Fisetin, a Diet-Derived Compound, Suppresses Immune Inflammation

Mr. Ziyu He, a third-year doctoral student at the United Graduate School of Agricultural Sciences (at the time of publication), has had his research accepted for publication in the peer-reviewed international journal Antioxidants (Impact Factor: 6.0) in February 2025.

In this study, the authors investigated how fisetin, a typical flavonol, regulates inflammation and metabolic dysfunction in macrophages induced by interferon-gamma (IFN-γ). Using RNA sequencing, metabolic flux analysis, and signaling pathway analysis, the study revealed the multi-layered anti-inflammatory and metabolic effects of fisetin.

In IFN-γ-stimulated RAW264 murine macrophages, fisetin suppressed the expression of pro-inflammatory genes such as Cxcl9, Il6, Cd80, Cd86, and Nos2, enhanced oxidative phosphorylation (OXPHOS), restored the oxygen consumption rate (OCR), and reduced lactate production. Further analysis indicated that fisetin inhibited the activation of IRF1 and suppressed the Jak1/2-STAT1-IRF1 signaling pathway, providing new insights into the mechanisms of dietary flavonoids in immune modulation.

[Article] The Effects of Fisetin on Gene Expression Profile and Cellular Metabolism in IFN-γ-Stimulated Macrophage Inflammation
[Author(s)] Ziyu He, Xuchi Pan, Kun Xie, Kozue Sakao, Jihua Chen, Masaharu Komatsu, De-Xing Hou
[Journal] Antioxidants
[DOI] https://doi.org/10.3390/antiox14020182