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

Bocui Song; Zhenning Wang; Yan Liu; Sisi Xu; Guoren Huang; Ying Xiong; Shuang Zhang; Linli Xu; Xuming Deng; Shuang Guan

doi:10.1371/journal.pone.0096502

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

PLoS One. 2014 May 6;9(5):e96502. doi: 10.1371/journal.pone.0096502. eCollection 2014.

Authors

Bocui Song¹, Zhenning Wang², Yan Liu¹, Sisi Xu², Guoren Huang², Ying Xiong¹, Shuang Zhang², Linli Xu², Xuming Deng¹, Shuang Guan³

Affiliations

¹ Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, People's Republic of China.
² Department of Food Quality and Safety, College of Light Industry Economics and Management, Jilin University, Changchun, People's Republic of China.
³ Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, People's Republic of China; Department of Food Quality and Safety, College of Light Industry Economics and Management, Jilin University, Changchun, People's Republic of China.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Proliferation / drug effects
Concanavalin A / immunology
Coumarins / immunology*
Coumarins / pharmacology
Down-Regulation / drug effects
Down-Regulation / immunology
G1 Phase / drug effects
G1 Phase / immunology
Hypersensitivity, Delayed / immunology
Immunosuppressive Agents / immunology*
Immunosuppressive Agents / pharmacology
Male
Mice
Mice, Inbred BALB C
NF-kappa B / immunology*
NFATC Transcription Factors / immunology*
Resting Phase, Cell Cycle / drug effects
Resting Phase, Cell Cycle / immunology
Signal Transduction / drug effects
Signal Transduction / immunology*
T-Lymphocytes / drug effects
T-Lymphocytes / immunology*
Umbelliferones / immunology*
Umbelliferones / pharmacology

Substances

Coumarins
Immunosuppressive Agents
NF-kappa B
NFATC Transcription Factors
Umbelliferones
Concanavalin A
coumarin
daphnetin

Grants and funding

The authors are grateful for help received from the College of Veterinary Medicine of Jilin University. This study was supported by the National Nature Science Foundation of China (No . 31130053). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.