ARC@DPBNPs suppress LPS-induced acute lung injury via inhibiting macrophage pyroptosis and M1 polarization by ERK pathway in mice

[Display omitted] •ARC@DPBNPs attenuated the LPS-induced lung injury at a lower concentration than ARC.•KEGG pathway analysis and molecular docking suggest that ARC's mechanism against ALI may involve the ERK signaling pathway.•ARC@DPBNPs inhibited macrophage pyroptosis and M1 polarization in vivo.•ARC and ARC@DPBNPs inhibited pyroptosis and M1 polarization in RAW264.7 cells induced by LPS.•ARC@DPBNPs attenuated macrophage pyroptosis and M1 polarization by inhibiting ERK pathway. Exploring the protective effect of ARC@DPBNP on lipopolysaccharides (LPS)-induced ALI and its underlying mechanism. ALI model was established by intransally administrating LPS (4 mg/kg) into C57BL/6 mice. The suppression effects of ALI was first compared between ARC (intragastric administrated, with doses ranging from 10 to 80 mg/kg) and ARC@BPBNPs (intratracheally administrated, with doses ranging from 1 to 4 mg/kg). Changes in lung histology post intratracheal intervention of 3 mg/kg ARC@DPBNPs were detected. The expression of pyrotosis pathway-related proteins in lungs as well as in RAW264.7 cells was detected by western blotting. The ASC expression in lung macrophages was examined using immune-fluorescent staining. The polarization of RAW264.7 cells and lung macrophages were detected by flow cytometry. The network pharmacology was constructed by Cytoscape, and the molecular docking was perfomed by AutoDock Vina. Docking predicted the high affinity of ARC to MAPK1 (ERK2). HE staining showed that ARC@DPBNPs attenuated LPS-induced ALI at a remarkably lower dose than ARC. The improved histopathological changes, lung W/D weight ratio, and decreased of inflammatory factor levels in lung collectively demonstrated the alleviation effects of ARC@DPBNPs. Compared with the LPS group, ARC@DPBNPs down-regulated the ERK pathway, resulted in a suppression of the macrophage pyroptosis and M1 polarization. This suppression effects could be removed by the ERK activator Ro 67-7476. ARC@DPBNPs attenuated ALI by suppressing LPS-induced macrophage pyroptosis and polarization, probably through down-regulation of the ERK pathway.