先兆子痫 (PE) 被归类为妊娠特异性高血压疾病，可导致严重的胎儿和孕产妇发病和死亡，影响发达国家和发展中国家约 3∼8% 的妊娠。然而，PE的确切病理机制尚未阐明，迫切需要寻找创新的PE治疗药物。最近的研究表明，胎盘氧化应激是 PE 病因的重要组成部分。因此，治疗PE，一种可能的治疗方法是减轻胎盘氧化应激。高山异黄酮 (AIF) 是一种异黄酮类异黄酮，源自柑橘浆果柘树，以其多种药物治疗特性而闻名，包括抗纤维化、抗炎、抗肿瘤和抗氧化活性。然而，AIF 对胎盘氧化应激下绒毛外滋养层 (EVT) 的保护作用尚未阐明。因此，我们评估了 AIF 对代表性 EVT 细胞系 HTR-8/SVneo 细胞的活力、侵袭、迁移和线粒体功能的刺激作用。此外，AIF 对 H2O2 的保护活性也得到了证实，包括减少细胞凋亡、ROS 产生和线粒体膜去极化。此外，我们通过分子对接分析和 SIRT1 介导的信号通路证实了 AIF 与 Sirtuin1 (SIRT1) 的直接相互作用，这些信号通路与 AIF 在氧化应激下对 HTR-8/SVneo 细胞的保护作用相关。最后，使用 BeWo 细胞（合体滋养层细胞系）进一步证实了 AIF 对抗氧化应激的有益功效。这些结果表明，AIF 可能通过激活人类滋养层细胞中的 SIRT1 来改善 H2O2 诱导的细胞内损伤。版权所有 © 2024。由 Elsevier Inc. 出版。

Pre-eclampsia (PE) is classified as pregnancy-specific hypertensive disease and responsible for severe fetal and maternal morbidity and mortality, which influenced an approximate 3 ∼ 8 % of all pregnancies in both developed and developing countries. However, the exact pathological mechanism underlying PE has not been elucidated and it is urgent to find innovate pharmacotherapeutic agents for PE. Recent studies have reported that a crucial part of the etiology of PE is played by placental oxidative stress. Therefore, to treat PE, a possible treatment approach is to mitigate the placental oxidative stress. Alpinumisoflavone (AIF) is a prenylated isoflavonoid originated in mandarin melon berry called Cudrania tricuspidate, and is well known for its versatile pharmacotherapeutic properties, including anti-fibrotic, anti-inflammatory, anti-tumor, and antioxidant activity. However, protective property of AIF on extravillous trophoblast (EVT) under placental oxidative stress has not been elucidated yet. Therefore, we assessed stimulatory effects of AIF on the viability, invasion, migration, mitochondria function in the representative EVT cell line, HTR-8/SVneo cell. Moreover, protective activities of AIF from H2O2 were confirmed, in terms of reduction in apoptosis, ROS production, and depolarization of mitochondrial membrane. Furthermore, we confirmed the direct interaction of AIF with sirtuin1 (SIRT1) using molecular docking analysis and SIRT1-mediated signaling pathways associated with the protective effects of AIF on HTR-8/SVneo cells under oxidative stress. Finally, beneficial efficacy of AIF against oxidative stress was further confirmed using BeWo cells, syncytiotrophoblast cell lines. These results suggest that AIF may ameliorate H2O2-induced intracellular damages through SIRT1 activation in human trophoblast cells.Copyright © 2024. Published by Elsevier Inc.