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

Abstract

Depression has been associated with a low-grade chronic inflammatory state, suggesting a potential therapeutic role for anti-inflammatory agents. Fisetin is a naturally occurring flavonoid in strawberries that has anti-inflammatory activities, but whether fisetin has antidepressant effects is unknown. In this study, we exposed mice to spatial restraint for 2 weeks with or without treatment with fisetin. Immobility time in the forced swimming and tail suspension test after this restraint increased in the untreated group, but this increase did not occur in the fisetin group. We administered fisetin to Abelson helper integration site-1 (Ahi1) knockout mice, which have depressive phenotypes. We found that fisetin attenuated the depressive phenotype of these Ahi1 knockout mice. We further investigated the potential mechanism of fisetin's antidepressant effects. Because TrkB is a critical signaling pathway in the mechanisms of depression, we examined whether phosphorylated TrkB was involved in the antidepressant effects of fisetin. We found that fisetin increased phosphorylated TrkB level without altering total TrkB; this increase was attenuated by K252a, a specific TrkB inhibitor. Taken together, our results demonstrated that fisetin may have therapeutic potential for treating depression and that this antidepressant effect may be mediated by the activation of the TrkB signaling pathway.

The Role of BDNF in the Neuroimmune Axis Regulation of Mood Disorders

“…The BDNF-TrkB pathway in the nucleus accumbens of α7 nACHR knockout mice was demonstrated to be up-regulated, which was considered to be involved in their depression-like behavior (48). The antidepressant role of fisetin was confirmed by Wang et al which was achieved by activating TrkB rather than regulating its overall level (49). All of these studies suggest that BDNF and the mediated TrkB signaling pathway may provide new approaches for the treatment of depression.…”

Neuropharmacology of Secondary Metabolites from Plants with Anxiolytic and Antidepressant Properties

“…Koumine has shown this effect on VCT in mice at doses of 0.167, 0.5, or 1.5 mg/kg [74]. Other reports indicate that the decoction of the African peach root (Nauclea latifolia) injected intraperitoneally in mice produces dose-dependent anxiolytic-like effects (16,40,80, and 160 mg/kg) in EPM. Its effect has been attributed to isoquinoline-type alkaloids [75], but no reports have yet substantiated this claim.…”

“…increased activation of the tropomyosin kinase B receptor (TrkB) by signaling and increasing its phosphorylation in the hippocampus. This suggests that fisetin produced pro-neurogenesis [40] related to its antidepressant effect on FST and TST after 1 or 2 weeks of treatment with a relatively short therapeutic latency compared to clinically-effective antidepressants. Fisetin also reversed depressionlike behaviors induced by spatial restraint stress in mice evaluated on FST and TST [40].…”

“…This suggests that fisetin produced pro-neurogenesis [40] related to its antidepressant effect on FST and TST after 1 or 2 weeks of treatment with a relatively short therapeutic latency compared to clinically-effective antidepressants. Fisetin also reversed depressionlike behaviors induced by spatial restraint stress in mice evaluated on FST and TST [40]. Other studies have found that the chemical standard dihydromyricetin activated the ERK1/2-CREB pathway and increased glycogen synthase kinase-3 beta (GSK-3β) phosphorylation at ser-9 with upregulation of BDNF expression in the hippocampus, while inhibiting neuroinflammation.…”

Loss of Tctn3 causes neuronal apoptosis and neural tube defects in mice

“…The tail suspension test was carried out according to previous reports 35 , 36 with slight modifications. Mouse tails were taped to the edge of a shelf and suspended 35 cm above the desktop.…”