ABSTRACT
BACKGROUND: Acute lung injury (ALI) is characterized by acute pulmonary inflammatory infiltration. Alveolar epithelial cells (AECs) release numerous pro-inflammatory cytokines, which result in the pathological changes seen in ALI. Ophiopogonin D (OD), extracted from the roots of Ophiopogon japonicus (Thunb.) Ker Gawl. (Liliaceae), reduces inflammation; however, the efficacy of OD in ALI has not been reported and the underlying molecular mechanisms remain unclear. PURPOSE: This study investigated the anti-inflammatory effects of OD, as well as the underlying mechanisms, in AECs and a mouse ALI model. METHODS: Lipopolysaccharide (LPS) and tumor necrosis factor-α (TNF-α) were used to stimulate macrophages and A549 cells, and a mouse ALI model was established by intratracheal LPS administration. The anti-inflammatory effects and mechanisms of OD in the TNF-α-induced in vitro inflammation model was evaluated using real-time quantitative polymerase chain reaction qPCR), enzyme-linked immunosorbent assay (ELISA), western blotting, nuclear and cytoplasmic protein extraction, and immunofluorescence. The in vivo anti-inflammatory activity of OD was evaluated using hematoxylin and eosin staining, qPCR, ELISA, and western blotting. RESULTS: The bronchoalveolar lavage fluid and lung tissue of LPS-induced ALI mice exhibited increased TNF-α expression. TNF-α induced a significantly greater pro-inflammatory effect in AECs than LPS. OD reduced inflammation and mitogen-activated protein kinase (MAPK) and transcription factor p65 phosphorylation in vivo and in vitro and promoted signal transducer and activator of transcription 3 (STAT3) phosphorylation and A20 expression, thereby inducing apoptosis signal-regulating kinase 1 (ASK1) proteasomal degradation. CONCLUSION: OD exerts an anti-inflammatory effect by promoting STAT3-dependent A20 expression and ASK1 degradation. OD may therefore have therapeutic value in treating ALI and other TNF-α-related inflammatory diseases.
Subject(s)
Acute Lung Injury , Anti-Inflammatory Agents , Lipopolysaccharides , STAT3 Transcription Factor , Saponins , Spirostans , Acute Lung Injury/drug therapy , Acute Lung Injury/chemically induced , Animals , Saponins/pharmacology , Spirostans/pharmacology , Mice , STAT3 Transcription Factor/metabolism , Humans , Anti-Inflammatory Agents/pharmacology , Male , MAP Kinase Kinase Kinase 5/metabolism , A549 Cells , Disease Models, Animal , Tumor Necrosis Factor-alpha/metabolism , RAW 264.7 Cells , Mice, Inbred C57BL , Ophiopogon/chemistry , Inflammation/drug therapy , Alveolar Epithelial Cells/drug effects , Alveolar Epithelial Cells/metabolism , Signal Transduction/drug effects , Plant Roots/chemistryABSTRACT
The high toxicity and persistence of polychlorinated biphenyls (PCBs) in the environment require effective remediation of PCBs-contaminated soil. This study used polylactic acid (PLA) and polyethylene glycol 4000 (PEG-4000) to modify zero-valent iron nanoparticles (nZVI) and conducted characterization analysis. It was found that when the addition amount of PLA was 2 %, the dispersion of modified nZVI was better. The initial pH and water to soil ratio were subjected to single factor experiments and fitted using RSM response surface methodology. The optimal reaction conditions were obtained as follows: the addition amount was 84 g·kg-1, the initial pH was 5.41, and the optimal removal rate was 74 % when the ratio of water to soil was 1.8:1. PLA and PEG-4000 were biodegradable substances that played crucial roles in enhancing the effectiveness of nZVI for PCBs-contaminated soil. By encapsulating nZVI with PLA, we significantly reduced its oxidation when exposed to air. Additionally, the inclusion of PEG-4000 helped prevent the particles from clumping together. The synergistic effect of them increased the effective reaction of nZVI and PCBs and ultimately leading to more efficient remediation. This study offered a new pathway for the efficient green remediation of PCBs-contaminated soil.
