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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 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, I?B?, NF-?B, and the mRNA levels of IL-1?, IL-6, and TNF-? 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-I?B?, and p-NF-?B. 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.

SUBMITTER: Yao H

PROVIDER: S-EPMC5359219 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Protective Effects of Dioscin against Lipopolysaccharide-Induced Acute Lung Injury through Inhibition of Oxidative Stress and Inflammation.

Yao Hong H Sun Yiping Y Song Shasha S Qi Yan Y Tao Xufeng X Xu Lina L Yin Lianhong L Han Xu X Xu Youwei Y Li Hua H Sun Huijun H Peng Jinyong J

Frontiers in pharmacology 20170321

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 th ...[more]

PMID: 28377715

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Project description:BackgroundAcute lung injury (ALI), characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema, and associated with a proteinaceous alveolar exudate, is a leading cause of morbidity and mortality. Currently, inflammation-oxidative stress interaction between TNF-α and NF-κB was identified as a key pathway of ALI. We hypothesized that a TNFR-Fc fusion protein would have beneficial effects in experimental ALI, and sought to test this idea in mice by blocking TNF-α.Methods and resultsIntratracheal instillation of lipopolysaccharide (LPS) into the lungs of ALI mice led to histiocyte apoptosis, and detection of serum and bronchoalveolar lavage fluid (BALF) cytokines, feedback between NF-κB and TNF-α, lung albumin leakage, lung damage, IκB kinase (IKK) and NF-κB activation, I-κB degradation, and oxidative injury. LPS administration raised pulmonary inflammation as reflected by increased inflammatory cytokines, alveoli protein concentration, and ALI scores. IKK is phosphorylated following LPS challenge, leading to I-κB degradation and NF-κB p65 phosphorylation. Furthermore, NF-κB is translocated into the nucleus and up-regulates TNF-α gene transcription. Infusion of TNFR-Fc 24h before LPS challenge significantly abrogated the increase of inflammatory cytokines, especially serum TNF-α concentration, as well as pulmonary alveoli protein levels, and diminished IKK and NF-κB activation and I-κB degradation. The nuclear translocation of NF-κB was inhibited, following by down-regulation of TNF-α gene transcription. In addition, LPS intratracheal instillation induced marked oxidative damage, such as a decrease in total anti-oxidation products and an increase in malondialdehyde (MDA), as well as up-regulation of oxidation enzymes. Histologic analysis and apoptosis scores revealed that the extent of tissue lesions was significantly reduced, but not abrogated, by TNF-α blockade.ConclusionTreatment with LPS alone increased inflammation and oxidative stress in ALI mice, while administration of TNFR-Fc 24h before LPS challenge broke the feedback between NF-κB and TNF-α, resulting in decreased pulmonary inflammation/oxidative damage and tissue destruction. These results suggest a potential role for TNF-α therapy to treat clinical ALI.

Dataset Information

Protective Effects of Dioscin against Lipopolysaccharide-Induced Acute Lung Injury through Inhibition of Oxidative Stress and Inflammation.

Publications

Protective Effects of Dioscin against Lipopolysaccharide-Induced Acute Lung Injury through Inhibition of Oxidative Stress and Inflammation.

Similar Datasets

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