Dammarane sapogenins attenuates stress‐induced anxiety‐like behaviors by upregulating ERK/CREB/BDNF pathways

Dammarane sapogenins (DS), an extract derived from ginseng by alkaline hydrolysis of total ginsenosides, possesses high pharmacological activity and higher bioavailability than ginsenosides. The present study was designed to investigate the anxiolytic-like effects of DS in a mouse model of chronic social defeat stress (CSDS). DS (40 and 80 mg/kg) significantly ameliorated social avoidance and anxiety-like behavior in four test models of CSDS, showing increased time in the interaction zone in the social interaction test and in the center of the field in the open field test, an increased percentage of entries and open arm time in the elevated plus maze, and reduced latency to eat in the novelty-suppressed feeding test. Biochemical analyses showed that DS significantly reduced serum corticosterone levels and increased brain concentration of neurotransmitter 5-HT and noradrenaline in CSDS mice. Treatment with DS significantly upregulated BDNF (brain-derived neurotrophic factor), p-CREB/CREB and p-ERK1/2/ERK1/2 protein expression in the hippocampus and prefrontal cortex of CSDS mice. Collectively, these results suggest that DS exerts anxiolytic-like effects in CSDS model mice and the action is mediated, at least in part, by modulating the HPA (hypothalamic-pituitary-adrenal) axis and monoamine neurotransmitter levels, and via ERK/CREB/BDNF signaling pathway.