Guangzhou University of Chinese Medicine, Guangzhou, 510405, People's Republic of China; Guangzhou Sport University, Guangzhou, 510500, People's Republic of China.
Guangzhou University of Chinese Medicine, Guangzhou, 510405, People's Republic of China.
J Ethnopharmacol. 2024 Jan 30;319(Pt 2):117028. doi: 10.1016/j.jep.2023.117028. Epub 2023 Aug 18.
Modified Shoutai Pill, also called Jianwei Shoutai Pill (JSP), is a traditional Chinese medicine prescription that has been used as an effective agent for the treatment of miscarriage.
To explore the potential molecular mechanism of JSP against recurrent pregnancy loss (RPL).
In vivo, CBA/J mated DBA/2 mice were used to conduct RPL model, while CBA/J mated BALB/c mice were seen as the control group. Mice were orally administered with JSP, Fer-1 (a ferroptosis inhibitor) or distilled water from day 0.5-12.5 of gestation (GD 0.5-12.5). Pregnancy outcomes were analyzed and ferroptosis related indexes of the whole implantation sites were measured on GD 12.5. In vitro, human trophoblast cell line HTR-8/SVneo was cultured and treated with RAS-selective lethal small molecule 3 (RSL3) (a ferroptosis agonist) or different concentrations of JSP. Then, ferroptosis related indexes were tested to analyze whether JSP could inhibit ferroptosis in HTR-8/SVneo cells.
In vivo consequences demonstrated that JSP or Fer-1 alleviated pregnancy outcomes including lower resorption rate and abortion rate. In addition, excessive iron accumulation and MDA level were inhibited, while GSH and GPX content were raised under JSP or Fer-1 exposure. Also, JSP or Fer-1 enhanced protein expressions of GPX4 and SLC7A11 which suppress ferroptosis, and lightened protein expression of ACSL4 which boosts ferroptosis. In vitro, JSP rescued HTR-8/SVneo cell death and migration ability that were injured by RSL3. Furthermore, JSP inhibited RSL3-induced intracellular reactive oxygen species (ROS), lipid ROS and iron deposition.
Collectively, our findings illustrated that the mechanism of JSP in treating RPL might be related to inhibiting ferroptosis, which provided a novel insight into the application of JSP in RPL intervention.
改良寿胎丸，又称健味寿胎丸（JSP），是一种传统的中药方剂，已被用作治疗流产的有效药物。
探讨 JSP 防治复发性流产（RPL）的潜在分子机制。
在体内，CBA/J 交配 DBA/2 小鼠用于建立 RPL 模型，而 CBA/J 交配 BALB/c 小鼠则作为对照组。从妊娠第 0.5-12.5 天（GD 0.5-12.5）开始，给小鼠口服 JSP、Fer-1（一种铁死亡抑制剂）或蒸馏水。分析妊娠结局，并在 GD 12.5 时测量整个着床部位的铁死亡相关指标。在体外，培养人滋养层细胞系 HTR-8/SVneo 并用 RAS 选择性致死小分子 3（RSL3）（一种铁死亡激动剂）或不同浓度的 JSP 处理。然后，测试铁死亡相关指标，以分析 JSP 是否能抑制 HTR-8/SVneo 细胞中的铁死亡。
体内结果表明，JSP 或 Fer-1 可改善妊娠结局，包括降低吸收率和流产率。此外，JSP 或 Fer-1 暴露后可抑制铁积累和 MDA 水平升高，同时提高 GSH 和 GPX 含量。此外，JSP 或 Fer-1 增强了抑制铁死亡的 GPX4 和 SLC7A11 蛋白表达，并减轻了促进铁死亡的 ACSL4 蛋白表达。在体外，JSP 挽救了 RSL3 损伤的 HTR-8/SVneo 细胞死亡和迁移能力。此外，JSP 抑制了 RSL3 诱导的细胞内活性氧（ROS）、脂质 ROS 和铁沉积。
综上所述，我们的研究结果表明，JSP 治疗 RPL 的机制可能与抑制铁死亡有关，为 JSP 在 RPL 干预中的应用提供了新的思路。
