PMID- 37465664
OWN - NLM
STAT- MEDLINE
DCOM- 20230721
LR  - 20230721
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - Reduning alleviates sepsis-induced acute lung injury by reducing apoptosis of 
      pulmonary microvascular endothelial cells.
PG  - 1196350
LID - 10.3389/fimmu.2023.1196350 [doi]
LID - 1196350
AB  - INTRODUCTION: Sepsis-induced acute lung injury (SALI) is a critical illness with 
      high mortality, and pulmonary microvascular endothelial cells (PMECs) barrier 
      dysfunction is a well-documented pathogenesis of SALI. The current study aimed to 
      investigate the underlying mechanism of Reduning (RDN) in the treatment of SALI. 
      METHODS: Network pharmacology and molecular dynamics simulation (MDS) were used 
      to confirm the possibility of key active components of RDN combining with AKT1. 
      Hematoxylin-eosin staining (HE) and immunohistochemistry (IHC) were used to 
      investigate the effect of RDN in vivo. Immunofluorescence (IF) and 
      co-immunoprecipitation (CoIP) were used to investigate the relationship between 
      mammalian target of rapamycin (mTOR) and Bax in PMECs. ELISA was used to test the 
      level of TNF-alpha. Flow cytometry was used to detect apoptosis. JC-1 and electron 
      microscopy were used to evaluate mitochondrial damage. The results showed that 
      RDN likely alleviated SALI via targeting AKT1. RESULTS: In vivo, RDN could 
      evidently decrease the expression levels of apoptosis-related proteins, alleviate 
      mitochondrial damage, reduce lung tissue edema, down-regulate the level of TNF-alpha 
      in the serum, and improve the mortality of sepsis in mice. In vitro, RDN had a 
      significant effect on reducing the level of apoptosis-related proteins and cell 
      apoptosis rate, while also mitigated mitochondrial damage. Furthermore, RDN could 
      effectively lower the level of Bax in PMECs and increase the level of mTOR both 
      in vivo and in vitro. Notably, mTOR has the ability to directly bind to Bax, and 
      RDN can enhance this binding capability. DISCUSSION: RDN could attenuate SALI 
      through reducing apoptosis of PMECs, which is a promising therapeutic strategy 
      for SALI prevention.
CI  - Copyright (c) 2023 Wang, Guo, Wang, Liao, Chen, Liu and Wang.
FAU - Wang, Ziyi
AU  - Wang Z
AD  - Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua 
      University, Beijing, China.
FAU - Guo, Zhe
AU  - Guo Z
AD  - Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua 
      University, Beijing, China.
FAU - Wang, Xuesong
AU  - Wang X
AD  - Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua 
      University, Beijing, China.
FAU - Liao, Haiyan
AU  - Liao H
AD  - Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua 
      University, Beijing, China.
FAU - Chen, Feng
AU  - Chen F
AD  - Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua 
      University, Beijing, China.
FAU - Liu, Yuxin
AU  - Liu Y
AD  - Department of Cardiovascular Thoracic Surgery, Tianjin Medical University General 
      Hospital, Tianjin, China.
FAU - Wang, Zhong
AU  - Wang Z
AD  - Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua 
      University, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20230703
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (reduning)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (bcl-2-Associated X Protein)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Apoptosis Regulatory Proteins)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Endothelial Cells/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - bcl-2-Associated X Protein
MH  - Lung/pathology
MH  - *Acute Lung Injury/metabolism
MH  - Apoptosis
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - *Pulmonary Edema/pathology
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - *Sepsis/metabolism
MH  - Mammals/metabolism
PMC - PMC10350519
OTO - NOTNLM
OT  - Bax
OT  - Reduning
OT  - SALI
OT  - apoptosis
OT  - mTOR
OT  - network pharmacology
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/07/19 06:42
MHDA- 2023/07/21 06:42
PMCR- 2023/01/01
CRDT- 2023/07/19 04:05
PHST- 2023/03/29 00:00 [received]
PHST- 2023/06/15 00:00 [accepted]
PHST- 2023/07/21 06:42 [medline]
PHST- 2023/07/19 06:42 [pubmed]
PHST- 2023/07/19 04:05 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1196350 [doi]
PST - epublish
SO  - Front Immunol. 2023 Jul 3;14:1196350. doi: 10.3389/fimmu.2023.1196350. 
      eCollection 2023.