Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice
© 2024. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
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| Enthalten in: |
Molecular medicine (Cambridge, Mass.) - 30(2024), 1 vom: 07. März, Seite 35 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wang, Bo [VerfasserIn] |
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| Links: |
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| Themen: |
9RMU91N5K2 |
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| Anmerkungen: |
Date Completed 11.03.2024 Date Revised 11.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s10020-024-00797-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369440617 |
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| 245 | 1 | 0 | |a Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice |
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| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Artemisinin | |
| 650 | 4 | |a Diabetic cognitive deficit | |
| 650 | 4 | |a Ferroptosis | |
| 650 | 4 | |a Hippocampus | |
| 650 | 4 | |a Nrf2 | |
| 650 | 7 | |a NF-E2-Related Factor 2 |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a artemisinin |2 NLM | |
| 650 | 7 | |a 9RMU91N5K2 |2 NLM | |
| 650 | 7 | |a Artemisinins |2 NLM | |
| 700 | 1 | |a Zhu, Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Miao |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Run-Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Ya-Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Ya-Xiong |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Hong-Feng |e verfasserin |4 aut | |
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