Polysaccharide from Tetrastigma hemsleyanum Diels et Gilg attenuates acute lung injury induced by lipopolysaccharide associated with inhibiting complement and neutrophil activation

Acute lung injury (ALI) refers to severe hypoxemia, respiratory distress, and other conditions caused by various factors. The etiology and treatment methods currently remain limited. The traditional Chinese herbal medicine Tetrastigma hemsleyanum Diels et Gilg and its extract T. hemsleyanum Diels et Gilg polysaccharide (THP) have a protective effect on ALI. However, the exact mechanism remains to be elucidated. This study aimed to investigate the specific mechanism of THP treatment for ALI and explore its potential correlation with anti-complement activity and the mitigation of neutrophil activation. The anti-complement activities of THP were determined using hemolytic assays in vitro. The therapeutic effects of THP on ALI were evaluated in mice intratracheally instilled with lipopolysaccharide (LPS). The possible regulatory mechanism of THP in treating ALI was revealed through proteomic methods. Hematoxylin and eosin staining, immunohistochemical staining, immunofluorescence, and detection of free DNA were employed for analysis. THP demonstrated anti-complement activity through classical pathways in vitro, and it reduced systemic inflammation, especially in the lungs of mice. The main proteins and signaling pathways involved were identified through lung proteomics. Experimental validation confirmed that THP alleviated histological changes while reducing the degree of complement C3 deposition, neutrophil infiltration, and the emergence of neutrophil extracellular traps (NETs) in vivo. The anti-complement activity of THP was verified in vitro and in vivo. This substance can reduce LPS-induced ALI in mice, and its mechanism is related to the inhibition of complement activation, neutrophil recruitment, and NETs’ formation.