title: Ankaflavin, a novel Nrf-2 activator for attenuating allergic airway inflammation.
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.
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei, 10617, Taiwan.
authors.forename: Wei-Hsuan
authors.initials: WH
authors.lastname: Hsu
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Lee
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Huang
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Hsu
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Pan
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005415:Flavins / Q000494:pharmacology* / Q000627:therapeutic use; D015870:Gene Expression / Q000187:drug effects; D055785:Gene Knockdown Techniques; D020397:Goblet Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology; D021381:Protein Transport / Q000187:drug effects; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D015815:Cell Adhesion Molecules; D005415:Flavins; D007378:Interleukins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C499916:ankaflavin; D010047:Ovalbumin