Ankaflavin, a novel Nrf-2 activator for attenuating allergic airway inflammation

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. (C) 2012 Elsevier Inc. All rights reserved.