Qian Ye, Xu Yue, Zhang Qiuyu, Huang Chengyu, Li Hui, Gao Lin, Wu Shidi, Qi Chengyu, Wen Xiangru, Zhou Xiaoyan, Ying Changjiang
The Graduate School, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
Department of Endocrinology, Shuyang County Hospital of Traditional Chinese Medicine, Jiangsu, 223600, China.
Metab Brain Dis. 2025 Jan 6;40(1):88. doi: 10.1007/s11011-024-01527-0.
The widely used Radix Astragali (RA) has significant therapeutic effects on cognitive impairment (CI) caused by type 2 diabetes (T2DM). However, the effective active ingredients and the precise mechanism underly RA alleviation of T2DM-induced CI still require further study. In this study, we aim to elucidate whether and how jaranol, a key effective active ingredient in RA, influences CI in db/db mice. We used various online databases and Cytoscape to screen jaranol as the most active ingredient of RA in the treatment of T2DM-induced CI. The fear conditioning experiment, new object recognition (NOR) test, and Morris water maze (MWM) test were conducted to assess the improvement effect of jaranol on CI in diabetic mice. The protein-protein interaction (PPI) network, Cytoscape, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify key genes. The levels of AKT and caspase-3 were determined by Western blotting. The number of surviving hippocampal neurons was verified through Nissl staining. AutoDock was utilized for predicting potential binding sites between jaranol and key genes.As a result, jaranol attenuated CI in db/db mice probably through activation of PI3K-AKT signaling pathway by inhibiting cell apoptosis in hippocampus. Furthermore, A329 near the active site of AKT1 had hydrogen bond with jaranol. In conclusion, we suggest that jaranol may have therapeutic applications in T2DM-induced CI by targeting the PI3K-AKT signaling pathway directly via key sites. Our study provides alternative drugs and potential therapeutic targets for the prevention and treatment of T2DM-induced CI.
广泛应用的黄芪对2型糖尿病（T2DM）所致的认知障碍（CI）具有显著治疗作用。然而，黄芪减轻T2DM诱导的CI的有效活性成分及确切机制仍需进一步研究。在本研究中，我们旨在阐明黄芪中的关键有效活性成分紫铆素是否以及如何影响db/db小鼠的CI。我们使用各种在线数据库和Cytoscape筛选出紫铆素作为黄芪治疗T2DM诱导的CI的最具活性成分。进行恐惧条件反射实验、新物体识别（NOR）测试和莫里斯水迷宫（MWM）测试以评估紫铆素对糖尿病小鼠CI的改善作用。进行蛋白质-蛋白质相互作用（PPI）网络、Cytoscape、基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析以鉴定关键基因。通过蛋白质印迹法测定AKT和半胱天冬酶-3的水平。通过尼氏染色验证存活海马神经元的数量。利用AutoDock预测紫铆素与关键基因之间的潜在结合位点。结果，紫铆素可能通过抑制海马细胞凋亡激活PI3K-AKT信号通路减轻db/db小鼠的CI。此外，AKT1活性位点附近的A329与紫铆素有氢键。总之，我们认为紫铆素可能通过关键位点直接靶向PI3K-AKT信号通路在T2DM诱导的CI中具有治疗应用。我们的研究为T2DM诱导的CI的预防和治疗提供了替代药物和潜在治疗靶点。
