Polygalaxanthone III downregulates inflammation in the lipopolysaccharide-stimulated RAW264.7 macrophages: A quantibody array analysis

J Pharmacol Sci. 2021 Oct;147(2):184-191. doi: 10.1016/j.jphs.2021.06.010. Epub 2021 Jul 3.

Abstract

Polygala japonica Houtt. (PJ), a member of the Polygala L. family that is suggested to exhibit detoxification properties in traditional Chinese medicine, is often used to treat upper respiratory tract infections. The anti-inflammatory effects of four main components of PJ (POL, PS-XLIX, PS-E, and PS-F) were examined using the LPS(0.3 μg·mL-1)-stimulated RAW264.7 macrophage model. The levels of NO, ROS, and iNOS were examined to analyze the anti-inflammatory activity of POL. Additionally, the levels of extracellular inflammation-related cytokines and chemokines were measured using quantibody array. The KEGG pathway analysis was performed to examine the anti-inflammatory mechanism of POL. The levels of NO in the POL-pretreated group were significantly downregulated when compared with those in the PS-E-pretreated, PS-F-pretreated, and PS-XLIX-pretreated groups. POL significantly inhibited the changes of iNOS, ROS, and inflammatory factors caused by LPS stimulation (p < 0.001). The expression levels of IL21 and GM-CSF were examined using qPCR, while those of JAK-STAT signaling pathway-related proteins in the LPS-stimulated RAW264.7 macrophages were analyzed using western blotting. POL significantly downregulated the expression of IL-21 and GM-CSF. The anti-inflammatory mechanism of POL is mediated through the JAK-STAT pathway. Thus, this study demonstrated that POL is an anti-inflammatory component of PJ and elucidated its mechanism.

Keywords: IL21; Inflammation modulation; Polygala japonica Houtt.; Polygalaxanthone III; Quantibody array.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents*
  • Cytokines / genetics
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Expression / drug effects
  • Glycosides / pharmacology*
  • Inflammation / etiology
  • Inflammation / genetics*
  • Inflammation Mediators / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism
  • Lipopolysaccharides / adverse effects
  • Mice
  • Nitric Oxide / genetics
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Polygala / chemistry*
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Xanthones / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drugs, Chinese Herbal
  • Glycosides
  • Inflammation Mediators
  • Interleukins
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Xanthones
  • polygalaxanthone III
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • interleukin-21