Immune-Stimulatory Effects of Althaea rosea Flower Extracts through the MAPK Signaling Pathway in RAW264.7 Cells

Molecules. 2017 Apr 25;22(5):679. doi: 10.3390/molecules22050679.

Abstract

Althaea rosea (Linn.) is a medicinal plant from China and Korea that has been traditionally used to control inflammation, to stop bedwetting and as a mouthwash in cases of bleeding gums. Its flowers are employed medicinally for their emollient, demulcent and diuretic properties, which make them useful in chest complaints. Furthermore, a flower extract decoction is used to improve blood circulation, for the treatment of constipation, dysmenorrhoea, haemorrhages, etc. However, the possible mechanisms of the immune-stimulatory effect remains to be elucidated. Therefore, we investigated the role of Althaea rosea flower (ARF) extracts in the immune-stimulatory effect of macrophages and the underlying mechanisms of action. ARF water extract (ARFW) could dose-dependently increase NO production and cytokines (IL-6 and TNF-α). We also found that ARFW significantly increased the expression of iNOS and COX-2 proteins in RAW264.7 cells. Consistent with these results, MAPK protein (JNK, ERK, p38) expression levels were induced after treatment with ARFW. Additionally, ARFW showed a marked increase in the phosphorylation level of IκBα and subsequent IκBα degradation allowing NF-κB nuclear translocation. These results suggest that the immune-stimulatory effect of A. rosea flower extracts is mediated through the translocation of NF-κB p65 subunit into the nucleus from the cytoplasm and subsequent activation of pro-inflammatory cytokines (IL-6 and TNF-α) and other mediators (iNOS and COX-2), which occurs mainly through MAPK signalling pathway. Thus, we suggest that ARFW could be considered as a potential therapeutic agent useful in the development of immune-stimulatory compounds.

Keywords: Althaea rosea; RAW264.7 cells; immune-stimulatory effect.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Althaea / chemistry*
  • Animals
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism
  • Drug Evaluation, Preclinical
  • Flowers / chemistry
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System / drug effects*
  • Mice
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells

Substances

  • Adjuvants, Immunologic
  • Lipopolysaccharides
  • Plant Extracts
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2