Abstract
In brief: Preeclampsia is a severe pregnancy-related complication that can result in adverse maternal and fetal outcomes. Current therapeutic options for preeclampsia remain limited. This study demonstrates that epicatechin can inhibit pyroptosis in extravillous trophoblasts and block the activation of the NF-κB signaling pathway, thereby offering a novel therapeutic approach for the management of preeclampsia. : Preeclampsia (PE) is characterized as new-onset hypertension and proteinuria after 20 weeks of gestation, and affects 5-7% pregnant women globally. PE is associated with a systemic inflammatory status that is overly activated and contributes to dysregulated extravillous trophoblasts (EVTs) invasion and impaired spiral vessel remodeling. Recent studies showed that inhibition of systematic inflammatory response significantly ameliorates the PE-like symptoms, suggesting that anti-inflammation could be a potential PE treatment. However, few effective therapeutic strategies have been shown to control systemic inflammation in PE patients. In the current study, we investigated the protective effects of epicatechin (EC), a small molecule compound that exhibits excellent anti-inflammatory activity on HTR8/SVneo cells and EVTs stimulated with lipopolysaccharide (LPS). Our results revealed that EC pretreatment significantly improved cellular viability and attenuated the inflammatory response of EVTs in response to LPS stimulation. Mechanistically, we found that EC significantly blocked the activation of the LPS-induced pyroptosis pathway of classical pyrin domain protein 3, cleaved caspase 1 and cleaved gasdermin D (NLRP3/caspase-1/GSDMD) in LPS-treated EVTs and inhibited interleukin-1β (IL-1β) expression (a hallmark of pyroptosis) by suppressing the nuclear factor-κB (NF-κB) signaling. Our study demonstrates the protective effects of EC on LPS-stimulated inflammation and provides the direct evidence in vitro that EC may be a promising compound that mitigates the PE-associated systemic inflammation.