The protective effect of ginsenoside Rg1 against sepsis-induced lung injury through PI3K-Akt pathway: insights from molecular dynamics simulation and experimental validation DOI Creative Commons

Kaiqiang Zhong,

Yingui Huang,

Rui Chen

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 11, 2024

Abstract Sepsis-induced acute lung injury (SALI) poses a significant threat with high incidence and mortality rates. Ginsenoside Rg1 (GRg1), derived from Ginseng in traditional Chinese medicine, has been found to reduce inflammation protect epithelial cells against tissue damage. However, the specific roles mechanisms by which GRg1 mitigates SALI have yet be fully elucidated. In this context, we employed relevant mouse model, alongside network pharmacology, molecular docking, dynamics simulation pinpoint GRg1's action targets, complemented vitro assays explore underlying mechanisms. Our research shows that alleviates CLP-induced SALI, decreasing damage levels of serum proinflammatory factor IL-6, TNF-α, IL-1β, also enhancing survival rate CLP mice. A total 116 common targets between ALI, core including AKT1, VEGFA, SRC, IGF1, ESR1, STAT3, ALB. Further experiments assessed intervention effects on MLE-12 exposed LPS, qRT-PCR analysis simulations confirming AKT1 as key target favorable binding activity for GRg1. Western blot results indicated increased Bcl-2/Bax protein expression ratio apoptosis decreased cleaved caspase-3 LPS-induced cells. More showed increases phosphorylation PI3K AKT1. Flow cytometric using PI Annexin-V further verified LPS-stimulated (from 14.85 6.54%, p < 0.05). The employment inhibitor LY294002 confirmed these trends, indicating AKT1’s inhibition negates GRg1’s protective conclusion, our highlights potential an effective adjunct therapy primarily inhibiting alveolar reducing pro-inflammatory cytokine secretion, thus significantly rates These beneficial are mediated through targeting activating PI3K-AKT pathway.

Language: Английский

The protective effect of ginsenoside Rg1 against sepsis-induced lung injury through PI3K-Akt pathway: insights from molecular dynamics simulation and experimental validation DOI Creative Commons

Kaiqiang Zhong,

Yingui Huang,

Rui Chen

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 11, 2024

Abstract Sepsis-induced acute lung injury (SALI) poses a significant threat with high incidence and mortality rates. Ginsenoside Rg1 (GRg1), derived from Ginseng in traditional Chinese medicine, has been found to reduce inflammation protect epithelial cells against tissue damage. However, the specific roles mechanisms by which GRg1 mitigates SALI have yet be fully elucidated. In this context, we employed relevant mouse model, alongside network pharmacology, molecular docking, dynamics simulation pinpoint GRg1's action targets, complemented vitro assays explore underlying mechanisms. Our research shows that alleviates CLP-induced SALI, decreasing damage levels of serum proinflammatory factor IL-6, TNF-α, IL-1β, also enhancing survival rate CLP mice. A total 116 common targets between ALI, core including AKT1, VEGFA, SRC, IGF1, ESR1, STAT3, ALB. Further experiments assessed intervention effects on MLE-12 exposed LPS, qRT-PCR analysis simulations confirming AKT1 as key target favorable binding activity for GRg1. Western blot results indicated increased Bcl-2/Bax protein expression ratio apoptosis decreased cleaved caspase-3 LPS-induced cells. More showed increases phosphorylation PI3K AKT1. Flow cytometric using PI Annexin-V further verified LPS-stimulated (from 14.85 6.54%, p < 0.05). The employment inhibitor LY294002 confirmed these trends, indicating AKT1’s inhibition negates GRg1’s protective conclusion, our highlights potential an effective adjunct therapy primarily inhibiting alveolar reducing pro-inflammatory cytokine secretion, thus significantly rates These beneficial are mediated through targeting activating PI3K-AKT pathway.

Language: Английский

Citations

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