A glycoprotein UGP2A from the medicinal insect Ulomoides dermestoides alleviates deep vein thrombosis via the TLR4/MyD88 signaling pathway.

Abstract

Ulomoides dermestoides (Fairmaire, 1893) (UD), an edible and medicinal insect, is rich in polysaccharides, proteins, and amino acids. Traditionally and clinically, UD has also been used for treating conditions such as stroke, paralysis, and cerebral thrombosis. However, its bioactive macromolecules and associated bioactivities remain unexplored. Here, UGP2A was obtained by water extraction and ethanol precipitation method, DEAE-ff, and Sephadex G-100 column. Comprehensive analyses using HPGPC, UV, CD, FT-IR, SEM, and NMR revealed that UGP2A was a protein-dominant glycoprotein with O-glycosidic bonds and a triple helix structure, containing 38.34% carbohydrate and 57.90% protein, consisting of 21 amino acids and 10 monosaccharides, with 41.3% β-sheet, indicating that it is a primarily β-sheet glycoprotein in terms of secondary structure. In vivo, UGP2A effectively inhibited thrombus formation in a deep vein thrombosis (DVT) mouse model by enhancing anticoagulant activity, relieving inflammation, and suppressing platelet activation. In vitro studies demonstrated that UGP2A markedly suppressed IL-1β-induced upregulation of vWF, P-selectin, IL-6, and NF-κB mRNA expression in HUVECs, with ELISA confirming reduced secretion of P-selectin, TNF-α, and IL-6. Furthermore, UGP2A may suppress endothelial activation and inflammation by modulating the TLR4/MyD88 signaling pathway, thereby alleviating DVT. Assessments of cytotoxicity, hemolysis, liver and kidney function, major organ histopathology, and mouse tail bleeding collectively demonstrated that UGP2A exhibits favorable biosafety both in vitro and in vivo. These findings suggest that UGP2A has high potential for both the prevention and treatment of thrombosis and holds promise as a potential novel therapeutic for individuals at high risk of thrombotic events.