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LZ205, a newly synthesized flavonoid compound, exerts anti-inflammatory effect by inhibiting M1 macrophage polarization through regulating PI3K/AKT/mTOR signaling pathway

Exp Cell Res. 2018 Mar 1;364(1):84-94. doi: 10.1016/j.yexcr.2018.01.033. Epub 2018 Jan 31.

Abstract

Macrophage polarization is involved in the process of inflammation. Regulation of macrophage polarization is considered to be an effective method for the treatment of various inflammatory diseases. In our study, we investigated the potential molecular mechanism of the flavonoid compound LZ205, which exhibits anti-inflammatory property. Results showed that LZ205 significantly reduced M1 macrophage-associated proinflammatory cytokines secretion by regulating PI3K/AKT/mTOR signaling pathway without affecting M2 macrophage-associated cytokines mRNA levels. In vivo studies showed that LZ205 significantly inhibited M1 macrophages polarization in DSS-induced colitis and alum-induced murine peritonitis. Consistent with in vitro studies, LZ205 significantly blocked expression of PI3K, p-AKT and p-mTOR in colon tissues and peritoneal macrophages. Taken together, LZ205 exerts anti-inflammatory effect by inhibiting M1 macrophage polarization via regulating PI3K/AKT/mTOR signaling pathway.

Keywords: Colitis; LZ205; M1 macrophage polarization; PI3K/AKT/mTOR signaling pathway; Peritonitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / pathology
  • Female
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / pathology
  • Mice
  • Mice, Inbred C57BL
  • Peritonitis / drug therapy*
  • Peritonitis / metabolism
  • Peritonitis / pathology
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Flavonoids
  • LZ205
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases