Fisetin inhibits inflammation and induces autophagy by mediating PI3K/AKT/mTOR signaling in LPS-induced RAW264.7 cells

  • Yue Sun Xiangya School of Public Health, Central South University, Changsha; and Inspecting Agency, Shanghai Municipal Health Commission, Shanghai, China
  • Hong Qin Xiangya School of Public Health, Central South University, Changsha, China
  • Huihui Zhang Xiangya School of Public Health, Central South University, Changsha, China
  • Xiangling Feng Xiangya School of Public Health, Central South University, Changsha, China
  • Lina Yang Xiangya School of Public Health, Central South University, Changsha, China
  • De-Xing Hou Course of Biological Science and Technology, The United Graduate School of Agricultural Sciences, Department of Food Science and Biotechnology, Faculty of Agriculture, Kagoshima University, Kagoshima, Japan
  • Jihua Chen Xiangya School of Public Health, Central South University, Changsha, China
Keywords: Fisetin; Macrophage; PI3K/AKT/mTOR pathway; Inflammatory response; Autophagy


Background: Fisetin, a natural potent flavonoid, has various beneficial, pharmacological activities. In this study, we investigated expression changes of the fisetin regulating genes in lipopolysaccharide (LPS)-treated RAW264.7 cells and explored the role of fisetin in inflammation and autophagy.

Methods and results: Microarray analysis identified 1,071 genes that were regulated by fisetin in LPS-treated RAW264.7 cells, and these genes were mainly related to the process of immune system response. Quantitative real-time polymerase chain reaction and Bio-Plex analysis indicated that fisetin decreased the expression and secretion of several inflammatory cytokines in cells administered with LPS. Western blot analysis and immunofluorescence assay showed that fisetin decreased microtubule-associated protein 1 light-chain 3B (LC3B) and lysosome-associated membrane protein 1 (LAMP1) expression in LPS-treated cells, while the autophagy inhibitor chloroquine (CQ) could partially reverse this effect. In addition, fisetin reduced the elevated expression of p-PI3K, p-AKT and p-mTOR induced by LPS in a concentration-dependent manner.

Conclusions: Fisetin diminished the expression and secretion of inflammatory cytokines and facilitated autophagosome- lysosome fusion and degradation in LPS-treated RAW264.7 cells via inhibition of the PI3K/ AKT/mTOR signaling pathway. Overall, the results of this study provide new clues for the anti-inflammatory mechanism of fisetin and explain the crosstalk between autophagy and inflammation to some extent.


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How to Cite
Sun Y., Qin H., Zhang H., Feng X., Yang L., Hou D.-X., & Chen J. (2021). Fisetin inhibits inflammation and induces autophagy by mediating PI3K/AKT/mTOR signaling in LPS-induced RAW264.7 cells. Food & Nutrition Research, 65.
Original Articles