Sinomenine ameliorates lipopolysaccharide-induced acute lung injury by stimulating M2 polarization and suppressing pyroptosis in alveolar macrophages

Objectives  Alveolar Macrophages (AMs), key defenders against Acute Lung Injury (ALI), are a potential therapeutic target. Sinomenine (SINO) has shown protective effects against ALI. This study investigates whether SINO exerts its protection by modulating AM polarization and pyroptosis.

Method  39 mice were divided into three groups: control, Lipopolysaccharide (LPS), and ALI+SINO groups. After administration of vehicle and SINO (60 mg/kg) for 1 h, mice were intratracheally injected with LPS at 10 mg/kg to induce ALI. A separate cohort received 20 mg/kg LPS for survival analysis. The survival rate, pathological alteration, lung Wet/Dry weight (W/D) ratio, and Myeloperoxidase (MPO) activity in the lung, as well as neutrophil count and protein content in Bronchoalveolar Lavage Fluid (BALF), were assessed in mice. Cytokine levels in BALF, serum, and AMs were measured using Enzyme-Linked Immunosorbent Assay (ELISA). The polarization type of AMs was determined by flow cytometry, western blot, and immunofluorescence analysis. Pyroptosis-associated molecules were determined by western blot.

Results  SINO significantly improved the survival rate and lung pathological alterations in ALI mice and reduced the W/D ratio, protein concentration, MPO activity, and inflammation of lung tissue. Both in vivo and in vitro analysis demonstrated that SINO could suppress pyroptosis and induce M2 polarization in LPS-induced AMs. Mechanistically, SINO repressed the LPS-activated NF-κB pathway.

Conclusions  The present findings illustrate that SINO exerts a protective effect on LPS-induced ALI via stimulating M2 polarization and suppressing pyroptosis in AMs, and its mechanism is related to the regulation of the NF-κB signaling pathway.

Keywords
Sinomenine (SINO); Acute lung injury (ALI); Alveolar macrophages (AMs); Protective effect