KR20230119767A - Pharmaceutical composition for preventing or treating osteoarthritis comprising 3,5-dicaffeoylquinic acid - Google Patents

Abstract

The present invention relates to a pharmaceutical composition for preventing or treating osteoarthritis, and more particularly, to a pharmaceutical composition comprising 3,5-dicaffeoylquinic acid (diCQA) or a pharmaceutically acceptable salt thereof, thereby inflammatory mediator and substrate in chondrocytes. It has a decomposing enzyme inhibitory effect, so it can help prevent, treat or improve osteoarthritis.

Description

Pharmaceutical composition for preventing or treating osteoarthritis comprising 3,5-dicaffeoylquinic acid

The present invention relates to a pharmaceutical composition for preventing or treating osteoarthritis.

The present invention relates to a food composition for preventing or improving osteoarthritis.

Arthritis is a disease caused by inflammation and pain in a joint, and includes osteoarthritis, rheumatoid arthritis, gout, and psoriatic arthritis, and 95% of arthritis patients suffer from degenerative arthritis. Degenerative arthritis is a disease in which local degenerative changes occur as articular cartilage wears away, and is also referred to as osteoarthritis. Osteoarthritis is a representative degenerative disease that is closely related to aging. About 10 to 15% of the total population suffers from it, and in particular, about 60 to 80% of the elderly population over 65 years old suffer from it.

The cause of osteoarthritis is closely related to aging or excessive weight, and it is more common in women as the age increases. Early symptoms include stiffness and tingling pain in one or two joints, and when prolonged, excessive formation of bone around the joint and deformation of the joint occur. The mechanism by which osteoarthritis is induced is the increased production of pro-inflammatory cytokines and the increased secretion of MMPs such as collagenase and stromelysin, resulting in damage to the articular cartilage matrix. do.

Currently used clinically for the treatment of osteoarthritis, drug treatments such as pain relievers, steroids, and non-steroidal anti-inflammatory drugs or chondroprotectors such as hyaluronic acid, glucosamine, and chondroitin are used, or arthroscopic surgery, proximal tibia osteotomy, joint part By surgical treatment such as arthroplasty and total knee arthroplasty. However, drug treatment only has an effect of non-specifically alleviating pain or inflammatory response itself, and chondroprotectors only play a role in protecting joints by supplying nutrients to cartilage cells or alleviating shock.

Korean Registered Patent No. 1896020

An object of the present invention is to provide a pharmaceutical composition for preventing or treating osteoarthritis.

An object of the present invention is to provide a food composition for preventing or improving osteoarthritis.

1. A pharmaceutical composition for preventing or treating osteoarthritis comprising 3,5-dicaffeoylquinic acid (diCQA) or a pharmaceutically acceptable salt thereof.

2. A food composition for preventing or improving osteoarthritis, comprising 3,5-dicaffeoylquinic acid (diCQA) or a food-acceptable salt thereof.

The pharmaceutical composition and food composition of the present invention have an inhibitory effect on inflammatory mediators and matrix degrading enzymes in cartilage cells, and thus can help prevent, treat, or improve osteoarthritis.

Figure 1 shows the effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) on the viability of white paper primary chondrocytes.
Figure 2 shows the nitrite inhibitory effect of 3,5-diCQA increased by IL-1β in white paper primary chondrocytes.
Figure 3 shows the inhibitory effect of 3,5-diCQA on iNOS, COX-2 and TNF-α increased by IL-1β in white paper primary chondrocytes through Western blot analysis.
Figure 4 shows the inhibitory effect of 3,5-diCQA on MMP-1, MMP-3 and MMP-13 increased by IL-1β in white paper primary chondrocytes through Western blot analysis.
Figure 5 shows the ADAMTS4 inhibitory effect of 3,5-diCQA increased by IL-1β in white paper primary chondrocytes through Western blot analysis.
7 shows the inhibitory effect of 3,5-diCQA on the activity of MMPs increased by IL-1β in white paper primary chondrocytes through gelatin zymography.

Hereinafter, the present invention will be described.

The present invention provides a pharmaceutical composition for preventing or treating osteoarthritis.

The pharmaceutical composition includes 3,5-dicaffeoylquinic acid (dicaffeoylquinic acid, diCQA) or a pharmaceutically acceptable salt thereof.

3,5-dicaffeoylquinic acid may be a compound having a structure represented by Formula 1 below.

[Formula 1]

The composition of the present invention inhibits inflammatory mediators and matrix degrading enzymes in cartilage cells, and thus has excellent preventive or therapeutic effects on osteoarthritis.

