Isoliquiritigenin attenuated cognitive impairment, cerebral tau phosphorylation and oxidative stress in a streptozotocin-induced mouse model of Alzheimers disease

Abstract

IntroductionTau hyperphosphorylation, mitochondrial dysfunction and oxidative stress play important roles in Alzheimers disease (AD). Isoliquiritigenin, a natural flavonoid isolated from the root of liquorice, has been shown to exert inhibitory effects on oxidative stress. Here, we assessed the neuroprotective effects of isoliquiritigenin on a streptozotocin-injected mouse model. MethodMolecular docking analysis performed for isoliquiritigenin with mTOR and ERK2. The mice (n = 27, male) were intracerebroventricularly injected with streptozotocin, treated with isoliquiritigenin (intraperitoneal, 2 days) and assessed using the Morris water maze. Oxidative stress, tau phosphorylation, mitochondrial dysfunction and synaptic impairment were evaluated in the cortex and hippocampal tissues of the mice by using biochemical assays and immunofluorescence staining. ResultsIsoliquiritigenin treatment mitigated the spatial memory capacity of streptozotocin-injected mice and alleviated tau phosphorylation at Ser396; the production of reactive oxygen species; the mitochondrial fission proteins Mfn1 and Mfn2; neuronal loss; and synaptic impairment (PSD95, SNAP25). Isoliquiritigenin treatment reduced the levels of mTOR Ser2448 and ERK1/2 T202/Y204 and upregulated the level of GSK-3{beta}Ser9 in the cortex and hippocampus of streptozotocin-injected mice. ConclusionIn conclusion, our findings suggest that isoliquiritigenin ameliorates streptozotocin-induced cognitive impairment, hyperphosphorylated tau, oxidative stress, mitochondrial dysfunction and synaptic impairment by decreasing mTOR and ERK activity and increasing GSK-3{beta} activity.