Gastrodin Ameliorates Cognitive Dysfunction in Vascular Dementia Rats by Suppressing Ferroptosis via the Regulation of the Nrf2/Keap1-GPx4 Signaling Pathway.

Abstract

Gastrodia elata Bl. has a long edible history and is considered an important functional food raw material. Gastrodin (GAS) is one of the main functional substances in G. elata BI. and can be used as a health care product for the elderly to enhance resistance and delay aging. This study investigated the ameliorative effect and mechanism of GAS on cognitive dysfunction in vascular dementia (VaD) rats, which provides a theoretical basis for development and utilization of functional food. The water maze test shows that GAS improves learning and memory impairment in VaD rats. Meanwhile; GAS significantly decreased the levels of Fe2+ and malondialdehyde (MDA); increased the content of glutathione (GSH); and significantly up-regulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPx4), the key regulatory factors of ferroptosis; while it down-regulated the expression of kelch-like ECH-associated protein (Keap1) and cyclooxygenase 2 (COX2). However, GAS does not directly regulate GPx4 and COX2 to inhibit ferroptosis. Furthermore, compared with GAS alone, GAS combined with Bardoxolone (an agonist of Nrf2) did not further affect the increase in GPx4 levels and decrease in COX2 levels, nor did it further affect the regulation of GAS on the biochemical parameters of ferroptosis in HT22 hypoxia injury. These findings revealed that GAS inhibited ferroptosis in hippocampal neurons by activating the Nrf2/Keap1-GPx4 signaling pathway, suggesting its possible application as a functional food for improving vascular dementia by inhibiting ferroptosis.

• Authors: Yue Li, Erdong Zhang, Hong Yang, Yongxin Chen, Ling Tao, Yini Xu, Tingting Chen, Xiangchun Shen
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 27 Issue 19 (Sep 24 2022) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 36234847 (Publication Type: Journal Article)

Chemical References

• Benzyl Alcohols
• Glucosides
• KEAP1 protein, rat
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• Malondialdehyde
• gastrodin
• Oleanolic Acid
• bardoxolone
• Phospholipid Hydroperoxide Glutathione Peroxidase
• Cyclooxygenase 2
• Glutathione

Topics

• Animals
• Benzyl Alcohols
• Cognitive Dysfunction (drug therapy, etiology)
• Cyclooxygenase 2 (metabolism)
• Dementia, Vascular (drug therapy)
• Ferroptosis
• Glucosides
• Glutathione (metabolism)
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• Malondialdehyde
• NF-E2-Related Factor 2 (metabolism)
• Oleanolic Acid (analogs & derivatives)
• Phospholipid Hydroperoxide Glutathione Peroxidase
• Rats
• Signal Transduction