PMID- 37036428
OWN - NLM
STAT- MEDLINE
DCOM- 20230814
LR  - 20230814
IS  - 1099-1573 (Electronic)
IS  - 0951-418X (Linking)
VI  - 37
IP  - 8
DP  - 2023 Aug
TI  - Cognitive protection of sinomenine in type 2 diabetes mellitus through regulating 
      the EGF/Nrf2/HO-1 signaling, the microbiota-gut-brain axis, and hippocampal 
      neuron ferroptosis.
PG  - 3323-3341
LID - 10.1002/ptr.7807 [doi]
AB  - Recent years have witnessed a growing research interest in traditional Chinese 
      medicine as a neuroprotective nutrient in the management of diabetic cognitive 
      dysfunction. However, the underlying molecular mechanisms of sinomenine in 
      mediating ferroptosis of hippocampal neurons have been poorly understood. This 
      study sought to decipher the potential effect and molecular mechanism of 
      sinomenine in the cognitive dysfunction following type 2 diabetes mellitus 
      (T2DM). Multi-omics analysis was conducted to identify the microbiota-gut-brain 
      axis in T2DM patient samples obtained from the publicly available database. In 
      HT-22 cells, erastin was utilized to create a ferroptosis model, and 
      streptozotocin was injected intraperitoneally to create a rat model of DM. It was 
      noted that intestinal flora imbalance occurred in patients with T2DM-associated 
      cognitive dysfunction. Sinomenine could reduce Erastin-induced hippocampus 
      neuronal ferroptosis by increasing EGF expression. EGF protected hippocampal 
      neurons against ferroptosis by activating the Nrf2/HO-1 signaling pathway. 
      Furthermore, in vivo results confirmed that sinomenine blocked ferroptosis of 
      hippocampal neurons and alleviated cognitive dysfunction in T2DM rats. 
      Collectively, these results suggest that sinomenine confers neuroprotective 
      effects by curtailing hippocampal neuron ferroptosis via the EGF/Nrf2/HO-1 
      signaling and microbiota-gut-brain axis. It may be a candidate for the treatment 
      of diabetic cognitive dysfunction.
CI  - (c) 2023 John Wiley & Sons Ltd.
FAU - Chen, Ji
AU  - Chen J
AD  - Department of Endocrinology, The First People's Hospital of Huaihua, Huaihua, 
      P.R. China.
FAU - Guo, Peng
AU  - Guo P
AD  - Department of Anesthesiology, The First People's Hospital of Huaihua, Huaihua, 
      P.R. China.
FAU - Han, Mingming
AU  - Han M
AD  - Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of 
      Life Sciences and Medicine, University of Science and Technology of China|, 
      Hefei, P.R. China.
FAU - Chen, Kemin
AU  - Chen K
AD  - Department of Anesthesiology, The First Affiliated Hospital, University of South 
      China, Hengyang, P.R. China.
FAU - Qin, Jie
AU  - Qin J
AD  - Department of Anesthesiology, The First Affiliated Hospital, University of South 
      China, Hengyang, P.R. China.
FAU - Yang, Fengrui
AU  - Yang F
AUID- ORCID: 0000-0003-0356-9086
AD  - Department of Anesthesiology, The First People's Hospital of Huaihua, Huaihua, 
      P.R. China.
AD  - Department of Anesthesiology, The First Affiliated Hospital, University of South 
      China, Hengyang, P.R. China.
LA  - eng
GR  - 2021JJ70043/Natural Science Foundation of Hunan Province/
GR  - 20200018/Project of Hunan Provincial Health Commission/
GR  - 20200037/Project of Hunan Provincial Health Commission/
GR  - 19B477/Project of the Education Department of Hunan Province/
PT  - Journal Article
DEP - 20230410
PL  - England
TA  - Phytother Res
JT  - Phytotherapy research : PTR
JID - 8904486
RN  - 63LT81K70N (sinomenine)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Animals
MH  - Rats
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Brain-Gut Axis
MH  - Epidermal Growth Factor
MH  - NF-E2-Related Factor 2
MH  - *Ferroptosis
MH  - Neurons
MH  - Signal Transduction
MH  - Hippocampus
MH  - Cognition
OTO - NOTNLM
OT  - EGF
OT  - Nrf2/HO-1 signaling pathway
OT  - Sinomenine
OT  - cognitive dysfunction
OT  - ferroptosis
OT  - microbiota-gut-brain axis
OT  - type 2 diabetes mellitus
EDAT- 2023/04/11 06:00
MHDA- 2023/08/14 06:42
CRDT- 2023/04/10 10:42
PHST- 2023/02/26 00:00 [revised]
PHST- 2022/08/23 00:00 [received]
PHST- 2023/03/05 00:00 [accepted]
PHST- 2023/08/14 06:42 [medline]
PHST- 2023/04/11 06:00 [pubmed]
PHST- 2023/04/10 10:42 [entrez]
AID - 10.1002/ptr.7807 [doi]
PST - ppublish
SO  - Phytother Res. 2023 Aug;37(8):3323-3341. doi: 10.1002/ptr.7807. Epub 2023 Apr 10.