Regulatory effects of fisetin on microglial activation

This Taiwanese neuroscience group studied microglia, the brain's resident immune cells, which become overactive during neurodegeneration and drive ongoing brain inflammation.

Fisetin reduced microglial cell migration and lowered production of reactive oxygen species (ROS) in the cells. When microglia were provoked with two different inflammatory triggers - a bacterial signal (LPS) combined with interferon-gamma, and peptidoglycan (a component of Gram-positive bacterial cell walls) - fisetin blunted their production of nitric oxide, the inflammatory enzyme iNOS, and the cytokine IL-1beta.

At the same time, fisetin switched on the microglia's own antioxidant defence system, boosting the protective enzyme heme oxygenase-1 (HO-1) through the PI3K/Akt and p38 signalling pathways - so fisetin was both dialling down inflammatory output and dialling up the cells' internal antioxidant response.

These laboratory effects carried through to mice, where fisetin reduced inflammation-related microglial activation and improved a motor coordination deficit associated with that inflammation, linking the cell-level findings to a functional, whole-animal outcome.

This adds to the neuroinflammation mechanism evidence for fisetin already represented in this Data Center (alongside the Alzheimer's and stroke papers), but it remains preclinical cell and mouse work rather than a clinical study of fisetin for neuroinflammatory or neurodegenerative disease in people.