Inflammatory mediators are messengers that act on blood vessels or cells to promote sequential inflammatory responses, such as cytokines, chemokines, nitric oxide, oxygen free radicals, proteins, It may be peptides, glycoproteins, arachidonic acid metabolites including prostaglandins and leukotrienes, and the like, specifically nitrite, iNOS, COX-2, TNF-α, L-1β, IL-6, IL -15, IL-8, GRO-α, and the like.

Cartilage matrix degradation enzyme is an enzyme that induces gradual degeneration of cartilage tissue by directly degrading the extracellular matrix (eg, aggrecan, type II collagen) surrounding cartilage cells. For example, MMPs and ADAMTS, which is an aggrecanase, may be used.

Arthritis is a disease caused by inflammation or pain in a joint, and includes osteoarthritis, rheumatoid arthritis, gout, and psoriatic arthritis, and each arthritis has a different cause or treatment method. Osteoarthritis, also called degenerative arthritis, is a disease in which local degenerative changes occur as articular cartilage wears away. Osteoarthritis is caused by increased production of pro-inflammatory cytokines or increased secretion of MMPs such as collagenase and stromelysin or aggrecanase, resulting in the articular cartilage matrix. This could be caused by damage.

The term "pharmaceutically acceptable" means that a compound or composition exhibits properties that do not cause serious irritation to an object, cell, tissue, etc. to which it is administered and do not impair the biological activity and physical properties of the compound.

The term "pharmaceutically acceptable salt" refers to a salt prepared using a specific compound according to the present invention and a relatively non-toxic acid or base. A pharmaceutically acceptable salt may be, for example, an acid addition salt or a metal salt.

Acid addition salts are formed with inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid or phosphorous acid, and aliphatic mono- and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanes. It can be formed from non-toxic organic acids such as dioates, aromatic acids, aliphatic and aromatic sulfonic acids. These pharmaceutically non-toxic salts are sulfate, pyrosulfate, bisulphate, sulphite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate, chloride, bromide, ioda Id, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propylate, oxalate, malonate, succinate, suberate, Sebacate, fumarate, maleate, butyne-1,4-dioate, nucleic acid-1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxy Benzoate, phthalate, terephthalate, benzenesulfonate, pertuenesulfonate, chlorobenzenesulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β_hydroxybutyrate, glycol rate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate or mandelate. For example, acid addition salts can be obtained by dissolving the compound in an excess of aqueous acid solution and precipitating the salt using a hydrating organic solvent such as methanol, ethanol, acetone or acetonitrile.

The metal salt may be a sodium, potassium or calcium salt. Metal salts can be prepared using a base, for example, an alkali metal or alkaline earth metal salt is obtained by dissolving the compound in an excess alkali metal hydroxide or alkaline earth metal hydroxide solution, filtering the undissolved compound salt and evaporating the filtrate and/or Or it can be obtained by drying.

The term “prevention” refers to prophylactic measures that result in any degree of reduction in the likelihood of developing a condition to be prevented or a recurrence or recurrent condition, including minor, substantial or major reduction in the likelihood of developing or recurring the condition, as well as total prevention. Refers to a measure, and the degree of likelihood reduction is at least a minor reduction.

The term "treatment" refers to treatment that results in a beneficial effect on a subject or patient suffering from the condition being treated, including not only cure but also relief of any degree, including minor, substantial, major relief, the degree of relief being At least a slight relief.

The pharmaceutical composition of the present invention is formulated according to conventional methods into oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions. It may, but is not limited thereto.

Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, dextrin, maltodextrin, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants, but is not limited thereto.

Solid preparations for oral administration include, but are not limited to, tablets, pills, powders, granules, capsules, etc., such solid preparations may contain at least one excipient such as starch or calcium carbonate in the compound. It is prepared by mixing sucrose or lactose, gelatin, etc. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.

Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.

The pharmaceutical composition of 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 with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is the type, severity, drug activity, It may be determined according to factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by a person skilled in the art.

In the pharmaceutical composition of the present invention, the effective amount may vary depending on the patient's age, sex, and body weight, and is generally 1 to 6000 mg per kg of body weight, preferably 60 to 600 mg may be administered once or divided into three times. there is. However, since it may increase or decrease according to the route of administration, severity of disease, sex, weight, age, etc., the dosage is not limited to the scope of the present invention in any way.

The present invention provides a food composition for preventing or improving osteoarthritis.

