Tomentosin Inhibits Lipopolysaccharide-Induced Acute Lung Injury and Inflammatory Response by Suppression of the NF-κB Pathway in a Mouse Model of Sepsis.

Abstract

Acute lung injury (ALI) is a severe inflammatory disorder that causes respiratory failure. Cases of ALI are reported with increasing mortality rates each year. In this study, we investigated the anti-inflammatory role of tomentosin and its fundamental mechanisms against lipopolysaccharide (LPS)-induced ALI via the suppression of Toll-like receptor (TLR4)/nuclear factor-kappa beta (NF-κB) pathway in a mouse model of sepsis. ALI was induced to BALB/c mice through the administration of 10 μg of LPS concomitantly with tomentosin (20 and 25 mg/kg) treatment. Dexamethasone was used as a standard drug. Inflammatory cells were measured using a hemocytometer; myeloperoxidase (MPO) enzyme activity and pro-inflammatory cytokines were determined using commercial kits. The lung tissues of animals were examined histologically. The expression level of TLR4/NF-κB signaling molecules were analyzed by Western blotting. Tomentosin treatment decreased lung edema and reduced the levels of macrophages, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Tomentosin also suppressed the status of pro-inflammatory markers and reduced the activation of iNOS, MPO, COX-2, and PGE2 in the lung. Tomentosin appreciably down-regulated the NF-κB/TLR4 signaling pathway in sepsis mice. Histological study also showed the protective effects of tomentosin. These findings show that tomentosin protects the LPS-induced ALI via suppression of TLR4/NF-κB signaling pathway in sepsis mice. Tomentosin could be a promising therapeutic agent to treat sepsis.