## 2 Materials and Methods  
Materials and extraction; The CTE and SKE samples used in the experiment were collected and air-dried in Sinan-gun, Jeollanam-do, South Korea, then boiled in the ratio of 1:50 (\(w/v\)) at 90 \({}^{\circ}\)C to 100 \({}^{\circ}\)C for four hours. Subsequently, these extracts were cooled down at 50 \({}^{\circ}\)C with water, then filtered to remove impurities. The filtered extracts were concentrated at 50 \({}^{\circ}\)C to 60 \({}^{\circ}\)C with a solid content of more than 10%, then sterilized, stirred, and spray-dried for one hour at 95 \({}^{\circ}\)C with the addition of a dose of dextrin (50:50, \(w/w\)). Cell culture; RAW264.7 mouse macrophage cells were purchased from the Korean Cell Line Bank (Seoul, Korea), then cultured in a growth medium. The RAW264.7 were cultured in Dulbecco's modified Eagle medium (Gibco Laboratories, Gaithersburg, MD, USA) supplemented with 10% fetal bovine serum (Gibco Laboratories) and 1% antibiotic antinycotic solution (Gibco Laboratories) at 37 \({}^{\circ}\)C in an incubator at 95% humidity and a 5% mixture of air and CO\({}_{2}\). Cell viability assay, Mouse macrophage RAW264.7 cells for in vitro experiments were dispensed into \(3\times 10^{5}\) cells/well in a 96-well plate and incubated for 24 h in a 5% CO\({}_{2}\) incubator at 37 \({}^{\circ}\)C. Subsequently, the cells were treated with different concentrations (0, 100, 200, 500, 1000, and 2000 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) of a mixture of CTE and SKE in various ratios. After incubation for 24 h, 10 \(\mathrm{\SIUnitSymbolMicro m}\) of the EZ cytox (DoGenBio, Seoul, South Korea) was added to each well and further incubated for 30 min at 37 \({}^{\circ}\)C and 5% CO\({}_{2}\). The index of the cell viability was determined by measuring the formazan production with an enzyme-linked immunosorbent assay (ELISA) reader (Thermo Fisher Scientific, Waltham, MA, USA) at an absorbance of 450 nm. Inhibition of nitric oxide (NO) production (Griess assay); mouse macrophage RAW264.7 cells for in vitro experiments were dispensed into \(3\times 10^{5}\) cells/well in a 96-well plate and incubated for 24 h in a 5% CO\({}_{2}\) incubator at 37 \({}^{\circ}\)C. Subsequently, the cells were treated with different concentrations (0, 100, 200, 500, 1000, and 2000 \(\mathrm{\SIUnitSymbolMicro g}\)/mL) of a mixture of CTE and SKE in various ratios. Simultaneously, 1 \(\mathrm{\SIUnitSymbolMicro g}\)/mL of lipopolysaccharideaschardies (LPS) (Sigma-Aldrich, St. Louis, MO, USA) was added and incubated for 24 h. Then, after adding and reacting the same amount of Griess reagent (Sigma-Aldrich) equal to 100 \(\mathrm{\SIUnitSymbolMicro m}\) of the culture solution, the absorbance was measured at 540 nm with an ELISA reader. The NO concentration in the culture medium was determined using a standard curve for each concentration of sodium nitrite. Animals and maintenance; previously, an antibody against collagen was found in the serum of rheumatoid arthritis patients, and it was conceived that type 2 collagen present in the joint could act as an autoanti. As a representative animal model of rheumatoid arthritis, collagen-induced arthritis (CIA) DBA/1 mice were introduced. The total experimental group included the following six mouse groups containing six DBA/1J mice each: a \"control\" group without CIA or treatment, a \"vehicle\" group with CIA but no treatment, a CTE-alone treatment group, a CTE/SKE 2:1 treatment group, a CTE/SKE treatment 1:1 group, and a CTE/SKE treatment 1:2 group, respectively. All mice were in cages and allowed to acclimize for one week before use. The temperature of the breeding room was maintained at 25 \({}^{\circ}\)C \(\pm\) 2 \({}^{\circ}\)C, the humidity was maintained at 5% \(\pm\) 10%, and a 12-h light/dark cycle was set. To observe the arthritis-prevention effect, oral administration was performed every two days after the date of the induction of arthritis.