Neuroprotective effects of vitexin against isoflurane-induced neurotoxicity by targeting the TRPV1 and NR2B signaling pathways

Vitexin is a bioactive compound extracted from hawthorn leaves, which reduces blood pressure and has anti-inflammatory and potential anticancer effects. However, the mechanisms underlying the protective effects of vitexin against isoflurane-induced neurotoxicity remain elusive. Therefore, the aim of the present study was to investigate these mechanisms further. Sprague Dawley rats received 1.4% isoflurane in a 100% oxygen environment for 2 h. Human PC12 pheochromocytoma neurosecretory cells were exposed to 2% isoflurane for 12 h before they were treated with 1, 10 or 100 mu M vitexin for a further 24 h. Vitexin inhibited the isoflurane-induced cell cytotoxicity and weakened isoflurane-induced neuroinflammation and oxidative stress pathways in PC12 cells. In addition, treatment with vitexin suppressed isoflurane-induced caspase-3 activation and increased beta-secretase 1 levels in PC12 cells. Furthermore, vitexin treatment decreased the levels of isoflurane-induced cytosolic calcium and reactive oxygen species, and down regulated the expression of transient receptor potential cation channel subfamily V member 1 (TRPV1) and glutamate ionotropic receptor NMDA type subunit 2B (NR2B) protein expression in isoflurane-treated PC12 cells. These results suggest that vitexin mediates its protective effects against isoflurane-induced neurotoxicity by targeting the TRPV1 and NR2B signaling pathways.