Fisetin regulates astrocyte migration and proliferation in vitro

Abstract

Fisetin (3,3′,4′,7-tetrahydroxyflavone) is a plant flavonol found in fruits and vegetables that has been reported to inhibit migration and proliferation in several types of cancer. Reactive astrogliosis involves astrocyte migration and proliferation, and contributes to the formation of glial scars in central nervous system (CNS) disorders. However, the effect of fisetin on the migration and proliferation of astrocytes remains unclear. In this study, we found that fisetin inhibited astrocyte migration in a scratch-wound assay and diminished the phosphorylation of focal adhesion kinase (FAK; Tyr576/577 and paxillin (Tyr118). It also suppressed cell proliferation, as indicated by the decreased number of 5-ethynyl-2′-deoxyuridine (EdU)-positive cells, induced cell cycle arrest in the G1 phase, reduced the percentage of cells in the G2 and S phase (as measured by flow cytometry), and decreased cyclin D1 expression, but had no effect on apoptosis. Fisetin also decreased the phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk)1/2, but had no effect on the phosphorylation of p38 mitogen-activated protein kinase (MAPK). These results indicate that fisetin inhibits aggressive cell phenotypes by suppressing cell migration and proliferation via the Akt/Erk signaling pathway. Fisetin may thus have potential for use as a therapeutic strategy targeting reactive astrocytes, which may lead to the inhibition of glial scar formation in vitro.

Multifaceted effects of milk-exosomes (Mi-Exo) as a modulator of scar-free wound healing

“…The scratch assay demonstrated that the migration of IEC-18 decreased depending on the NP of 10 8 , 10 9 , or 10 10 Mi-Exo, as compared to the untreated group (80.8 ± 2.5%, 59.1 ± 11.2%, and 22.5 ± 10.9% closing effect, respectively), after Mi-Exo treatment for 24 h. There is recent evidence that controlled cell migration corresponds to minimizing the extent of scar formation. 30 It might be assumed that the anti-cell migration activity can be induced by the expression level of TGFβ isoforms. Relative TGF-β1 and TGF-β3 mRNA levels were quantified, and compared by RT-PCR.…”

Abnormal Cannabidiol Affects Production of Pro-Inflammatory Mediators and Astrocyte Wound Closure in Primary Astrocytic-Microglial Cocultures

“…Quantification of scratch-wound assays is often done by microscopic measurement at one defined time point [93,[95][96][97]. For the present study, a new protocol was developed using the possibilities of live cell microscopy.…”

Fisetin provides antidepressant effects by activating the tropomyosin receptor kinase B signal pathway in mice

“…Consistent with the previously demonstrated pro‐neurogenesis effects of fisetin in the hippocampus (Wang et al . ), we found that fisetin increased the activation of TrkB signaling in the hippocampus (Fig. ).…”