Baicalin alleviates H2O2-induced oxidative stress injury in human umbilical vein endothelial cells by regulating the TNF-$$\upalpha$$-mediated MAPK/ERK1/2/MPO pathway

Preeclampsia (PE) is a leading cause of morbidity and mortality among pregnant women, postpartum mothers, and perinatal infants worldwide. Currently, there are no effective pharmacological interventions for the prevention or treatment of PE. Oxidative stress in vascular endothelial cells represents a key pathophysiological mechanism underlying PE. Baicalin, a flavonoid compound derived from the traditional Chinese medicine Scutellaria baicalensis, exhibits anti-inflammatory, antioxidant, antiapoptotic, and immunoregulatory properties. However, its potential application in PE remains insufficiently investigated. In vitro experiments were conducted to establish an oxidative stress model using human umbilical vein endothelial cells (HUVECs) exposed to hydrogen peroxide. Transcriptomic analysis was employed to identify genes significantly expressed differently. The effects of baicalin on HUVEC viability were assessed using the CCK-8 assay. Myeloperoxidase (MPO) levels were quantified via ELISA and colorimetric assays; while, the expression of MAPK/ERK1/2 signaling pathway components was analyzed using RT-qPCR and Western blotting. Cell apoptosis was evaluated by flow cytometry. Clinical studies have shown elevated MPO levels in the peripheral blood of patients with PE. Transcriptomic analysis identified the MAPK/ERK1/2 signaling pathway as a central pathway associated with oxidative stress model. Exposure to H₂O₂ (800 [Formula: see text]M) for 30 min reduced cell viability to 66.36%, confirming the successful establishment of the oxidative stress model in HUVECs. Treatment with baicalin at concentrations of 100/200/400 [Formula: see text]M significantly downregulated MAPK/ERK1/2 expression (P < 0.05). Moreover, baicalin reduced apoptosis at all tested concentrations (P < 0.01). Notably, while 200 and 400 [Formula: see text]M baicalin de-creased MPO secretion, 100 [Formula: see text]M baicalin increased MPO release (P < 0.05). Co-administration of 200 [Formula: see text]M baicalin with TNF-[Formula: see text] antagonists did not produce additive effects on these parameters (P > 0.05). Baicalin effectively restored MPO secretion levels, inhibited MAPK/ERK1/2 activation, and reduced apoptosis, thereby alleviating oxidative stress-induced endothelial injury under conditions mimicking preeclamptic pathology. Importantly, treatment with 100 [Formula: see text]M baicalin induced adaptive changes in MPO secretion dynamics. Furthermore, the lack of additive effects between baicalin and TNF-[Formula: see text] antagonists suggests overlapping mechanisms of action. These findings enhance our our understanding of baicalin's molecular mechanisms and highlight its therapeutic potential for PE-related vascular endothelial dysfunction.