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Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice.
Wang, Bo; Zhu, Sheng; Guo, Miao; Ma, Run-Dong; Tang, Ya-Ling; Nie, Ya-Xiong; Gu, Hong-Feng.
Afiliação
  • Wang B; Institute of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Zhu S; Department of Nuclear Medicine, Affiliated Hospital of Xiangnan University, No. 25 Renmin West Road, Beihu District, Chenzhou, 423001, Hunan, China.
  • Guo M; Department of Physiology and Institute of Neuroscience, Key Laboratory of Hunan Province for Major Brain Diseases, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Ma RD; Institute of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Tang YL; Department of Physiology and Institute of Neuroscience, Key Laboratory of Hunan Province for Major Brain Diseases, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Nie YX; Institute of Anesthesiology, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
  • Gu HF; Department of Physiology and Institute of Neuroscience, Key Laboratory of Hunan Province for Major Brain Diseases, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China. ghf513@sina.com.
Mol Med ; 30(1): 35, 2024 Mar 07.
Article em En | MEDLINE | ID: mdl-38454322
ABSTRACT

BACKGROUND:

Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region.

METHODS:

STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and Fe2+ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively.

RESULTS:

Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe2+, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin.

CONCLUSION:

Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artemisininas / Diabetes Mellitus Tipo 2 / Disfunção Cognitiva / Ferroptose Limite: Animals Idioma: En Revista: Mol Med Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Artemisininas / Diabetes Mellitus Tipo 2 / Disfunção Cognitiva / Ferroptose Limite: Animals Idioma: En Revista: Mol Med Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China