Li Mengyongwei, Liu Mian, Mei Jiaoqi, Dai Haofu, Chen Huiqin, Jie Qiuling, Mei Jingjing, Yang Xiaohui, Kang Jinyu, Ma Yanlin, Mei Wenli
Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Hainan Provincial Clinical Research Center for Thalassemia, Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, China.
Key Laboratory of Reproductive Health Diseases Research and Translation (Hainan Medical University), Ministry of Education, Haikou, Hainan, China.
Reproduction. 2025 Aug 5;170(3). doi: 10.1530/REP-24-0182. Print 2025 Sep 1.
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.
子痫前期是一种严重的妊娠相关并发症，可导致不良的母婴结局。目前子痫前期的治疗选择仍然有限。本研究表明，表儿茶素可抑制绒毛外滋养层细胞的焦亡并阻断核因子κB信号通路的激活，从而为子痫前期的治疗提供了一种新的治疗方法。
子痫前期（PE）的特征是妊娠20周后新发高血压和蛋白尿，全球5%-7%的孕妇受其影响。PE与过度激活的全身炎症状态有关，这种炎症状态导致绒毛外滋养层细胞（EVT）侵袭失调和螺旋动脉重塑受损。最近的研究表明，抑制全身炎症反应可显著改善PE样症状，这表明抗炎可能是一种潜在的PE治疗方法。然而，很少有有效的治疗策略被证明可以控制PE患者的全身炎症。在本研究中，我们研究了表儿茶素（EC）的保护作用，EC是一种小分子化合物，对脂多糖（LPS）刺激的HTR8/SVneo细胞和EVT具有优异的抗炎活性。我们的结果显示，EC预处理显著提高了细胞活力，并减弱了EVT对LPS刺激的炎症反应。从机制上讲，我们发现EC显著阻断了LPS诱导的经典含吡咯结构域蛋白3、裂解的半胱天冬酶1和裂解的gasdermin D（NLRP3/半胱天冬酶-1/GSDMD）焦亡途径在LPS处理的EVT中的激活，并通过抑制核因子κB（NF-κB）信号传导抑制白细胞介素-1β（IL-1β）表达（焦亡的标志）。我们的研究证明了EC对LPS刺激的炎症的保护作用，并在体外提供了直接证据，表明EC可能是一种有前景的化合物，可减轻PE相关的全身炎症。
