Gut microbiota mediated inflammation, neuroendocrine and neurotrophic functions involved in the antidepressant-like effects of diosgenin in chronic restraint stress.

BACKGROUND: Diosgenin is a well-known steroid saponin possessing neuroprotective activities. However, it is unknown whether diosgenin could alleviate depression-like symptoms. METHODS: The antidepressant-like effect of diosgenin was investigated in mice induced by chronic restraint stress. The effects of diosgenin on behaviors, inflammation, neuroendocrine, neurotrophic function, and gut microbiota were evaluated. RESULTS: The results showed that diosgenin alleviated the depressive-like behaviors in mice. In addition, diosgenin was found to reduce serum concentrations of proinflammatory cytokines and the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Besides, diosgenin could activate hippocampal brain-derived neurotrophic factor (BDNF)/TrkB/ERK/CREB signaling pathway and improve the expression of postsynaptic protein PSD95. Meanwhile, the neurogenesis which was inhibited by chronic restraint stress, was totally reversed by diosgenin. Moreover, diosgenin increased the abundance of phylum Firmicutes and the genus Lactobacillus in stressed mice. The results further showed that diosgenin caused a strong correlation between gut microbiota composition and inflammation, the HPA axis activity, or hippocampus neurotrophic function. LIMITATIONS: Only male mice were used for evaluation in the present study, which limits the understanding of effects of diosgenin on the both sexes. In addition, the results only indicate microbiota at the phylum or genus mediate the regulation of neuroinflammation, neuroendocrine, and neurotrophic function, but does not elucidate how microbiota modulate the systems via their primary or secondary metabolites. CONCLUSIONS: The present study shows that diosgenin exerts the antidepressant activity, which is associated with the enhancement of neurotrophic function and the inhibition of inflammatory and neuroendocrine activities via the regulation of gut microbiota.

Effect of silencing E6-associated protein on level of p53 protein in human papilloma virus negative cervical cancer cells / 中国生物制品学杂志

@#Objective To investigate the effect of silencing E6-associated protein(E6AP)on the level of p53 protein in human papilloma virus(HPV)negative cervical cancer cells(C33A cells).Methods The siRNA sequence silencing E6AP(siE6AP)and silencing control disordered siRNA sequence(siControl)were transfected into C33A cells with the mediation of LipofectamineTM2000 transfection reagent respectively.The silencing effect of siRNA on E6AP and the expression of p53and cleaved-caspase-3 proteins were detected by Western blot.Results The levels of E6AP protein in C33A cells of siE6AP group were significantly lower(t =-4.597,P<0.05),while the levels of p53 and cleaved-caspase-3 proteins were significantly higher than those of siControl group(t = 4.533 and 7.099 respectively,each P<0.05).Conclusion Silencing of E6AP significantly increased the expression of p53 protein in C33A cells,indicating that silencing of E6AP may restore the activity and function of p53 protein in C33A cells.