Diosmetin alleviates acute lung injury caused by lipopolysaccharide by targeting barrier function

AbstractAcute lung injury (ALI) is an acute and devastating disease caused by systemic inflammation e.g. patients infected with bacteria and viruses such as SARS-CoV-2 have an unacceptably high mortality rate. It has been well documented that endothelial cell damage and repair play a central role in the pathogenesis of ALI because of its barrier function. Nevertheless, the leading compounds that effectively accelerate endothelial cell repair and improve barrier dysfunction in ALI are largely unknown. In the present study, we found that diosmetin had promising characteristics to inhibit the inflammatory response and accelerate the repair of endothelial cells. Our results indicated that diosmetin accelerated wound healing and barrier repair by improving the expression of the barrier-related proteins, including zonula occludens-l (ZO-1) and occludin, in human umbilical vein endothelial cells (HUVECs) treated with lipopolysaccharide (LPS). Meanwhile, diosmetin administration significantly inhibited inflammatory response by decreasing the content of TNF α and IL-6 in the serum, alleviated lung injury by reducing lung wet/dry (W/D) ratio and histologic score, improved endothelial hyperpermeability by decreasing protein levels and neutrophil infiltration in the bronchoalveolar lavage fluid (BALF) and increasing ZO-1 and occludin expression in the lu ng tissues of LPS-treated mice. Mechanistically, diosmetin also mediated the expression of Rho A and ROCK1/2 in HUVECs treated with LP...
Source: Inflammopharmacology - Category: Drugs & Pharmacology Source Type: research