Ganoderma lucidum polysaccharide peptides GL-PPSQ alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps.

Ganoderma lucidum polysaccharides peptides (GLPP) are the main effective ingredients from G. lucidum (Leyss. ex Fr.) Karst with anti-inflammatory, antioxidant, and immunoregulatory activities. We extracted and characterized a novel GLPP, named GL-PPSQ, which were found to have 18 amino acids and 48 proteins, connected by O-glycosidic bonds. The monosaccharide composition of GL-PPSQ was determined to be composed of fucose, mannose, galactose and glucose with a molar ratio of 1:1.45:2.37:16.46. By using asymmetric field-flow separation technique, GL-PPSQ were found to have a highly branched structure. Moreover, in an intestinal ischemia-reperfusion (I/R) mouse model, GL-PPSQ significantly increased the survival rate and alleviated intestinal mucosal hemorrhage, pulmonary permeability, and pulmonary edema. Meanwhile, GL-PPSQ significantly promoted intestinal tight junction, decreased inflammation, oxidative stress and cellular apoptosis in the ileum and lung. Analysis with Gene Expression Omnibus series indicates that neutrophil extracellular trap (NET) formation plays an important role in intestinal I/R injury. GL-PPSQ remarkedly inhibited NETs-related protein myeloperoxidase (MPO) and citrulline-Histone H3 (citH3) expression. GL-PPSQ could alleviate intestinal I/R and its induced lung injury via inhibiting oxidative stress, inflammation, cellular apoptosis, and cytotoxic NETs formation. This study proves that GL-PPSQ is a novel drug candidate for preventing and treating intestinal I/R injury.