Atractylenolide II prevents radiation damage via MAPKp38/Nrf2 signaling pathway

Abstract Ionizing radiation (IR) can act as a negative factor for human homeostasis, by causing and even aggravating a series of pathological conditions. To protect the intactness of normal tissues, effective anti-radiation drugs are urgently needed for alleviating the outcomes of radioactive damage. In this study, we demonstrate that atractylenolide II (ATR II), a sesquiterpenoid monomer extracted from traditional Chinese medicine atractylodes macrocephala, can markedly suppress IR damage by promoting the expression of antioxidant factors heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone oxido-reductase 1 (NQO-1), which are mediated by nuclear factor-erythroid 2-like 2 (Nrf2) signaling pathway. Furthermore, here we reveal that ATR II effectively upregulates the expression of mitogen-activated protein kinase p38 (MAPKp38), which also acts as a regulator of Nrf2 signaling cascade. Indeed, treatment with a MAPKp38 inhibitor can significantly downregulate the expression of Nrf2 and its downstream target genes HO-1 and NQO-1 and, consequently, abolish the protective effect of ATR II against IR. Consistently, ATR II also has a protective function against IR-induced damage in animal models. In conclusion, our study provides an unexpected function of ATR II in preventing IR-induced damage by modulating MAPKp38/Nrf2 signaling pathway.