PMID- 37482219
OWN - NLM
STAT- MEDLINE
DCOM- 20230811
LR  - 20230812
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 812
DP  - 2023 Aug 24
TI  - Dihydromyricetin alleviates hippocampal ferroptosis in type 2 diabetic cognitive 
      impairment rats via inhibiting the JNK-inflammatory factor pathway.
PG  - 137404
LID - S0304-3940(23)00363-4 [pii]
LID - 10.1016/j.neulet.2023.137404 [doi]
AB  - Type 2 diabetes mellitus (T2DM) is frequently associated with diabetic cognitive 
      impairment (DCI), and recent studies have shown a strong association between DCI 
      and hippocampal ferroptosis. In this study, we administered dihydromyricetin 
      (DHM) or JNK inhibitor SP600125, to T2DM rats and monitored changes in blood 
      glucose levels, conducted behavioral tests, and detected changes in JNK, 
      inflammatory factors and ferroptosis-related indicators. Our findings 
      demonstrated that T2DM rats displayed signs of cognitive impairment (CI), with 
      ferrozine assays indicating elevated iron content in the hippocampus. 
      Concurrently, there was an increase in p-JNK activity and inflammatory factors 
      IL-6 and TNF-alpha in the hippocampal region of these rats. Furthermore, we observed 
      elevated levels of Fe(2+), MDA, ROS, LPO, and ACSL4, along with a decrease in 
      GPX4 and GSH, suggesting the occurrence of hippocampal ferroptosis. SP600125 
      application reversed these changes in the T2DM rats, although it exhibited no 
      significant effects in the control group. Treatment with high and low doses of 
      DHM led to a reduction in p-JNK expression, inflammatory factor-related proteins, 
      and iron accumulation in the hippocampal region, effectively alleviating 
      hippocampal ferroptosis in T2DM rats. No notable effects of DHM were observed in 
      the control group. To conclude, our study suggests that DHM can potentially 
      alleviate hippocampal ferroptosis of T2DM cognitive impairment rats, primarily by 
      suppressing the JNK-inflammatory factor pathway in the hippocampus.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Wang, Zihan
AU  - Wang Z
AD  - Department of Physiology, Hengyang Medical School, University of South China, 
      Hengyang 421001, Hunan, China; School of Medicine, The Chinese University of Hong 
      Kong, Shenzhen 518172, Guangdong, China.
FAU - Feng, Shuidong
AU  - Feng S
AD  - Department of Social Medicine and Health Service Management, School of Public 
      Health, University of South China, Hengyang 421001, Hunan, China.
FAU - Li, Qi
AU  - Li Q
AD  - Department of Physiology, Hengyang Medical School, University of South China, 
      Hengyang 421001, Hunan, China.
FAU - Song, Zhenjiang
AU  - Song Z
AD  - Department of Physiology, Hengyang Medical School, University of South China, 
      Hengyang 421001, Hunan, China.
FAU - He, Jianqin
AU  - He J
AD  - Department of Physiology, Hengyang Medical School, University of South China, 
      Hengyang 421001, Hunan, China.
FAU - Yang, Sisi
AU  - Yang S
AD  - Department of Physiology, Hengyang Medical School, University of South China, 
      Hengyang 421001, Hunan, China.
FAU - Yan, Canqun
AU  - Yan C
AD  - The Health Management Center, The Second Affiliated Hospital, Hengyang Medical 
      School, University of South China, Hengyang 421001, Hunan, China.
FAU - Ling, Hongyan
AU  - Ling H
AD  - Department of Physiology, Hengyang Medical School, University of South China, 
      Hengyang 421001, Hunan, China. Electronic address: linghongyan0203@126.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230721
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 1TW30Y2766 (pyrazolanthrone)
RN  - KD8QND6427 (dihydromyricetin)
RN  - E1UOL152H7 (Iron)
SB  - IM
MH  - Animals
MH  - Rats
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - *Ferroptosis
MH  - Hippocampus
MH  - *Cognitive Dysfunction/drug therapy
MH  - Iron
OTO - NOTNLM
OT  - Cognitive impairment
OT  - Dihydromyricetin
OT  - Ferroptosis
OT  - JNK-inflammatory factor pathway
OT  - Type 2 diabetes mellitus
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/07/24 00:41
MHDA- 2023/08/11 06:43
CRDT- 2023/07/23 19:25
PHST- 2023/05/25 00:00 [received]
PHST- 2023/07/15 00:00 [revised]
PHST- 2023/07/18 00:00 [accepted]
PHST- 2023/08/11 06:43 [medline]
PHST- 2023/07/24 00:41 [pubmed]
PHST- 2023/07/23 19:25 [entrez]
AID - S0304-3940(23)00363-4 [pii]
AID - 10.1016/j.neulet.2023.137404 [doi]
PST - ppublish
SO  - Neurosci Lett. 2023 Aug 24;812:137404. doi: 10.1016/j.neulet.2023.137404. Epub 
      2023 Jul 21.