PMID- 34703269
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220427
IS  - 1178-7031 (Print)
IS  - 1178-7031 (Electronic)
IS  - 1178-7031 (Linking)
VI  - 14
DP  - 2021
TI  - Capsaicin Protects Against Lipopolysaccharide-Induced Acute Lung Injury Through 
      the HMGB1/NF-kappaB and PI3K/AKT/mTOR Pathways.
PG  - 5291-5304
LID - 10.2147/JIR.S309457 [doi]
AB  - PURPOSE: Capsaicin (8-methyl-N-geranyl-6-nonamide; CAP) is an alkaloid isolated 
      from chili peppers, which has complex pharmacological properties, including 
      beneficial effects against various diseases. The aim of this study was to 
      investigate the role of CAP in lipopolysaccharide (LPS)-induced acute lung injury 
      (ALI), and the possible underlying mechanisms. MATERIALS AND METHODS: ALI was 
      induced by intranasal administration of LPS (0.5 mg/kg), and CAP (1 mg/kg) 
      injected intraperitoneally 3 days before exposure to LPS. Then, the 
      histopathological changes were evaluated by hematoxylin and eosin staining. 
      Enzyme-linked immunosorbent assay and qPCR were used to detect pro-inflammatory 
      cytokines in serum and lung tissue. The expressions of HMGB1/NF-kappaB, PI3K/AKT/mTOR 
      signaling pathways and apoptosis-associated molecules were determined by Western 
      blot and/or qPCR. In addition, the lung cell apoptosis was analyzed by TUNEL 
      staining, and the expression and location of cleaved caspase-3 were detected by 
      immunofluorescence analysis. RESULTS: CAP pretreatment significantly protected 
      mice from LPS-induced ALI, with reduced lung wet/dry weight ratio, lung 
      histological damage, myeloperoxidase (MPO) activity, malondialdehyde (MDA) 
      content and pro-inflammatory cytokine levels, and significant increased 
      superoxide dismutase (SOD) activity. In addition, CAP pretreatment significantly 
      inhibited the high-mobility group protein B1 (HMGB1) expression, nuclear 
      factor-kappa B (NF-kappaB) activation, and the PI3K/AKT/mTOR signaling pathway. 
      Furthermore, mice pre-treated with CAP exhibited reduced apoptosis of lung 
      tissues, with associated down-regulation of caspase-3, cleaved caspase-3, and BAX 
      expression, and up-regulation of BCL-2. CONCLUSION: Our data demonstrate that CAP 
      can protect against LPS-induced ALI by inhibiting oxidative stress, inflammatory 
      responses and apoptosis through down-regulation of the HMGB1/NF-kappaB and 
      PI3K/AKT/mTOR pathways.
CI  - (c) 2021 Chen et al.
FAU - Chen, Hui
AU  - Chen H
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
FAU - Li, Na
AU  - Li N
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
AD  - Department of Oncology, First Affiliated Hospital of Yangtze University, 
      Jingzhou, Hubei, People's Republic of China.
FAU - Zhan, Xiang
AU  - Zhan X
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
FAU - Zheng, Ting
AU  - Zheng T
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
FAU - Huang, Xinzhou
AU  - Huang X
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
FAU - Chen, Qianglin
AU  - Chen Q
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
FAU - Song, Zihao
AU  - Song Z
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
FAU - Yang, Fei
AU  - Yang F
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
AD  - Clinical Molecular Immunology Center, School of Medicine, Yangtze University, 
      Jingzhou, People's Republic of China.
FAU - Nie, Hao
AU  - Nie H
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
AD  - Clinical Molecular Immunology Center, School of Medicine, Yangtze University, 
      Jingzhou, People's Republic of China.
FAU - Zhang, Yanxiang
AU  - Zhang Y
AD  - Clinical Molecular Immunology Center, School of Medicine, Yangtze University, 
      Jingzhou, People's Republic of China.
FAU - Zheng, Bing
AU  - Zheng B
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
AD  - Clinical Molecular Immunology Center, School of Medicine, Yangtze University, 
      Jingzhou, People's Republic of China.
FAU - Gong, Quan
AU  - Gong Q
AD  - Department of Immunology, School of Medicine, Yangtze University, Jingzhou, 
      People's Republic of China.
AD  - Clinical Molecular Immunology Center, School of Medicine, Yangtze University, 
      Jingzhou, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20211014
PL  - New Zealand
TA  - J Inflamm Res
JT  - Journal of inflammation research
JID - 101512684
PMC - PMC8524366
OTO - NOTNLM
OT  - HMGB1/NF-kappaB
OT  - PI3K/AKT/mTOR
OT  - acute lung injury
OT  - apoptosis
OT  - capsaicin
OT  - inflammation
COIS- The authors declare no conflicts of interest.
EDAT- 2021/10/28 06:00
MHDA- 2021/10/28 06:01
PMCR- 2021/10/14
CRDT- 2021/10/27 07:04
PHST- 2021/03/04 00:00 [received]
PHST- 2021/09/27 00:00 [accepted]
PHST- 2021/10/27 07:04 [entrez]
PHST- 2021/10/28 06:00 [pubmed]
PHST- 2021/10/28 06:01 [medline]
PHST- 2021/10/14 00:00 [pmc-release]
AID - 309457 [pii]
AID - 10.2147/JIR.S309457 [doi]
PST - epublish
SO  - J Inflamm Res. 2021 Oct 14;14:5291-5304. doi: 10.2147/JIR.S309457. eCollection 
      2021.