莫里斯水上航行任务
细胞凋亡
内科学
流式细胞术
内分泌学
活性氧
药理学
医学
化学
生物
细胞生物学
分子生物学
生物化学
海马体
作者
Zhuanzhuan Wang,Xin Cui,Wenhui Yan,Na Liu,Shang Jia,Xinyao Yi,Tingli Guo,Xiaotong Wei,Yuzhuo Sun,Hao Hu,Weina Ma,Wei Cui,Lina Chen
出处
期刊:Life Sciences
[Elsevier]
日期:2023-08-21
卷期号:331: 122026-122026
被引量:1
标识
DOI:10.1016/j.lfs.2023.122026
摘要
The incidence of diabetic cognitive dysfunction is increasing year by year, and it has gradually become a research hot spot. Studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists can improve cognitive dysfunction in diabetic patients. This study focuses on whether small molecule GLP-1R agonists from traditional Chinese medicine (TCM) can improve the diabetic cognitive dysfunction.The small molecules from TCM were screened by cell membrane chromatography (CMC) with GLP-1R-HEK293 cell membrane column. MTT assay, flow cytometry, immunofluorescence cytochemistry and other methods were used to determine the effects of mollugin on the apoptosis rate and reactive oxygen species (ROS) level of high glucose (HG)/hydrogen peroxide (H2O2) induced PC12 cells. Real-Time PCR was used to detect mRNA expression in mouse cerebral cortex. Water maze test was further used to confirm the effect of mollugin on cognitive dysfunction in T2DM mice.Mollugin bound to GLP-1R, promoted Ca2+ influx, increased insulin secretion and cAMP content in β-TC-6 cells. Mollugin enhanced the cell viability, ameliorated apoptosis, reduced intracellular ROS levels in HG/H2O2-injured PC12 cells. Mollugin reduced the T2DM mice's escape latency, improved neuronal cell damage, decreased the expression of Pik3ca, Akt1 and Mapk1 mRNA in the cerebral cortex tissue.The results suggest that mollugin could improve cognitive dysfunction in T2DM mice through activating GLP-1R/cAMP/PKA signal pathway.
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