Targeting NF-κB Signaling Pathway by Cryptotanshinone Prevents Preeclampsia-Like Symptoms: Involvement of Placental Angiogenesis and Oxidative Stress.

Preeclampsia (PE) is a pregnancy complication that requires urgent attention, with early recognition and timely management being crucial to ensure the safety of both mother and child. Cryptotanshinone (CTS), a fat-soluble diterpenoid quinone compound derived from Salvia miltiorrhiza Bunge, exhibits various pharmacological activities, including anti-inflammatory, antioxidative stress, and immunomodulatory effects. This study investigates the preventive role of CTS in PE. In this research, an in vivo rat model of PE was established through intraperitoneal injection of N(ω)-nitro-L-arginine methyl esters (L-NAME). CTS was administered at dosages of 30 and 60 mg/kg/day to evaluate its impact on symptoms resembling those of PE. The results indicated that CTS ameliorates the maternal and fetal outcomes associated with PE and mitigates placental injury. Treatment with CTS restored inflammatory markers as well as oxidative stress and vascular molecular indicators. Additionally, we developed an in vitro model induced by hypoxia/reoxygenation (H/R) in HTR-8/SVneo cells and treated the cells with 20 and 40 μM of CTS. Our findings demonstrated that CTS reduces H/R-induced damage in HTR-8/SVneo cells while alleviating oxidative stress and promoting angiogenesis in human umbilical vein endothelial cells. Mechanistically, we identified NF-κB as a target for CTS through network pharmacology analysis combined with molecular docking. Subsequent experiments confirmed that CTS mitigates trophoblast cell damage via inhibiting the NF-κB signaling pathway. In conclusion, our study reveals that CTS prevents the development of PE-like symptoms by reducing oxidative damage within trophoblastic cells and enhancing angiogenesis through inhibiting the NF-κB pathway. These findings provide a novel strategy for the treatment of PE.