Flavonoids as Cytokine Immunomodulators to Reduce Airway Inflammation via Inhibition of the NF‐κB Signalling Pathway: A Systematic Overview

Abstract

Asthma is a chronic inflammatory respiratory disease with increasing prevalence which has been linked to the interaction of genetic and environmental factors. Specific types of infections and environmental exposure, alongside a predisposed set of genes, can lead to a systemic propensity for allergic T‐helper (Th) type 2 cells to induce cytokine responses, resulting in allergic airway inflammation. The key event in the pathogenesis of asthma is infiltration of inflammatory cells into the airways and lungs, resulting in mucus hypersecretion and intermittent obstructive events. Cytokines play a vital role in the pathogenesis of immune responses and also have a complex mode of action in inflammatory processes. Peer‐reviewed articles investigating flavonoids with therapeutic evidence for the management of asthma were acquired from Pubmed, Embase, Scopus and Web of Science. We provide an extensive overview of the modulation of cytokines by flavonoids to assess how these natural products trigger immune responses, modulate immunity and lower airway inflammation. Seventeen flavonoids were reported as cytokine modulators of nuclear transcription factor kappa B (NF‐κB) signalling in the identified articles. These flavonoids predominantly modulated the release of the production and expressions of the pro‐ and anti‐inflammatory cytokines TNF‐α, IL‐1β, IL‐8, Th17 (IL‐17), Th1 (IFN‐γ, IL‐2 and IL‐12) and Th2 (IL‐4, IL‐5, IL‐6 and IL‐13), inhibited eosinophil infiltration and decreased the activity and expression of NF‐κB. Key Concepts Bronchial asthma is a chronic inflammatory airway syndrome which endangers human health. Corticosteroids and β2‐agonists are effective drugs for asthma; however, their prolonged use is associated with side effects such as drug tolerance, osteoporosis and immune suppression. Asthma increases the number of inflammatory cells such as eosinophils and lymphocytes in peripheral blood, bronchoalveolar lavage fluid (BALF) and lung tissue and immunoglobulin E (IgE). Flavonoids are plant‐derived active compounds reputed to have therapeutic potential. The use of flavonoids in experimentally induced asthma models is associated with lower levels of Th2 cytokines such as IL‐4, IL‐5, IL‐6 and IL‐13 and modulation of pro‐inflammatory cytokines such as TNF‐α, IL‐1β and IL‐8. Flavonoids generally inhibit pulmonary nuclear transcription factor kappa‐B (NF‐κB) or mitogen‐activated protein kinase (MAPK) signalling pathways and reduce airway inflammation in experimental models. Flavonoids reduce airway hyperresponsiveness, mucus cell hyperplasia and fixed airway flow obstruction. Flavonoids demonstrated significant in vitro and in vivo properties in animal models on homeostasis within the immune system and on the inflammatory response.