In summary, our study provides evidence that DS from Panax ginseng significantly alleviated the depressive-like behaviors and cognitive impairment induced by HLSI in rats, and the psychotic and neuroprotective effects may be related to mediate the cholinergic system and oxidative stress, including activation of ChAT and SOD activities and inhibition of AChE activity. Here, SOD1 is linked to Cognitive impairment.