Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Dehydrocavidine alleviates lipopolysaccharide-induced acute liver injury by activating Nrf2 signaling pathway to inhibit hepatocyte ferroptosis.
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.
Liang Hongbiao, Hu Guizimeng, Yang Dongmin, Song Yuwei, Zhang Peng, Chen Tianqi, Zhu Xiangrui, Li Peiyi, Wang Yuan, Huo Xinmei, Wang Xiaoyi, Zhang Yi, Zhang Yujie, Liu Jian, Feng Juan
Аннотация
BACKGROUND: Sepsis-induced acute liver injury (SALI) remains a major challenge with limited effective treatments. Although Corydalis saxicola Bunting (CSB) exhibits anti-inflammatory and hepatoprotective properties, its role in SALI remains poorly understood.
PURPOSE: To identify the active components and molecular mechanisms of CSB in protecting against SALI.
METHODS: In vivo LPS-induced rat liver injury and in vitro cytokine-induced HepG2 injury models were established, treated with CSB extract or dehydrocavidine (DC). A series of advanced techniques including ferroptosis PCR array, super-resolution stimulated emission depletion (STED) microscopy, assay for transposase-accessible chromatin with sequencing (ATAC-seq), cellular thermal shift assay (CETSA), surface plasmon resonance (SPR), molecular dynamics simulation, and site-directed mutation were employed to investigate the underlying mechanisms.
RESULTS: DC significantly mitigated LPS-induced liver injury, microcirculatory disorder, and leukocyte adhesion. It also alleviated liver ferroptosis under LPS challenge. In vitro studies revealed that LPS-activated macrophages secreted tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), which triggered hepatocyte ferroptosis. DC countered this process by inhibiting the production of these cytokines and correcting cytokine-induced mitochondrial abnormalities in hepatocytes. Mechanistically, DC bound to Kelch-like ECH-associated protein 1 (Keap1) at arginine 415 (R415), disrupting the formation of the Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) complex. This enabled Nrf2 nuclear translocation and promoted antioxidant gene expression, thereby correcting LPS-induced redox imbalance in hepatocytes.
CONCLUSIONS: In addition to inhibiting LPS-induced macrophage activation, DC activates the Nrf2 signaling pathway in hepatocytes to alleviate inflammation-enhanced liver ferroptosis. It provides potential therapeutic strategies for sepsis and Gram-negative bacteria-associated liver injury.
PURPOSE: To identify the active components and molecular mechanisms of CSB in protecting against SALI.
METHODS: In vivo LPS-induced rat liver injury and in vitro cytokine-induced HepG2 injury models were established, treated with CSB extract or dehydrocavidine (DC). A series of advanced techniques including ferroptosis PCR array, super-resolution stimulated emission depletion (STED) microscopy, assay for transposase-accessible chromatin with sequencing (ATAC-seq), cellular thermal shift assay (CETSA), surface plasmon resonance (SPR), molecular dynamics simulation, and site-directed mutation were employed to investigate the underlying mechanisms.
RESULTS: DC significantly mitigated LPS-induced liver injury, microcirculatory disorder, and leukocyte adhesion. It also alleviated liver ferroptosis under LPS challenge. In vitro studies revealed that LPS-activated macrophages secreted tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), which triggered hepatocyte ferroptosis. DC countered this process by inhibiting the production of these cytokines and correcting cytokine-induced mitochondrial abnormalities in hepatocytes. Mechanistically, DC bound to Kelch-like ECH-associated protein 1 (Keap1) at arginine 415 (R415), disrupting the formation of the Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2) complex. This enabled Nrf2 nuclear translocation and promoted antioxidant gene expression, thereby correcting LPS-induced redox imbalance in hepatocytes.
CONCLUSIONS: In addition to inhibiting LPS-induced macrophage activation, DC activates the Nrf2 signaling pathway in hepatocytes to alleviate inflammation-enhanced liver ferroptosis. It provides potential therapeutic strategies for sepsis and Gram-negative bacteria-associated liver injury.