The food composition includes 3,5-dicaffeoylquinic acid (diCQA) or a food-acceptable salt thereof.

The composition of the present invention inhibits inflammatory mediators and matrix degrading enzymes in chondrocytes, and thus has excellent effects in preventing or improving osteoarthritis.

3,5-dicaffeoylquinic acid, inflammatory mediators, matrix degrading enzymes, osteoarthritis, the terms “prevention” and “treatment” may be within the foregoing scope, but are not limited thereto.

The term "improvement" means any action that at least reduces the severity of a parameter associated with the condition being treated, eg a symptom.

The term "acceptable food" means that the compound or composition does not cause serious irritation to the organism, cells, tissues, etc. to which it is administered, and exhibits characteristics that do not impair the biological activity and physical properties of the compound.

The term "acceptable food salt" refers to a salt prepared using a specific compound according to the present invention and a relatively non-toxic acid or base, and a salt acceptable in food science is, for example, an acid addition salt or a metal salt. The acid addition salt and the metal salt may be within the above range, but are not limited thereto.

The food composition of the present invention can be prepared and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. for the purpose of preventing or improving osteoarthritis.

The food composition of the present invention may contain conventional food additives, and the suitability as a food additive is determined according to the general rules of the Food Additive Code and General Test Methods approved by the Food and Drug Administration, unless otherwise specified. and judged by criteria.

Items listed in the Food Additives Codex include, for example, chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; natural additives such as persimmon pigment, licorice extract, crystalline cellulose, kaoliang pigment, and guar gum; It includes, but is not limited to, mixed preparations such as sodium L-glutamate preparations, alkali additives for noodles, preservative preparations, and tar color preparations.

For example, a food composition in the form of a tablet is obtained by granulating a mixture obtained by mixing the composition with an excipient, a binder, a disintegrant, and other additives in a conventional manner, and then adding a lubricant or the like to compression molding or directly compressing the mixture. can be molded. In addition, the food composition in the form of a tablet may contain a flavoring agent and the like, if necessary.

Hard capsules among food compositions in the form of capsules can be prepared by filling a mixture of the composition mixed with additives such as excipients in a normal hard capsule, and soft capsules can be prepared by mixing the composition with additives such as excipients and gelatin. It can be prepared by filling the same capsule base. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a colorant, a preservative, and the like, if necessary.

The food composition in the form of a ring may be prepared by molding a mixture obtained by mixing the composition with an excipient, a binder, a disintegrant, etc. by a conventionally known method, and, if necessary, may be coated with sucrose or other coating agent, or starch, The surface can also be coated with a material such as talc.

A food composition in the form of a granule may be prepared by a conventionally known method of a mixture of the composition and an excipient, a binder, a disintegrant, etc., and may contain a flavoring agent, a flavoring agent, and the like, if necessary.

Food compositions include beverages, meat, chocolate, foods, and confectionery. It may be pizza, ramen, other noodles, chewing gum, candy, ice cream, alcoholic beverages, vitamin complexes, and health supplements.

The food composition may be applied orally for use as a nutrient, and the application form is not particularly limited. For example, when administered orally, the daily intake is preferably 5000 mg or less, more preferably 2000 mg or less, and most preferably 500 to 1500 mg or 650 mg daily. When formulated into capsules or tablets, one tablet can be administered with water once a day.

The present invention provides a composition for inhibiting the expression of a cartilage matrix degrading enzyme.

The composition includes 3,5-dicaffeoylquinic acid (diCQA) or a pharmaceutically acceptable salt thereof.

The 3,5-dicaffeoylquinic acid and the matrix degrading enzyme may be within the above range, but are not limited thereto.

The composition may be a composition for inhibiting the expression of a cartilage matrix degrading enzyme in vitro.

The cartilage matrix degrading enzyme may be at least one selected from the group consisting of MMP-1, MMP-3, MM-13 and ADAMTS4.

In one embodiment, the cartilage matrix degrading enzyme may be MMP-1, MMP-3, MM-13 and ADAMTS4.

Hereinafter, examples will be described in detail to explain the present invention in detail.

