Geraniin protects bone marrow-derived mesenchymal stem cells against hydrogen peroxide-induced cellular oxidative stress in vitro

摘要

Administration of bone marrow-derived mesenchymal stem cells (MSCs) has emerged as a potential therapeutic approach for the treatment of myocardial infarction (MI). However, the increase in reactive oxygen species (ROS) in ischemic cardiac tissue compromises the survival of transplanted MSCs, thus resulting in limited therapeutic efficiency. Therefore, strategies that attenuate oxidative stress-induced damage and enhance MSC viability are required. Geraniin has been reported to possess potent antioxidative activity and exert protective effects on numerous cell types under certain conditions. Therefore, geraniin may be considered a potential drug used to modulate MSC-based therapy for MI. In the present study, MSCs were pretreated with geraniin for 24 h and were exposed to hydrogen peroxide (H2O2) for 4 h. Cell apoptosis, intracellular ROS levels and mitochondrial membrane potential were measured using Annexin V-fluorescein isothiocyanate/propidium iodide staining, the 2,7-dichlorodihydrofluorescein diacetate fluorescent probe and the membrane permeable dye JC-1, respectively. Glutathione and malondialdehyde levels were also investigated. The expression levels of apoptosis-associated proteins and proteins of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway were analyzed by western blotting. The results demonstrated that geraniin could significantly attenuate H2O2-induced cell damage by promoting MSC survival, reducing cellular ROS production and maintaining mitochondrial function. Furthermore, geraniin modulated the expression levels of phosphorylated-Akt in a time- and dose-dependent manner. The cytoprotective effects of geraniin were suppressed by LY294002, a specific PI3K inhibitor. In conclusion, the present study revealed that geraniin protects MSCs from H2O2-induced oxidative stress injury via the PI3K/Akt pathway. These findings indicated that cotreatment of MSCs with geraniin may optimize therapeutic efficacy for the clinical treatment of MI.