Acteoside exerts neuroprotection effects in the model of Parkinson's disease via inducing autophagy: Network pharmacology and experimental study

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. At present, the incidence rate of PD is increasing worldwide, there is no effective cure available so far, and currently using drugs are still limited in efficacy due to serious side effects. Acteoside (ACT) is an active ingredient of many valuable medicinal plants, possesses potential therapeutic effects on many pathological conditions. In this study, we dissected the neuroprotection effects of ACT on PD and its potential molecular mechanism in our PD model pathology based on network pharmacology prediction and experimental assays. Network pharmacology and bioinformatics analysis demonstrated that ACT has 381 potential targets; among them 78 putative targets associated with PD were closely related to cellular autophagy and apoptotic processes. Our experimental results showed that ACT exerted significant neuroprotection effects on Rotenone (ROT) -induced injury of neuronal cells and Drosophila melanogaster (D. melanogaster). Meanwhile, ACT treatment induced autophagy in both neuronal cell lines and fat bodies of D. melanogaster. Furthermore, ACT treatment decreased ROT induced apoptotic rate and reactive oxygen species production, increased mitochondrial membrane potentials in neuronal cells, and promoted clearance of α-synuclein (SNCA) aggregations in SNCA overexpressed cell model through the autophagy-lysosome pathway. Interestingly, ACT treatment significantly enhanced mitophagy and protected cell injury in neuronal cells. Taken together, ACT may represent a potent stimulator of mitophagy pathway, thereby exerts preventive and therapeutic effects against neurodegenerative diseases such as PD by clearing pathogenic proteins and impaired cellular organelles like damaged mitochondria in neurons.