刺五加通过抑制子痫前期 TLR4-MyD88-NF-κB 通路抑制滋养层细胞的氧化应激和炎症过程

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Journal of Clinical Pharmacy and Therapeutics Pub Date : 2024-05-20 DOI:10.1155/2024/2296727
Xiangyun Deng, Hu Chen, Yang Zhang, Fengmei Xu, Qian Zhou
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引用次数: 0

摘要

背景。子痫前期(PE)是一种常见的产科疾病,其特点是滋养细胞侵袭能力受损,并偏向于炎症性免疫反应。Echinatin是一种黄酮类化合物,具有公认的抗炎、抗氧化和抗癌活性,可能对子痫前期有治疗作用。我们的研究旨在探讨紫锥菊素在体外和体内对子痫前期的影响,并揭示其潜在的分子作用机制。研究方法将18只成年雌性Sprague Dawley大鼠随机分为三个实验组:子痫模型组、子痫+紫锥菊素治疗组和子痫+紫锥菊素治疗并TLR4过表达组。通过免疫组化评估胎盘组织 CK7 的表达。TUNEL 免疫荧光染色可量化胎盘细胞凋亡。细胞活力、增殖和迁移分别通过细胞计数试剂盒-8、EdU结合和Transwell试验进行评估。还测量了丙二醛、超氧化物歧化酶和谷胱甘肽过氧化物酶等氧化应激参数。流式细胞术测定了细胞凋亡和细胞内活性氧(ROS)水平。Western 印迹法评估了与 TLR4-MyD88-NF-κB 信号通路相关的蛋白质表达,并用 ELISA 试剂盒测定了 TNF-α、IL-6 和 IL-18 的浓度。结果棘白苷减轻了胎盘损伤,减少了细胞凋亡,增加了CK7的表达。它能明显增强 HTR-8/SVneo 细胞的活力和迁移。棘白还能抵消 H2O2 诱导的 ROS 生成和 HTR-8/SVneo 细胞的死亡。此外,它还抑制了 TLR4-MyD88-NF-κB 信号级联中蛋白质的表达。过量表达 TLR4 会抵消棘白蛋白的保护作用。结论刺五加通过靶向TLR4-MyD88-NF-κB途径对子痫前期的氧化应激和炎症产生保护作用,这表明刺五加具有治疗子痫前期的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Echinatin Inhibits Oxidative Stress and Inflammatory Processes in Trophoblast Cells by Inhibiting TLR4-MyD88-NF-κB Pathway in Preeclampsia

Background. Preeclampsia (PE) is a common obstetric disorder hallmarked by impaired trophoblast invasion and a skew toward an inflammatory immune response. Echinatin, a flavonoid with established anti-inflammatory, antioxidant, and anticancer activities, may offer therapeutic benefits in PE. Our study aimed to investigate the effect of echinatin on preeclampsia in vitro and in vivo and to reveal the potential molecular mechanism of its action. Methods. Eighteen adult female Sprague Dawley rats were randomized into three experimental groups: a PE model group, a PE + echinatin treatment group, and a PE + echinatin treatment group with TLR4 overexpression. Placental tissue CK7 expression was assessed by immunohistochemistry. TUNEL immunofluorescence staining quantified placental cell apoptosis. Cell viability, proliferation, and migration were evaluated using cell counting kit-8, EdU incorporation, and Transwell assays, respectively. Oxidative stress parameters of malondialdehyde, superoxide dismutase, and glutathione peroxidase were measured. Flow cytometry determined cell apoptosis and intracellular reactive oxygen species (ROS) levels. Western blotting evaluated the expression of proteins related to the TLR4-MyD88-NF-κB signaling pathway, and the concentrations of TNF-α, IL-6, and IL-18 were measured with ELISA kits. Results. Echinatin mitigated placental damage, reduced apoptosis, and increased CK7 expression. It significantly enhanced HTR-8/SVneo cell viability and migration. Echinatin also counteracted H2O2-induced ROS production and cell death in HTR-8/SVneo cells. Moreover, it inhibited the expression of proteins within the TLR4-MyD88-NF-κB signaling cascade. Overexpression of TLR4 negated echinatin’s protective effects. Conclusion. Echinatin exerts protective effects against oxidative stress and inflammation in PE by targeting the TLR4-MyD88-NF-κB pathway, suggesting its therapeutic potential for the management of preeclampsia.

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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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