Plumbagin suppresses dendritic cell functions and alleviates experimental autoimmune encephalomyelitis

J Neuroimmunol. 2014 Aug 15;273(1-2):42-52. doi: 10.1016/j.jneuroim.2014.05.014. Epub 2014 Jun 7.

Abstract

Plumbagin (PL, 5-hydroxy-2-methyl-1,4-naphthoquinone) is a herbal compound derived from medicinal plants of the Droseraceae, Plumbaginaceae, Dioncophyllaceae, and Ancistrocladaceae families. Reports have shown that PL exerts immunomodulatory activity and may be a novel drug candidate for immune-related disease therapy. However, its effects on dendritic cells (DCs), the most potent antigen-presenting cells (APCs), remain unclear. In this study, we demonstrate that PL inhibits the differentiation, maturation, and function of human monocyte-derived DCs. PL can also restrict the expression of Th1- and Th17-polarizing cytokines in mDC. In addition, PL suppresses DCs both in vitro and in vivo, as demonstrated by its effects on the mouse DC line DC2.4 and mice with experimental autoimmune encephalomyelitis (EAE), respectively. Notably, PL ameliorated the clinical symptoms of EAE, including central nervous system (CNS) inflammation and demyelination. Our results demonstrate the immune suppressive and anti-inflammatory properties of PL via its effects on DCs and suggest that PL could be a potential treatment for DC-related autoimmune and inflammatory diseases.

Keywords: Dendritic cells; Experimental autoimmune encephalomyelitis; Inflammation; Multiple sclerosis; Plumbagin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use
  • Animals
  • Antigens, CD / metabolism
  • Apoptosis / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / physiology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Endocytosis / drug effects
  • Female
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred C57BL
  • Naphthoquinones / pharmacology*
  • Naphthoquinones / therapeutic use*
  • Spinal Cord / pathology

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • Cytokines
  • Lipopolysaccharides
  • Naphthoquinones
  • plumbagin