Cartilage cell activity improver and application thereof in preparation of osteoarthritis treatment medicine

Abstract

The invention belongs to the technical field of bone joint medicines, and particularly relates to a cartilage cell activity improver and application thereof in preparation of a medicine for treating osteoarthritis. The cartilage cell activity improver is prepared by mixing the following raw materials: physalis alkekengi A, sodium pyruvate and sanggenone A in a mass ratio of 100: (2-5): (1-2). The chondrocyte activity improver disclosed by the invention can generate an effect of improving chondrocyte activity, can improve osteoarthritis from the cell activity level, and has a prospect of preparing osteoarthritis medicines.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of bone joint drugs, and particularly relates to a chondrocyte activity improver and application thereof in preparation of bone arthritis treatment drugs. BACKGROUND

[0002] Cartilage is an important component of bone joints, mainly playing the roles of protection, buffering and assisting joint movement, and the two are interdependent and complementary in function. Specifically, the cartilage surface is smooth, which can reduce the frictional resistance between bones, avoiding direct wear of bones during movement; the cartilage is elastic, which can absorb the impact force generated during movement or weight bearing, protecting the bone joint from damage; the thickness and shape of the cartilage are adapted to the joint surface, which can ensure the normal alignment and range of motion of the joint.

[0003] The core pathology of osteoarthritis is the wear, degeneration and even loss of articular cartilage, which leads to increased joint surface friction, pain and limited movement. Adult cartilage has no blood and nerve supply, and has very weak self-repairing ability. Once damaged, it is difficult to heal by itself, and the disease is prone to progress gradually.

[0004] Studies have shown that glucosamine and chondroitin sulfate are currently the most effective cartilage treatment drugs, and scholars are constantly developing new drugs that can improve the recovery effect of cartilage.

[0005] In previous studies, Physalin A (PA) has been confirmed to have a protective effect on osteoarthritis and can inhibit the secretion of inflammatory factors. As shown in the results of the mouse in vitro experiment in “Lu Rui, Qu Yun Kun, Yang Qing, et al. Physalin A delays the progression of osteoarthritis through anti-inflammatory and anti-apoptotic pathways [J]. Orthopedics, 2022, 13(5):426-432. DOI:10.3969 / j.issn.1674-8573.2022.05.009”, PA plays a protective role in chondrocytes by inhibiting the MAPK and NF-κB signaling pathways through integrin alphaVbeta3, and in vivo experiments have confirmed that intra-articular injection of PA can alleviate the wear and degeneration of knee cartilage.

[0006] However, our further experiments show that the effect of Physalin A on improving the activity of chondrocytes is limited and still needs to be improved. SUMMARY

[0007] To solve the above technical problems, the application provides a chondrocyte activity improver and application thereof in preparation of bone arthritis treatment drugs.

[0008] The purpose of the application is to provide a chondrocyte activity improver, which is prepared by mixing the following raw materials in a mass ratio: Physalin A, sodium pyruvate and moracenone A in a mass ratio of 100:2-5:1-2. Store in the dark.

[0009] wherein the physalin A has a powder appearance, and has a CAS number of 23027-91-0. The physalin A used in the experiments of the present application was purchased from ChemFaces, China.

[0010] Sodium pyruvate, as a substrate of the tricarboxylic acid cycle, can supplement metabolic energy, has an antioxidant effect, can scavenge free radicals, reduce oxidative damage, and maintain mitochondrial membrane potential. In addition to being able to inhibit IL-1β-induced apoptosis of chondrocytes, physalin A can also achieve the effect of improving the activity of chondrocytes.

[0011] Mulberrocamph A, with a CAS number of 76464-71-6, has been confirmed to have anti-inflammatory, antioxidant, and anti-tumor effects, but no other applications have been found so far.

[0012] Preferably, the mass ratio of the above-mentioned chondrocyte activity enhancer, physalin A, sodium pyruvate, and mulberrocamph A is 100:3:1.

[0013] Preferably, the above-mentioned chondrocyte activity enhancer is used for preparing a drug for treating osteoarthritis.

[0014] Preferably, the above-mentioned chondrocyte activity enhancer is the only active ingredient in the drug for treating osteoarthritis.

[0015] Preferably, the above-mentioned chondrocyte activity enhancer is compounded with a pharmaceutically acceptable excipient when preparing the drug for treating osteoarthritis.

