Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade

Kaempferol (KFL), the major constituent of various fruits and vegetables, could attenuate oxidaitve stress and inflammation. The aims of the present study were to explore the ameliorative abilities of KFL on the depressive-like behaviors in a chronic social defeat stress (CSDS) mouse model, and to determine the potential mechanisms on oxidative stress, neuroinflammation, and AKT/β-catenin signaling pathway. Three behavioral tests, sucrose preference test (SPT), social interaction test (SIT), and tail suspension test (TST), were used to evaluate the antidepressive effects of KFL in CSDS mice. Activity levels of antioxidant enzyme, superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione s-transferase (GST), and concentrations of malonaldehyde (MDA) and protein carbonylation in the prefrontal cortex were assessed by commercial kits, respectively. Elisa was used to detect the levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α). Q-PCR was used to determine the mRNA level of CD-11b. Furthermore, activity level of AKT/β-catenin signaling in the prefrontal cortex of CSDS mice was investigated by western blot. In addition, LY294002, a PI3-K inhibitor, was used to investigate the role of AKT/β-catenin signaling in the antidepressant effects of KFL. Social defeat stress reduced the bodyweights, sucrose consumptions, social interaction times, and the tail suspension mobility times in mice. CSDS mice were also exhibited remarkablely increased levels in oxidative stress markers, inflammatory mediators, and decreased activity of AKT/β-catenin cascade in the prefrontal cortex, which were reversed by treatment with KFL. Interestingly, LY294002 appeared to partly inhibit the overall KFL-mediated protective effects in the CSDS mice. These results confirmed that KFL exerted antidepressive effects, which might be mediated, at least in part, by enhanced antioxidant abilities and anti-inflammation effects via up-regulation AKT/β-catenin cascade activity in the prefrontal cortex of CSDS mice. Thus, KFL might be a promising, effective, and safe food medicine for depression treatment.