机构：[1]Shenzhen Institute of Translational Medicine/Shenzhen Institute of Geriatrics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China深圳市第二人民医院深圳医学信息中心[2]Department of Spine Surgery, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China深圳市第二人民医院深圳市康宁医院深圳医学信息中心[3]School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China[4]Shenzhen Institute of Translational Medicine/Shenzhen Institute of Geriatrics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China深圳市第二人民医院深圳医学信息中心
Oxidative stress is considered as an important mechanism underlying the pathology of neurodegenerative disorders. In this study, we utilized an in vitro model where oxidative stress process was evoked by exogenous hydrogen peroxide (H2O2) in HT22 murine hippocampal neurons and evaluated the neuroprotective effects of geissoschizine methyl ether (GME), a naturally occurring alkaloid from the hooks of Uncaria rhynchophylla (Miq.) Jacks. After a 24 h H2O2 (350 mu M) insult, a significant decrease in cell survival and a sharp increase in intracellular reactive oxygen species were observed in HT22 cells. Encouragingly, GME (10-200 mu M) effectively reversed these abnormal cellular changes induced by H2O2. Moreover, mechanistic studies using Western blot revealed that GME inhibited the increase of phospho-ERK protein expression, but not phospho-p38, caused by H2O2. Molecular docking simulation further revealed a possible binding mode that GME inhibited ERK protein, showing that GME favorably bound to ERK via multiple hydrophobic and hydrogen bond interactions. These findings indicate that GME provide effective neuroprotection via inhibiting ERK pathway and also encourage further ex vivo and in vivo pharmacological investigations of GME in treating oxidative stress-mediated neurological disorders.
基金：
GuangDong Basic and Applied Basic Research Foundation [2020A1515011427, 2020A1515010758, 2022A1515011777]; Shenzhen Municipal Science and Technology Project [JSGG20210901145539016, JCYJ20190812171005713, JCYJ20190812171611467, JCYJ20210324121611032]; Shenzhen Baoan Chinese Medicine Development Foundation [2020KJCX-KTYJ-215]
第一作者机构：[1]Shenzhen Institute of Translational Medicine/Shenzhen Institute of Geriatrics, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Hu Shengquan,Yang Lei,Ma Yucui,et al.Protection against H2O2-evoked toxicity in HT22 hippocampal neuronal cells by geissoschizine methyl ether via inhibiting ERK pathway[J].TRANSLATIONAL NEUROSCIENCE.2022,13(1):369-378.doi:10.1515/tnsci-2022-0243.
APA：
Hu, Shengquan,Yang, Lei,Ma, Yucui,Li, Limin,Li, Zhiyue...&Wu, Zhengzhi.(2022).Protection against H2O2-evoked toxicity in HT22 hippocampal neuronal cells by geissoschizine methyl ether via inhibiting ERK pathway.TRANSLATIONAL NEUROSCIENCE,13,(1)
MLA：
Hu, Shengquan,et al."Protection against H2O2-evoked toxicity in HT22 hippocampal neuronal cells by geissoschizine methyl ether via inhibiting ERK pathway".TRANSLATIONAL NEUROSCIENCE 13..1(2022):369-378