[0016] Preferably, the above-mentioned chondrocyte activity enhancer has at least one of a filler, a binder, a disintegrant, and a coating agent as the pharmaceutically acceptable excipient.

[0017] Preferably, the above-mentioned chondrocyte activity enhancer has starch, lactose, or microcrystalline cellulose as the filler. Preferably, the above-mentioned chondrocyte activity enhancer has starch paste or polypropylmethyl cellulose as the binder. Preferably, the above-mentioned chondrocyte activity enhancer has sodium carboxymethyl starch or cross-linked polyvinylpyrrolidone as the disintegrant. Preferably, the above-mentioned chondrocyte activity enhancer has carboxymethyl cellulose as the coating agent.

[0018] It should be noted that the above-mentioned excipients are only exemplary and should not be construed as limiting the present application.

[0019] Preferably, the above-mentioned chondrocyte activity enhancer has a greater effect on improving the activity of chondrocytes than on improving the activity of fibroblasts.

[0020] Preferably, the above-mentioned chondrocyte activity enhancer is used for inhibiting IL-1β-induced apoptosis of chondrocytes.

[0021] Preferably, the above-mentioned cartilage cell activity enhancer is used to inhibit IL-1β-induced cartilage cell inflammatory response.

[0022] Compared with the prior art, the present application has the following beneficial effects: The present application compounds Fructus Physalis Bitter A, sodium pyruvate and mulberry root ketone A in a mass ratio of 100:2~5:1~2 to produce an effect of enhancing cartilage cell activity, which can directly improve osteoarthritis from the aspect of cell activity and has the prospect of preparing osteoarthritis drugs.

[0023] Further research shows that the cartilage cell activity enhancer of the present application is used to inhibit IL-1β-induced cartilage cell apoptosis and IL-1β-induced cartilage cell inflammatory response. Moreover, the cartilage cell activity enhancer of the present application has a greater effect on enhancing the activity of cartilage cells than on enhancing the activity of fibroblasts, and is a selective promoting agent.

[0024] In order to provide better application prospects, the present application also provides an exemplary formula of a corresponding osteoarthritis treatment drug, in which the cartilage cell activity enhancer is compounded with a filler to fill a capsule shell to form a capsule dosage form, which is stored in the dark. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 Results of the effect of Fructus Physalis Bitter A on cartilage cell activity; Wherein, A is the result of the effect of different concentrations of Fructus Physalis Bitter A on cartilage cell activity, and B is the result of the effect of different concentrations of Fructus Physalis Bitter A combined with IL-1β on cartilage cell activity.

[0026] Figure 2 Results of down-regulation of IL-1β-induced cartilage cell catabolism marker protein expression by Fructus Physalis Bitter A; Wherein, A is the Western blot result; B is the MMP13 protein gray value quantitative analysis column chart, and C is the ADAMTS5 protein gray value quantitative analysis column chart.

[0027] Figure 3 Effect of Fructus Physalis Bitter A on IL-1β-induced cartilage cell inflammatory response; Wherein, A is the Western blot result; B is the iNOS protein gray value quantitative analysis column chart, C is the COX-2 protein gray value quantitative analysis column chart, and D is the IL-6 protein gray value quantitative analysis column chart.

[0028] Figure 4 Effect of Fructus Physalis Bitter A on IL-1β-induced cartilage cell apoptosis level; Wherein, A is the Western blot result; B is the protein gray value quantitative analysis column chart.

[0029] Figure 5 is the main research route. DETAILED DESCRIPTION

[0030] In order to enable those skilled in the art to better understand the technical solutions of the present application and to implement them, the present application will be further described below in conjunction with specific examples and drawings.

[0031] In the description of the present application, unless otherwise specified, the reagents used are commercially available, and the methods used are conventional techniques in the art.

[0032] In our previous research results, it has been confirmed that the acid lemon bitter A (PA) can play a protective role in joint cartilage through anti-inflammatory and anti-apoptotic pathways, but this effect is subject to conditions, and the related results are described in Figures 1-4 . Figures 1-4 The specific experimental methods and more detailed results analysis can be found in “Lu R, Qu YK, Yang Q, et al. Acid lemon bitter A delays the progression of osteoarthritis through anti-inflammatory and anti-apoptotic pathways [J]. Orthopedics, 2022, 13(5):426-432. DOI:10.3969 / j.issn.1674-8573.2022.05.009”. It should be noted that the present application is a re-innovation based on the above research, and therefore part of the research results of the above paper are cited to assist in explaining the mechanism of the present application.