Example

method

1. Reagents

3,5-dicaffeoylquinic acid (catalog No. SMB00131), Sulfanilamide, N-(1-naphthyl) ethylenediamine dihydrochloride, phosphoric acid and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT ) was purchased from Sigma-Aldrich (St. Louis, MO, USA). Interleukin-1β (IL-1β) was purchased from ProSpec-Protein Specialists (Rehovot, Israel). Dulbecco's modified Eagle's medium/nutrient mixture F-12 (DMEM/F12) and penicillin-streptomycin solution were purchased from WELGENE (Daegu, Republic of Korea). Fetal bovine serum (FBS) was purchased from iNtRON Biotechnology (Gyeonggido, Republic of Korea). Collagenase type II was purchased from Worthington Biochemical Corporation (Lakewood, NJ, USA). Primary and secondary antibodies were all Cell Signaling Technology (Danvers, MA, USA). The kilodaltons (kDa) of all antibodies used are: iNOS (130-140 kDa), COX-2 (74 kDa), TNF-α (17 kDa), MMP1 (54 kDa), MMP3 (60 kDa), MMP13 (60 kDa), Adamts-4 (90 kDa) and α-tubulin (56 kDa).

2. Primary chondrocyte isolation and culture

Under sterile conditions, dissected knee cartilages from 5-day-old Sprague-Dawley rats were enzymatically digested with 0.3% (w/v) collagenase type II dissolved in DMEM/F12 and incubated at 37°C with gentle agitation. Repeated twice in 45 minutes. Then, once again, the cartilage was digested with 0.3% (w/v) collagenase type II at 37°C for 5 hours with gentle stirring. After enzymatic digestion, undigested cells and debris were filtered through a cell strainer (0.45 μm), and chondrocytes were isolated. Chondrocytes were cultured in DMEM/F12 containing 10% FBS and antibiotics (100 U/mL penicillin and 100 mg/mL streptomycin) at 37°C with 5% CO ₂ . All methods of breeding and operating experimental animals were approved by the Animal Experimentation Ethics Committee (CIACUC2018-S0046) of Chosun University.

3. Cell viability analysis (MTT assay)

For cell viability analysis, primary chondrocytes of isolated white paper were inoculated into a 6-well plate at 1x10 ⁶ cells/mL and cultured for 5 days. And after culturing overnight without nutrients, they were treated with various concentrations of 3,5-diCQA (0, 5, 10, 20, 40 and 80 uM). After reacting for 24 hours, MTT solution (5 mg/mL) was added to each well (100 μL/well). After reacting for 3 hours, the supernatant was removed, leaving only the cells, and DMSO was added by 1 mL per well. Then, the formed formazan was dissolved and dispensed in duplicates of 300 ul into a 96-well plate, and then absorbance was measured at 590 nm using a microplate reader (Epoch BioTek Instruments Inc., Winooski, VT, USA).

4. Reactive Nitrogen Species (RNS) Measurement

White paper primary chondrocytes were inoculated in a 6-well culture plate at 1×10 ⁶ cells/mL and cultured for 5 days. And after culturing overnight without nutrients, they were treated with various concentrations of 3,5-diCQA (0, 5, 10, 20, 40 and 80 uM). After reacting for 1 hour, IL-1β ng/ml) was treated for 24 hours. Nitrite oxide (NO) production was shown by measuring the accumulation of nitrite (NO ₂ ^- , nitrite), a stable oxidation product of NO, using Griess reagent. In order to measure the accumulated nitrite secreted into the culture medium, the supernatant and Griess reagent were mixed in a ratio of 1:1 and the absorbance was measured at 540 nm. Nitrite was quantified based on the Na ₂ NO ₃ standard curve.

5. Western blot analysis

White paper primary chondrocytes were inoculated in a 6-well culture plate at 1×10 ⁶ cells/mL and cultured for 5 days. After culturing overnight without nutrients, they were treated with various concentrations of 3,5-diCQA (0, 10, 20 and 40 uM). After reacting for 1 hour, IL-1β ng/ml) was treated for 24 hours. To extract total intracellular protein, PRO-PREP protein extraction solution (iNtRON Biotechnology, Republic of Korea) was used on ice for 30 minutes, followed by centrifugation at 4°C for 15 minutes at 15,000 xg, followed by total intracellular protein got Protein concentration was quantified using BCA (bicinchoninic acid) protein assay (Pierce, Rockford, IL, USA). The same amount of protein (20 μg) was loaded on 8%, 10% or 15% sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE) and then transferred to a polyvinylidene difluoride membrane (PVDF membrane). The trans-blotted membrane was blocked with TBST (0.1% Tween-20 + TBS) containing 5% bovine serum albumin (BSA) for 30 minutes. Then, the membrane was reacted with a specific primary antibody (1:1000, except α-tubulin; 1:5000) overnight at 4°C, followed by horseradish peroxidase (HRP)-conjugated secondary antibody (1:2500) at room temperature. reacted for 1 hour. Protein bands were detected and visualized with a MicroChemi 4.2 imager (DNR Bioimaging Systems, Jerusalem, Israel) using an enhanced chemiluminescence (ECL) kit (Millipore, Bedford, MA, USA).

