Protective Effects of Glabridin against Cytotoxicity and Oxidative Stress Induced by Doxorubicin in PC12 Cells

This study was aimed at investigating effects of glabridin (Glab) isolated from Glycyrrhiza glabra (G. glabra) against cytotoxicity and oxidative stress induced by Doxorubicin (Dox), a chemotherapeutic agent with neurotoxic side effects, in PC12 cells. Glab was obtained from ethyl acetate extract of licorice roots by using solid phase extraction (SPE) and preparative HPLC. To evaluate whether Glab protects PC12 cells from Dox-induced cytotoxicity, we examined the direct cytotoxic effect of Dox on PC12 cells in the presence and absence of Glab at different time interval. Dox-induced cytotoxicity in a concentration-dependent manner. The IC50 value was 20.1 𝜇M for 24 h exposure. However, 24 h pretreatment of cells with Glab protected cells from Dox-induced cytotoxicity. For evaluation of the effect of Glab on Dox-induced oxidative stress, the generation of reactive oxygen species (ROS) and also the glutathione (GSH) level were assayed. Adding Dox to PC12 cells caused a significant increase in ROS level (164%). Pretreatment with Glab (2.5μM) decreased significantly intracellular ROS levels to 86±4.3% in PC12 cells. Moreover, Dox decreased the GSH level by more than 40% of the control. Pretreatment with 2.5 and 5 μM of Glab increased significantly the GSH level to 77±3.3% and 86±3.8%, respectively. Taken together our observation indicated that Glab has the protective effect against cytotoxicity induced by Dox in the PC12 cells. The results highlighted that Glab may exert neuroprotective effects through its antioxidant actions.