title: Neuroprotective effects of vitexin against isoflurane-induced neurotoxicity by targeting the TRPV1 and NR2B signaling pathways.
abstract: 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 µM 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 β-secretase 1 levels in PC12 cells. Furthermore, vitexin treatment decreased the levels of isoflurane‑induced cytosolic calcium and reactive oxygen species, and downregulated 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.
authors.affiliation: Department of Anesthesiology, The Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Shan
authors.affiliation: Department of Anesthesiology, The Cangzhou Central Hospital, Cangzhou, Hebei 061000, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007530:Isoflurane / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016194:Receptors, N-Methyl-D-Aspartate; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D047310:Apigenin; C032731:vitexin; D007530:Isoflurane; D053148:Caspase 3; D002118:Calcium