Fraxin Alleviates LPS-Induced ARDS by Downregulating Inflammatory Responses and Oxidative Damages and Reducing Pulmonary Vascular Permeability.

Acute respiratory distress syndrome (ARDS) is a severe acute disease that threatens human health, and few drugs that can effectively treat this disease are available. Fraxin, one of the main active ingredients of Cortex Fraxini, a Chinese herbal medicine, has presented various pharmacological and biological activities. However, the effects of fraxin on ARDS have yet to be reported. In the present study, the protective effect of fraxin in lipopolysaccharide (LPS)-induced ARDS in a mouse model was analyzed. Results from the hematoxylin and eosin staining showed that fraxin might alleviate pathological changes in the lung tissues of mice with ARDS. ELISA and Western blot results revealed that fraxin might inhibit the production of inflammatory factors, namely, IL-6, TNF-α, and IL-1ß, and the activation of NF-κB and MAPK signaling pathways in the lungs. Thus, the inflammatory responses were reduced. Fraxin might inhibit the increase in reactive oxygen species (ROS) and malondialdehyde (MDA), a product of lipid peroxidation in lung tissues. Fraxin might increase the superoxide dismutase (SOD) activity to avoid oxidative damage. Vascular permeability was also assessed through Evans blue dye tissue extravasation and fluorescein isothiocyanate-labeled albumin (FITC-albumin) leakage. Fraxin might inhibit the increase in pulmonary vascular permeability and relieve pulmonary edema. Fraxin was also related to the inhibition of the increase in matrix metalloproteinase-9, which is a glycocalyx-degrading enzyme, and the relief of damages to the endothelial glycocalyx. Thus, fraxin elicited protective effects on mice with LPS-induced ARDS and might be used as a drug to cure ARDS induced by Gram-negative bacterial infection.

Berberine alleviates endothelial glycocalyx degradation and promotes glycocalyx restoration in LPS-induced ARDS.

In the pathogenesis of acute respiratory distress syndrome (ARDS), an increase in vascular endothelial permeability may trigger pulmonary edema and ultimately lead to respiratory failure. Endothelial glycocalyx damage is an important factor that causes an increase in vascular endothelial permeability. Berberine (BBR) is an isoquinoline alkaloid extracted from Coptis chinensis, a plant used in traditional Chinese medicine that exerts multiple pharmacological effects. In this study, pretreatment with BBR inhibited the increase in vascular endothelial permeability in mice with lipopolysaccharide (LPS)-induced ARDS. BBR pretreatment inhibited the shedding of syndecan-1 (SDC-1) and heparan sulfate (HS), which are important components of the endothelial glycocalyx that lessen endothelial glycocalyx damage. BBR further significantly inhibited increases in important endothelial glycocalyx damage factors, including reactive oxygen species (ROS), heparanase (HPA), and matrix metalloproteinase 9 (MMP9) in LPS-induced ARDS mice and in LPS-stimulated human umbilical vein endothelial cells. BBR pretreatment also decreased the production of pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and inhibited NF-κB signaling pathway activation in LPS-induced ARDS. In addition, BBR promoted the recovery of SDC-1 and HS content in injured endothelial glycocalyx after LPS treatment and accelerated its restoration. This is the first report of BBR maintaining the integrity of endothelial glycocalyx. These results provide a new theoretical basis for the use of BBR in the treatment of ARDS and other diseases related to endothelial glycocalyx damage.