Effect of diosmetin on airway remodeling in a murine model of chronic asthma

Bronchial asthma, one of the most common allergic diseases, is characterized by airway hyperre- sponsiveness （AHR）, inflammation, and remodeling. The anti-oxidant flavone aglycone diosmetin ameliorates the inflammation in pancreatitis, but little is known about its impact on asthma. In this study, the effects of diosmetin on chronic asthma were investigated with an emphasis on the modu- lation of airway remodeling in BALB/c mice challenged with ovalbumin （OVA）. It was found that diosmetin significantly relieved inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition in the lungs of asthmatic mice and notably reduced AHR in these animals. The OVA- induced increases in total cell and eosinophil counts in bronchoalveolar lavage fluid were reversed, and the level of OVA-specific immunoglobulin E in serum was attenuated by diosmetin administra- tion, implying an anti-Th2 activity of diosmetin. Furthermore, diosmetin remarkably suppressed the expression of smooth muscle actin alpha chain, indicating a potent anti-proliferative effect of dios- metin on airway smooth muscle cells （ASMCs）. Matrix metallopeptidase-9, transforming growth fac- tor-β1, and vascular endothelial growth factor levels were also alleviated by diosmetin, suggesting that the remission of airway remodeling might be attributed to the decline of these proteins. Taken together, our findings provided a novel profile of diosmetin with anti-remodeling therapeutic bene- fits, highlighting a new potential of diosmetin in remitting the ASMC proliferation in chronic asthma.