Fisetin inhibits inflammation and induces autophagy by mediating PI3K/AKT/mTOR signaling in LPS-induced RAW264.7 cells
Open Access
- 25 March 2021
- journal article
- research article
- Published by SNF Swedish Nutrition Foundation in Food & Nutrition Research
Abstract
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.Keywords
This publication has 65 references indexed in Scilit:
- Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammationProceedings of the National Academy of Sciences of the United States of America, 2012
- The Flavonoid Fisetin Attenuates Postischemic Immune Cell Infiltration, Activation and Infarct Size after Transient Cerebral Middle Artery Occlusion in MiceJournal of Cerebral Blood Flow & Metabolism, 2012
- Role of Interleukin 10 Transcriptional Regulation in Inflammation and Autoimmune DiseaseCritical Reviews™ in Immunology, 2012
- Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1βThe EMBO Journal, 2011
- Autophagy in immunity and inflammationNature, 2011
- Akt and Autophagy Cooperate to Promote Survival of Drug-Resistant GliomaScience Signaling, 2010
- Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cellsCarcinogenesis: Integrative Cancer Research, 2010
- An Overview of the Molecular Mechanism of AutophagyPublished by Springer Science and Business Media LLC ,2009
- Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphomaJCI Insight, 2007
- Dietary flavonoids and cancer risk in the Zutphen elderly studyNutrition and Cancer, 1994