Resveratrol has protective effects against airway remodeling and airway hyperreactivity in a murine model of allergic airways disease

Abstract

BackgroundNew therapies for asthma which can address three main interrelated features of the disease, airway inflammation, airway remodeling and airway hyperreactivity, are urgently required. Resveratrol, a well known red wine polyphenol has received much attention due to its potential anti-aging properties. This compound is an agonist of silent information regulator two histone deacetylases and has many effects that are relevant to key aspects of the pathophysiology of asthma including inflammation, cell proliferation and fibrosis. Therefore, resveratrol may offer a novel asthma therapy that simultaneously inhibits airway inflammation, and airway remodeling which are the main contributors to airway hyperreactivity and irreversible lung function loss.MethodsWe evaluated the effects of systemic resveratrol treatment in a murine model of chronic allergic airways disease which displays most of the clinicopathological features of severe human asthma. Wild-type Balb/c mice with allergic airways disease were treated with 12.5 mg/kg resveratrol or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and histological examination of lung tissue sections. Further, remodeling was assessed by morphometric analysis and lung function was assessed by invasive plethysmography measurement of airway resistance and dynamic compliance.ResultsMice treated with resveratrol exhibited reduced tissue inflammation as compared to vehicle treated mice (p<0.05). Additionally, resveratrol treatment resulted in reduced subepithelial collagen deposition as compared to vehicle treated mice (p<0.05) and attenuated airway hyperreactivity (p<0.05).ConclusionsThese novel findings demonstrate that treatment with resveratrol can reduce structural airway remodeling changes and hyperreactivity. This has important implications for the development of new therapeutic approaches to asthma.

Inhibition of airway epithelial-to-mesenchymal transition and fibrosis by kaempferol in endotoxin-induced epithelial cells and ovalbumin-sensitized mice

“…[1][2][3] The polyphenol resveratrol reduces subepithelial collagen deposition with concomitant airway hyper-reactivity. 23 A cyclic terpene limonene found in lemon and other citrus fruits inhibits airway smooth muscle thickness and goblet cell and smooth muscle metaplasia in dermatophagoides farinae-treated mice. 24 Administration of Skullcapflavone II suppresses subepithelial collagen deposition and goblet cell hyperplasia by acting on TGFb1/Smad signaling pathways.…”

“…22 Resveratrol present in red wine reduces subepithelial collagen deposition and attenuates airway hyperreactivity. 23 In addition, goblet cell metaplasias, thickness of airway smooth muscle, airway fibrosis and AHR to acetylcholine were markedly abrogated in limonene-treated mice. 24 However, the inhibitory effects of kaempferol on airway fibrosis are not well defined.…”

Targeting extracellular matrix remodeling in disease: Could resveratrol be a potential candidate?

“…60 Similar observations were made on animals models of hepatic fibrosis, 22,23 enterocolitis, 25 allergic airways disease 30 and in MCF-7/TR cells. 61 TGF-b is also a potent inducer of the differentiation of fibroblasts to myofibroblasts, which are an important source of ECM proteins.…”

Managing the Adaptive Proteostatic Landscape: Restoring Resilience in Alpha-1 Antitrypsin Deficiency

“…In contrast, SIRT1 has been found to protect against emphysema by deacetylation of the FOXO3 transcription factor [ 272 ]. Consistent with these results, the SIRT1 activator resveratrol [ 262 ] and SRT1720 [ 273 ] were shown to alleviate lung infl ammation.…”