Abstract
The protective effects of dioscin, a natural steroidal saponin from some medicinal plants including Dioscorea nipponica Makino, against lipopolysaccharide (LPS)- induced acute liver and renal damages have been reported in our previous works. However, the actions of dioscin against LPS-induced acute lung injury (ALI) is still unknown. In the present study, we investigated the effects and mechanisms of dioscin against LPS-induced ALI in vitro and in vivo. The results showed that dioscin obviously inhibited cell proliferation and markedly decreased reactive oxidative species level in 16HBE cells treated by LPS. In addition, dioscin significantly protected LPS-induced histological changes, inhibited the infiltration of inflammatory cells, as well as decreased the levels of MDA, SOD, NO and iNOS in mice and rats (p < 0.05). Mechanistically, dioscin significantly decreased the protein levels of TLR4, MyD88, TRAF6, TKB1, TRAF3, phosphorylation levels of PI3K, Akt, IκBα, NF-κB, and the mRNA levels of IL-1β, IL-6, and TNF-α against oxidative stress and inflammation (p < 0.05). Dioscin significantly reduced the overexpression of TLR4, and obviously down-regulated the levels of MyD88, TRAF6, TKB1, TRAF3, p-PI3K, p-Akt, p-IκBα, and p-NF-κB. These findings provide new perspectives for the study of ALI. Dioscin has protective effects on LPS-induced ALI via adjusting TLR4/MyD88- mediated oxidative stress and inflammation, which should be a potent drug in the treatment of ALI.
Highlights
Acute lung injury (ALI) often poses a great threat to human health (Bhatia and Moochhala, 2004; Rubenfeld et al, 2005)
We have reported that dioscin has significant effects on l LPS-induced liver injury (Yao et al, 2016), LPS-induced kidney injury (Qi et al, 2016), non-alcoholic fatty liver disease (NAFLD) (Xu et al, 2014), hepatic ischemiareperfusion damage (Tao et al, 2014), and hepatic fibrosis (Zhang et al, 2015)
Dioscin was prepared from Dioscorea nipponica Makino in our laboratory with the purity over 98% analyzed by high-performance liquid chromatography (Yin et al, 2010; Hu et al, 2013)
Summary
Acute lung injury (ALI) often poses a great threat to human health (Bhatia and Moochhala, 2004; Rubenfeld et al, 2005). ALI is due to a large number of neutrophils into the lungs, and the release of a large number of pro-inflammatory mediators, resulting in damage to lung epithelial cells and endothelial cells (Sibille and Reynolds, 1990). Dioscin Alleviated Lipopolysaccharide-Induced Lung Injury pathophysiology and treatment of ALI, the mortality rate remains unchanged (Steinberg et al, 2006). It is urgent to improve the effective treatment strategy for the patients. The onset of ALI, an early symptom of organ failure, is associated with lipopolysaccharide (LPS) or the elevated blood levels of endotoxin (Jeyaseelan et al, 2004). LPS has been widely used to establish experimental model for drug development against ALI
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