induces arthritis and to control its mechanism. Treatment of degenerative arthritis, which is currently being used clinically, can be performed by using drugs (analgesics, steroids, nonsteroidal anti-inflammatory drugs) or cartilage protectants (hyaluronic acid, glucosamine, chondroitin, etc.) Tibial proximal osteotomy, joint replacement, and total knee arthroplasty). However, these methods are not directly related to the removal of underlying causes such as chondrocyte degeneration or control of MMP activity and synthesis. In other words, the drug treatment agent only has the effect of nonspecifically alleviating the pain or the inflammatory reaction itself, and the cartilage protecting agent only serves to protect the joints by nourishing the cartilage cells or mitigating the impact. In addition, these drugs should be used with caution because they exhibit side effects such as weight gain, hypertension induction, and peptic ulcer induction. Recently, it has been urgently required to develop a new therapeutic agent which has a relatively low side effect when applied in vivo and has an effect of alleviating symptoms of arthritis.

[0002] The present invention relates to a method for producing a natural herbal medicine extract, which induces a joint protecting activity, and is characterized in that it contains Chunma, Hwanggi, and Cordyceps Discloses an extract of arthritic neuronal cell death inhibitory activity which is prepared by mixing antler antler with hot water or extracting with alcohol, methanol and ethyl ether fractions.

In addition, a mixed extract containing Juniper berry extract, European grape skin extract and European grape seed extract extracted by hot water extraction method or alcohol extraction method is used as an active ingredient in the patent document 10-2010-0115489 (public date: October 28, 2010) Or a pharmaceutically acceptable salt thereof, for the treatment of arthritis.

Accordingly, the present invention provides a pharmaceutical composition for prevention or treatment of arthritis, which has few side effects when administered in vivo and effectively inhibits the activity of cartilage matrix metalloproteinase, Composition.

The present invention provides a pharmaceutical composition for preventing or treating arthritis comprising at least one compound selected from the group consisting of compounds represented by the following formulas (1) to (2) and pharmaceutically acceptable salts thereof.

According to a preferred embodiment of the present invention, the pharmaceutical composition for preventing or treating arthritis may include a compound represented by Formula 1 and a compound represented by Formula 2 below.

According to another preferred embodiment of the invention, the compound represented by the formula (2) or compound of the formula (1) is Astragalus (Astragali radix ).

According to another preferred embodiment of the present invention, the pharmaceutical composition for preventing or treating arthritis is selected from the group consisting of cartilage matrix metalloprotease (MMP) -1, MMP-2, MMP-3, MMP- 13 < / RTI > activity and may have arthritis prevention or therapeutic activity.

According to another preferred embodiment of the present invention, the arthritis may be degenerative arthritis.

The present invention also provides a health functional food composition for preventing or ameliorating arthritis comprising at least one compound selected from the group consisting of the compounds represented by formulas (1) to (2) and the pharmaceutically acceptable salts thereof.

According to a preferred embodiment of the present invention, the compound represented by the formula (2) or compound of the formula (1) is Astragalus (Astragali radix ).

According to another preferred embodiment of the present invention, the arthritis may be degenerative arthritis.

According to another preferred embodiment of the present invention, the health functional food composition contains at least one of matrix metalloprotease (MMP) -1, MMP-2, MMP-3, MMP-9 and MMP- Inhibiting or improving arthritis activity.

Hereinafter, terms of the present invention will be described.

The "matrix metalloproteinase (MMP)" of the present invention is an enzyme that decomposes extracellular matrix (ECM) proteins as a zinc-dependent endopeptidase. MMP plays an important role in tissue remodeling associated with various physiological and pathological processes such as morphogenesis, angiogenesis, tissue repair, cirrhosis, arthritis and metastasis.

The term " treatment "or" improvement "as used herein means all actions that inhibit arthritis or delay the onset of arthritis by administration of the composition. It means all acts that change.

