Targeted metabolomics reveals the role of ginsenoside Rb1 in modulating inflammation and cellular senescence in sepsis-induced acute lung injury
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...
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Tsinghua University Press
2025-06-01
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| Series: | Food Science and Human Wellness |
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| Online Access: | https://www.sciopen.com/article/10.26599/FSHW.2025.9250658 |
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| author | Fushuang Zheng Wei Wang Linlin Gao Zhiling Fu |
| author_facet | Fushuang Zheng Wei Wang Linlin Gao Zhiling Fu |
| author_sort | Fushuang Zheng |
| collection | DOAJ |
| description | 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 type Ⅱ (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. |
| format | Article |
| id | doaj-art-aa1b9543e3d644a3a1a994d653d2042e |
| institution | Kabale University |
| issn | 2097-0765 2213-4530 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-aa1b9543e3d644a3a1a994d653d2042e2025-08-20T03:41:15ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302025-06-01146925065810.26599/FSHW.2025.9250658Targeted metabolomics reveals the role of ginsenoside Rb1 in modulating inflammation and cellular senescence in sepsis-induced acute lung injuryFushuang Zheng0Wei Wang1Linlin Gao2Zhiling Fu3Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaDepartment of Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaDepartment of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, ChinaSepsis-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 type Ⅱ (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.https://www.sciopen.com/article/10.26599/FSHW.2025.9250658sepsis-induced acute lung injuryginsenoside rb1ampk/sirt1 pathwayalveolar type ⅱ epithelial cells |
| spellingShingle | Fushuang Zheng Wei Wang Linlin Gao Zhiling Fu Targeted metabolomics reveals the role of ginsenoside Rb1 in modulating inflammation and cellular senescence in sepsis-induced acute lung injury Food Science and Human Wellness sepsis-induced acute lung injury ginsenoside rb1 ampk/sirt1 pathway alveolar type ⅱ epithelial cells |
| title | Targeted metabolomics reveals the role of ginsenoside Rb1 in modulating inflammation and cellular senescence in sepsis-induced acute lung injury |
| title_full | Targeted metabolomics reveals the role of ginsenoside Rb1 in modulating inflammation and cellular senescence in sepsis-induced acute lung injury |
| title_fullStr | Targeted metabolomics reveals the role of ginsenoside Rb1 in modulating inflammation and cellular senescence in sepsis-induced acute lung injury |
| title_full_unstemmed | Targeted metabolomics reveals the role of ginsenoside Rb1 in modulating inflammation and cellular senescence in sepsis-induced acute lung injury |
| title_short | Targeted metabolomics reveals the role of ginsenoside Rb1 in modulating inflammation and cellular senescence in sepsis-induced acute lung injury |
| title_sort | targeted metabolomics reveals the role of ginsenoside rb1 in modulating inflammation and cellular senescence in sepsis induced acute lung injury |
| topic | sepsis-induced acute lung injury ginsenoside rb1 ampk/sirt1 pathway alveolar type ⅱ epithelial cells |
| url | https://www.sciopen.com/article/10.26599/FSHW.2025.9250658 |
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