Berberine Ameliorates Sevoflurane-Induced Neurotoxicity through Activating Nrf2/HO-1 Signaling Pathway

Abstract

Background and Purpose: The aim of this study was to investigate the effects of berberine on sevoflurane-induced neurotoxicity and its mechanism of action. Methods: Ninety-seven-day-old Sprague Dawley (SD) rats had their primary hippocampal neuron cells anesthetized with 3% sevoflurane for 6 hours, to establish the sevoflurane-induced neurotoxicity model. They were split into two groups;One treated with 100 mg/kg berberine per day, and their neurons treated neurons with different concentrations of berberine and a control group, which was treated with normal saline. Afterwards, the changes of learning and memory ability, cell proliferation, apoptosis, reactive oxygen species (ROS), inflammatory cytokines, and expressions of nuclear factor NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and quinone oxidoreductase 1 (NQO1) were measured. Results: Compared with the control group, the learning and memory ability of rats in the “3% sevoflurane for 6 hours” (Sev) group was significantly impaired, and the neurons in their hippocampus were atrophied and disordered. The apoptosis rate, ROS content, and inflammatory cytokines levels were significantly increased, and the expressions of Nrf2, HO-1, and NQO1 were significantly reduced (p < 0.05). Compared with the “3% sevoflurane for 6 hours and treated with normal saline per day” (Sev+NS) group, the learning and memory ability of rats in the “3% sevoflurane for 6 hours and treated with 100 mg/kg berberine per day” (Sev+Ber) group was significantly improved, with which cells arranged neatly, and the pyknosis was significantly improved. At the same time, the apoptotic rate, ROS content, and inflammatory cytokines levels were significantly decreased, while the expressions of Nrf2, HO-1, and NQO1 increased significantly (p < 0.05). Knocking down significantly Nrf2 attenuated the protective effect of berberine on hippocampal neuron cells. Conclusions: Berberine ameliorates sevoflurane-induced neurotoxicity, and its mechanism may be related to the Nrf2/HO-1 signaling pathway.