The present invention relates to a pharmaceutical composition for prevention or treatment of arthritis which has few side effects when applied in vivo and which effectively inhibits the activity of cartilage matrix degrading enzyme and alleviates and alleviates the symptoms of arthritis and a health functional food composition for preventing or improving arthritis .

Hereinafter, the present invention will be described in more detail.

As described above, conventional medicines have only an effect of nonspecifically relieving the pain or the inflammatory reaction itself. The cartilage protecting agent only serves to protect joints by supplying nutrition to cartilage cells or alleviating impact, In addition, these drugs have side effects such as weight gain, hypertension induction, and peptic ulcer induction, so there is a problem that they should be careful in selection. Therefore, it is urgently required to develop a new therapeutic agent which has a relatively low side effect when applied in vivo and has an effect of alleviating symptoms of arthritis.

The present invention solves the above-mentioned problems by providing a pharmaceutical composition for preventing or treating arthritis comprising at least one compound selected from the group consisting of compounds represented by the following formulas (1) to (2) and pharmaceutically acceptable salts thereof. Accordingly, the present invention provides a pharmaceutical composition for preventing or treating arthritis, which has few side effects when applied in vivo and effectively inhibits the activity of cartilage matrix metalloproteinase and has a remarkable effect of alleviating symptoms of arthritis, and a health functional food composition for preventing or improving arthritis .

[Chemical Formula 1]

(2)

The compound represented by formula (2) or compound of the formula (1) is so long that can be purchased or extracted in a conventional manner is not particularly limited, preferably the Astragalus (Astragali radix ).

The pharmaceutically acceptable salt of the compound represented by the formula (1) or the compound represented by the formula (2) may be an acid addition salt formed by a pharmaceutically acceptable free acid, and the free acid may be an organic acid And inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, sulfuric acid, phosphoric acid and the like can be used as the inorganic acid. Examples of the organic acid include citric acid, acetic acid, maleic acid, fumaric acid, gluconic acid, , Succinic acid, tartaric acid, 4-toluenesulfonic acid, galacturonic acid, embonic acid, glutamic acid, citric acid, and arpartic acid.

The addition salt according to the present invention can be obtained by a conventional method, that is, dissolving the compound represented by Formula 1 or the compound represented by Formula 2 in a water-miscible organic solvent such as acetone, methanol, ethanol or acetonitrile, By adding an organic acid or by adding an aqueous acid solution of an inorganic acid, followed by precipitation or crystallization, or by evaporating a solvent or an excess of an acid, followed by drying or precipitating the salt by suction filtration.

The present invention encompasses the compounds represented by the above general formula (1), the compounds represented by the general formula (2) or their respective salts as well as solvates, hydrates and stereoisomers which exhibit the same effects as those which can be prepared therefrom.

As shown in Experimental Example 2 and FIGS. 1 to 4, the pharmaceutical composition for the prevention or treatment of arthritis inhibits the activity of matrix metalloprotease (MMP), which is a major cause of arthritis, Therapeutic activity was confirmed.

In addition, the arthritis is not particularly limited as long as it is a common non-inflammatory arthritis and inflammatory arthritis, but it may preferably be degenerative arthritis.

The pharmaceutical composition of the present invention may be formulated into a unit dosage form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container.

The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But may include calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, But is not limited thereto.

The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention can be administered orally or parenterally. In the case of parenteral administration, intravenous injection, subcutaneous injection, muscle injection, intraperitoneal injection, endothelial administration, topical administration, intranasal administration, And the like. When administered orally, the protein or peptide is extinguished and the oral composition should be formulated to coat the active agent or protect it from degradation from above. The pharmaceutical composition may also be administered by any device capable of transferring the active agent to the target cell.

The appropriate dosage of the pharmaceutical composition of the present invention varies depending on factors such as the formulation method, the administration method, the age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate and responsiveness of the patient, Usually, a skilled physician can readily determine and prescribe dosages effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001 to 100 mg / kg. As used herein, the term "pharmaceutically effective amount" means an amount sufficient to prevent or treat vascular disease and / or an amount sufficient to inhibit angiogenesis.

