Validation of CIA model establishment. (A) To induce CIA, Sprague-Dawley rats were given an initial injection of CFA containing collagen II (day 0). After 7 days, boost immunization was induced via CFA injection. Drug administration began on day 14 and continued daily for 20 days. The rats were sacrificed on day 34. (B) Macroscopic observation of toe swelling on day 0 (CIA initiation), day 14 (beginning of drug treatment), and day 34 (end of drug treatment). (C) Toe volume was measured on day 0, 4, 7, 12, 14, 24, 32, and 34. (D) Relative toe swelling was calculated using the following equation (Vx–V0)/V0 × 100%, where Vx is the toe volume measured on day x and V0 is the initial toe volume of the respective drug treatment group measured on day 0. All data are expressed as the mean ± standard deviation (n = 3 rats). #p < 0.05; Δ, ΔΔ, and ΔΔΔ denote p < 0.05 compared to day 4, 7, and 12, respectively, in the same drug treatment group; *, **, and *** denote p < 0.05 compared to day 14, 24, and 32, respectively, in the same drug treatment group. Low, medium, and high doses of COR and PAE were administered, but the medium doses (COR-M and PAE-M) were selected as representatives for analysis. CIA: collagen-induced arthritis; COR: Cornus officinalis; PAE: Paeonia lactiflora; PF: paeoniflorin; UA: ursolic acid; DEX: dexamethasone.