Chrysin prevents lipopolysaccharide-induced acute lung injury in mice by suppressing the IRE1α/TXNIP/NLRP3 pathway

Abstract

Acute lung injury (ALI) remains a serious challenge in the intensive care unit. Inflammation plays a key role in the progression of ALI. Chrysin (CHR) is a natural flavonoid with anti-inflammatory functions. We investigated the anti-inflammatory effects in a mouse model of ALI induced by lipopolysaccharide (LPS), and identified the underlying mechanisms of its action. Following CHR administration, mice were challenged with LPS intratracheally for 6 h to induce ALI. Compared to mice challenged with LPS alone, the presence of CHR showed a reduction in the development of lung injuries, as confirmed by histopathological observation. Pre-treatment with CHR attenuated inflammation by reducing the production of myeloperosidase (MPO), and pro-inflammatory cytokine levels in the lung and bronchoalveolar lavage fluid (BALF). Furthermore, CHR improved lung edema by reducing the vascular permeability, as demonstrated by less evans blue staining in the lung tissue and low levels of protein in BALF. In addition, our results proved that CHR improved the antioxidant capacity by increasing the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the lung tissue. Results of western blot assays suggested that CHR suppressed the LPS-induced expression of glucose-regulated protein 78 (GRP78) and phosphorylated inositol-requiring enzyme 1α (p-IRE1α). We also found that CHR suppressed the expression of thioredoxin interaction protein (TXNIP), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and cleaved caspase-1. In conclusion, CHR improved vascular permeability and mitigated the inflammatory response of lung tissue by suppressing the IRE1α/TXNIP/NLRP3 pathway, thereby alleviating LPS-induced ALI in the lungs of mice.