2. Academic Validation
  3. Gastrodin relieves cognitive impairment by regulating autophagy via PI3K/AKT signaling pathway in vascular dementia

Gastrodin relieves cognitive impairment by regulating autophagy via PI3K/AKT signaling pathway in vascular dementia

  • Biochem Biophys Res Commun. 2023 Sep 3:671:246-254. doi: 10.1016/j.bbrc.2023.06.011.
Yong-Xin Chen 1,  Hong Yang 2,  Da-Song Wang 1,  Yu-Ting Yao 1,  Ting-Ting Chen 2,  Ling Tao 3,  Yan Chen 4,  Xiang-Chun Shen 5
Affiliations

Affiliations

  • 1 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guiyang, 550025, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, 550025, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, 550025, China.
  • 2 The Maternal and Child Health Care Hospital of Guizhou Medical University, Guiyang, 550003, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, 550025, China.
  • 3 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guiyang, 550025, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, 550025, China.
  • 4 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guiyang, 550025, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, 550025, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, 550025, China. Electronic address: [email protected].
  • 5 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, University Town, Guiyang, 550025, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, 550025, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guiyang, 550025, China. Electronic address: [email protected].
PMID: 37307708 DOI: 10.1016/j.bbrc.2023.06.011
Abstract

Vascular dementia (VaD), the second most common type of dementia, is attributed to lower cerebral blood flow. To date, there is still no available clinical treatment for VaD. The phenolic glucoside gastrodin (GAS) is known for its neuroprotective effects, but the role and mechanisms of action on VD remains unclear. In this study, we aim to investigate the neuroprotective role and underlying mechanisms of GAS on chronic cerebral hypoperfusion (CCH)-mediated VaD rats and hypoxia-induced injury of HT22 cells. The study showed that GAS relieved learning and memory deficits, ameliorated hippocampus histological lesions in VaD rats. Additionally, GAS down-regulated LC3II/I, Beclin-1 levels and up-regulated p62 level in VaD rats and hypoxia-injured HT22 cells. Notably, GAS rescued the phosphorylation of PI3K/Akt pathway-related proteins expression, which regulates Autophagy. Mechanistic studies verify that YP-740, a PI3K agonist, significantly resulted in inhibition of excessive Autophagy and Apoptosis with no significant differences were observed in the YP-740 and GAS co-treatment. Meantime, we found that LY294002, a PI3K Inhibitor, substantially abolished GAS-mediated neuroprotection. These results revealed that the effects of GAS on VaD are related to stimulating PI3K/Akt pathway-mediated Autophagy, suggesting a potentially beneficial therapeutic strategy for VaD.

Keywords

Autophagy; Chronic cerebral hypoperfusion; Gastrodin; PI3K/AKT pathway; Vascular dementia.

Figures
Products