Picrasma quassiodes (D. Don) Benn. attenuates lipopolysaccharide (LPS)-induced acute lung injury

Abstract

Picrasma quassiodes (D.Don) Benn. (PQ) is a medicinal herb belonging to the family Simaroubaceae and is used as a traditional herbal remedy for various diseases. In this study, we evaluated the effects of PQ on airway inflammation using a mouse model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) and LPS-stimulated raw 264.7 cells. ALI was induced in C57BL/6 mice by the intranasal administration of LPS, and PQ was administered orally 3 days prior to exposure to LPS. Treatment with PQ significantly attenuated the infiltration of inflammatory cells in the bronchoalveolar lavage fluid (BALF). PQ also decreased the production of reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 in BALF. In addition, PQ inhibited airway inflammation by reducing the expression of inducible nitric oxide synthase (iNOS) and by increasing the expression of heme oxygenase-1 (HO-1) in the lungs. Furthermore, we demonstrated that PQ blocked the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in the lungs of mice with LPS-induced ALI. In the LPS-stimulated RAW 264.7 cells, PQ inhibited the release of pro-inflammatory cytokines and increased the mRNA expression of monocyte chemoattractant protein-1 (MCP-1). Treatment with PQ decreased the translocation of nuclear factor (NF)-κB to the nucleus, and increased the nuclear translocation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of HO-1. PQ also inhibited the activation of p38 in the LPS-stimulated RAW 264.7 cells. Taken together, our findings demonstrate that PQ exerts anti-inflammatory effects against LPS-induced ALI, and that these effects are associated with the modulation of iNOS, HO-1, NF-κB and MAPK signaling. Therefore, we suggest that PQ has therapeutic potential for use in the treatment of ALI.

Peroxisome proliferator‐activated receptor gamma coactivator‐1α/HSF1 axis effectively alleviates lipopolysaccharide‐induced acute lung injury via suppressing oxidative stress and inflammatory response

“…Macrophage activation induced by endotoxin leads to the overproduction of inflammatory cytokines, such as IL‐6 and TNF‐α, which are important factors in the pathogenesis of ALI . Based on the above result, we further elucidated whether PGC1α has an anti‐inflammatory effects in LPS‐stimulated RAW264.7 macrophages.…”

“…Oxidative stress is caused by an imbalance between oxidation and anti‐oxidation systems. When neutrophils are activated, they release oxidants and proteases that damage the lungs . ROS play a major pathogenic role in a many human diseases.…”

Mesenchymal Stem Cells Modified with Heme Oxygenase-1 Have Enhanced Paracrine Function and Attenuate Lipopolysaccharide-Induced Inflammatory and Oxidative Damage in Pulmonary Microvascular Endothelial Cells

“…HO-1 activity restores homeostasis and implements cytoprotective defense functions in many pathologic states by the anti-oxidant activity of biliverdin and its metabolite, bilirubin, as well as the anti-inflammatory effects of carbon monoxide (CO) [25,26]. Accumulated research has demonstrated that HO-1 upregulation protects against endotoxin shock and allograft rejection, and attenuates hyperoxia and post-liver transplantation ALI [24,[26][27][28]. Further, HO-1 deficiency is related to a chronic inflammatory state and increased leukocyte recruitment in HO-1 gene-deficient mice [29,30].…”

“…Heme oxygenase-1 (HO-1) is an inducible stress protein that responds to multiple stressors, including hypoxia, hyperoxia, acidosis, shear stress, and reactive oxygen species [24]. HO-1 activity restores homeostasis and implements cytoprotective defense functions in many pathologic states by the anti-oxidant activity of biliverdin and its metabolite, bilirubin, as well as the anti-inflammatory effects of carbon monoxide (CO) [25,26].…”

Physalis peruviana L. inhibits airway inflammation induced by cigarette smoke and lipopolysaccharide through inhibition of extracellular signal-regulated kinase and induction of heme oxygenase-1

“…Measurement of ROS and pro-inflammatory cytokines in the BALF. The intracellular levels of ROS were determined using 2',7'-dichlorofluorescein diacetate (DCF-DA; Sigma-Aldrich, St. Louis, MO, USA) as previously described (21). Briefly, BALF cells were washed with PBS and incubated with 20 µM DCF-DA for 10 min at 37˚C.…”