Glabretal-type triterpenoid from the root bark of Dictamnus dasycarpus ameliorates collagen-induced arthritis by inhibiting Erk-dependent lymphocyte proliferation. (3rd February 2016)

• Record Type: Journal Article
• Authors: Choi, Sang-Pil; Choi, Chang-Yong; Park, Kyungmin; Kim, Nahyun; Moon, Hyun-Seuk; Lee, Dongho; Chun, Taehoon
• Is Part Of: Journal of ethnopharmacology. Volume 178(2016)
• Page Start: 13
• Page End: 16
• Publication Date: 2016-02-03
• Subjects: CFSE carboxyfluorescein succinimidyl ester -- ChIP chromatin immunoprecipitation -- CIA collagen induced arthritis -- IRE internal regulatory element -- OVA ovalbumin peptide -- PI propidium iodide -- URE upstream regulatory element; Cell cycle -- Collagen induced arthritis -- Dictabretol A -- Lymphocyte -- Signal transduction; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2015.10.043
• Languages: English
• ISSNs: 0378-8741

Abstract

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 G1 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. Graphical abstract: