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

Abstract

Bronchial asthma, one of the most common allergic diseases, is characterized by airway hyperresponsiveness (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 modulation 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 OVAinduced 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 administration, 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 diosmetin on airway smooth muscle cells (ASMCs). Matrix metallopeptidase-9, transforming growth factor-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 benefits, highlighting a new potential of diosmetin in remitting the ASMC proliferation in chronic asthma.

Role of Estrogen Receptors α and β in a Murine Model of Asthma: Exacerbated Airway Hyperresponsiveness and Remodeling in ERβ Knockout Mice

“…Estimation of total and differential leukocyte count (DLC) in BALF was performed following previously published methods (Thompson et al, 1996;Raju et al, 2014;Ge et al, 2015;Ambhore et al, 2019a;Kalidhindi et al, 2019a). BALF was centrifuged at 2000 rpm for 5 min at 4°C and the supernatant was discarded.…”

Fatty Acid Binding to Human Serum Albumin in Blood Serum Characterized by EPR Spectroscopy

“…Although other labeling positions along the methylene-backbone of the stearic acid are available and could be used, it is shown that 16-DSA displays the widest difference in spectral parameters (hyperfine coupling and correlation time as described upon binding to Bovine Serum Albumin (BSA)). [17,18] The vast majority of our studies (and other reports in literature) specifically study HSA and BSA in in vitro situations (mostly buffered solutions). With the exception of a few studies that used empirical spectral parameters [8,9,19,20] to analyze paramagnetic FA binding to HSA in actual blood samples, no systematic understanding of the effects, differences, possibilities and caveats for albumin studies that ensue when one exposes FA ligands to HSA (and all other proteins and small molecules contained in blood plasma) has been achieved.…”

Regioselective Glucuronidation of Diosmetin and Chrysoeriol by the Interplay of Glucuronidation and Transport in UGT1A9-Overexpressing HeLa Cells

“…These isomers have been shown to exhibit common biological effects, such as osteoporosis prevention [5]. Diosmetin is an active ingredient of some medications [6] and has been reported to display several biological properties, including anticancer effects [7,8] and antibacterial actions [9] - . Similar to diosmetin, chrysoeriol is mainly distributed in many plant products, such as parsley [10] and peanut hull [11].…”