PMID- 38454322
OWN - NLM
STAT- MEDLINE
DCOM- 20240311
LR  - 20240311
IS  - 1528-3658 (Electronic)
IS  - 1076-1551 (Print)
IS  - 1076-1551 (Linking)
VI  - 30
IP  - 1
DP  - 2024 Mar 7
TI  - Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal 
      ferroptosis via Nrf2 activation in T2DM mice.
PG  - 35
LID - 10.1186/s10020-024-00797-9 [doi]
LID - 35
AB  - 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 Fe(2+) 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 Fe(2+), 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.
CI  - (c) 2024. The Author(s).
FAU - Wang, Bo
AU  - Wang B
AD  - Institute of Anesthesiology, The First Affiliated Hospital, Hengyang Medical 
      School, University of South China, Hengyang, 421001, Hunan, China.
FAU - Zhu, Sheng
AU  - Zhu S
AD  - Department of Nuclear Medicine, Affiliated Hospital of Xiangnan University, No. 
      25 Renmin West Road, Beihu District, Chenzhou, 423001, Hunan, China.
FAU - Guo, Miao
AU  - Guo M
AD  - 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.
FAU - Ma, Run-Dong
AU  - Ma RD
AD  - Institute of Anesthesiology, The First Affiliated Hospital, Hengyang Medical 
      School, University of South China, Hengyang, 421001, Hunan, China.
FAU - Tang, Ya-Ling
AU  - Tang YL
AD  - 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.
FAU - Nie, Ya-Xiong
AU  - Nie YX
AD  - Institute of Anesthesiology, The First Affiliated Hospital, Hengyang Medical 
      School, University of South China, Hengyang, 421001, Hunan, China.
FAU - Gu, Hong-Feng
AU  - Gu HF
AUID- ORCID: 0009-0004-2884-8246
AD  - 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.
LA  - eng
GR  - 81500349/the National Natural Science Foundation of China/
GR  - 2022JJ30509/the Natural Science Foundation of Hunan Province, China/
GR  - 2022JJ30534/the Natural Science Foundation of Hunan Province, China/
GR  - 21A0273/the key program of Educational Commission of Hunan Province, China/
GR  - 2021SK51813/Clinical Medical Technology Innovation Guidance Project of Hunan 
      Province/
PT  - Journal Article
DEP - 20240307
PL  - England
TA  - Mol Med
JT  - Molecular medicine (Cambridge, Mass.)
JID - 9501023
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Reactive Oxygen Species)
RN  - 9RMU91N5K2 (artemisinin)
RN  - 0 (Artemisinins)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Diabetes Mellitus, Type 2
MH  - NF-E2-Related Factor 2
MH  - *Ferroptosis
MH  - Reactive Oxygen Species
MH  - *Cognitive Dysfunction/drug therapy/etiology
MH  - Hippocampus
MH  - *Artemisinins/pharmacology/therapeutic use
MH  - Neurons
PMC - PMC10921734
OTO - NOTNLM
OT  - Artemisinin
OT  - Diabetic cognitive deficit
OT  - Ferroptosis
OT  - Hippocampus
OT  - Nrf2
COIS- There is no competing interest.
EDAT- 2024/03/08 06:43
MHDA- 2024/03/11 06:44
PMCR- 2024/03/07
CRDT- 2024/03/08 00:32
PHST- 2023/11/17 00:00 [received]
PHST- 2024/01/31 00:00 [accepted]
PHST- 2024/03/11 06:44 [medline]
PHST- 2024/03/08 06:43 [pubmed]
PHST- 2024/03/08 00:32 [entrez]
PHST- 2024/03/07 00:00 [pmc-release]
AID - 10.1186/s10020-024-00797-9 [pii]
AID - 797 [pii]
AID - 10.1186/s10020-024-00797-9 [doi]
PST - epublish
SO  - Mol Med. 2024 Mar 7;30(1):35. doi: 10.1186/s10020-024-00797-9.