Quercetin alleviates chronic unpredictable mild stress-induced depressive-like behaviors by promoting adult hippocampal neurogenesis via FoxG1/CREB/ BDNF signaling pathway.

Quercetin, a naturally occurring flavonoid, has been reported to exert antidepressant effects, however, the underlying mechanisms are still uncertain. Recent studies have demonstrated that Forkhead box transcription factor G1 (FoxG1) regulates the process of adult hippocampal neurogenesis (AHN) and exerts neuroprotective effects. In this study, we explored whether quercetin plays an anti-depressant role via regulation of FoxG1 signaling in mice and revealed the potential mechanisms. To explore the antidepressant effects of quercetin, mice were subjected to behavioral tests after a chronic unpredictable mild stress (CUMS) exposure. We found that chronic quercetin treatment (15 mg/kg, 30 mg/kg) obviously restored the weight loss of mice caused by CUMS and alleviated CUMS-induced depression-like behaviors, such as increased sucrose consumption, improved locomotor activity and shorten immobility time. In addition, to clarify the relationship between quercetin and AHN, we detected neurogenesis markers in the dentate gyrus (DG) of the hippocampus. Furthermore, FoxG1-siRNA was employed and then stimulated with quercetin to further investigate the mechanism by which FoxG1 participates in the antidepressant effects of quercetin. Our results indicate that chronic quercetin treatment dramatically increased the number of doublecortin (DCX)-positive and BrdU/NeuN-double positive cells. Besides, the expression levels of FoxG1, p-CREB and Brain-derived neurotrophic factor (BDNF) were also enhanced by quercetin in the DG. Strikingly, quercetin failed to reverse the levels of p-CREB and BDNF after FoxG1-siRNA was performed in SH-SY5Y cells and Neural Progenitor Cells (NPCs). Our results thus far suggest that quercetin might exert antidepressant effects via promotion of AHN by FoxG1/CREB/ BDNF signaling pathway.

ROS induces epithelial-mesenchymal transition via the TGF-ß1/PI3K/Akt/mTOR pathway in diabetic nephropathy.

Oxidative stress has been reported to serve an important role in the development and progression of diabetic nephropathy (DN). Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells promotes renal fibrosis in DN, while the mechanism of reactive oxygen species (ROS)-mediated EMT is not fully understood. The aim of the present study was to investigate the effect of high glucose-induced ROS on the activation of the transforming growth factor (TGF)-ß1/phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in a normal rat kidney tubular epithelial cell line (NRK-52E) and rats with type 1 diabetes. In vitro, high glucose-stimulated ROS production resulted in increased TGF-ß1 expression as well as an increase in the Akt and mTOR phosphorylation ratio, resulting in EMT. When cells were pre-treated with ROS inhibitors, changes in TGF-ß1, Akt and mTOR were significantly ameliorated. In vivo, diabetic rats experienced a significant decline in renal function and severe renal fibrosis compared with control rats at 8 weeks following streptozocin injection. Levels of malondialdehyde and TGF-ß1/PI3K/Akt/mTOR pathway activation were increased in the renal cortex of rats with diabetes compared with the control rats. Furthermore, renal fibrosis was further aggravated in DN compared with the control rats. The results of the present study suggest that ROS serves an important role in mediating high glucose-induced EMT and inhibits activation of the TGF-ß1/PI3K/Akt/mTOR pathway. ROS may therefore have potential as a treatment approach to prevent renal fibrosis in DN.

Swimming training alleviated insulin resistance through Wnt3a/ß-catenin signaling in type 2 diabetic rats.

OBJECTIVES: Increasing evidence suggests that regular physical exercise improves type 2 diabetes mellitus (T2DM). However, the potential beneficial effects of swimming on insulin resistance and lipid disorder in T2DM, and its underlying mechanisms remain unclear. MATERIALS AND METHODS: Rats were fed with high fat diet and given a low dosage of Streptozotocin (STZ) to induce T2DM model, and subsequently treated with or without swimming exercise. An 8-week swimming program (30, 60 or 120 min per day, 5 days per week) decreased body weight, fasting blood glucose and fasting insulin. RESULTS: Swimming ameliorated lipid disorder, improved muscular atrophy and revealed a reduced glycogen deposit in skeletal muscles of diabetic rats. Furthermore, swimming also inhibited the activation of Wnt3a/ß-catenin signaling pathway, decreased Wnt3a mRNA and protein level, upregulated GSK3ß phosphorylation activity and reduced the expression of ß-catenin phosphorylation in diabetic rats. CONCLUSION: The trend of the result suggests that swimming exercise proved to be a potent ameliorator of insulin resistancein T2DM through the modulation of Wnt3a/ß-catenin pathway and therefore, could present a promising therapeutic measure towards the treatment of diabetes and its relatives.