中国药理学通报2026,Vol.42Issue(4):660-666,7.DOI:10.12360/CPB202507090
毛蕊花糖苷调节ERK1/2-CREB-BDNF信号通路改善糖尿病大鼠的认知障碍
Acteoside ameliorates cognitive impairment in diabetic rats by modulating the ERK1/2-CREB-BDNF signaling pathway
摘要
Abstract
Aim To investigate the improvement ef-fect of acteoside(ACT)on cognitive impairment in diabetic rats and its regulatory role in the ERK1/2-CREB-BDNF signaling pathway.Methods Sprague-Dawley(SD)rats were randomly divided into the fol-lowing groups(15 rats per group):normal control group,model group,donepezil group,metformin group,and low-,medium-,and high-dose ACT groups.Diabetic rat models were established by feed-ing a high-fat/high-sucrose diet combined with strepto-zotocin(STZ)injection.Fasting blood glucose levels were measured before and after drug administration.Spatial learning and memory were assessed using the Morris water maze test.Hippocampal pathology was observed via hematoxylin-eosin(HE)staining.Corti-cal inflammatory factors and β-amyloid content were detected by ELISA.Hippocampal expression levels of ERK1/2,p-ERK1/2,CREB,p-CREB,BDNF,and TrkB proteins were analyzed by Western blotting.Re-sults Compared with the normal group,the model group exhibited significantly prolonged escape latency and reduced platform time in the water maze test,se-vere neuronal damage in hippocampal CA1 and CA3 regions,elevated fasting blood glucose,increased cor-tical inflammatory factors and Aβ content,and el-evated hippocampal p-ERK1/2 to ERK1/2 ratio(P<0.05),while showing reduced hippocampal p-CREB to CREB ratio and decreased BDNF and TrkB expres-sion levels(P<0.05).Compared with the model group,both ACT-treated groups and the metformin group demonstrated significantly reduced fasting blood glucose(P<0.05).ACT-treated groups and the done-pezil group showed significantly shortened escape la-tency,prolonged platform time,and increased hippo-campal p-CREB/CREB ratio(P<0.05).ACT-treated groups,donepezil group,and metformin group exhib-ited reduced cortical inflammatory factors and Aβ con-tent,and decreased hippocampal p-ERK1/2 to ERK1/2 ratio(P<0.05).ACT-treated groups specifically dis-played significantly elevated hippocampal BDNF and TrkB expression(P<0.01).All drug-administered groups showed marked improvement in hippocampal neuronal pathology.Conclusion ACT may exert neu-roprotective effects by modulating the ERK1/2-CREB-BDNF signaling pathway,suppressing inflammatory factors,reducing Aβ deposition,and lowering fasting blood glucose levels,thereby ameliorating cognitive impairment in diabetic rats.关键词
毛蕊花糖苷/糖尿病/认知障碍/神经保护/炎症/ERK1/2-CREB-BDNF信号通路Key words
acteoside/diabetes mellitus/cognitive impairment/neuroprotection/inflammation/ERK1/2-CREB-BDNF signaling pathway分类
医药卫生引用本文复制引用
马玉彩,吕英爽,黄秀环,李建梅,闫明,高莉..毛蕊花糖苷调节ERK1/2-CREB-BDNF信号通路改善糖尿病大鼠的认知障碍[J].中国药理学通报,2026,42(4):660-666,7.基金项目
新疆维吾尔自治区自然科学基金重点项目(No 2022D01D25) (No 2022D01D25)
新疆维吾尔自治区重点研发计划项目(No 2022B02047) (No 2022B02047)