HMGB1 as a Mediator of Endothelial Dysfunction in Preeclampsia: Protective Effects of Glycyrrhizic Acid use this title in cover letter

Background: Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality. It involves systemic inflammation, oxidative stress, and endothelial dysfunction. High Mobility Group Box 1 (HMGB1), a danger-associated molecular pattern (DAMP), may contribute to these processes. Objective: To evaluate the role of extracellular HMGB1 in endothelial dysfunction in a rat model of PE induced by NG-nitro-L-arginine methyl ester (L-NAME), and to assess the therapeutic effect of glycyrrhizic acid (GA), an HMGB1 inhibitor. Methods: : Pregnant Wistar rats were divided into four groups: control, pregnant control, PE (L-NAME-treated), and PE+GA. On gestational day 21, systolic, diastolic, and mean arterial pressure, proteinuria, and heart rate were measured. Plasma and placental nitric oxide (NO), oxidative stress markers (MDA, SOD, GSH), and inflammatory markers (HMGB1, IL-6, TNF-α, ICAM-1, NE, vWF) were analyzed via ELISA. Immunofluorescence was used to evaluate HMGB1, IL-6, NE, and vWF expression in placentae. Results: : L-NAME treatment resulted in increased blood pressure, proteinuria, and elevated HMGB1 and inflammatory markers, with decreased NO and antioxidant levels. GA treatment improved NO bioavailability, reduced inflammation, and normalized endothelial markers. Conclusion: HMGB1 contributes to endothelial dysfunction and oxidative stress in PE. GA attenuates these effects, indicating its potential as a therapeutic agent targeting HMGB1 in preeclampsia.