PMID- 35266443
OWN - NLM
STAT- MEDLINE
DCOM- 20220411
LR  - 20220716
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 13
IP  - 3
DP  - 2022 Mar
TI  - Suppression of NOD-like receptor protein 3 inflammasome activation and macrophage 
      M1 polarization by hederagenin contributes to attenuation of sepsis-induced acute 
      lung injury in rats.
PG  - 7262-7276
LID - 10.1080/21655979.2022.2047406 [doi]
AB  - Acute lung injury (ALI) is a major leading cause of death in sepsis patients. 
      Hederagenin (HG), derived from Hedera helix Linne, has anti-inflammatory effects, 
      while its role in sepsis-induced ALI has not been elucidated. In vivo, rats were 
      subjected to cecal ligation and puncture to induce ALI and then treated with HG 
      (12.5, 25, or 50 mg/kg) by gavage. Administration of HG raised survival rate, 
      ameliorated lung injury, and decreased lung wet/dry ratio and inflammatory cell 
      accumulation in bronchoalveloar lavage fluid (BALF) of ALI rats. HG inhibited 
      macrophage polarization toward the M1 phenotype as evidenced by decreased CD86 
      expression in rat lung tissues. Moreover, HG decreased the secretion of TNF-alpha, 
      IL-6 and monocyte chemoattractant protein-1 (MCP-1) in BALF and the levels of 
      inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lung 
      tissues. In vitro, phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 
      macrophages were stimulated with 100 ng/mL lipopolysaccharide. HG treatment 
      inhibited M1 macrophage polarization and the production of M1-related 
      pro-inflammatory mediators (IL-6, MCP-1, iNOS, and COX-2). Mechanistically, HG 
      inhibited NLRP3 inflammasome activation and subsequent release of IL-18 and 
      IL-1beta, and suppressed NF-kappaB signaling pathway both in vivo and in vitro. Notably, 
      HG treatment further emphasized the inhibitory effect of NF-kappaB inhibitor 
      BAY11-7082 on NLRP3 inflammasome activation and macrophage M1 polarization. Taken 
      together, HG exerts a protective effect against sepsis-induced ALI by reducing 
      the inflammatory response and macrophage M1 polarization, which may involve NF-kappaB 
      pathway-modulated NLRP3 inflammasome activation.
FAU - Wang, Lin
AU  - Wang L
AD  - Department of Emergency Medicine, Shengjing Hospital of China Medical University, 
      Shenyang, Liaoning, China.
FAU - Zhao, Min
AU  - Zhao M
AD  - Department of Emergency Medicine, Shengjing Hospital of China Medical University, 
      Shenyang, Liaoning, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLR Proteins)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - RQF57J8212 (hederagenin)
SB  - IM
MH  - *Acute Lung Injury/chemically induced
MH  - Animals
MH  - Cyclooxygenase 2
MH  - Humans
MH  - Inflammasomes/adverse effects
MH  - Interleukin-6
MH  - Lipopolysaccharides/pharmacology
MH  - Lung/metabolism
MH  - Macrophages
MH  - NF-kappa B/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism
MH  - NLR Proteins
MH  - Oleanolic Acid/analogs & derivatives
MH  - Rats
MH  - *Sepsis/complications
PMC - PMC9208453
OTO - NOTNLM
OT  - Hederagenin
OT  - NF-kappaB
OT  - NLRP3
OT  - macrophage
OT  - sepsis-induced acute lung injury
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/03/11 06:00
MHDA- 2022/04/12 06:00
PMCR- 2022/03/10
CRDT- 2022/03/10 08:39
PHST- 2022/03/10 08:39 [entrez]
PHST- 2022/03/11 06:00 [pubmed]
PHST- 2022/04/12 06:00 [medline]
PHST- 2022/03/10 00:00 [pmc-release]
AID - 2047406 [pii]
AID - 10.1080/21655979.2022.2047406 [doi]
PST - ppublish
SO  - Bioengineered. 2022 Mar;13(3):7262-7276. doi: 10.1080/21655979.2022.2047406.