Angelica Polysaccharide Ameliorates Sepsis-Induced Acute Lung Injury through Inhibiting NLRP3 and NF-κB Signaling Pathways in Mice

Abstract

Objective. This study aimed to explore the role of angelica polysaccharide (AP) in sepsis-induced acute lung injury (ALI) and its underlying molecular mechanism. Methods. A sepsis model of cecal ligation and puncture (CLP) in male BALB/C mice was used. Then, 24 h after CLP, histopathological changes in lung tissue, lung wet/dry weight ratio, and inflammatory cell infiltration were analyzed. Next, levels of inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-18), as well as the activity of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH), were measured to assess the role of AP. The protein expression of NF-κB p65, p-NF-κB p65, IκBα, p-IκBα, nucleotide-binding domain- (NOD-) like receptor protein 3 (NLRP3), ASC, and caspase-1 was detected by western blot. In addition, the expression of p-NF-κB p65 and NLRP3 was detected by immunohistochemistry. Results. AP treatment ameliorated CLP-induced lung injury and lung edema, as well as decreased the number of total cells, neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF). AP reduced the levels of TNF-α, IL-1β, IL-6, and IL-18 in BALF, as well as in serum. Moreover, AP decreased MPO activity and MDA content, whereas increased SOD and GSH levels. AP inhibited the expression of p-NF-κB p65, p-IκBα, NLRP3, ASC, and caspase-1, while promoted IκBα expression. Conclusion. This study demonstrated that AP exhibits protective effects against sepsis-induced ALI by inhibiting NLRP3 and NF-κB signaling pathways in mice.

Study the mechanism of peimisine derivatives on NF‐κB inflammation pathway on mice with acute lung injury induced by lipopolysaccharide

“…According to the literature, the severity of lung injury can be judged by the degree of lung tissue injury, the degree of pulmonary edema, and the release of multiple inflammatory mediators such as macrophages, neutrophils, and cytokines (Yuan et al, 2014). When ALI occurs, it causes abnormal release of neutrophils, macrophages, and various inflammatory factors (IL‐1β, NLRP3, NF‐κB, HIF‐1α, and TNF‐α) and leads to alveolar cell‐associated protein abnormalities (Zhu et al, 2021). The results were shown in Figures 4–6.…”