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

Abstract

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 (H₂O₂) 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 H₂O₂, 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 H₂O₂ 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.