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Periploca forrestii Schltr. has been used as a Chinese folk medicine due to its versatile pharmacological effects such as promoting wounds and rheumatoid arthritis. However, the antiarthritic activity of Periploca forrestii saponin (PFS) and its active compound Periplocin has still not been demonstrated. Here, we evaluated the antiarthritic effects of PFS in adjuvant-induced arthritis (AIA) rats by intragastric administration at a dose of 50 mg/kg. The anti-inflammatory activities of Periplocin were also examined in LPS-induced AIA splenocytes and synoviocytes. PFS significantly ameliorated joint swelling; inhibited bone erosion in joints; lowered levels of IL-6 and TGF- β 1 in AIA rat splenocyte; and reduced joint protein expression levels of phospho-STAT3 and IKK α . Using LPS-induced AIA splenocytes, we demonstrate that Periplocin suppressed the key proinflammatory cytokines levels of IL-6, IFN- γ , TGF- β 1, and IL-13 and IL-22 and transcription factor levels of T-bet, GATA3, and C-Jun genes. Periplocin also suppressed LPS-induced cytokine secretion from synoviocytes. Our study highlights the antiarthritic activity of PFS and its derived Periplocin and the underlying mechanisms. These results provide a strong rationale for further testing and validation of the use of Periploca forrestii Schltr. as an alternative modality for the treatment of RA., Competing Interests: The authors declare that there are no competing interests regarding the publication of this paper.

Background: Due to the steadily increasing incidence of atopic dermatitis, there is a great medical need for new therapies and improved animal models., Objective: To provide more detailed analysis of a Sprague-Dawley rat dermatitis model., Methods: Sprague-Dawley rats were actively sensitized by intraperitoneal injections of dinitrophenylated ovalbumin (DNP-OVA) plus alum. Skin reactions were elicited by repeated epicutaneous challenge with 2,4-dinitrofluorobenzene (DNFB)., Results: The ear thickness exhibited a significant increase from the first challenge. A relatively steep increase in ear thickness was observed at the fifth DNFB application. After the fifth DNFB application, total serum immunoglobulin (Ig) E and IgG1 levels reached a plateau at 1 h compared with the normal group. The peak production of tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 was found at 1 h, while that of intercellular adhesion molecule (ICAM)-1 was found at 24 h. Infiltration of CD4+ T cells, CD8+ T cells, eosinophils and mast cells increased in the skin lesion., Conclusions: The indices such as thickness and inflammatory cell infiltration in the lesional skin were increased by repeated hapten application; TNF-α, MCP-1 and ICAM-1 increased with the development of the dermatitis.

Objective: Periploca forrestii Schltr has been used as a Chinese folk medicine for the treatment of rheumatism, arthralgia and fractures. However, the anti-arthritic activity of Periploca forrestii saponin (PFS) and the active compound has still not been revealed. This study aimed to investigate the protective effects and mechanisms of PFS on collagen type II (CII) collagen-induced arthritis (CIA) mice. We sought to investigate whether PFS and Periplocin could regulate osteoclastogenesis, and if so, further investigation on its mechanism of action. Methods: Arthritis was induced in female BALB/c mice by CIA method. PFS was administered at a dose of 50 mg/kg body weight once daily for five weeks. The effects of treatment in mice were assessed by histological and biochemical evaluation in sera and paws. Anti-osteoclastogenic action of PFS and Periplocin was identified using an osteoclast formation model induced by RANKL. Results: PFS ameliorated paw erythema and swelling, inhibited bone erosion in ankle joint histopathological examination. PFS treatment resulted in decreased IgG2a, and increased IgG1 levels in the serum of CIA mice. Decreased TNF-α, and increased interleukin (IL)-4 and IL-22 levels were also found in PFS-treated mice. PFS inhibited the I-κBα phosphorylation, blocked nuclear factor (NF)-κB/p65 phosphorylation and abrogated AP-1/c-Fos activity. PFS downregulated toll-like receptor (TLR) 4, STAT3 and MMP-9 expression in CIA mice and RANKL-induced osteoclastogenesis. PFS and Periplocin inhibited RANKL-induced osteoclast formation in a dose dependent manner within nongrowth inhibitory concentration, and PFS decreased osteoclastogenesis-related marker expression, including cathepsin K and MMP-9. Conclusion: This study revealed that the protective mechanism of PFS on CIA was associated with regulatory effects on proinflammatory factors and further on the crosstalk between NF-κB and c-Fos/AP-1 in vivo and in vitro. Therefore, PFS is a promising therapeutic alternative for the treatment of RA, evidencing the need to conduct further studies that can identify their active components in treating and preventing RA. [ABSTRACT FROM AUTHOR]