Ginsenoside Rb1 alleviates endothelial dysfunction and vascular remodeling in preeclampsia via activation of the PI3K-Akt-eNOS pathway.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation. Endothelial dysfunction and abnormal placental vascular remodeling are central to its pathogenesis. Despite its significant impact on maternal and fetal health, current therapeutic options remain limited and largely symptomatic. This study aimed to investigate the protective effects and underlying mechanisms of ginsenoside Rb1 (Rb1) on endothelial function and vascular remodeling in PE, with a particular focus on the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway. Plasma and placental samples from PE patients and normotensive pregnant women were analyzed for vascular markers and histological changes. A PE-like rat model was induced using NG-Nitro-L-arginine Methyl Ester, Hydrochloride (L-NAME) and treated with low, medium, or high doses of Rb1. Blood pressure, urinary protein excretion, nitric oxide (NO) and endothelin-1 (ET-1) levels, placental pathology, and related protein expression were evaluated. In vitro, an angiotensin II (Ang II)-induced human umbilical vein endothelial cell (HUVEC) injury model was used to assess the involvement of the PI3K/Akt/eNOS pathway using pharmacological inhibitors and activators. PE patients exhibited reduced NO levels, increased ET-1 levels, placental vascular damage, suppressed vascular endothelial growth factor (VEGF) expression, and elevated alpha-smooth muscle actin (α-SMA) expression. In the L-NAME-induced PE-like rat model, Rb1 treatment significantly reduced systolic blood pressure and urinary protein excretion, restored endothelial function, and alleviated placental structural damage. Rb1 also reversed inhibition of the PI3K/Akt/eNOS pathway observed in PE. In vitro, Rb1 improved HUVEC viability, angiogenesis, oxidative stress, and apoptosis, effects that were abolished by PI3K inhibition, while PI3K activation mimicked the protective effects of Rb1. Rb1 exerts significant protective effects against endothelial dysfunction and placental vascular remodeling in PE, likely through activation of the PI3K/Akt/eNOS signaling pathway. These findings suggest that Rb1 may represent a promising therapeutic candidate for the management of PE.