[0033] The main research route of the present application is shown in Figure 5 , including the analysis of the anti-inflammatory mechanism of acid lemon bitter A, the design of cartilage cell activity enhancer, and control experiments.

[0034] Experiment one (1) Experimental method: The methods of isolation and culture of mouse chondrocytes, cell viability detection, total protein extraction of chondrocytes, and Western blot detection of protein expression are all referred to “Lu R, Qu YK, Yang Q, et al. Acid lemon bitter A delays the progression of osteoarthritis through anti-inflammatory and anti-apoptotic pathways [J]. Orthopedics, 2022, 13(5):426-432. DOI:10.3969 / j.issn.1674-8573.2022.05.009”.

[0035] (2) Experimental results: Figure 1The results of b show that different concentrations (0, 2.5 μmol / L, 5 μmol / L, 10 μmol / L) of bitter A of Physalis alkekengi L. alone have no significant change on the viability of chondrocytes (P>0.05); b: different concentrations of bitter A of Physalis alkekengi L. combined with IL-1β (5 ng / mL) have no significant change on the viability of chondrocytes (P>0.05). It is shown that bitter A of Physalis alkekengi L. alone, or bitter A of Physalis alkekengi L. combined with IL-1β, cannot directly affect the viability of chondrocytes.

[0036] Figure 2 In the results of b, compared with the control group, #P<0.05; compared with the IL-1β group, *P<0.05, **P<0.01, ***P<0.001. The results of b show that bitter A of Physalis alkekengi L. down-regulates the expression of IL-1β-induced catabolic marker proteins of chondrocytes. Compared with the control group, IL-1β can enhance the catabolic level of chondrocytes, i.e. up-regulate the expression of catabolic marker proteins (MMP13 and ADAMTS5) of chondrocytes (P<0.05). Compared with the IL-1β group, the expression levels of key catabolic proteins MMP13 and ADAMTS5 in the IL-1β+PA (2.5 μmol / L) group, the IL-1β+PA (5 μmol / L) group and the IL-1β+PA (10 μmol / L) group appear to be down-regulated (P<0.05) in a concentration-dependent manner. This indicates that IL-1β can enhance the catabolism of chondrocytes, while different concentrations of bitter A of Physalis alkekengi L. can reverse the catabolic effect of IL-1β.

[0037] Further, Figure 3 In the results of b, compared with the control group, #P<0.05; compared with the IL-1β group, *P<0.05, **P<0.01, ***P<0.001. Figure 3 The results of b show that bitter A of Physalis alkekengi L. inhibits the inflammatory response of chondrocytes induced by IL-1β. Compared with the control group, the expression levels of inflammatory proteins (iNOS, COX-2, IL-6) in the IL-1β group increase after IL-1β stimulation (P<0.05); compared with the IL-1β group, the expression levels of inflammatory proteins iNOS, COX-2, IL-6, etc. in the IL-1β+PA (2.5 μmol / L) group, the IL-1β+PA (5 μmol / L) group and the IL-1β+PA (10 μmol / L) group appear to be decreased in a concentration-dependent manner (P<0.05).

[0038] Figure 4 In the results of b, compared with the control group, #P<0.05; compared with the IL-1β group, *P<0.05, ***P<0.001. Figure 4 The results of b show that bitter A of Physalis alkekengi L. inhibits the apoptosis of chondrocytes induced by IL-1β. As shown in Figure 4In the IL-1β group, compared with the control group, it can be seen that IL-1β inhibits the expression of Bcl-2 protein. Compared with the IL-1β group, the expression level of Bcl-2 white in the IL-1β+PA (2.5 μmol / L) group, the IL-1β+PA (5 μmol / L) group and the IL-1β+PA (10 μmol / L) group presents a certain degree of rebound.

