title: Protective Effects of Dioscin against Lipopolysaccharide-Induced Acute Lung Injury through Inhibition of Oxidative Stress and Inflammation.
abstract: The protective effects of dioscin, a natural steroidal saponin from some medicinal plants includingDioscorea nipponicaMakino, 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 ALIin vitroandin 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.
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Lab of Medical Function, College of Basic Medical Sciences, Dalian Medical University, Dalian China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Song
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Tao
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Lina
authors.initials: L
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Lianhong
authors.initials: L
authors.lastname: Yin
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Xu
authors.initials: X
authors.lastname: Han
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Youwei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Dalian Medical University, Dalian China.
authors.forename: Jinyong
authors.initials: J
authors.lastname: Peng
keywords: TLR4 signal pathway; acute lung injury; dioscin; inflammation; lipopolysaccharide; oxidative stress