Platycodin D Ameliorates Cognitive Impairment in Type 2 Diabetes Mellitus Mice via Regulating PI3K/Akt/GSK3β Signaling Pathway

  • J Agric Food Chem. 2024 Mar 16. doi: 10.1021/acs.jafc.3c08490.
Ya-Wei Lu  1 ,  Li-Ya Xie  1 ,  Meng-Han Qi  1 ,  Shen Ren  1 ,  Yue-Qi Wang  1 ,  Jun-Nan Hu  1 ,  Zi Wang  1 ,  Shan Tang  1 ,  Jing-Tian Zhang  1 ,  Wei Li  1  2  3
Affiliations
  • 1. College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China.
  • 2. College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China.
  • 3. Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun 130118, China.
PMID: 38491972 DOI: 10.1021/acs.jafc.3c08490
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.

Keywords
PI3K/Akt/GSK3β; Platycodin D; Tau protein; cognitive dysfunction; type 2 diabetes mellitus.
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