Butein, isoliquiritigenin, and scopoletin attenuate neurodegeneration via antioxidant enzymes and SIRT1/ADAM10 signaling pathway

Neuronal cell death is a key feature of neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Plant polyphenols, namely butein, isoliquiritigenin, and scopoletin, have been shown to exhibit various biological activities including anti-inflammatory, antimicrobial, and antioxidant activities. Herein, butein, isoliquiritigenin, and scopoletin were explored for their neuroprotective properties against oxidative stress-induced human dopaminergic SH-SY5Y cell death. The cells exposed to hydrogen peroxide (H(2)O(2)) revealed a reduction in cell viability and increases in apoptosis and levels of reactive oxygen species (ROS). Interestingly, pretreatment of SH-SY5Y cells with 5 μM of butein, isoliquiritigenin, or scopoletin protected against the cell death induced by H(2)O(2), and decreased the levels of apoptotic cells and ROS. In addition, the levels of SIRT1, FoxO3a, ADAM10, BCL-2, and antioxidant enzymes (catalase and SOD2) were maintained in the cells pretreated with butein, isoliquiritigenin, or scopoletin before H(2)O(2) treatment compared to cells without pretreatment and the reference (resveratrol). Molecular docking analysis revealed that the interactions between the activator-binding sites of SIRT1 and the phenolic compounds were similar to those of resveratrol. Taken together, the data suggest that these polyphenolic compounds could be potential candidates for prevention and/or treatment of neurodegeneration.