Objective:To investigate the effects and underlying mechanisms of echinacoside(ECH)on ame-liorating cognitive impairment in diabetic mice.Methods:The db/m mice were selected as the control group.The db/db mice were divided into the model group(db/db group),the ECH treatment group(db/db-ECH group),and the metformin(MET)treatment group(db/db-MET group).The db/m and db/db groups were gavaged with 0.9%sodium chloride injection(0.05 mL/[10 g·d]),the db/db-ECH group with ECH 300 mg/(kg·d),and the db/db-MET group with MET 200 mg/(kg·d),for a duration of 14 weeks.Measurements included body mass,systolic and diastolic blood pressure,fasting blood glucose(FPG),and homeostasis model assessment-insulin resistance(HOMA-IR).Morris water maze test was conducted to evaluate their cognitive function.Serum levels of tumor ne-crosis factor α(TNF-α)and interleukin 1β(IL-1β)were quantified using ELISA.Immunohistochemis-try was performed to detect the expression levels of IL-1β and TNF-α in the hippocampal CA1 region;Western Blot analysis was conducted to assess the expression levels of IL-1β,TNF-α,Tau,phos-phorylated Tau(P-Tau)at S202/T205,glycogen synthase kinase 3β(GSK-3β),phosphorylated GSK-3β(Ser9),mitogen-activated extracellular signal-regulated kinase(MEK),extracellular signal-regulated kinase(ERK).Results:(1)General condition:The db/db-ECH group exhibited significant improvements in body mass,systolic blood pressure,fasting blood glucose,and HOMA-IR as com-pared with the db/db group(P<0.05).(2)Morris water maze:Compared with the db/db group,the db/db-ECH group showed shorter escape latency time and longer residence time in the target quadrant(P<0.05).(3)TNF-α and IL-β:Compared with the db/db group,the db/db-ECH and db/db-MET groups showed significantly reduced peripheral TNF-α levels(P<0.05),diminished IL-1β and TNF-α immunostaining in the hippocampal CA1 area,and preserved hippocampal cellular morphology and structural integrity.(4)Western Blot:Compared with the db/db group,there was a significant lower phosphorylated Tau(S202/T205)to total Tau ratio,and an elevated phosphorylated GSK-3β(Ser9)to total GSK-3β ratio,as well as a reduction in P-MEK to total MEK ratio,a lower phosphorylated ERK to total ERK ratio(P<0.05).Conclusion:ECH attenuates inflammatory responses and neuronal damage,and inhibits the hyperphosphorylation of Tau protein,leading to improved spatial learning and memory in diabetic mice.This enhancement is potentially associated with ECH's inhibition of GSK-3β and MEK/ERK pathway overactivation.
EchinacosideDiabetes-Related Cognitive ImpairmentInflammatory ResponsePhosphorylation Tau Protein
万方数据
维普
