Schisantherin A improves learning and memory abilities partly through regulating the Nrf2/Keap1/ARE signaling pathway in chronic fatigue mice

Chronic fatigue is frequently accompanied by decreased learning and memory capabilities. Schizantherin A (SCA) is one of the main active monomer components in Schisandra chinensis lignans. In the present study, a chronic fatigue mouse model was established using the exhausted swimming approach to investigate the effects of SCA on learning and memory and its associated mechanism of action. Learning and memory abilities were tested by step through tests and water maze methods. Levels of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) in hippocampal tissue were measured by corresponding assays. The effect of SCA on the expression of kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Bcl2, Bax and cleaved caspase-3 were determined by western blot. The present results showed that SCA can improve the learning and memory capabilities of chronic fatigue mice. SCA was found to increase the activities of SOD and CAT in addition to increasing the levels of GSH but reduced the levels of MDA in hippocampus tissues. Furthermore, SCA treatment downregulated the protein expression levels of Keap1, Bax and cleaved caspase-3 and upregulated the protein expression levels of Nrf2, HO1 and Bcl2 in the hippocampus. These results suggested that modulations in the Nrf2-Keap1-antioxidant response element pathway, anti-oxidative and anti-apoptosis effects are the causes underlying the improvements from SCA treatment on the learning and memory abilities of chronic fatigue mice.