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Quercetin: A promising therapy for diabetic encephalopathy through inhibition of hippocampal ferroptosis

Xin Cheng, Jian-Hua I. Huang, Hong-Li Li, Di Zhao, Zhao Liu, Lemei Zhu, Zhen Zhang, Wei-Xi Peng

Phytomedicine, 2023

285 citations

Abstract

BACKGROUND

The pathophysiology of diabetic encephalopathy (DE), a significant diabetes-related pathological complication of the central nervous system, is poorly understood. Ferroptosis is an iron-dependent regulated necrotic cell death process that mediates the development of neurodegenerative and diabetes-related lesions. Quercetin (QE) exerts anti-ferroptotic effects in various diseases. However, the roles of ferroptosis in DE and the potential anti-ferroptotic mechanisms of QE are unclear.

PURPOSE

This study aimed to investigate if quercetin can ameliorate DE by inhibiting ferroptosis and to elucidate the potential anti-ferroptotic mechanisms of QE, thus providing a new perspective on the pathogenesis and prevention of DE.

METHODS

The spontaneously type 2 diabetic Goto-Kakizak rats and high glucose (HG)-induced PC12 cells were used as animal and in vitro models, respectively. The Morris water maze test was performed to evaluate the cognition of rats. Pathological damage was examined using hematoxylin and eosin staining. Mitochondrial damage was assessed using transmission electron microscopy. Lipid peroxidation was evaluated by examining the levels of malondialdehyde, superoxide dismutase, and glutathione. Additionally, the contents of iron ions were quantified. Immunofluorescence and western blotting were carried out to poke the protein levels. Network pharmacology analysis was conducted to construct a protein-protein interaction network for the therapeutic targets of…

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