PMID- 37641705
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230829
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 16
DP  - 2023
TI  - Esculetin Alleviates Inflammation, Oxidative Stress and Apoptosis in Intestinal 
      Ischemia/Reperfusion Injury via Targeting SIRT3/AMPK/mTOR Signaling and 
      Regulating Autophagy.
PG  - 3655-3667
LID - 10.2147/JIR.S413941 [doi]
AB  - AIM: Intestinal ischemia/reperfusion (I/R) injury is a challenging pathological 
      phenomenon accountable for significant mortality in clinical scenarios. 
      Substantial evidence has supported the protective role of esculetin in myocardial 
      I/R injury. This study is designed to reveal the specific impacts of esculetin on 
      intestinal I/R injury and disclose the underlying mechanism. METHODS: First, 
      intestinal I/R injury model and intestinal epithelial cell line 
      hypoxia/reoxygenation (H/R) model were established. Pathologic damages to 
      intestinal tissues were observed through H&E staining. Serum diamine oxidase 
      (DAO) levels were examined. RT-qPCR and Western blot examined the expression of 
      inflammatory mediators. Commercial kits were used for detecting the levels of 
      oxidative stress markers. TUNEL assay and caspase 3 activity assay measured cell 
      apoptosis. Immunofluorescence (IF) staining measured autophagy levels. Western 
      blot analyzed the expression of apoptosis-, Sirtuin 3 (SIRT3)/AMP activated 
      protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling- and 
      autophagy-related proteins. Molecular docking verified the interaction of 
      esculetin with SIRT3. Cell viability was explored via CCK-8 assay. RESULTS: The 
      experimental results revealed that esculetin treatment mitigated pathological 
      damage of intestinal tissues, reduced serum DAO level, ameliorated inflammation, 
      oxidative stress and apoptosis and promoted autophagy in intestinal I/R rats. 
      Moreover, esculetin bond to SIRT3 and activated SIRT3/AMPK/mTOR signaling both in 
      vitro and in vivo. Furthermore, esculetin treatment enhanced cell viability and 
      SIRT3 silencing reversed the impacts of esculetin on autophagy, inflammation, 
      oxidative stress and apoptosis in H/R cell model. CONCLUSION: In a word, 
      esculetin activated SIRT3/AMPK/mTOR signaling and autophagy to protect against 
      inflammation, oxidative stress and apoptosis in intestinal I/R injury.
CI  - (c) 2023 Shen et al.
FAU - Shen, Xin
AU  - Shen X
AD  - Department of Gastrointestinal Surgery, Xi'an Daxing Hospital, Xi'an, 710016, 
      People's Republic of China.
FAU - Shi, Hai
AU  - Shi H
AD  - Department of Gastrointestinal Surgery, Xi'an Daxing Hospital, Xi'an, 710016, 
      People's Republic of China.
FAU - Chen, Xinli
AU  - Chen X
AD  - Department of Gastrointestinal Surgery, Xi'an Daxing Hospital, Xi'an, 710016, 
      People's Republic of China.
FAU - Han, Junwei
AU  - Han J
AD  - Department of Gastrointestinal Surgery, Xi'an Daxing Hospital, Xi'an, 710016, 
      People's Republic of China.
FAU - Liu, Haiwang
AU  - Liu H
AD  - Department of Gastrointestinal Surgery, Xi'an Daxing Hospital, Xi'an, 710016, 
      People's Republic of China.
FAU - Yang, Jie
AU  - Yang J
AD  - Department of Gastrointestinal Surgery, Xi'an Daxing Hospital, Xi'an, 710016, 
      People's Republic of China.
FAU - Shi, Yuan
AU  - Shi Y
AD  - Department of Gynecology and Obstetrics, Xijing Hospital, Air Force Military 
      Medical University, Xi'an, 710032, People's Republic of China.
FAU - Ma, Jiajia
AU  - Ma J
AD  - Department of Gynecology and Obstetrics, Xijing Hospital, Air Force Military 
      Medical University, Xi'an, 710032, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20230823
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC10460583
OTO - NOTNLM
OT  - SIRT3/AMPK/mTOR signaling
OT  - autophagy
OT  - esculetin
OT  - intestinal I/R injury
COIS- The authors declare that there are no conflicts of interest in this work.
EDAT- 2023/08/29 06:42
MHDA- 2023/08/29 06:43
PMCR- 2023/08/23
CRDT- 2023/08/29 03:38
PHST- 2023/03/23 00:00 [received]
PHST- 2023/07/06 00:00 [accepted]
PHST- 2023/08/29 06:43 [medline]
PHST- 2023/08/29 06:42 [pubmed]
PHST- 2023/08/29 03:38 [entrez]
PHST- 2023/08/23 00:00 [pmc-release]
AID - 413941 [pii]
AID - 10.2147/JIR.S413941 [doi]
PST - epublish
SO  - J Inflamm Res. 2023 Aug 23;16:3655-3667. doi: 10.2147/JIR.S413941. eCollection 
      2023.