An alkali-extracted acidic heteropolysaccharide from Portulaca oleracea L. ameliorates acute lung injury in septic mice by inhibiting macrophage pyroptosis

Sepsis-induced acute lung injury (S-ALI) is characterized by an uncontrolled inflammatory response and lacks pharmacotherapy with minimal adverse effects. Portulaca oleracea L., a traditional Chinese medicine, is known for its benefits in treating inflammatory diseases. However, the protective effect of Portulaca oleracea L. polysaccharide against S-ALI remains unclear. Herein, we alkali-extracted an acidic heteropolysaccharide (POPAA-1) from Portulaca oleracea L., and found POPAA-1 (51.00 kDa) was mainly constituted by GalA, Rha, Ara, and Gal. Structural analyses revealed that the backbone of POPAA-1 consisted of 4-α-GalpA and 2,4-α-Rhap, with complex branching at C-4 of 2,4-α-Rhap. In vivo, POPAA-1 markedly mitigated lung injury and inflammation of lipopolysaccharide-induced S-ALI C57BL/6 mice. Notably, we found the alleviative effects of POPAA-1 were associated with alveolar macrophage Pyroptosis. However, when macrophages were depleted, the mitigative effects of POPAA-1 were significantly diminished, highlighting involvement of macrophages in the anti-pyroptotic effects of POPAA-1 in S-ALI mice. In vitro, the POPAA-1 inhibited MH-S cell Pyroptosis via suppressing the NF-κB and NLRP3/Caspase-1/GSDMD pathways, which was mediated by disrupting LPS-TLR4 binding. Overall, POPAA-1 can ameliorate S-ALI via inhibiting macrophage Pyroptosis. This presents POPAA-1 may serve as a potential anti-inflammatory agent for S-ALI.