[0039] Although acid lemon bitter A can alleviate IL-1β-induced chondrocyte apoptosis, these previous research results show that acid lemon bitter A alone does not directly improve chondrocyte activity, and the present application further enhances its efficacy by compounding acid lemon bitter A, sodium pyruvate and mulberry root ketone A in a mass ratio of 100:2-5:1-2 to produce an improvement effect on chondrocyte activity, which can directly improve osteoarthritis from the aspect of cell activity and has the prospect of preparing osteoarthritis drugs. Sodium pyruvate, as a substrate of the tricarboxylic acid cycle, can supplement metabolic energy, has antioxidant effect, can scavenge free radicals, reduce oxidative damage, maintain mitochondrial membrane potential, acid lemon bitter A can not only inhibit IL-1β-induced chondrocyte apoptosis, but also can improve the activity of chondrocytes.

[0040] The structural formula of mulberry root ketone A is as follows: .

[0041] Mulberry root ketone A has been proved to have anti-inflammatory, antioxidant and antitumor effects. In the present application, the multiple hydroxyl groups of mulberry root ketone A are used to regulate the cell membrane potential, thereby improving the anti-stress ability of chondrocytes and the proliferation activity of chondrocytes.

[0042] The chondrocyte activity improver of the present application includes the following examples.

[0043] Example 1 A chondrocyte activity improver is prepared by mixing the following raw materials in a mass ratio of 100:2:1: acid lemon bitter A, sodium pyruvate and mulberry root ketone A. It is stored in the dark and ready for use.

[0044] Example 2 A chondrocyte activity improver is prepared by mixing the following raw materials in a mass ratio of 100:3:1: acid lemon bitter A, sodium pyruvate and mulberry root ketone A. It is stored in the dark and ready for use.

[0045] Example 3 A chondrocyte activity improver is prepared by mixing the following raw materials in a mass ratio of 100:5:1: acid lemon bitter A, sodium pyruvate and mulberry root ketone A. It is stored in the dark and ready for use.

[0046] Example 4 A chondrocyte activity enhancer is prepared by mixing raw materials in the following mass ratio: the mass ratio of physalin A, sodium pyruvate and mulberrocytin A is 100:2:2. The product is stored in the dark and ready for use.

[0047] Example 5 A chondrocyte activity enhancer is prepared by mixing raw materials in the following mass ratio: the mass ratio of physalin A, sodium pyruvate and mulberrocytin A is 100:3:2. The product is stored in the dark and ready for use.

[0048] Example 6 A chondrocyte activity enhancer is prepared by mixing raw materials in the following mass ratio: the mass ratio of physalin A, sodium pyruvate and mulberrocytin A is 100:5:2. The product is stored in the dark and ready for use.

[0049] Control group 1 Reagent A: physalin A alone. The product is stored in the dark and ready for use.

[0050] Control group 2 Reagent B: sodium pyruvate alone. The product is stored in the dark and ready for use.

[0051] Control group 3 Reagent C: mulberrocytin A alone. The product is stored in the dark and ready for use.

[0052] Control group 4 Reagent D: prepared by mixing raw materials in the following mass ratio: the mass ratio of physalin A and sodium pyruvate is 100:2. The product is stored in the dark and ready for use.

[0053] Control group 5 Reagent E: prepared by mixing raw materials in the following mass ratio: the mass ratio of physalin A and mulberrocytin A is 100:1. The product is stored in the dark and ready for use.

[0054] Control group 6 stored in the dark and ready for use.

[0055] Reagent F: prepared by mixing raw materials in the following mass ratio: the mass ratio of sodium pyruvate and mulberrocytin A is 2:1. The product is stored in the dark and ready for use.

[0056] It should be noted that, in order to exclude the influence of storage conditions on the effect of the reagent, the application uniformly adopts the method of storing in the dark, and all reagents are stored in the same environment. The reagent formulations of each example and each control group are shown in Table 1.