The pharmaceutical composition of the present invention may be administered as an individual prophylactic agent or a therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents.

Further, the present invention provides a health functional food composition for preventing or ameliorating arthritis comprising at least one compound selected from the group consisting of the compounds represented by Formulas 1 to 2 and the pharmaceutically acceptable salts thereof.

The compound represented by formula (2) or compound of the formula (1) is so long that can be purchased or extracted in a conventional manner is not particularly limited, preferably the Astragalus (Astragali radix ).

As shown in Experimental Example 2 and FIGS. 1 to 4, the pharmaceutical composition for the prevention or treatment of arthritis inhibits the activity of matrix metalloprotease (MMP), which is a major cause of arthritis, Therapeutic activity was confirmed.

In addition, the arthritis is not particularly limited as long as it is a common non-inflammatory arthritis and inflammatory arthritis, but it may preferably be degenerative arthritis.

The kind of health functional food composition is not particularly limited as long as it is usually produced and / or sold. For example, dairy products such as meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums and ice cream, soups, drinks, tea, drinks, alcoholic beverages, And can be used in the form of pills, powders, granules, infusions, tablets, capsules or beverages and includes all of the health functional food compositions in the conventional sense.

The health beverage composition of the present invention is not particularly limited as long as it contains at least one member selected from the group consisting of the compounds represented by the formulas (1) to (2) and salts thereof, and includes various flavors or natural carbohydrates Or the like as an additional component.

Usually, the amount of the compound comprising at least one of the compounds represented by the above formulas (1) to (2) and salts thereof contained in the health functional food composition is 0.1 to 50% by weight, preferably 1 To 40% by weight. In addition, in the case of long-term ingestion 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.

Hereinafter, the present invention will be described in more detail with reference to the following Examples. However, these drawings and the following embodiments are only illustrative of the contents and scope of the technical idea of the present invention, and the technical scope of the present invention is not limited or changed. It will be apparent to those skilled in the art that various modifications and variations are possible within the scope of the technical idea of the present invention based on these examples.

[ Example ]

Example  One. Hwanggi  Separation of single compounds derived

1-1. Hwanggi  Extract preparation

10 kg of dried peat hulls were pulverized to an appropriate size, and then 36 liters of 80 wt% methanol aqueous solution was added. After extraction at 25 DEG C for 24 hours, the mixture was filtered through a filter paper and concentrated under reduced pressure to obtain 1,387 g of methanol extract.

1-2. Hwanggi  From the extract, Fraction  Produce

1,387 g of the crude extract of Example 1-1 in Example 1-1 was subjected to partition extraction with ethyl acetate (3 L × 2) and water (3 L), and water was further subjected to partition-extraction with n-butanol (2.5 L × 3). Ethyl acetate fraction, water fraction and n-butanol fraction were prepared by concentrating the ethyl acetate distribution extract, the water distribution extract and the n-butanol distribution extract under reduced pressure.

1-3. Organic solvent From the fraction  Preparation of compounds

The ethyl acetate fraction of Example 1-2 (57 g) was dissolved in methylene chloride-methanol-water (CH ₂ Cl ₂ -MeOH-H ₂ O; v / v) using a silica gel column (diameter × height = 10 cm × 21 cm) v / v, 15: 3: 1 → 12: 3: 1 → 9: 3: 1 → 7: 3: 1 → MeOH, to give the 23 fractions using the solvent conditions of each 2.5 ℓ) (E ₁ ~ E ₂₃ ).

Since with respect to the fraction 17 (E _17), reversed-phase silica gel column (diameter × height = 4.5㎝ × 8㎝) and methanol-water (MeOH-H ₂ O) of 2.5: 1 (v / v) total 1.5 ℓ at a rate And fractionated with a mixed solvent to obtain 25 mg of compound AR4.

