ReferenceID 2017

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

Bioengineered

Acute lung injury (ALI) is a major leading cause of death in sepsis patients. Hederagenin (HG), derived from Hedera helix Linné , has anti-inflammatory effects, while its role in sepsis-induced ALI has not been elucidate

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Reference Id
2017
Evidence Id
18607
Core Evidence Id
18607
Source Reference Id
4045
Herb2 Reference Id
HBREF004842
Subject Paper Key
HBIN028847_35266443
Pubmed Id
35266443
Doi
10.1080/21655979.2022.2047406
Paper Title
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
Paper Abstract
Acute lung injury (ALI) is a major leading cause of death in sepsis patients. Hederagenin (HG), derived from Hedera helix Linné , 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-α, 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-1β, and suppressed NF-κB signaling pathway both in vivo and in vitro . Notably, HG treatment further emphasized the inhibitory effect of NF-κB 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-κB pathway-modulated NLRP3 inflammasome activation.
Journal
Bioengineered
Publish Year
2022
Experiment Subject
rat; patient; phorbol-12-myristate-13-acetate (pma)-differentiated thp-1 macrophages
Experiment Type
Animal Experiment
Phenotype Related
Acute Lung Injury; Sepsis; Lung Injury
Paper Title Cn
Paper Title En
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
Bilingual Status
semi_complete