Songorine inhibits oxidative stress-related inflammation through PI3K/AKT/NRF2 signaling pathway to alleviate lipopolysaccharide-induced septic acute lung injury
OBJECTIVE: The present study aimed to investigate the protective action and mechanism of songorine on sepsis-induced acute lung injury (ALI).
METHODS: The sepsis-induced ALI mouse and cell models were established by lipopolysaccharide (LPS) induction. Lung injury was assayed by hematoxylin and eosin staining, lung injury score, and lung wet-to-dry (W/D) weight ratio. Apoptosis in lung tissues was evaluated by TUNEL assay, and the expression of apoptosis-related markers (Bcl2, Bax, and caspase-3) was measured by western blotting. Levels of pro-inflammatory factors and oxidative stress markers in the bronchoalveolar lavage fluid (BALF) of mice were measured by ELISA and RT-qPCR. The expression of PI3K/AKT/NRF2 pathway-related proteins was analyzed by western blotting.
RESULTS: Songorine treatment at 40 mg/kg mitigated sepsis-induced ALI, characterized by improved histopathology, lung injury score, and lung W/D weight ratio (p < 0.05). Moreover, songorine markedly attenuated sepsis-induced apoptosis in lung tissues; this was evidenced by an increase in Bcl2 levels and a decrease in Bax and caspase-3 levels (p < 0.01). Also, songorine reduced levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β and MPO) and oxidative stress regulators (SOD and GSH) in the BALF of LPS-induced sepsis mice and RAW264.7 cells (p < 0.05). In addition, songorine upregulated the PI3K/AKT/NRF2 pathway-related proteins in LPS-induced sepsis mice and RAW264.7 cells (p < 0.05). Furthermore, LY294002 (a PI3K inhibitor) treatment reversed the protective effect of songorine on sepsis-induced ALI.
CONCLUSION: Songorine inhibits oxidative stress-related inflammation in sepsis-induced ALI via the activation of the PI3K/AKT/NRF2 signaling pathway.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:46 |
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| Enthalten in: |
Immunopharmacology and immunotoxicology - 46(2024), 2 vom: 01. März, Seite 152-160 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fang, Jingjing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/08923973.2023.2281902 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM364687436 |
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| 245 | 1 | 0 | |a Songorine inhibits oxidative stress-related inflammation through PI3K/AKT/NRF2 signaling pathway to alleviate lipopolysaccharide-induced septic acute lung injury |
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| 500 | |a Date Revised 25.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVE: The present study aimed to investigate the protective action and mechanism of songorine on sepsis-induced acute lung injury (ALI) | ||
| 520 | |a METHODS: The sepsis-induced ALI mouse and cell models were established by lipopolysaccharide (LPS) induction. Lung injury was assayed by hematoxylin and eosin staining, lung injury score, and lung wet-to-dry (W/D) weight ratio. Apoptosis in lung tissues was evaluated by TUNEL assay, and the expression of apoptosis-related markers (Bcl2, Bax, and caspase-3) was measured by western blotting. Levels of pro-inflammatory factors and oxidative stress markers in the bronchoalveolar lavage fluid (BALF) of mice were measured by ELISA and RT-qPCR. The expression of PI3K/AKT/NRF2 pathway-related proteins was analyzed by western blotting | ||
| 520 | |a RESULTS: Songorine treatment at 40 mg/kg mitigated sepsis-induced ALI, characterized by improved histopathology, lung injury score, and lung W/D weight ratio (p < 0.05). Moreover, songorine markedly attenuated sepsis-induced apoptosis in lung tissues; this was evidenced by an increase in Bcl2 levels and a decrease in Bax and caspase-3 levels (p < 0.01). Also, songorine reduced levels of proinflammatory cytokines (TNF-α, IL-6, IL-1β and MPO) and oxidative stress regulators (SOD and GSH) in the BALF of LPS-induced sepsis mice and RAW264.7 cells (p < 0.05). In addition, songorine upregulated the PI3K/AKT/NRF2 pathway-related proteins in LPS-induced sepsis mice and RAW264.7 cells (p < 0.05). Furthermore, LY294002 (a PI3K inhibitor) treatment reversed the protective effect of songorine on sepsis-induced ALI | ||
| 520 | |a CONCLUSION: Songorine inhibits oxidative stress-related inflammation in sepsis-induced ALI via the activation of the PI3K/AKT/NRF2 signaling pathway | ||
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| 700 | 1 | |a Wang, Xinnian |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Biqing |e verfasserin |4 aut | |
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