Quinic acid derivatives from Salicornia herbacea alleviate HMGB1-mediated endothelial dysfunction

The high mobility group box 1 protein (HMGB1) has been targeted in the discovery of dietary supplements or medicinal resources to treat vascular inflammatory diseases. Salicornia herbacea has been utilized as a seasoned vegetable, salad, and traditional medicinal resource as well. Two new (1 and 2) and four known (3-. 6) caffeoylated quinic acids (CQAs) were isolated from the crude extract of S. herbacea exhibiting anti-HMGB1 activity. The isolated CQAs were further evaluated for their potential to ameliorate HMGB1-mediated vascular barrier disruption. Compounds 1, 3, 5, and 6 exerted vascular protective activity against HMGB1-induced inflammatory responses in both cellular and animal models and their mechanisms were also addressed. The active CQAs increased survival rates of cecal ligation and puncture-induced severe septic models to 20-40%. This study may serve the groundwork for commercializing CQAs as functional food components for prevention and treatment of pathogenic conditions related to endothelial hyperpermeability.