Abstract
Medicinal plants and their derived compounds have received increasing attention as adjuvant therapies in the treatment of Parkinson's disease (PD). Syzygium cumini (L.) Skeels has been used in Vietnamese folk medicine to improve neurological disorders, its antineurodegenerative potential remains largely underexplored. This study aimed to investigate the effect of S. cumini leaf phenolic-rich crude extract (SCLE) in a PD phenotype model and the possible active mechanisms of phenolic compounds. The SCLE was investigated for in vitro antioxidant activity and chemical composition by UHPLC-Q-TOF-MS/MS analysis. A Drosophila ubiquitin carboxyl-terminal hydrolase (dUCH)-knockdown Drosophila model of PD was established to examine therapeutic potential of SCLE in vivo. The possible mechanisms of SCLE phenolic compounds targeting PD-relevant molecular targets were explored by in silico study. The SCLE had strong antioxidant activity with IC50 values in DPPH, ABTS, reducing power, and lipid peroxidation assays of 14.83, 13.83, 16.39, and 17.90 μg/mL, respectively. The SCLE (1.0 or 2.0 mg/mL) could significantly ameliorate locomotor ability and reduced the degeneration of dopaminergic neurons in dUCH-knockdown-induced larval or adult Drosophila. Also, the SCLE was considered safe in flies and mice. The UHPLC-Q-TOF-MS/MS analysis revealed that phenolic compounds were major components of SCLE and molecular docking analysis suggested dopaminergic neurons protection, dopamine degradation prevention, and dopaminergic receptors activation are possible mechanisms for it therapeutic effect. The study outcomes suggested that the SCLE and phenolic compounds might have the potential to improve PD. This study would lay a foundation for further research to elucidate the mechanisms of SCLE's phenolic compounds in PD treatment.
