Xiangyun Deng, Hu Chen, Yang Zhang, Fengmei Xu, Qian Zhou
{"title":"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","authors":"Xiangyun Deng, Hu Chen, Yang Zhang, Fengmei Xu, Qian Zhou","doi":"10.1155/2024/2296727","DOIUrl":null,"url":null,"abstract":"<div>\n <p><i>Background</i>. 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 <i>in vitro</i> and <i>in vivo</i> and to reveal the potential molecular mechanism of its action. <i>Methods</i>. 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-<i>κ</i>B signaling pathway, and the concentrations of TNF-<i>α</i>, IL-6, and IL-18 were measured with ELISA kits. <i>Results</i>. Echinatin mitigated placental damage, reduced apoptosis, and increased CK7 expression. It significantly enhanced HTR-8/SVneo cell viability and migration. Echinatin also counteracted H<sub>2</sub>O<sub>2</sub>-induced ROS production and cell death in HTR-8/SVneo cells. Moreover, it inhibited the expression of proteins within the TLR4-MyD88-NF-<i>κ</i>B signaling cascade. Overexpression of TLR4 negated echinatin’s protective effects. <i>Conclusion</i>. Echinatin exerts protective effects against oxidative stress and inflammation in PE by targeting the TLR4-MyD88-NF-<i>κ</i>B pathway, suggesting its therapeutic potential for the management of preeclampsia.</p>\n </div>","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/2296727","citationCount":"0","resultStr":"{\"title\":\"Echinatin Inhibits Oxidative Stress and Inflammatory Processes in Trophoblast Cells by Inhibiting TLR4-MyD88-NF-κB Pathway in Preeclampsia\",\"authors\":\"Xiangyun Deng, Hu Chen, Yang Zhang, Fengmei Xu, Qian Zhou\",\"doi\":\"10.1155/2024/2296727\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n <p><i>Background</i>. 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 <i>in vitro</i> and <i>in vivo</i> and to reveal the potential molecular mechanism of its action. <i>Methods</i>. 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-<i>κ</i>B signaling pathway, and the concentrations of TNF-<i>α</i>, IL-6, and IL-18 were measured with ELISA kits. <i>Results</i>. Echinatin mitigated placental damage, reduced apoptosis, and increased CK7 expression. It significantly enhanced HTR-8/SVneo cell viability and migration. Echinatin also counteracted H<sub>2</sub>O<sub>2</sub>-induced ROS production and cell death in HTR-8/SVneo cells. Moreover, it inhibited the expression of proteins within the TLR4-MyD88-NF-<i>κ</i>B signaling cascade. Overexpression of TLR4 negated echinatin’s protective effects. <i>Conclusion</i>. Echinatin exerts protective effects against oxidative stress and inflammation in PE by targeting the TLR4-MyD88-NF-<i>κ</i>B pathway, suggesting its therapeutic potential for the management of preeclampsia.</p>\\n </div>\",\"PeriodicalId\":15381,\"journal\":{\"name\":\"Journal of Clinical Pharmacy and Therapeutics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-05-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1155/2024/2296727\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Pharmacy and Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1155/2024/2296727\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Pharmacy and Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1155/2024/2296727","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
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.
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.