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Protective effects of VMY-2-95 on corticosterone-induced injuries in mice and cellular models

Acta Pharmaceutica Sinica B 2021年第7期11卷 1903-1913页

作者： Ziru Yu Dewen Kong Yu Liang Xiaoyue Zhao Guanhua Du State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing Key Laboratory of Drug Target and Screening ResearchInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

Nicotinicα4β2 receptor antagonists have drawn increasing attention in the development of new *** this study,we aimed to investigate the protective effect of VMY-2-95,the new selective antagonist ofα4β2 nicotinic acetylcholine receptor(nachr)on corticosterone(CORT)injured mice and cellular *** was applied as a positive control,and the effects of VMY-2-95 were investigated with three different doses or concentrations(1,3,10 mg/kg in mice,and 0.003,0.03,0.1μmol/L in cells).As a result,VMY-2-95 showed significant antidepressant-like effects in the CORT injured mice by improving neuromorphic function,promoting hippocampal nerve proliferation,and regulating the contents of monoamine ***,VMY-2-95 exhibited protective effects on cell viability,cell oxidant,cell apoptosis,and mitochondrial energy metabolism on corticosterone-impaired SH-SY5 Y ***,the PKA-CREB-BDNF signaling pathway was up-regulated by VMY-2-95 both in vitro and in vivo,and pathway blockers were also combined with VMY-2-95 to verify the effects ***,we preliminarily proved that VMY-2-95 had protective effects in depressed mice and SH-SY5 Y cells against injuries induced by *** work indicated that the application of VMY-2-95 is a potential pharmacological solution for *** study also supported the development ofα4β2 nachr antagonists towards neuropsychiatric dysfunctions.

关键词： α4β2 nachr antagonist VMY-2-95 Cholinergiceadrenergic theory Depression Corticosterone SH-SY5Y cells PKA-CREB-BDNF signaling pathway

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