Later fractions 2 and 3 _{(E 2 + E 3, 11.7g} ) on silica gel column (diameter × height = 6.5㎝ × 20㎝) using hexane for-ethyl acetate (Hexane-EtOAc; v / v , 1.5: 1 → 1: 1, 1.5 L each) to obtain eight fractions (AER1 to AER8). Of these, fraction 3 (AER3, 890 mg) was fractionated with a resin of Sephadex LH-20 and an elution solvent of 90% methanol to obtain a total of 11 fractions (AEMR1 to AEMR11). Among them, fraction 4 (AEMR4, 53.5 mg) was fractionated by reversed phase silica gel column (diameter × height = 1 cm × 25 cm) and methanol-water (1: 1; v / v, .

Comparative Example  One.

A compound represented by the following formula (3) was used as a material derived from the horsetail.

Comparative Example  2.

A compound represented by the following formula (4) was used as a material derived from the horsetail.

Comparative Example  3.

A compound represented by the following general formula (5) was used as a material derived from yam.

Comparative Example  4.

A compound represented by the following formula (6) was used as a material derived from the horsetail.

Comparative Example  5.

A compound represented by the following general formula (7) was used as a material derived from the sulfur-containing group.

Comparative Example  6.

A compound represented by the following formula (8) was used as a material derived from the horsetail.

Comparative Example  7.

10 kg of the dried peat hull was pulverized to an appropriate size, and then 36 liters of a 50 wt% ethanol aqueous solution was added thereto. The resulting mixture was extracted twice at 80 ° C for 4 hours, and then filtered through a filter paper to obtain a crude extract.

Experimental Example  One: AR4  And AR8 Structural Analysis of.

Structures of AR4 and AR8 of Example 1-3 were obtained by ¹ H NMR, ¹³ C NMR and 2D spectroscopy through a nuclear magnetic resonance (NMR) analyzer (Verian 400 MHz) to determine the molecular structure. The chemical structure of AR4 was determined by the following structure, and the chemical structure of AR8 was determined by the following structure.

AR4:

1) White amorphous powder.

^{2) 1 H-NMR (400} ㎒, pyridine-d5): 1.39 (3H, s, 18-CH 3), 1.28 (6H, s, 21, 27-CH 3), 1.58 (3H, s, 26-CH _{3), 2.02 (6H, s} , 28-CH 3, OAc), 1.25 (3H, s, 29-CH 3), 0.93 (3H, s, 30-CH 3), 0.18 (1H, d, J = 4.0 D, J = 3.6, 11.4 (1H, d, J = 9.0 Hz, H-19a), 0.55 (Hz, H-3), 3.77 (1H, ddd, J = 4.2, 8.2, 8.2 Hz, H-6), 4.94 D, J = 5.4, 8.7 Hz, H-24), 4.76 (1H, d, J = 7.8 Hz, 1H), 3.13 (1H, dd, J = 10.8,21.0 Hz, , H-1 '), 4.94 (1H, d, J = 8.0 Hz, H-1 ");

3) ¹³ C-NMR (100 MHz, pyridine-d5) ?: 32.2 (C-1), 30.2 (C-2), 88.8 (C-3), 42.7 , 79.4 (C-6), 34.7 (C-7), 46.3 (C-8), 21.2 (C-9), 28.9 45.1 (C-13), 46.3 (C-14), 45.8 (C-15), 73.4 (C-16), 58.3 (C-20), 27.2 (C-21), 35.0 (C-22), 26.6 (C-23), 81.7 C-27), 29.0 (C-28), 16.5 (C-29), 19.9 (C-30), 105.1 (C-4 '), 66.7 (C-5'), 104.7 (C-1 ''), 75.6 C-5 "), 63.1 ( C-6"), 21.2 (COCH 3), 170.0 (COCH 3)

