4.6 Article

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

Journal

EXPERIMENTAL CELL RESEARCH
Volume 364, Issue 1, Pages 84-94

Publisher

ELSEVIER INC
DOI: 10.1016/j.yexcr.2018.01.033

Keywords

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

Funding

  1. National Natural Science Foundation of China [81603135, 81673461, 81373448, 81373449]
  2. National Science & Technology Major Project [2017ZX09301014, 2017ZX09101003-003-007, 2017ZX09101003-005-023]
  3. Program for Changjiang Scholars and Innovative Research Team in University [IRT1193]
  4. Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZCX201606]

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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 proin-flammatory cytokines secretion by regulating PI3K/AKT/mTOR signaling pathway without affecting M2 macrophage-associated cytokines mRNA levels. In vivo studies showed that 12205 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.

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