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Salecan ameliorates LPS-induced acute lung injury through regulating Keap1-Nrf2/HO-1 pathway in mice.
- Source :
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International Immunopharmacology . Feb2024, Vol. 128, pN.PAG-N.PAG. 1p. - Publication Year :
- 2024
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Abstract
- • Salecan mitigates LPS-induced ALI by preserving alveolar structure, reducing edema, and suppressing inflammation. • Salecan modulates oxidative stress pathways, reversing ALI-associated metabolic alterations. • Salecan may inhibit LPS-induced ALI through Keap1-Nrf2/HO-1 pathway. • Salecan interacts with macrophages, alleviating LPS-triggered apoptosis and inflammation. Acute lung injury (ALI) is a severe clinical condition with high mortality, characterized by rapid onset and limited treatment options. The pathogenesis of ALI involves inflammation and oxidative stress. The polysaccharide salecan, a water-soluble β-(1,3)-D-glucan, has been found to possess numerous pharmaceutical effects, including anti-inflammatory properties, inhibition of oxidative stress, and anti-fatigue effects. This study aims to investigate the protective effect and underlying mechanism of salecan against LPS-induced ALI in mice. Using an in vivo LPS-induced ALI mouse model and an in vitro RAW264.7 cell system, we investigated the role of salecan in ALI with various experimental approaches, including histological staining, quantitative real-time PCR, flow cytometry, western blot analysis, and other relevant assays. Pre-treatment with salecan effectively attenuated LPS-induced ALI in vivo, reducing the severity of pulmonary edema, inflammation, and oxidative stress. NMR-based metabolomic profiling analysis revealed that salecan attenuated LPS-induced metabolic imbalances associated with ALI. Furthermore, salecan downregulated Keap1 and upregulated Nrf2 and HO-1 protein levels, indicating its modulation of the Keap1-Nrf2/HO-1 signaling pathway as a potential mechanism underlying its protective effects against ALI. In vitro studies on RAW264.7 cells revealed that salecan exhibited binding affinity towards macrophages, thereby alleviating LPS-induced apoptosis and inflammation, which underpin its therapeutic potential against ALI. Our study suggests that salecan can alleviate LPS-induced ALI by modulating oxidative stress, inflammatory response, and apoptosis through the activation of the Keap1-Nrf2/HO-1 pathway. These findings provide novel insights into the potential therapeutic use of salecan for the treatment of ALI. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 128
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 175242399
- Full Text :
- https://doi.org/10.1016/j.intimp.2024.111512