4) Structure analysis technology for compounds

(3.48 (1H, dd, J = 3.6, 11.4 Hz, H-3), 3.77 (1H, ddd, J = 4.2) in the ¹ H-NMR (400 MHz, pyridine- H-16)] and 7 singlet methyl groups (1.39, 1.28 (× 2), 1.58, 1.25, 0.93, and 2.02) were observed in the high magnetic field region, And a single acetal group (2.02) were observed. The carbon signal was also observed in seven signals in the high field region, and one acetyl carbon (21.2) was observed. Signals of 0.18 (1H, d, J = 4.0 Hz H-19a) and 0.55 (1H, d, J = 4.0 Hz, H-19b) were observed, indicating that methyl of the cyclopropyl group exhibiting germinal coupling Respectively. Two anomeric hydrogen signals observed from the sugar molecule were observed [4.76 (1H, d, J = 7.8 Hz, H-1 ') and 4.94 (1H, d, J = 8.0 Hz, H- As a result of the cleavage, the bound sugars were expected to be beta-bonded. The types of bound sugars were determined by comparing the chemical shifts of carbon NMR with those of β-xylose and β-glucose. The HMBC experiment was conducted to confirm the binding sites of the two sugars. The signal of the first anomer proton, 4.76, confirmed the signal and cross-peak of 88.9, confirming that the first xylose sugar binds to position 3 of the aglycon. The binding position of the second sugar was confirmed by confirming the 79.4 carbon signal and the cross peak of the proton signal of 4.94 and binding to the 6th of the aglycon. The ester carbon signal (170.0 ppm) showed two proton signals (5.52, H-2 ') and cross peak of Xylose, and the binding site was determined.

AR8:

1) White amorphous powder.

^{2) 1 H-NMR (400} ㎒, pyridine-d4): 8.11 (1H, s, H-2), 8.03 (1H, d, J = 8.8 Hz), 7.03 (1H, dd, J = 8.4, 2.2, D, J = 8.4 Hz, H-5 '), 6.93 (1H, d, J = 2.2 Hz, H-2'), 6.92 2.4, H-6), 6.83 (1H, d, H-2.4 ㎐, H-8), 3.86 (3H, s, OCH 3).

3) Structure analysis technology for compounds

Separate the AR8 is a signal resulting from the benzene ring in the ^{1 H-NMR (400 ㎒,} methanol-d4) as a colorless shaping powder of white [8.11 (1H, s, H -2), 6.92 (1H, dd, J = 8.8, 2.4, H-6), 6.83 (1H, d, H-2.4 Hz, H-8) D, J = 8.4, 2.2, H-6 '), 6.95 (1H, d, J = 8.4 Hz, H-5'), 6.93 -2 '), it was confirmed that one 1,2,4-substituted benzene was present. In addition, oxygen substituted methoxy was observed in the high magnetic field region. We expected hydrogen to be present around the quaternary carbon in which the oxygen was replaced by [8.11 (1H, s, H-2)] from the signal that traveled from the ring structure to the very author. As a result of synthesizing the hydrogen data, the basic skeleton of isoflavone was confirmed.

Preparation Example  1. Chondrocyte culture

SW1353 human chondrocyte cell line was purchased from ATCC (HTB-94, Rockville, MD, USA). Human-derived SW1353 cells were cultured in DMEM (Dubecco's Modified Eagle Medium) medium (1509667) containing fetal bovine serum (FBS, 1456396, Gibco Life Technologies) in a flask for cell culture of various sizes depending on the purpose of measurement (Gibco® Life Technologies) for 48 hours in an incubator (37 ° C, 5% CO ₂ ) and treated with 0.25% (w / v) trypsin -0.53 mM EDTA (ethylene diaminetetraacetic acid) The cells were subcultured at intervals and used for experiments.

