Acta Pharmacologica Sinica (2009) 30: 1144-1152; doi: 10.1038/aps.2009.101; published online 13 July 2009

Aim: The aim of this study was to determine the therapeutic effect of Periplocoside A (PSA), a natural product isolated from the traditional Chinese herbal medicine Periploca sepium Bge, in MOG_35?5 (myelin oligodendrocyte glycoprotein 35?5)-induced experimental autoimmune encephalomyelitis (EAE).

Methods: Female C57BL/6 mice immunized with MOG_35?5 were treated with (50 mg/kg or 25 mg/kg) or without PSA following immunization and continuously throughout the study.  The degree of CNS inflammation was evaluated by H&E staining.  Anti-MOG-specific recall responses were analyzed by [³H]-Thymidine incorporation, ELISA, and RT-PCR.  The proportion of IL-17-producing T cells was measured by flow cytometry.

Results: Oral administration of PSA significantly reduced the incidence and severity of EAE, which closely paralleled the inhibition of MOG_35?5-specific IL-17 production.  Importantly, PSA inhibited the transcription of IL-17 mRNA and RORγt. Further studies examining intracellular staining and adoptive transfer EAE validated the direct suppressive effect of PSA on Th17 cells.  In vitro studies also showed that PSA significantly inhibited the differentiation of Th17 cells from murine purified CD4⁺ T cells in a dose-dependent manner.

Conclusion: PSA ameliorated EAE by suppressing IL-17 production and inhibited the differentiation of Th17 cells in vitro.  Our results provide new insight into the potential mechanisms underlying the immunosuppressive and anti-inflammatory effects of PSA.

Keywords: P sepium Bge; Periplocoside A; experimental autoimmune encephalomyelitis; Th17 cells