Theaflavin ameliorates ionizing radiation-induced hematopoietic injury via the NRF2 pathway

Ionizing radiation (IR) increases reactive oxygen species (ROS) levels in hematopoietic stem cells (HSCs) and the oxidative stress induces DNA damage, resulting in an increase in p16Ink4a expression. Theaflavin (TF) inhibits ROS production and DNA damage, and down-regulates p16Ink4a expression in HSCs. TF promotes NRF2 transportation into nucleus where it binds to the antioxidant response element (ARE), leading to the transcriptional activation of hemeoxygenase 1 (HO1), NAD (P) H: quinine oxidoreductase 1 (NQO1) and superoxide dismutase-2 (SOD2). The up-regulation of these antioxidant enzymes reduces the oxidative stress in HSCs. Consequently, TF ameliorates IR-induced hematopoietic injury of wild-type mice by increasing HSC reserve and reconstitution, and inhibiting skewed differentiation of HSCs and HSC senescence.262