Abstract
Acute lung injury (ALI) is characterized by inflammation of the lung tissue and oxidative injury caused by excessive accumulation of reactive oxygen species. Studies have suggested that anti-inflammatory or antioxidant agents could be used for the treatment of ALI with a good outcome. Therefore, our study aimed to test whether the mycelium extract of Sanghuangporus sanghuang (SS-1), believed to exhibit antioxidant and anti-inflammatory properties, could be used against the excessive inflammatory response associated with lipopolysaccharides (LPS)-induced ALI in mice and to investigate its possible mechanism of action. The experimental results showed that the administration of SS-1 could inhibit LPS-induced inflammation. SS-1 could reduce the number of inflammatory cells, inhibit myeloperoxidase (MPO) activity, regulate the TLR4/PI3K/Akt/mTOR pathway and the signal transduction of NF-κB and MAPK pathways in the lung tissue, and inhibit high mobility group box-1 protein 1 (HNGB1) activity in BALF. In addition, SS-1 could affect the synthesis of antioxidant enzymes Heme oxygenase 1 (HO-1) and Thioredoxin-1 (Trx-1) in the lung tissue and regulate signal transduction in the KRAB-associated protein-1 (KAP1)/nuclear factor erythroid-2-related factor Nrf2/Kelch Like ECH associated Protein 1 (Keap1) pathway. Histological results showed that administration of SS-1 prior to induction could inhibit the large-scale LPS-induced neutrophil infiltration of the lung tissue. Therefore, based on all experimental results, we propose that SS-1 exhibits a protective effect against LPS-induced ALI in mice. The mycelium of S. sanghuang can potentially be used for the treatment or prevention of inflammation-related diseases.
Highlights
Acute Lung Injury (ALI) is a condition where lung tissue is injured by excessive nonspecific acute inflammatory response in the lungs [1]
Excessive concentrations of NO and pro-inflammatory cytokines in the body play a key role in the pathogenesis of LPS-induced ALI
Antibodies against iNOS, COX-2, p-ERK1/2, p-JNK, JNK, Trx-1, Keap-1, KRAB-associated protein-1 (KAP1), GPX1, CAT, superoxide dismutase (SOD)-1, TLR4, AKT and HMGB1 were purchased from Gene Tex (San Antonio, TX, USA)
Summary
Acute Lung Injury (ALI) is a condition where lung tissue is injured by excessive nonspecific acute inflammatory response in the lungs [1]. The inhibition of mTOR reduces LPS-induced synthesis of pro-inflammatory cytokines and NF-κB phosphorylation, indicating that the PI3K/Akt/mTOR/IKK signal transduction pathways greatly affect the activation of NF-κB [8,9,10,11]. Effects of SS-1 on LPS-Induced Antioxidative Enzymes and HO-1, Trx-1, KAP1/Nrf Protein Expressions in Macrophage. Effect of SS-1 on BALF Cytokine Levels and iNOS, COX-2 Protein Expressions in LPS-Induced ALI Mice. Excessive concentrations of NO and pro-inflammatory cytokines in the body play a key role in the pathogenesis of LPS-induced ALI. The administration of SS-1 prior to induction increased the cytoplasmic expression levels of NF-κB p65 and IκBα, while reducing
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