[0057] Table 1 reagent formulations of each example and each control group Experiment two, chondrocyte activity test (1) The acquisition of primary chondrocytes, see "Lu R, Qu YK, Yang Q, et al. Acid-taste A delays the progression of osteoarthritis through anti-inflammatory and anti-apoptotic pathways [J]. Orthopedics, 2022, 13(5):426-432. DOI:10.3969 / j.issn.1674-8573.2022.05.009". The specific steps are as follows:

[0058] 5-day-old C57BL / 6 mice were purchased from Wuhan Mouse Biotechnology Co., Ltd. After the mice were sacrificed, they were soaked in 75% alcohol for disinfection. The knee joint cartilage particles of C57BL / 6 mice were taken out, and the joint capsule, synovial tissue and tendon around the cartilage particles were removed. The cartilage particles were cut and moved to a sterile EP tube containing 0.25% trypsin-EDTA, and incubated in a 37°C cell incubator containing 5% CO2 for 30 min. Then centrifuged at 1500 r / min for 5 min, remove the trypsin, then add 0.2% type II collagenase, continue to digest in a hybrid oven at 37°C for 6 h. Centrifuged at 1500 r / min for 5 min, remove the type II collagenase, resuspend the chondrocytes and seed them in a T25 cell culture flask. The cell culture medium is HyClone DMEM / F12 medium containing 10% fetal bovine serum. The primary chondrocytes were obtained by culturing.

[0059] (2) Cell viability detection, the specific steps are as follows: The primary chondrocytes were seeded in a 96-well plate at a concentration of 10,000 cells per well. 100 μL of HyClone DMEM / F12 medium containing 10% fetal bovine serum was added to each well, followed by the addition of IL-1β to a final concentration of 10 ng / mL, and the addition of the test reagent to a final concentration of 10 μg / mL. It should be noted that in previous experiments, low concentration (5 ng / mL) of IL-1β did not directly cause damage to the viability of chondrocytes. In order to explore the effect of different chondrocyte activity enhancers on chondrocyte viability, high concentration 10 ng / mL of IL-1β was used to avoid light intervention on chondrocytes for 48 h to achieve cell viability damage. Then, discard the old culture medium, add 100 μL of new HyClone DMEM / F12 medium containing 10% fetal bovine serum and 10 μL of CCK-8 to each well, and incubate at 37°C in the dark for 2 h. The absorbance at 450 nm was measured, and the chondrocyte viability obtained by CCK-8 method was calculated.

[0060] Among them, without adding any experimental reagent as the positive control group. Without adding any experimental reagent and IL-1β as the blank control group, the cell viability of the blank control group was set to 100%.

[0061] Each experiment was set up in triplicate, and the average value was taken.

[0062] The results are shown in Table 2. The results of Table 2 show that the chondrocyte cells are damaged when treated with IL-1β at a high concentration of 10 ng / mL for 48 h, and the cell viability is significantly decreased compared with the blank control group. The bitter compound A of Fructus Physalis alone (control group 1) cannot improve the cell viability of chondrocyte cells, and has no significant difference with the positive control group. However, the bitter compound A of Fructus Physalis, when combined with sodium pyruvate and mulberry root ketone A, or combined with sodium pyruvate and mulberry root ketone A, can improve the cell viability of chondrocyte cells to different degrees. In particular, the three-factor combination of each embodiment can significantly improve the cell viability of chondrocyte cells. It is shown that the chondrocyte cell activity enhancer of the present application can significantly inhibit the apoptosis of chondrocyte cells induced by IL-1β.

[0063] Table 2: Chondrocyte cell viability test results of different experimental reagents Further, the present application uses GAPDH as a reference to test the expression levels of inflammatory proteins iNOS, COX-2 and IL-6 in chondrocyte cells of representative Example 2 (highest chondrocyte cell viability) and single-factor control groups 1-3. The results are shown in Table 3. The results of Table 3 show that the chondrocyte cell activity enhancer of Example 2 of the present application can be used to inhibit the inflammatory response of chondrocyte cells induced by IL-1β. It is suggested that the chondrocyte cell activity enhancer of the present application can achieve an anti-inflammatory effect by reducing the expression levels of inflammatory proteins iNOS, COX-2 and IL-6.

[0064] Table 3: Relative expression levels of inflammatory proteins iNOS, COX-2 and IL-6 in different groups Experiment three, selective enhancement of cell viability (1) Skin-derived fibroblasts were used as primary cells. The cells were inoculated in a 96-well plate at a concentration of 10,000 cells per well, 100 μL of HyClone DMEM / F12 medium containing 10% fetal bovine serum was added to each well, and IL-1β was added to a final concentration of 10 ng / mL. Then, 10 μg / mL of test reagent was added. The cells were incubated at 37°C in the dark for 24 h to achieve a cell viability damage state. Then, the old culture medium was discarded, and 100 μL of new HyClone DMEM / F12 medium containing 10% fetal bovine serum and 10 μL of CCK-8 were added to each well. The cells were incubated at 37°C in the dark for 2 h, and the absorbance at 450 nm was measured. The cell viability of fibroblasts was calculated by CCK-8 method.

