Schisandrin A ‌ameliorates the diabetes-associated memory impairment by alleviating inflammation and ferroptosis

Schisandrin A (SchA), a bioactive lignan that was isolated from the dried fruit of Schisandra chinensis, has attracted much attention because of its diverse spectrum of pharmacological effects. The aim of this study is to clarify the function of SchA in diabetes-related fear memory impairment and its molecular causes. Four rat groups are chosen at random: the control group (Con group), the DM group, the DM + SchA group, and the Con + SchA group. These findings demonstrate that SchA treatment improves insulin sensitivity, reduced blood glucose, and significantly reduced memory impairment. SchA treatment also prevents histological damage, enhances synaptic protein production, and significantly decreases Aβ₄₂ formation in the diabetic prefrontal cortex. Further research reveals that SchA therapy decreases microglial activation and the expression levels of variables linked to inflammation while increasing the phosphorylation of proteins implicated in the insulin resistance signaling pathway. Furthermore, in the prefrontal cortex of diabetic patients, SchA decreases ferroptosis by increasing the protein expression of GPX4, SLC7A11, Nrf2, HO-1, and SIRT1. Overall, our findings suggest that SchA may lessen diabetes-associated fear memory impairment symptoms by, most likely, lowering ferroptosis and inflammatory responses in the prefrontal brain of diabetic patients. SchA may prove to be a useful therapy for diabetes, including for memory impairment.