Toll-Like Receptor 4–Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Shikonin Treatment of CIA by Regulating Treg/Th17 Expression

Figure 1

(a) Frequency of arthritis. (c) Mean arthritis macroscopic score. (d) Survival proportions of CIA mice. Immunized DBA/1 mice without signs of CIA were selected and divided into five separate groups. Mice were treated with shikonin (three doses), celecoxib, and with 0.1ml PBS as control group for 60 days. Clinical arthritis score and incidence were monitored throughout the experiment. The data represent macroscopic score and mean incidence of arthritis in every group. indicates P<0.05 between treated and control groups. (b) Hindpaw thickness of every group. The effect of shikonin on the clinical progression of developing CIA as monitored by foot swelling. Measurements of the hindpaw depth were performed every six days. (e) The level of anti-CII IgG antibody in serum. Levels of Collagen Type II in blood of CIA were measured using ELISA kits. Note: S-h: high dose of shikonin, S-m: medium dose of shikonin, and S-l: low dose of shikonin. (f) HE staining of the knee joint. Sections of the knee were collected on day 81 and stained with H&E stain (40X). Left: PBS-treated mice with Collagen II induced arthritis, showing severe cartilage surface disruption, infiltrate of inflammatory cells, and bone erosion (arrows). Right: Mice with CIA treated with 5mg/kg shikonin, showing marked improvements with intact cartilage surface (arrows). Note: CA: cartilage.

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