Eleutheroside E supplementation prevents radiation-induced cognitive impairment and activates PKA signaling via gut microbiota

Radiation affects not only cognitive function but also gut microbiota. Eleutheroside E (EE), a principal active compound of Acanthopanax senticosus, has a certain protective effect on the nervous system. Here, we find a four-week EE supplementation to the 60 Co-γ ray irradiated mice improves the cognition and spatial memory impairments along with the protection of hippocampal neurons, remodels the gut microbiota, especially changes of Lactobacillus and Helicobacter, and altered the microbial metabolites including neurotransmitters (GABA, NE, ACH, 5-HT) as well as their precursors. Furthermore, the fecal transplantation of EE donors verifies that EE alleviated cognition and spatial memory impairments, and activates the PKA/CREB/BDNF signaling via gut microbiota. Our findings provide insight into the mechanism of EE effect on the gut-brain axis and underpin a proposed therapeutic value of EE in cognitive and memory impairments induced by radiation.