Immunosuppressive activity of daphnetin, one of coumarin derivatives, is mediated through suppression of NF-κB and NFAT signaling pathways in mouse T cells

• Published in: PloS one 2014-05, Vol.9 (5), p.e96502
• Main Authors: Song, Bocui, Wang, Zhenning, Liu, Yan, Xu, Sisi, Huang, Guoren, Xiong, Ying, Zhang, Shuang, Xu, Linli, Deng, Xuming, Guan, Shuang
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants; Autoimmune diseases; Biology and Life Sciences; Cell cycle; Cell Proliferation - drug effects; Concanavalin A; Concanavalin A - immunology; Coumarin; Coumarins - immunology; Coumarins - pharmacology; Cytokines; Dinitrofluorobenzene; Down-Regulation - drug effects; Down-Regulation - immunology; Education; Food; Food quality; G1 Phase - drug effects; G1 Phase - immunology; Hypersensitivity; Hypersensitivity (delayed); Hypersensitivity, Delayed - immunology; Immunoglobulins; Immunology; Immunosuppressive agents; Immunosuppressive Agents - immunology; Immunosuppressive Agents - pharmacology; Inflammation; Kinases; Laboratories; Light; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; NF-AT protein; NF-kappa B - immunology; NF-κB protein; NFATC Transcription Factors - immunology; Pathways; Physical Sciences; Plant cells; Plant extracts; Plants; Proteins; Research and Analysis Methods; Resting Phase, Cell Cycle - drug effects; Resting Phase, Cell Cycle - immunology; Signal transduction; Signal Transduction - drug effects; Signal Transduction - immunology; Signaling; Studies; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Umbelliferones - immunology; Umbelliferones - pharmacology; Veterinary colleges; Veterinary medicine; Zoonoses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0096502

Daphnetin, a plant-derived dihydroxylated derivative of coumarin, is an effective compound extracted from a plant called Daphne Korean Nakai. Coumarin derivates were known for their antithrombotic, anti-inflammatory, and antioxidant activities. The present study was aimed to determine the immunosuppressive effects and the underlying mechanisms of daphnetin on concanavalin A (ConA) induced T lymphocytes in mice. We showed that, in vitro, daphnetin suppressed ConA-induced splenocyte proliferation, influenced production of the cytokines and inhibited cell cycle progression through the G0/G1 transition. The data also revealed that daphnetin could down-regulate activation of ConA induced NF-κB and NFAT signal transduction pathways in mouse T lymphocyte. In vivo, daphnetin treatment significantly inhibited the 2, 4- dinitrofluorobenzene (DNFB) -induced delayed type hypersensitivity (DTH) reactions in mice. Collectively, daphnetin had strong immunosuppressive activity both in vitro and in vivo, suggesting a potential role for daphnetin as an immunosuppressive agent, and established the groundwork for further research on daphnetin.