1. Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K/Akt/GSK3β Signaling Pathway.
- Author
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Lu YW, Xie LY, Qi MH, Ren S, Wang YQ, Hu JN, Wang Z, Tang S, Zhang JT, and Li W
- Subjects
- Animals, Humans, Male, Mice, Blood Glucose metabolism, Glycogen Synthase Kinase 3 beta metabolism, Glycogen Synthase Kinase 3 beta genetics, Hippocampus drug effects, Hippocampus metabolism, Mice, Inbred C57BL, Neurons drug effects, Neurons metabolism, Oxidative Stress drug effects, Phosphatidylinositol 3-Kinases metabolism, Phosphatidylinositol 3-Kinases genetics, Proto-Oncogene Proteins c-akt metabolism, Proto-Oncogene Proteins c-akt genetics, Cognitive Dysfunction drug therapy, Cognitive Dysfunction etiology, Cognitive Dysfunction metabolism, Diabetes Mellitus, Type 2 drug therapy, Diabetes Mellitus, Type 2 metabolism, Saponins pharmacology, Saponins administration & dosage, Signal Transduction drug effects, Triterpenes pharmacology, Triterpenes administration & dosage
- Abstract
Objectives: The aim of this study was to investigate the ameliorative effect of platycodin D (PD) on cognitive dysfunction in type 2 diabetes mellitus (T2DM) and its potential molecular mechanisms of action in vivo and in vitro. Materials and methods: An animal model of cognitive impairment in T2DM was established using a single intraperitoneal injection of streptozotocin (100 mg/kg) after 8 weeks of feeding a high-fat diet to C57BL/6 mice. In vitro, immunofluorescence staining and Western blot were employed to analyze the effects of PD on glucose-induced neurotoxicity in mouse hippocampal neuronal cells (HT22). Results: PD (2.5 mg/kg) treatment for 4 weeks significantly suppressed the rise in fasting blood glucose in T2DM mice, improved insulin secretion deficiency, and reversed abnormalities in serum triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein levels. Meanwhile, PD ameliorated choline dysfunction in T2DM mice and inhibited the production of oxidative stress and apoptosis-related proteins of the caspase family. Notably, PD dose-dependently prevents the loss of mitochondrial membrane potential, promotes phosphorylation of phosphatidylinositol 3 kinase and protein kinase B (Akt) in vitro, activates glycogen synthase kinase 3β (GSK3β) expression at the Ser9 site, and inhibits Tau protein hyperphosphorylation. Conclusions: These findings clearly indicated that PD could alleviate the neurological damage caused by T2DM, and the phosphorylation of Akt at Ser473 may be the key to its effect.
- Published
- 2024
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