[0065] The positive control group is without any experimental reagent. The blank control group is without any experimental reagent and IL-1β, and the cell viability of the blank control group is set as 100%. The drug control group is a common fibroblast cell viability promoter, basic fibroblast growth factor (bFGF).

[0066] Each experiment is set with 3 parallels, and the average value is taken. The results are shown in Table 4.

[0067] Table 4: Fibroblast cell viability test results of different experimental reagents Note: " / " in the table indicates that there is no data for the item.

[0068] Chondrocytes are more difficult to proliferate than common somatic cells, so common cell activity promoters (such as bFGF) cannot directly promote chondrocyte activity. The present application has a special compound, and the obtained chondrocyte activity promoter can selectively promote the activity of chondrocytes. However, by comparing the chondrocyte activity data and the fibroblast cell activity data, it is found that the chondrocyte activity promoter of the present application does not obviously promote the activity of common fibroblasts, which indicates that the chondrocyte activity promoter of the present application has strong targeting, and if it is used to promote the activity of other cells, the formula still needs to be adjusted for further research.

[0069] Based on the same inventive concept, the present application also provides a formula example of a drug for treating osteoarthritis, including the following embodiments.

[0070] Embodiment 7 The present application provides a chondrocyte activity promoter, which is made into a capsule, and the preparation method is as follows: Prepare microcrystalline cellulose, add chondrocyte activity promoter equivalent to 5% of the mass of the microcrystalline cellulose, and mix thoroughly to obtain a mixture.

[0071] Fill the mixture into a capsule shell to obtain a capsule dosage form.

[0072] It should be noted that when numerical ranges are involved in the present application, both endpoints of each numerical range and any number between the two endpoints can be selected. Since the same steps and examples are used, in order to prevent repetition, the preferred embodiments of the present application are described. Although the preferred embodiments of the present application have been described, those skilled in the art can make further changes and modifications to these embodiments once they know the inventive concept of the present application, and these changes and modifications all fall within the scope of the present application.

[0073] It will be apparent to those skilled in the art that various modifications and variations can be made to the present application without departing from the spirit or scope of the application. Such modifications and variations are considered to be within the scope of the application.

Claims

1. A cartilage cell activity enhancer, characterized by, The raw materials are mixed in the following mass ratio: The mass ratio of acidulatus bitter A, sodium pyruvate and mulberry root ketone A is 100:2-5:1-2.

2. The cartilage cell activity enhancer according to claim 1, characterized by, The mass ratio of acidulatus bitter A, sodium pyruvate and mulberry root ketone A is 100:3:

1.

3. The use of the cartilage cell activity enhancer according to claim 1, wherein The chondrocyte activity enhancer is used for preparing a medicine for treating osteoarthritis.

4. The use of the cartilage cell activity enhancer according to claim 1, wherein The medicine for treating osteoarthritis takes the chondrocyte activity enhancer as the only active ingredient.

5. Use according to claim 4, characterized in that, In the preparation of the medicine for treating osteoarthritis, the chondrocyte activity enhancer is compounded with pharmaceutically acceptable adjuvants.

6. Use according to claim 5, characterized in that, The pharmaceutically acceptable adjuvants are at least one of fillers, binders, disintegrants and coating agents.

7. The cartilage cell activity enhancer according to claim 6, wherein The fillers are starch, lactose or microcrystalline cellulose; The binders are starch paste or polyvinylpyrrolidone; The disintegrants are sodium starch glycolate or cross-linked polyvinylpyrrolidone; The coating agents are carboxymethylcellulose.

8. The use of the cartilage cell activity enhancer according to claim 1, wherein The chondrocyte activity enhancer has a greater effect on the activity enhancement of chondrocytes than on the activity enhancement of fibroblasts.

9. The use according to claim 1, characterized in that, The chondrocyte activity enhancer is used for inhibiting IL-1β-induced apoptosis of chondrocytes.

10. The cartilage cell activity enhancer according to claim 1, wherein The chondrocyte activity enhancer is used for inhibiting IL-1β-induced inflammatory response of chondrocytes.

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