Glabretal-type triterpenoid from the root bark of Dictamnus dasycarpus ameliorates collagen-induced arthritis by inhibiting Erk-dependent lymphocyte proliferation

Abstract

Ethnopharmacological relevance: The root bark of Dictamnus dasycarpus Turcz. (Rutaceae) has been used as a traditional herbal medicine to treat various inflammatory diseases in East Asia. We have showed previously that a glabretal type triterpenoid (dictabretol A) from D. dasycarpus root bark has immunosuppressive activity. Aim of the study: This study was conducted to define the molecular mechanism of how dictabretol A inhibits lymphocyte proliferation and to evaluate the therapeutic efficacy of dictabretol A in an animal model of rheumatoid arthritis. Materials and methods: Various murine immune cells (T cells, B cells, and macrophages) and splenocytes were used to study the anti-proliferative effect of dictabretol A in vitro. A collagen-induced arthritis model was also used to examine the therapeutic effect of dictabretol A in vivo. Results: Dictabretol A specifically inhibited lymphocyte proliferation by blocking the cell cycle transition from the G(1) to the S phase. This effect was achieved by blocking Erk1/2, nuclear factor kappa B, and the C-myc axis of cell cycle progression. Further dictabretol A treatment alleviated the severity of collagen induced arthritis. Conclusion: Our results reveal the molecular mechanism for the anti-lymphoproliferative effect of dictabretol A and show the therapeutic efficacy of dictabretol A for rheumatoid arthritis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.