6. Gelatin zymography

White paper primary chondrocytes were pretreated with 3,5-diCQA (0, 10, 20, and 40 uM) for 1 hour and then cultured with IL-1β (5 ng/mL) for 24 hours. After incubation for 24 hours, 30 ul of the supernatant of each sample was mixed with a non-reducing buffer, and electrophoresis was performed on an 8% SDS-PAGE gel containing 10 mg/mL of gelatin. After electrophoresis, it was immersed in a 2.5% (v/v) Triton X-100 solution and reacted for 30 minutes while stirring, then immersed in zymography renaturing buffer and reacted at 37 ° C for 48 hours. After that, 0.1% (w / v) Coomassie blue staining was performed for 20 minutes, and then the unstained area was washed with destain buffer, and a photograph was taken of the area where the matrix degradation occurred in white.

7. Statistical Analysis

All data were obtained from at least three independent experiments. Results are expressed as mean ± standard deviation (SD). A one-way analysis of variance (ANOVA) and Dunnett's test were used for multiple comparisons using GraphPad Prism (GraphPad Software Inc., CA, USA). A p value < 0.05 was considered significant.

result

1. Cytotoxicity analysis of 3,5-dicaffeoylquinic acid (3,5-diCQA) in rat primary chondrocytes

To evaluate the cytotoxicity of 3,5-diCQA, chondrocytes were treated with various concentrations of 3,5-diCQA (0, 5, 10, 20, 40, and 80 uM), and MTT assay was performed 24 hours later. FIG. 1 As shown, 3,5-diCQA treatment was not cytotoxic up to 80 uM treatment compared to the control group.

2. Inhibitory effect of 3,5-diCQA on IL-1β-induced nitrite, iNOS, COX-2 and TNF-α in rat primary chondrocytes

Inflammation by nitrite, inflammatory mediators (iNOS, COX-2), and pro-inflammatory cytokines (TNF-α) is one of the major factors in the multi-factor etiology of osteoarthritis. Therefore, the present inventors investigated the effect of 3,5-diCQA on IL-1β-induced expression of inflammatory mediators such as nitrite, iNOS, COX-2, and TNF-α in primary chondrocytes of white paper by nitric oxide assay and western blot. Evaluated using the assay.

Chondrocytes stimulated with IL-1β significantly increased the expression of nitrite, iNOS, COX-2, and TNF-α compared to unstimulated chondrocytes. , iNOS, COX-2 and TNF-α expressions were inhibited in a dose-dependent manner (FIGS. 2 and 3). These results suggest that 3,5-diCQA has a strong anti-inflammatory effect on the IL-1β-induced inflammatory response in rat primary chondrocytes.

3. Inhibition of IL-1β-induced MMP-1, MMP-3, MMP-13, and ADAMTS4 by 3,5-diCQA in rat primary chondrocytes

Degradation of cartilage matrix by activation of matrix degrading enzymes such as MMPs and ADAMTS4, an aggrecanase, is a typical feature of osteoarthritis. Therefore, the present inventors confirmed the effect of 3,5-diCQA on the expression of MMP-1, MMP-3, MMP-13 and ADAMTS4 induced by IL-1β in white paper primary chondrocytes.

The inventors found that the protein expression of MMP-1, MMP-3, MMP-13, and ADAMTS4 increased in chondrocytes stimulated with IL-1β compared to the control group, but the activity was significant in chondrocytes pretreated with 3,5-diCQA. It was observed that it was inhibited (FIGS. 4 and 5).

In addition, through gelatin zymography performed to analyze MMP-1, MMP-3 and MMP-13 activities, IL-1β treatment significantly increased the secretion of these enzymes and their gelatinolytic activity, but 3 It was confirmed that ,5-diCQA was inhibited in a dose-dependent manner by pretreatment (FIG. 6). This suggests that 3,5-diCQA reduced the expression of IL-1β-induced matrix degrading enzymes.

Claims (2)

A pharmaceutical composition for preventing or treating osteoarthritis, comprising 3,5-dicaffeoylquinic acid (diCQA) or a pharmaceutically acceptable salt thereof.
A food composition for preventing or improving osteoarthritis, comprising 3,5-dicaffeoylquinic acid (diCQA) or a pharmaceutically acceptable salt thereof.