Predication of the Underlying Protective Effect of Saffron on Parkinson's Disease via Network Pharmacology and Molecular Docking

Abstract

BackgroundReports indicate that saffron originated from Iran then introduced into mainland China through the earlier established trans-Tibet trade routes in ancient China. Based to the theory of traditional Chinese medicine, saffron functions by promoting blood circulation and removing blood stasis, cooling blood and detoxification, as well as relieving depression for tranquilization. Modern medical research has demonstrated several properties of saffron including antitumor, antidepressant, enhancement of immunity, cardioprotection. Notably, recent studies introduce that saffron has a neuroprotective effect, specifically in the treatment of Parkinson's disease in recent years. Nevertheless, the underlying molecular mechanism remains elusive so far. As such, this study aims to predict the underlying mechanism of saffron on Parkinson's disease through network pharmacology and molecular docking.MethodsA functional-based network pharmacology and molecular docking model was constructed for dissecting the underlying mechanism of saffron on Parkinson's disease. Based on the Traditional Chinese Medicine System Pharmacology database (TCMSP) and the literature reviews, the putative targets of Saffron were collected. Further, the interaction networks of Drug- candidate compounds targets-Therapeutic targets-Disease were mined using the Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted and the String database was used to analyze the protein interaction network. Finally, Molecular docking was used to predict the interaction between the components in Saffron and key targets by MOE 2014.09 software.ResultsA total of 9 candidate compounds from saffron corresponding to 52 therapeutic targets of Parkinson's disease were identified. The neuroprotective effect of saffron in the treatment of PD was attributed to the strong binding between crocin (including crocin I and crocin II) as well as key targets including CASP3, IL6, and MAPK8. Additionally, the auxiliary neuroprotective effects might have originated from quercetin, kaempferol, isorhamnetin, crocetin, safranal, and picrocrocin because of their slightly weaker binding capacity to the key targets.ConclusionSaffron exhibits a synergistic effect via multiple targets and pathways in the treatment of Parkinson's disease and our systemic pharmacological analysis provides a basis for the clinical application and in-depth study of saffron.