Inhalation toxicology · 2025
Saikosaponin D ameliorates sepsis-induced acute lung injury by maintaining alveolar epithelial barrier integrity and inhibiting ferroptosis via Nrf2/HO-1 pathway.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Song Lijie, Tao Yanyan, Lu Guoyu, Wu Chenchen
Аннотация
BACKGROUND: Saikosaponin D (SSD), a triterpenoid saponin extracted from Bupleurum chinensis, has many pharmacological properties. The goal of our study is to assess the roles and mechanisms of SSD in septic acute lung injury (ALI).
METHODS: ALI in mice was induced by cecal ligation and puncture (CLP). After CLP surgery, mice were intragastrically administered with SSD (4 mg/kg) or vehicle for five consecutive days. Alveolar epithelial barrier function was detected by measuring total protein in BALF and tight junction proteins in lung tissues. Morphological changes of lung tissues were examined by hematoxylin-eosin staining. ROS content in lung tissues was measured by DHE staining. GSH and MDA levels were estimated to evaluate oxidative stress. Western blotting was used to evaluate protein levels. An in vitro model of septic lung injury was established in MLE-12 cells via LPS stimulation. Cytotoxicity, TEER values, and FITC-dextran flux were detected. Intracellular ROS content was evaluated by DCFH-DA staining.
RESULTS: SSD improved alveolar epithelial barrier function and suppressed ferroptosis in CLP-induced septic mice. SSD activated Nrf2/HO-1 signaling in CLP mice and LPS-exposed MLE-12 cells. ML385 (an Nrf2 inhibitor) attenuated SSD-mediated protective effects against ferroptosis and alveolar epithelial cell barrier dysfunction in vitro.
CONCLUSION: SSD ameliorates septic ALI by maintaining alveolar epithelial barrier integrity and suppressing ferroptosis via the activation of Nrf2 signaling.
METHODS: ALI in mice was induced by cecal ligation and puncture (CLP). After CLP surgery, mice were intragastrically administered with SSD (4 mg/kg) or vehicle for five consecutive days. Alveolar epithelial barrier function was detected by measuring total protein in BALF and tight junction proteins in lung tissues. Morphological changes of lung tissues were examined by hematoxylin-eosin staining. ROS content in lung tissues was measured by DHE staining. GSH and MDA levels were estimated to evaluate oxidative stress. Western blotting was used to evaluate protein levels. An in vitro model of septic lung injury was established in MLE-12 cells via LPS stimulation. Cytotoxicity, TEER values, and FITC-dextran flux were detected. Intracellular ROS content was evaluated by DCFH-DA staining.
RESULTS: SSD improved alveolar epithelial barrier function and suppressed ferroptosis in CLP-induced septic mice. SSD activated Nrf2/HO-1 signaling in CLP mice and LPS-exposed MLE-12 cells. ML385 (an Nrf2 inhibitor) attenuated SSD-mediated protective effects against ferroptosis and alveolar epithelial cell barrier dysfunction in vitro.
CONCLUSION: SSD ameliorates septic ALI by maintaining alveolar epithelial barrier integrity and suppressing ferroptosis via the activation of Nrf2 signaling.