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
Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ f...Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short-or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019(COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury,chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.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.
基金supported by the Technology Bureau of Liaoning Province(No.17-230-9-45),China。
文摘Molecular hydrogen exerts biological effects on nearly all organs. It has anti-oxidative, anti-inflammatory, and anti-aging effects and contributes to the regulation of autophagy and cell death. As the primary organ for gas exchange, the lungs are constantly exposed to various harmful environmental irritants. Short-or long-term exposure to these harmful substances often results in lung injury, causing respiratory and lung diseases. Acute and chronic respiratory diseases have high rates of morbidity and mortality and have become a major public health concern worldwide. For example, coronavirus disease 2019(COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) has become a global pandemic. An increasing number of studies have revealed that hydrogen may protect the lungs from diverse diseases, including acute lung injury,chronic obstructive pulmonary disease, asthma, lung cancer, pulmonary arterial hypertension, and pulmonary fibrosis. In this review, we highlight the multiple functions of hydrogen and the mechanisms underlying its protective effects in various lung diseases, with a focus on its roles in disease pathogenesis and clinical significance.
