Albiflorin attenuates sepsis-induced acute lung injury (ALI) via the TLR-4/NF-κB pathway

Abstract

Objective: Approximately 40% of acute lung injury (ALI) cases are caused by sepsis. Albiflorin (AF), a traditional Chinese medicine, has shown exceptional therapeutic effects against pain and inflammation in various immune-related disorders. This study aimed to evaluate the protective effect of AF against sepsis-induced ALI in cecal ligation and puncture (CLP) mouse model, and investigate the associated mechanisms. Materials and methods: To demonstrate the protective effects of AF, lipopolysaccharide (LPS)-stimulated RAW264.7 cell line and CLP-induced sepsis were used as the in vitro and in vivo models, respectively. Cell Counting Kit (CCK)-8 assay was used to determine the cell viability of AF-treated RAW264.7 cells upon LPS challenge. The expression levels of pro-inflammatory cytokines and oxidative stress markers were evaluated by enzyme-linked immunosorbent assay (ELISA), Western blot analysis and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), including toll-like receptor (TLR)-4, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), phosphorylated nuclear factor-kappa B (p-NF-κB)/p65, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. Results: AF administration alleviated the inflammation and oxidative stress in the pulmonary tissues of mice with CLP-induced sepsis, as well as in LPS-stimulated RAW264.7 cells. The protective effect of AF could be attributed to the attenuation of TLR-4/NF-κB/p65 activation. AF treatment reduced TLR-4 expression and dampened NF-κB signaling. In LPS-stimulated RAW264.7 cells, TLR-4 overexpression abrogated the protective effects of AF. In the mouse mode, the protective effect of AF against sepsis-induced ALI was comparable to the treatment effect of dexamethasone (DEX). Conclusion: These findings suggest that AF could serve as a protective agent against sepsis-induced lung injury by inhibiting the TLR-4/NF-κB pathway.

Keywords

• Sepsis
• Acute lung injury
• Malondialdehyde
• Toll-like receptor (TLR)-4
• Nuclear factor-kappa B