Figure 11. The potential mechanism of chronic PS and ZBPYR treatment. Chronic PS causes proteomic alterations in brain MAM of ZDF rats, including in proteins related to lipid and protein metabolism, energy metabolism, synaptic function, and calcium signaling. ZBPYR treatment results in proteomic alterations in PSD rats, including in proteins related to lipid and protein metabolism, energy metabolism, synaptic function, and autophagy. This may trigger the molecular basis of chronic PS aggravated diabetes-associated cognitive decline (i.e., persistent hyperactivity of the HPA axis, decreased exploratory behavior, and aggravated memory impairment) and provides a potential therapeutic mechanism of ZPBYR.