PFS alleviates bone destruction in collagen-induced arthritis mice associated with macrophage polarization

Periploca forrestii Schltr is a clinical traditional Chinese medicine for the treatment of Rheumatoid arthritis (RA). This study aimed to investigate effects of Periploca forrestii Schltr saponin (PFS) on bone destruction and macrophage polarization in arthritis model mice and to explore its possible mechanism. Arthritis was induced in two species, BALB/c and C57BL/6 mice, by immunization with type II chicken collagen. The arthritic mice were administered PFS for four weeks. The hindfeet, blood and spleen were harvested. Molecular expression was determined by ELISA, RT-PCR and immunoblotting. PFS treatment resulted in a significant reduction in paw swelling in both species of mice. PFS also reduced cartilage destruction and infiltration of osteoclasts in BALB/c mice. Furthermore, it decreased the levels of M1 macrophage cytokines while increasing the levels of M2 macrophage cytokines in the paw and plasma. Micro-CT results in C57BL/6 mice showed that PFS attenuated microstructural damage in bone tissue. PFS inhibited CD68 and affected the expression of M1 macrophage factors such as CCL-2, TLR4, and IL-1{beta} in the mouse paw. In addition, PFS treatment increased the M2 macrophage factor CD206 and CD163. PFS inhibits the activation of ERK, JNK, and p38 and the expression of transcription factors, including STAT3, p65, and c-Fos. PFS may modulate pleiotropic macrophage polarization and thus play an ameliorative role in bone damage, therefore PFS may be an effective alternative drug for the treatment of RA.