Ankaflavin, a novel Nrf-2 activator for attenuating allergic airway inflammation
Journal
Free Radical Biology and Medicine
Journal Volume
53
Journal Issue
9
Pages
1643-1651
Date Issued
2012
Author(s)
Abstract
The role of inflammation-induced oxidative stress in the pathogenesis and progression of chronic inflammatory airways diseases has received increasing attention in recent years. Nuclear factor-erythroid 2 related factor 2 (Nrf-2) is the primary transcription factor that regulates the expression of antioxidant and detoxifying enzymes. In this study, yellow pigment ankaflavin (AK), derived from Monascus-fermented products, elevated nuclear Nrf-2 protein translocation in both the A549 lung cell line and the lungs of ovalbumin (OVA)-challenged mice. Furthermore, AK increased the mRNA expression of antioxidant enzymes regulated by Nrf-2, leading to a reduction in allergen-driven airway inflammation, mucus cell hyperplasia, and eosinophilia in OVA-challenged mice. Additionally, AK prevented T-cell infiltration and Th2 cytokines including interleukin (IL)-4, IL-5, and IL-13 generation in bronchial alveolar lavage fluid. The adhesion molecules ICAM-1, VCAM-1, and eotaxin were substantially reduced by AK treatment. Importantly, the inhibitory effect of AK on adhesion molecule production and immune cell infiltration was abolished by Nrf-2 small interfering RNA. This is the first study to illustrate that AK acts as a novel Nrf-2 activator for modulating the oxidative stress pathway to improve the lung injury and ameliorate the development of airway inflammation. ? 2012 Elsevier Inc. All rights reserved.
Subjects
Airway inflammation; Ankaflavin; Antioxidant; Nrf-2; Oxidative stress
SDGs
Other Subjects
ankaflavin; eotaxin; glyceraldehyde 3 phosphate dehydrogenase; heme oxygenase 1; intercellular adhesion molecule 1; interleukin 13; interleukin 4; interleukin 5; lamin B; messenger RNA; natural product; ovalbumin; small interfering RNA; transcription factor Nrf2; unclassified drug; vascular cell adhesion molecule 1; allergic airway inflammation; animal experiment; animal model; animal tissue; article; cell hyperplasia; controlled study; cytokine production; disease course; eosinophilia; female; gene expression; human; human cell; immunocompetent cell; inflammation; inflammatory infiltrate; lung injury; lung lavage; lymphocytic infiltration; Monascus purpureus; mouse; nonhuman; oxidative stress; priority journal; protein localization; T lymphocyte; Th2 cell; Allergens; Animals; Anti-Inflammatory Agents; Antioxidants; Cell Adhesion Molecules; Cell Line, Tumor; Female; Flavins; Gene Expression; Gene Knockdown Techniques; Goblet Cells; Humans; Interleukins; Lung; Mice; Mice, Inbred BALB C; NF-E2-Related Factor 2; Ovalbumin; Protein Transport; Respiratory Hypersensitivity; Th2 Cells; Monascus; Mus
Type
journal article