Abstract: Objective   To explore the mechanism of orientin in improving cognitive impairment in epileptic mice by inhibiting PERK/ATF4/CHOP pathway.   Methods    The epilepsy mouse model was established by intraperitoneal injection of scopolamine and pilocarpine hydrochloride. The mice were randomly divided into five groups: control group, model group, orientin (50 mg/kg) group, MK-28 (PERK activator, 1 mg/kg) group, orientin (50 mg/kg) + MK-28 (1 mg/kg) group. After grouping, the epileptic seizures of the mice were observed. Morris water maze test was used to detect the cognitive function of mice. TUNEL staining was used to detect the apoptosis rates of hippocampal neurons of mice. ELISA was used to measure the levels of serum COX-2, IL-18 and IL-6 of mice. Western blotting was used to detect the expression of apoptosis and PERK/ATF4/CHOP pathway protein in the hippocampus of mice.    Results   The number and duration of attacks per day, escape latency, hippocampal neuronal apoptosis rate, serum COX-2, IL-18 and IL-6 levels, and hippocampal tissue caspase-3, Bax, ATF4, CHOP protein expression and p-PERK/PERK in the orientin group were lower than those in the model group and the orientin+MK-28 group (P<0.05), the change trend of each index in MK-28 group was opposite to that in orientin group.    Conclusions    Orientin can inhibit the activation of the PERK/ATF4/CHOP pathway to prevent inflammation, reduce the apoptosis of hippocampal neurons in epileptic mice and improve their cognitive function.

Key words: Orientin; ,  , PERK/ATF4/CHOP; ,  ,  Epilepsy; ,  ,  Cognitive function dysfunction