Anxiolytic and neuroprotective effects of the Traditional Chinese Medicinal formulation Dan-zhi-xiao-yao-san in a rat model of chronic stress.

ABSTRACT

Dan-zhi-xiao-yao-san is a Traditional Chinese Medicinal formulation widely used for the treatment of neuropsychological disorders. The present study examined the anxiolytic and neuroprotective effects of Dan-zhi-xiao-yao-san in a rat model of chronic stress. The results of an elevated plus maze test showed that Dan­zhi­xiao­yao­san significantly attenuated the levels of anxiety-induced stress as evidenced by increases in the time spent in the open arm region, as well as the percentage of entries into this area. In addition, Dan-zhi-xiao-yao-san alleviated stress­induced neuronal death, as indicated by histological examination. Furthermore, mechanistic studies suggested that the anxiolytic and neuroprotective effects of Dan-zhi-xiao-yao-san may be mediated via attenuation of chronic stress­induced upregulation of α­synuclein and corticosterone, and downregulation of protein phosphatase 2A (PP2A) in the hippocampal region of the brain at the mRNA and protein level. In addition, Dan­zhi­xiao­yao­san decreased the serum levels of stress­induced corticosterone in the model animals. In conclusion, the present study demonstrated that Dan­zhi­xiao­yao­san exerted anxiolytic and neuroprotective effects in a rat model of chronic stress via attenuation of stress­induced upregulation of α­synuclein and corticosterone, and downregulation of PP2A in the hippocampus.