Unravelling the role of neuroactive small molecule interactions in oxidopamine induced Parkinsonism in zebrafish

Abstract

Parkinson s disease (PD) is a widely occurring newlineneurodegenerative disease. Although the clinical manifestations and newlineaetiology of the disease has been widely studied, there is still a lack of newlineunderstanding about the complexity of the disease. This very complexity newlinemakes it difficult for the existing drugs to fully treat the disease and curb newlineits progression. This study aimed at understanding the underlying newlinemechanisms and interactions in Parkinson s and evaluate the potential of newlineselected compounds against multiple targets in the neurodegenerative newlinecondition in a zebrafish model. newlineFirst, we selected naringenin (NAR), hesperidin (HES), and newlineTephrosia purpurea extract (TPE) to evaluate their potential against newlineParkinsonism. Oxidopamine (6-OHDA) was used for inducing newlineParkinsonian-like conditions. An in vitro model using SH-SY5Y cells newlinewas established; the activity of catalase, superoxide dismutase, and newlineglutathione were measured. 6-OHDA significantly reduced the levels of newlinethese enzymes indicative oxidative damage. Furthermore, the increased newlinelevel of reactive oxygen species (ROS) and the depleted potential of the newlinemitochondria in the 6-OHDA-treated cells confirmed oxidative stress newlinedamage. Treatment with NAR, HES, and TPE significantly alleviated newlineoxidative stress damages. The positive control levodopa (L-DOPA) also newlinereduced the oxidative stress. newlineFollowing the in vitro studies, a Parkinsonian model was newlineinduced in zebrafish larvae using 6-OHDA. Behavioral and locomotion newlineviii newlineassessment showed that 6-OHDA treated fish exhibited locomotor newlineimpairments and reduced swimming. Treatment with NAR, HES, and newlineTPE improved the locomotor and swimming pattern of the embryos. newlineLastly, the molecular expressions of genes involved in PD newlinewere studied in the zebrafish model. The expression of casp3a and newlinecasp9, which are involved in the intrinsic apoptosis pathway,