Pedunculoside alleviates lipopolysaccharide-induced acute lung injury/acute respiratory distress syndrome by inhibiting NF-κB pathway.

Acute lung injury (ALI) is a severe respiratory disease characterized by various clinical manifestations, including intractable hypoxemia, alveolar hypertension, parenchymal edema, and progressive respiratory distress. If left untreated, ALI can progress into acute respiratory distress syndrome (ARDS). A promising therapeutic option for ALI is Pedunculoside (PE), a major bioactive flavonoid found in Butcher's broom (Ruscus aculeatus). PE has been shown to possess significant anti-inflammatory and antioxidant effects. This study aimed to investigate the therapeutic effects of PE on ALI in mice and to understand the underlying mechanism of action. Initially, we established a mouse model of acute lung epithelial cell (MLE-12) injury induced by lipopolysaccharide (LPS). Subsequently, we treated the MLE-12 cells with PE and observed a significant improvement in cell viability and a reduction in apoptosis. Moreover, when ALI mice were treated with PE, we observed an enhancement in lung histopathological structure, a decrease in lung tissue wet-to-dry (W/D) ratio, and reduced total protein concentrations in bronchoalveolar lavage fluid (BALF). Additionally, there was a decrease in apoptotic epithelial cells in lung tissue and an increase in proliferating cells after PE intervention. PE treatment also led to reduced levels of intracellular interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and malondialdehyde (MDA), while increasing glutathione (GSH) levels and superoxide dismutase (SOD) activity in both MLE-12 cell supernatants and BALF of ALI mice. Our mechanistic studies demonstrated that PE effectively downregulated the expression of p-p65 and p-IκBα proteins. However, the induced activation of the transcription factor p65 reversed the regulatory effects of PE, partially counteracting its anti-apoptotic, anti-inflammatory, and antioxidant activities in MLE-12 cells. These findings demonstrate that PE treatment has the potential to mitigate LPS-induced ALI by inhibiting NF-κB signaling-mediated oxidative stress and inflammatory responses.