Evodileptin B (1) is a natural anthranilate derivative isolated from the ethanol extract of the aerial parts of Evodia lepta (Spreng.) Merr., a traditional medicinal plant of the family Rutaceae. We readily synthesized 1 via the amidation of phloretic with methyl anthranilate and evaluate its neuroprotective activity using a C. elegans Parkinson's disease (PD) model. The results showed that evodilpetin B ameliorated MPP+ -induced dopaminergic (DA) neurodegeneration in a dose-dependent manner. Evodileptin B treatment also significantly improved the DA neurotransmission-related behavioral defects such as reduced locomotory and food-sensing ability of worms under MPP+ exposure conditions, suggesting its potential application for the functional restoration of DA neurons. In addition, we found that 1 has an ability to regulate aggregation of α-synuclein by increasing proteasome activity in the human α-synuclein-expressing mutant worms. These results demonstrate that evodileptin B has strong neuroprotective properties and may be useful in the treatment of PD.
Keywords: C. elegans; Parkinson's disease; anthranilate; dopaminergic neuroprotection; evodileptin B.
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