![]() ![]() Compared with the nomifensine (Nomi) treatment, Th A had a more potent protective effect on 6-OHDA-induced ferroptosis during PD pathology in zebrafish, which was associated with assuaging the reduction of the total swimming distance, glutathione (GSH) depletion, iron accumulation, lipid peroxidation, and aggregation of α-synuclein (α-syn). Th A treatment significantly facilitated the nuclear factor erythroid 2-like 2 (Nrf2) nuclear translocation and subsequently increased the heme oxygenase-1 (HO-1) protein level through inhibiting the protein–protein interaction (PPI) of Keap1 and Nrf2. ![]() The results of molecular docking and other binding assays collectively demonstrated that Th A can strongly target the Kelch domain of Keap1. This work aims to explore the neuroprotective effect and mechanism of thonningianin A (Th A), a polyphenolic compound in natural plant foods, against 6-hydroxydopamine (6-OHDA)-induced ferroptosis in dopaminergic cells. Besides, polyphenols have been proven to be effective in preventing the death of dopaminergic neurons. Previous studies demonstrated that ferroptosis is implicated in the death of dopaminergic neurons. The death of dopaminergic neurons is a dominant factor during the occurrence and development of Parkinson's disease (PD). ![]()
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