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Acteoside has been reported to have antioxidant and neuroprotective effect, which is a promising therapeutic way in prevention and treatment of Parkinson's disease. The present study was aimed to understand the neuroprotective effect of acteoside and to elucidate its underlying mechanism. 6-hydroxydopamine (6-OHDA)-induced neural damage in zebrafish model was used to study the protective effect of acteoside on Parkinson's disease (PD). Locomotion behavioral test showed that acteoside could prevent 6-OHDA-stimulated movement disorders. Anti-tyrosine hydroxylase (TH) whole-mount immunostaining analysis showed that acteoside could prevent 6-OHDA-induced dopaminergic neuron death. In addition, pretreatment with acteoside could upregulate antioxidative enzymes by activating the Nrf2/ARE signaling pathway in zebrafish. Meanwhile, acteoside was found to be distributed in the brain after intraperitoneal injection into the adult zebrafish, indicating that this compound could penetrate the blood-brain-barrier (BBB). This study demonstrated that acteoside could penetrate BBB and have potential therapeutic value for PD by activating the Nrf2/ARE signaling pathway and attenuating the oxidative stress. [ABSTRACT FROM AUTHOR]

Various phytochemicals have been reported to protect against oxidative stress. However, the mechanism underlying has not been systematically evaluated, which limited their application in disease treatment. Nuclear factor erythroid 2−related factor 2 (Nrf2), a central transcription factor in oxidative stress response related to numerous diseases, is activated after dissociating from the cytoskeleton−anchored Kelch−like ECH−associated protein 1 (Keap1). The Keap1–Nrf2 protein–protein interaction has become an important drug target. This study was designed to clarify whether antioxidantive phytochemicals inhibit the Keap1–Nrf2 protein–protein interaction and activate the Nrf2-ARE signaling pathway efficiently. Molecular docking and 3D−QSAR were applied to evaluate the interaction effects between 178 antioxidant phytochemicals and the Nrf2 binding site in Keap1. The Nrf2 activation effect was tested on a H 2 O 2 −induced oxidative−injured cell model. Results showed that the 178 phytochemicals could be divided into high−, medium−, and low−total−score groups depending on their binding affinity with Keap1, and the high−total−score group consisted of 24 compounds with abundant oxygen or glycosides. Meanwhile, these compounds could bind with key amino acids in the structure of the Keap1−Nrf2 interface. Compounds from high−total−score group show effective activation effects on Nrf2. In conclusion, phytochemicals showed high binding affinity with Keap1 are promising new Nrf2 activators. • 178 phytochemicals were collected and the Keap1-binding-affinity was estimated. • 24 compounds with high Keap1-binding-affinity was obtained. • Compounds with high Keap1-binding-affinity effectively activated Nrf2. [ABSTRACT FROM AUTHOR]