Experimental Example  2. Cartilaginous substance  Measurement of degradative enzyme inhibitory activity

The chondrocytes cultured in Preparation Example 1 were treated with 20 ng / mL of interleukin-1 beta (IL-1 beta), 40 μM of AR4 and 40 μM of AR8, 40 μM of the compound of Comparative Example 1, 40 μM of the compound of the comparative example 5, 40 μM of the compound of the comparative example 5, and 40 μM of the compound of the comparative example 3, 20 μM of the compound of the comparative example 4, 20 μM of the compound of the comparative example 4, Or 200 占 퐂 / ml, and quantitatively analyzed by fluorescence ELISA after 5 to 30 minutes.

MMP-1 (71150, AnaSpec Inc.), MMP-2 (71151, AnaSpec Inc.), MMP-3 (71152, AnaSpec Inc.), MMP-9 , AnaSpec Inc.), MMP-13 (71156, AnaSpec Inc.), and the absorbance was measured at 520 nm after enzyme reaction for 5 to 30 minutes. The MMP inhibitory activity (%) in the chondrocyte cell line among the analyzed results is shown in Table 1 below.

division Treatment concentration MMP-1 MMP-2 MMP-3 MMP-9 MMP-13 AR4 10 μM 21.3% 16.8% 18.8% 8.2% 23.5% AR8 40 μM 23.5% 39.8% 13.7% 15.9% 23.4% The compound of Comparative Example 1 40 μM - - 12.6% - 6.5% The compound of Comparative Example 2 40 μM - - - - - The compound of Comparative Example 3 20 μM - - - 11.2% 7.1% The compound of Comparative Example 4 20 μM - - - - - The compound of Comparative Example 5 40 μM - - - - - The compound of Comparative Example 6 40 μM - - - - - The extract of Comparative Example 7
(Hwanggi's ethanol extract) 200 [mu] g / ml 10.5% 4.5% 11.0% 2.8% 17.8%

As can be seen in Table 1, in the chondrocyte cell line treated with the compound of the present invention, AR4 or AR8, compared to the chondrocyte cell line treated with the compound of Comparative Examples 1 to 6 or the wild-type ethanol extract of Comparative Example 7, MMP-1, MMP-2 , MMP-3, MMP-9 and MMP-13 were significantly inhibited.

Thus, it was confirmed that AR4 and AR8 of the present invention are highly suitable for use in the prevention or treatment of arthritis because of their high inhibitory activity against MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13.

Claims (9)

A pharmaceutical composition for preventing or treating arthritis, comprising at least one compound selected from the group consisting of compounds represented by the following formulas (1) and (2) and pharmaceutically acceptable salts thereof:
[Chemical Formula 1]

(2)

The pharmaceutical composition for preventing or treating arthritis according to claim 1, wherein the pharmaceutical composition for preventing or treating arthritis comprises a compound represented by Formula 1 or a compound represented by Formula 2 below. The method of claim 1, wherein the compound represented by the formula (2) or compound of the formula (1) is Astragalus (Astragali The present invention relates to a pharmaceutical composition for preventing or treating arthritis. The pharmaceutical composition for preventing or treating arthritis according to claim 1, which inhibits the activity of matrix metalloproteases (MMP) -1, MMP-2, MMP-3, MMP-9 and MMP-13 A pharmaceutical composition for preventing or treating arthritis, which has an arthritis prevention or therapeutic activity. The pharmaceutical composition for preventing or treating arthritis according to claim 1, wherein the arthritis is degenerative arthritis. A health functional food composition for preventing or improving arthritis comprising at least one compound selected from the group consisting of compounds represented by the following formulas (1) to (2) and pharmaceutically acceptable salts thereof:
[Chemical Formula 1]

(2)

The method of claim 6, wherein the compound represented by the formula (2) or compound of the formula (1) is Astragalus (Astragali radix ). < / RTI > The health functional food composition according to claim 6, wherein the arthritis is degenerative arthritis. The composition according to claim 6, wherein the health functional food composition inhibits the activity of matrix metalloproteases (MMP) -1, MMP-2, MMP-3, MMP-9 and MMP-13 to prevent or ameliorate arthritis Or a pharmaceutically acceptable salt thereof.