In vitro inhibitory effects of cirsiliol on IL-6-induced STAT3 activation through anti-inflammatory activity

Bioorg Med Chem Lett. 2019 Jul 1;29(13):1586-1592. doi: 10.1016/j.bmcl.2019.04.053. Epub 2019 May 2.

Abstract

Many studies have identified and described various medicinal effects of cirsiliol. Here, we investigated the signaling pathway involved in the anti-inflammatory effects of cirsiliol on IL-6-induced activity. Cirsiliol showed no cytotoxicity and inhibited pSTAT3-induced luciferase activity. At the molecular level, cirsiliol suppressed the expression of IL-6-induced inflammatory marker genes such as CRP, IL-1β, ICAM-1 and SOCS3, IL-6-induced activation of Jak2, gp130, STAT3 and ERK and nuclear translocation of STAT3, as measured by PCR, immunofluorescence staining and western blot analysis. However, the interaction between IL-6 and its receptor was not affected by cirsiliol treatment. These results indicate that cirsiliol attenuates IL-6-induced cellular signaling by regulating Jak2 phosphorylation. Therefore, cirsiliol could be a therapeutic agent for IL-6-related inflammatory diseases.

Keywords: Cirsiliol; IL-6; Inflammation; Jak2; STAT3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Flavones / pharmacology
  • Flavones / therapeutic use*
  • Humans
  • In Vitro Techniques
  • Interleukin-6 / metabolism*
  • STAT3 Transcription Factor / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Flavones
  • Interleukin-6
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • cirsiliol