Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Harpagide alleviates sepsis-induced acute respiratory distress syndrome via gut microbiota modulation.
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.
Sun Yuting, Xie Di, Fu Huimin, He Meilin, Li Jiaqi, Wu Chaomin, Pan Shuming
Аннотация
BACKGROUND: Sepsis-associated acute respiratory distress syndrome (ARDS) remains a leading cause of mortality in critically ill patients, with limited therapeutic options beyond supportive care. The gut-lung axis is critical in sepsis pathogenesis, yet effective targeting strategies remain scarce. Harpagide (HPG), an iridoid glycoside from Scrophularia ningpoensis, exhibits anti-inflammatory properties, but whether it protects against sepsis-induced ARDS through gut microbiota modulation remains unexplored.
METHODS: Sepsis-induced ARDS was established using the cecal ligation and puncture (CLP) model. Gut microbiota dependency was assessed via antibiotic depletion (ABX) and fecal microbiota transplantation (FMT). Ffar2-/- mice were used to verify receptor necessity. Microbial composition and SCFAs were analyzed by 16S rRNA sequencing and GC-MS. Lung signaling was assessed by RNA-seq, Western blot, and RT-qPCR. Plasma SCFAs were quantified in sepsis-induced ARDS patients (n = 12) and healthy controls (n = 12) by LC-MS/MS.
RESULTS: HPG significantly improved survival, attenuated lung injury, and suppressed cytokine storm in septic mice. These effects were abolished by ABX but transferable via FMT, confirming microbiota dependency. HPG enriched acetate-producing taxa, elevating fecal and plasma acetate. Transcriptomic analysis revealed simultaneous suppression of NF-κB signaling and excessive IFN-γ/STAT1 activation. HPG-mediated protection was completely abrogated in Ffar2-/- mice, and exogenous sodium acetate recapitulated these effects in a Ffar2-dependent manner. Clinically, plasma acetate was significantly depleted in ARDS patients and correlated with disease severity.
CONCLUSIONS: HPG alleviates sepsis-induced ARDS by reshaping gut microbiota to boost acetate production, which activates FFAR2 to orchestrate immune reprogramming via NF-κB and IFN-γ/STAT1 pathways, offering a novel microbial-metabolic therapeutic strategy.
METHODS: Sepsis-induced ARDS was established using the cecal ligation and puncture (CLP) model. Gut microbiota dependency was assessed via antibiotic depletion (ABX) and fecal microbiota transplantation (FMT). Ffar2-/- mice were used to verify receptor necessity. Microbial composition and SCFAs were analyzed by 16S rRNA sequencing and GC-MS. Lung signaling was assessed by RNA-seq, Western blot, and RT-qPCR. Plasma SCFAs were quantified in sepsis-induced ARDS patients (n = 12) and healthy controls (n = 12) by LC-MS/MS.
RESULTS: HPG significantly improved survival, attenuated lung injury, and suppressed cytokine storm in septic mice. These effects were abolished by ABX but transferable via FMT, confirming microbiota dependency. HPG enriched acetate-producing taxa, elevating fecal and plasma acetate. Transcriptomic analysis revealed simultaneous suppression of NF-κB signaling and excessive IFN-γ/STAT1 activation. HPG-mediated protection was completely abrogated in Ffar2-/- mice, and exogenous sodium acetate recapitulated these effects in a Ffar2-dependent manner. Clinically, plasma acetate was significantly depleted in ARDS patients and correlated with disease severity.
CONCLUSIONS: HPG alleviates sepsis-induced ARDS by reshaping gut microbiota to boost acetate production, which activates FFAR2 to orchestrate immune reprogramming via NF-κB and IFN-γ/STAT1 pathways, offering a novel microbial-metabolic therapeutic strategy.