American ginseng (Panax quinquefolius L.) extracts (G1899) reverse stress-induced behavioral abnormalities in mice

Abstract Stress affects brain functions, which leads to the development of mental disorders like anxiety, depression, cognitive decline, and social dysfunction. There is increasing focus on the role of nutritional, herbal and nutraceutical compounds on mental and cognitive functioning. Interestingly, studies suggest that American ginseng (Panax quinquefolius L.) extracts (G1899) improve cognition. We thus examined whether G1899 showed protective effects on stress-induced behavioral changes in animals. 200 mg/kg G1899 was orally administered daily for 4 weeks to 2-3-month-old female and male mice before inducing stress. To induce acute stress in animals, we intraperitoneally injected a low dose of lipopolysaccharides (LPS) (10 μg/kg), and saline was used as a control. We also used chronic restraint stress (CRS) as a chronic stress model in mice. After LPS injection or CRS, multiple behavioral assays were carried out – a sucrose preference test, an open filed test, reciprocal social interaction, contextual fear conditioning, and a tail suspension test – to determine whether acute or chronic stress affected animals’ behaviors and whether G1899 had protective effects against stress-induced behavioral dysfunction. We found that both LPS injection and CRS induced stress-related behavioral dysfunction, including depression-like behavior, anhedonia, social dysfunction, and fear memory impairments in both females and males. However, G1899 treatment was sufficient to reverse stress-induced behavioral abnormalities in animals. Our data further suggested that G1899 reduced the activity of hippocampal neurons by suppressing glutamatergic activity. Our study suggests that G1899 supplements can be protective against both acute and chronic stress in mice by suppressing neuronal and synaptic activity. Highlights American ginseng (Panax quinquefolius L.) extract (G1899) treatment reverses acute stress-induced behavioral dysfunction in mice. G1899 treatment reverses chronic stress-induced behavioral dysfunction in mice. G1899 treatment reduces serum corticosterone levels in chronically stressed mice. G1899 treatment suppresses glutamatergic activity in hippocampal neurons. Competing Interest Statement Jaehoon Lee and Byung-Cheol Han are employees of Korea Ginseng Corporation. Other authors declare no competing financial interests. Footnotes Conflict of interest statement: Jaehoon Lee and Byung-Cheol Han are employees of Korea Ginseng Corporation. Other authors declare no competing financial interests.