Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin

Abstract

Multiple factors have been implicated in the age-related declines in brain function. Thus, it is unlikely that modulating only a single factor will be effective at slowing this decline. A better approach is to identify small molecules that have multiple biological activities relevant to the maintenance of brain function. Over the last few years, we have identified an orally active, novel neuroprotective and cognition-enhancing molecule, the flavonoid fisetin. Fisetin not only has direct antioxidant activity but it can also increase the intracellular levels of glutathione, the major intracellular antioxidant. Fisetin can also maintain mitochondrial function in the presence of oxidative stress. In addition, it has anti-inflammatory activity against microglial cells and inhibits the activity of 5-lipoxygenase, thereby reducing the production of lipid peroxides and their pro-inflammatory by-products. This wide range of actions suggests that fisetin has the ability to reduce the age-related decline in brain function.

Inhibition of c-Jun N-terminal kinase and nuclear factor κ B pathways mediates fisetin-exerted anti-inflammatory activity in lipopolysccharide-treated RAW264.7 cells

“…(1,2) Numerous studies have reported the biological effects of fisetin on anti-tumor, (3)(4)(5)(6)(7) anti-oxidant, (8) antimetastatic, (9) anti-diabetic, (10) neuroprotective, (11) and antiaging activities. (12) Inflammation, a biological response to physical or chemical injurious stimuli, (13) is closely associated with the release of pro-inflammatory mediators such as inducible nitric oxide synthase (iNOS), nitric oxide (NO) and cyclooxygenase 2 (COX-2), (14) and proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor α (TNF-α). (15) The expression of these inflammation-related genes is controlled by the intracellular signaling pathways such as mitogenactivated protein kinases (MAPKs) and nuclear factor κ B (NF-κB) at both transcriptional and post-transcriptional levels.…”

Evaluating the ameliorative potential of plant flavonoids and their nanocomposites in bleomycin induced idiopathic pulmonary fibrosis

“…Fisetin prevents neuroinflammation by suppressing activated neuroinflammatory mediators and gliosis (Ahmad et al, 2016). It has also been shown to affect multiple pathways involved in neuronal function in the process of aging (Maher, 2009). Fisetin is reported to have anti-inflammatory, and other health beneficial effects.…”

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

“…Fisetin is a potent anti-inflammatory, anti-cancer, and anti-oxidant compound (Suh et al 2008;FunakoshiTago et al 2011;Jash and Mondal 2014). Moreover, it has been demonstrated to have a neuroprotective effect and also to limit the complications of type I diabetes (Maher 2009;Maher et al 2011). Based on the molecular structure of this compound, we hypothesized that its biosynthesis should follow the general pathway of flavonol biosynthesis (Figs.…”