FIGURE 3.

Effects and mechanisms of paeoniflorin on learning and memory impairment. Paeoniflorin administration may ameliorate 1) learning and memory impairment induced by common carotid artery occlusion by inhibiting neuroinflammation in a cannabinoid receptor 2-dependent manner; paeoniflorin-triggered activation of cannabinoid receptor 2 induces activation of PI3K-Akt signaling and inhibition of mTOR-NF-κB signaling, thereby improving learning and memory impairment induced by carotid artery occlusion, 2) diabetes-induced learning and memory impairment by inhibiting neuroinflammation and oxidative stress, decreasing SOCS2 expression and tau phosphorylation, increasing IRS-1 activity, promoting Akt and GSK-3β phosphorylation, increasing cytochrome c oxidase activity, ATP synthesis, and synaptic density, and restoration of mitochondrial membrane potential, 3) Alzheimer’s disease-associated learning and memory impairment by inhibiting Aβ burden and GSK-3β, increasing the Akt activity, SOD and catalase activity, inhibiting p38, NF-κB and caspase-3 activity, increasing Bcl-2/Bax ratio and GSH content, reducing MDA content and acetylcholine esterase activity, increasing choline acetyltrasferase activity and tyrosine kinase A receptor expression, and 4) CUS-induced learning and memory impairment by enhancing PSD-95 and BDNF expression in the brain.