Histology and histopathology · 2025
Luteoloside ameliorates sepsis-induced acute lung injury via AMPK-ULK1 pathway-mediated autophagy.
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Xu Bo, Huang Min, Qi Hang, Liu Cheng, Xu Hongzhou, Cai Liang
Аннотация
BACKGROUND: Septic patients are at high risk of acute lung injury (ALI). Luteoloside is a flavonoid isolated from natural herbs and has many beneficial effects. This study aimed to investigate the protective role of luteoloside in sepsis-induced ALI.
METHODS: Sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Inflammation was induced by lipopolysaccharide (LPS) in MLE-12 cells. The survival rate over 12 days, histological changes in lung and heart, pulmonary edema, vascular leakage, hypoxemia, and inflammation were examined. Apoptosis was detected by TUNEL staining in vivo and flow cytometry in vitro. The levels of autophagy-related proteins, the AMPK/ULK1 pathway, and the NLRP3 inflammasome were evaluated by western blotting. Cell viability was estimated by MTT assays. LC3 expression was evaluated by immunofluorescence staining.
RESULTS: Luteoloside attenuated lung and cardiac injury, pulmonary edema, vascular leakage, hypoxemia, and inflammation and improved the survival of septic mice. Luteoloside (20 mg/kg) had no toxic effect on the heart, liver, spleen, and kidney in normal mice. Luteoloside enhanced autophagy to inhibit apoptosis in vivo and in vitro, and autophagy induction was responsible for the protective effect of luteoloside. Luteoloside activated AMPK/ULK1 signaling to enhance autophagy. Luteoloside also inhibited the activation of the NLRP3 inflammasome in LPS-challenged MLE-12 cells.
CONCLUSION: Overall, luteoloside activates AMPK/ULK1 signaling to stimulate autophagy, thereby inhibiting apoptosis and alleviating sepsis-induced ALI.
METHODS: Sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Inflammation was induced by lipopolysaccharide (LPS) in MLE-12 cells. The survival rate over 12 days, histological changes in lung and heart, pulmonary edema, vascular leakage, hypoxemia, and inflammation were examined. Apoptosis was detected by TUNEL staining in vivo and flow cytometry in vitro. The levels of autophagy-related proteins, the AMPK/ULK1 pathway, and the NLRP3 inflammasome were evaluated by western blotting. Cell viability was estimated by MTT assays. LC3 expression was evaluated by immunofluorescence staining.
RESULTS: Luteoloside attenuated lung and cardiac injury, pulmonary edema, vascular leakage, hypoxemia, and inflammation and improved the survival of septic mice. Luteoloside (20 mg/kg) had no toxic effect on the heart, liver, spleen, and kidney in normal mice. Luteoloside enhanced autophagy to inhibit apoptosis in vivo and in vitro, and autophagy induction was responsible for the protective effect of luteoloside. Luteoloside activated AMPK/ULK1 signaling to enhance autophagy. Luteoloside also inhibited the activation of the NLRP3 inflammasome in LPS-challenged MLE-12 cells.
CONCLUSION: Overall, luteoloside activates AMPK/ULK1 signaling to stimulate autophagy, thereby inhibiting apoptosis and alleviating sepsis-induced ALI.