AUTHOR=Du Wanqing , Liang Xiao , Wang Shanze , Lee Philip , Zhang Yunling 

TITLE=The Underlying Mechanism of Paeonia lactiflora Pall. in Parkinson’s Disease Based on a Network Pharmacology Approach

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.581984

DOI=10.3389/fphar.2020.581984

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, yet as of currently, there is no disease-modifying therapy that could delay its progression. <italic>Paeonia lactiflora</italic> Pall. is the most frequently used herb in formulas for PD in Traditional Chinese Medicine and also a potential neuroprotective agent for neurodegenerative diseases, while its mechanisms remain poorly understood. In this study, we aim to explore the underlying mechanism of <italic>P. lactiflora</italic> in treating PD utilizing a network pharmacology approach.</p><p><bold>Methods:</bold> The protein targets of <italic>P. lactiflora</italic> ingredients and PD were first obtained from several databases. To clarify the key targets, a Protein-Protein-Interaction (PPI) network was constructed and analyzed on the String database, and then enrichment analysis was performed by the Metascape platform to determine the main Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the Ingredient-Target-Pathway (I-T-P) network was constructed and analyzed by Cytoscape software.</p><p><bold>Results:</bold> Six active ingredients of <italic>P. lactiflora</italic> (kaempferol, ß-sitosterol, betulinic acid, palbinone, paeoniflorin and (+)-catechin) as well as six core targets strongly related to PD treatment [AKT1, interleukin-6, CAT, Tumor necrosis factor (TNF), CASP3, and PTGS2] were identified. The main pathways were shown to involve neuroactive ligand-receptor interaction, Calcium signaling pathway, PI3-Akt signaling pathway, TNF signaling pathway, and apoptosis signaling pathway. The main biological process included the regulation of neurotransmitter levels.</p><p><bold>Conclusion:</bold><italic>P. lactiflora</italic> may retard neurodegeneration by reducing neuroinflammation, inhibiting intrinsic and extrinsic apoptosis, and may improve motor and non-motor symptoms by regulating the levels of neurotransmitters. Our study has revealed the mechanism of <italic>P. lactiflora</italic> in the treatment of PD and may contribute to novel drug development for PD.</p>