Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model

Abstract

BACKGROUND AND PURPOSEAsthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice. EXPERIMENTAL APPROACHMale BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg -1 per mice) or dexamethasone (5 mg kg -1 per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-a, IFN-g and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry. KEY RESULTSWe have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation. CONCLUSIONS AND IMPLICATIONSThese results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma. Abbreviations

Structure-Activity Association of Flavonoids in Lung Diseases

“…The anti-inflammatory effects of phenolic compounds are related to the ability in modulating the expression of pro-inflammatory genes, such as NOS, cyclooxygenase, lipoxygenase but also by acting throughout nuclear factor (NF-κB) signaling and mitogen-activated protein kinase [57,58] and activating the Nrf2/Keap1 pathway [59]. NF-κB has been reported as one of the most notable pro-inflammatory gene expression regulators and mediates several cytokines synthesis, such as TNF-α, IL-1β, IL-6, and IL-8 as well as COX-2 [60].…”

“…Finally, due to the anti-inflammatory potential and antioxidant activity of sakuranetin (11) [124], our research group recently tested the effects of this flavonoid in models of lung disease [58]. We showed that sakuranetin (11) has a great potential to treat asthma since it reduced eosinophilic inflammation and reversed lung remodeling in mice.…”

“…Lung Effect Reference Naringin (1) Anti-ARDS [104] Kaempferol (12) Anti-allergic Anti-ARDS Anti-asthmathic [35,109,110] [100] [101] (11) Anti-asthmathic and COPD [58,125] …”

Prunus yedoensis Bark Inhibits Lipopolysaccharide-Induced Inflammatory Cytokine Synthesis by IκBα Degradation and MAPK Activation in Macrophages

“…19 Sakuranetin showed anti-inflammatoy activity in an experimental asthma model in vivo via control of NF-jB activation. 20 Amygdalin, a cynogenic compound, occurs in several species of the Prunus genus. The presence of amygdalin may account for the cytotoxicity observed in PYE.…”

Efeito do tratamento com PNU-282987, agonista do receptor colinérgico nicotínico alfa7, na resposta inflamatória e de remodelamento brônquico em modelo experimental de asma

“…Considerando que não houve diferença entre o comprimento da membrana basal entre os grupos estudados, a área de edema, músculo liso e epitélio interesse foi determinada pela contagem do número de pontos que coincidia com esta área, no aumento de 400x, sem necessidade de correções (174) . Foram avaliadas 5 vias aéreas selecionadas aleatoriamente por animal de cada grupo e o resultado expresso em área em µm 2 .…”