Sepsis-induced acute lung injury(ALI)is a major clinical challenge,with limited treatment options and high mortality.Ginsenoside Rb1,a bioactive compound derived from ginseng,has shown promising anti-inflammatory and ...Sepsis-induced acute lung injury(ALI)is a major clinical challenge,with limited treatment options and high mortality.Ginsenoside Rb1,a bioactive compound derived from ginseng,has shown promising anti-inflammatory and antioxidative effects.This study is the first to systematically investigate the metabolites of ginsenoside Rb1,specifically F2 and CK,in the context of sepsis-induced ALI modeled by lipopolysaccharide(LPS)administration,a widely used preclinical approach to mimic key inflammatory features of clinical sepsis.Unlike other studies,which primarily focus on ginsenoside Rb1 itself,our research specifically emphasizes the role of its metabolites in this process.We demonstrated that ginsenoside Rb1 significantly improved lung histopathological damage,reduced inflammation,and inhibited cell apoptosis in a sepsis-induced ALI mouse model.Metabolomics and proteomics analyses revealed that Rb1 is metabolized into F2 and CK,which activate the AMP-activated protein kinase(AMPK)/Sirtuin 1(SIRT1)signaling pathway.This activation promotes Forkhead Box O1(FOXO1)deacetylation,inhibiting its cytoplasmic translocation and enhancing mitochondrial unfolded protein response(mtUPR)gene transcription.In vitro experiments confirmed that ginsenoside Rb1 protected alveolar typeⅡ(AT2)cells from oxidative stress and senescence,while restoring mitochondrial function.Blocking the AMPK/SIRT1 pathway or silencing FOXO1 reversed these protective effects,highlighting their crucial roles in Rb1's mitigation of ALI.Our findings provide new insights into the molecular mechanisms by which ginsenoside Rb1 alleviates sepsis-induced ALI and offer a potential therapeutic approach for treating sepsis-related lung injuries.展开更多
基金supported by the High-Quality Development Projects of China Medical Universitysupported by the Science and Technology Bureau of Liaoning Province(2023JH2/20200121)。
文摘Sepsis-induced acute lung injury(ALI)is a major clinical challenge,with limited treatment options and high mortality.Ginsenoside Rb1,a bioactive compound derived from ginseng,has shown promising anti-inflammatory and antioxidative effects.This study is the first to systematically investigate the metabolites of ginsenoside Rb1,specifically F2 and CK,in the context of sepsis-induced ALI modeled by lipopolysaccharide(LPS)administration,a widely used preclinical approach to mimic key inflammatory features of clinical sepsis.Unlike other studies,which primarily focus on ginsenoside Rb1 itself,our research specifically emphasizes the role of its metabolites in this process.We demonstrated that ginsenoside Rb1 significantly improved lung histopathological damage,reduced inflammation,and inhibited cell apoptosis in a sepsis-induced ALI mouse model.Metabolomics and proteomics analyses revealed that Rb1 is metabolized into F2 and CK,which activate the AMP-activated protein kinase(AMPK)/Sirtuin 1(SIRT1)signaling pathway.This activation promotes Forkhead Box O1(FOXO1)deacetylation,inhibiting its cytoplasmic translocation and enhancing mitochondrial unfolded protein response(mtUPR)gene transcription.In vitro experiments confirmed that ginsenoside Rb1 protected alveolar typeⅡ(AT2)cells from oxidative stress and senescence,while restoring mitochondrial function.Blocking the AMPK/SIRT1 pathway or silencing FOXO1 reversed these protective effects,highlighting their crucial roles in Rb1's mitigation of ALI.Our findings provide new insights into the molecular mechanisms by which ginsenoside Rb1 alleviates sepsis-induced ALI and offer a potential therapeutic approach for treating sepsis-related lung injuries.
