In vitro and in vivo immunostimulatory effects of hot water extracts from the leaves of Artemisia princeps Pampanini cv. Sajabal

J Ethnopharmacol. 2013 Aug 26;149(1):254-62. doi: 10.1016/j.jep.2013.06.030. Epub 2013 Jun 27.

Abstract

Ethnopharmacological relevance: Artemisia princeps Pampanini (Asteraceae) is used as a traditional medicine to immune function-related diseases, such as dysmenorrhea, inflammation, cancer, and ulcers.

Aim of the study: The purpose of this study is to evaluate the immunostimulatory effects of the hot water extract from the leaves of Artemisia princeps Pampanini (WAPP) in recombinant interferon-γ (rIFN-γ)-primed RAW 264.7 macrophages and in cyclophosphamide (20mg/kg, i.p.)-induced immunosuppressed Sprague-Dawley rats.

Materials and methods: RAW 264.7 macrophages were treated with WAPP and production and expressions of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) via nuclear factor-κB (NF-κB) were detected by immunoassay, western blot, qRT-PCR and reporter gene assay. In addition, in vivo immunomodulatory activity was studied by cyclophosphamide-induced myelosuppression in rats.

Results: In rIFN-γ-primed RAW 264.7 macrophages, pretreatment with WAPP increased the productions of nitric oxide (NO) and tumor necrosis factor-α (TNF-α),and increased the expressions of inducible nitric oxide synthase (iNOS) at the protein level and of iNOS and TNF-α at the mRNA level. Molecular data revealed that WAPP upregulated the transcriptional activity and translocation of nuclear factor-κB (NF-κB) by activating inhibitory kappa B-α (IκB-α) degradation and phosphorylation. Furthermore, WAPP upregulated the phosphorylations of p38 MAP kinase, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase 1/2 (ERK1/2). In cycloheximide-induced immunosuppressed rats, pretreatment with WAPP (100, 200, or 400mg/kg, p.o.) increased the serum levels of albumin and globulin, and reduced immobility times.

Conclusion: Our results suggest that upregulations of the expressions of iNOS and TNF-α via the activations of NF-κB and MAPK are responsible for the immunostimulatory effects of WAPP.

Keywords: Artemisia princeps Pampanini cv. Sajabal; Cyclophosphamide; ERK1/2; Immunostimulatory activity; IκB-α; JNK; NF-κB; NO; Nitric oxide; TNF-α; Tumor necrosis factor-α; WAPP; c-Jun NH2-terminal kinase; extracellular signal-regulated kinase1/2; hot water extract from the leaves of Artemisia princeps Pampanini; iNOS; inducible nitric oxide synthase; inhibitory kappa B-α; nitric oxide; nuclear factor-κB; qRT-PCR; quantitative reverse-transcriptase polymerase chain reaction; rIFN-γ; recombinant interferon-γ; tumor necrosis factor-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / isolation & purification
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Artemisia / chemistry*
  • Cell Culture Techniques
  • Cell Line
  • Ethnopharmacology*
  • Hot Temperature
  • Macrophages / drug effects
  • Macrophages / immunology
  • Medicine, Korean Traditional*
  • Mice
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / immunology
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Republic of Korea
  • Swimming
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / immunology
  • Water / chemistry

Substances

  • Adjuvants, Immunologic
  • Plant Extracts
  • Tumor Necrosis Factor-alpha
  • Water
  • Nitric Oxide