Wild simulated ginseng activates mouse macrophage, RAW264.7 cells through TRL2/4-dependent activation of MAPK, NF-κB and PI3K/AKT pathways

J Ethnopharmacol. 2020 Dec 5:263:113218. doi: 10.1016/j.jep.2020.113218. Epub 2020 Aug 2.

Abstract

Ethnopharmacological relevance: Ginseng (Panax ginseng Meyer) is a very well-known traditional herbal medicine that has long been used to enhance the body's immunity. Because it is a type of ginseng, it is believed that wild simulated ginseng (WSG) also has immune-enhancing activity. However, study on the immune-enhancing activity of WSG is quite insufficient compared to ginseng.

Aim of the study: In this study, we evaluated immune-enhancing activity of WSG through macrophage activation to provide a scientific basis for the immune enhancing activity of WSG.

Materials and methods: The effect of WSG on viability of RAW264.7 cells was evaluated by MTT assay. The NO level was measured by Griess reagent. The expression levels of mRNA or protein in WSG-treated RAW264.7 cells were analyzed by RT-PCR and Western blot, respectively.

Results: WSG increased the production of immunomodulators such as NO, iNOS, COX-2, IL-1β, IL-6 and TNF-α and activated phagocytosis in mouse macrophages RAW264.7 cells. Inhibition of TLR2 and TLR4 reduced the production of immunomodulators induced by WSG. WSG activated MAPK, NF-κB and PI3K/AKT signaling pathways, and inhibition of such signaling activation blocked WSG-mediated production of immunomodulators. In addition, activation of MAPK, NF-κB and PI3K/AKT signaling pathways by WSG was reversed by TLR2 or TLR4 inhibition.

Conclusion: Based on the results of this study, WSG is thought to activate macrophages through the production of immunomodulators and phagocytosis activation through TLR2/4-dependent MAPK, NF-κB and PI3K/AKT signaling pathways. Therefore, it is thought that WSG have the potential to be used as an agent for enhancing immunity.

Keywords: Immune enhancement; Immunomodulators; Macrophages; Wild simulated ginseng.

MeSH terms

  • Animals
  • Enzyme Activation / drug effects
  • Enzyme Activation / physiology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology
  • Macrophage Activation / drug effects*
  • Macrophage Activation / physiology
  • Mice
  • NF-kappa B / metabolism*
  • Panax*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RAW 264.7 Cells
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • NF-kappa B
  • Plant Extracts
  • Tlr2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Proto-Oncogene Proteins c-akt