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天然阿朴啡类生物碱罗梅碱的神经活性。

Neuroactivity of the naturally occurring aporphine alkaloid, roemerine.

机构信息

Faculty of Pharmacy, Department of Pharmacognosy, Hacettepe University, Sihhiye, Ankara, Turkey.

Faculty of Pharmacy, Department of Analytical Chemistry, Hacettepe University, Sihhiye, Ankara, Turkey.

出版信息

Nat Prod Res. 2021 Dec;35(24):6147-6152. doi: 10.1080/14786419.2020.1830395. Epub 2020 Oct 7.

Abstract

Roemerine is a naturally occurring aporphine alkaloid. In this study, we screened a conformer library of Food and Drug Administration (FDA)-approved drugs to identify similar drugs that can assist in identifying the biological targets of roemerine. To assess the neuroactivity , we measured the levels of cell metabolites, Brain-Derived Neurotrophic Factor (BDNF) and serotonin (5-HT) in SH-SY5Y cell line. By means of structure-based virtual screening, we identified five drugs that are similar to roemerine; mirtazapine, atomoxetine, epinastine, diphenhydramine and orphenadrine. GC-MS metabolomics study revealed that roemerine has a high impact on alanine-aspartate-glutamate pathway in cell lysate and cultured medium. Additionally, roemerine increased intercellular 5-HT level and intracellular BDNF protein expression at 10 µM. In conclusion, roemerine - a major alkaloid in antidepressant-like effect possessing plants () - has a neuronal activity through increasing BDNF protein expression and affecting serotonergic and glutamatergic systems in SH-SY5Y cell line.

摘要

罗梅灵是一种天然存在的阿朴啡生物碱。在这项研究中,我们筛选了美国食品和药物管理局 (FDA) 批准药物的构象文库,以确定类似的药物,以帮助识别罗梅灵的生物靶标。为了评估神经活性,我们测量了 SH-SY5Y 细胞系中细胞代谢物、脑源性神经营养因子 (BDNF) 和 5-羟色胺 (5-HT) 的水平。通过基于结构的虚拟筛选,我们鉴定了五种与罗梅灵相似的药物:米氮平、阿托西汀、依帕司他、苯海拉明和奥芬那君。GC-MS 代谢组学研究表明,罗梅灵对细胞裂解物和培养基中的丙氨酸-天冬氨酸-谷氨酸途径有很大影响。此外,罗梅灵在 10μM 时增加了细胞间 5-HT 水平和细胞内 BDNF 蛋白表达。总之,罗梅灵——一种存在于具有抗抑郁作用的植物中的主要生物碱——通过增加 BDNF 蛋白表达和影响 SH-SY5Y 细胞系中的 5-羟色胺能和谷氨酸能系统,具有神经元活性。

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