3-Deoxysappanchalcone Inhibited High Mobility Group Box Protein 1-Mediated Severe Inflammatory Responses.

Phytochemicals are increasingly recognized for their therapeutic potential in treating various diseases, including vascular disorders. High mobility group box 1 (HMGB1), a key mediator of late-stage sepsis, triggers the release of proinflammatory cytokines, leading to inflammation and systemic complications. Elevated plasma levels of HMGB1 impair diagnosis and prognosis while worsening outcomes in inflammatory conditions. 3-deoxysappanchalcone (3-DSC), a compound derived from (L.) Tod., has demonstrated anti-influenza and anti-allergic effects, though its role in HMGB1-mediated severe vascular inflammation remains unclear. This study hypothesized that 3-DSC could modulate lipopolysaccharide-induced HMGB1 activity and its downstream inflammatory pathways in human umbilical vein endothelial cells (HUVECs). : In vitro and in vivo permeability; cell viability, adhesion, and excavation of leukocytes; the development of cell adhesion molecules; and lastly, the production of proinflammatory substances were investigated on human endothelial cells and mouse disease models to investigate the efficacy of 3-DSC in inflammatory conditions. : Experiments revealed that 3-DSC inhibited HMGB1 translocation from HUVECs, reduced neutrophil adhesion and extravasation, suppressed HMGB1 receptor formation, and blocked nuclear factor-κB (NF-κB) activation and tumor necrosis factor-α (TNF-α) synthesis. : These findings suggest that 3-DSC effectively mitigates HMGB1-driven inflammation, offering promise as a therapeutic candidate for inflammatory diseases.