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

• • SchA treatment reduced blood glucose and improved insulin sensitivity in STZ-induced diabetic rats, addressing the 20–60% increased risk of cognitive dysfunction in T2DM patients; this directly targets the metabolic root of diabetes-associated memory impairment. • • SchA significantly decreased Aβ42 formation and enhanced synaptic protein production in the diabetic prefrontal cortex, correlating with improved fear memory; this suggests a disease-modifying effect on amyloid pathology, a hallmark of cognitive decline. • • SchA suppressed microglial activation and inflammatory cytokine expression while increasing phosphorylation of insulin resistance pathway proteins, indicating dual anti-inflammatory and insulin-sensitizing mechanisms that could halt neuroinflammation-driven neurodegeneration. • • SchA upregulated GPX4, SLC7A11, Nrf2, HO-1, and SIRT1, reducing ferroptosis in the diabetic prefrontal cortex; this identifies ferroptosis as a novel therapeutic target and supports SchA as a multi-target agent for diabetic encephalopathy.