Isoliquiritigenin attenuates emodin-induced hepatotoxicity in vivo and in vitro through Nrf2 pathway

Abstract

Emodin (EMO), the main bioactive component of Polygonum multiflorum, Rheum palmatum, Aloe vera and Cassia acutifolia, can cause severe hepatotoxicity. Isoliquiritigenin (ISL), a flavonoid compound from the Glycyrrhiza, has been reported to be the most potent antioxidant response element (ARE)-luciferase inducer among the main components of licorice. But the protective effect and underlying mechanism of ISL on liver injury induced by EMO has not been reported. This study aims to explore the role of nuclear transcription factor 2 (Nrf2) in EMO-induced hepatotoxicity and the protective effect of ISL. EMO treatment caused cytotoxicity in L-02 cells. Combined treatment of EMO with ISL effectively reversed changes in cell viability, reduced reactive oxygen species (ROS) generation and malondialdehyde (MDA) generation, enhanced the levels of glutathione (GSH) and super oxide dismutase (SOD) induced by EMO in L-02 cells. Furthermore, ISL could also phosphorylate mitogen-activated protein kinases (MAPKs) and up-regulate Kelth-like ECH-associated protein (Keap1). The pathways of MAPKs and Keap1 lead to the separation of Keap1 and Nrf2. Free Nrf2 transferred to the nucleus and enhanced the expression of phase II detoxification enzymes. In conclusion, our results are the first to highlight the beneficial role and relevant mechanisms of ISL in EMO-induced liver injury and provide novel insight into its application.