Abstract
Objective To investigate the potential active compounds and underlying mechanisms of Paeonia lactiflora Pall. (PLP) on the treatment of Alzheimer's disease (AD) based on network pharmacology. Methods The active components of PLP were collected from Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible target proteins were predicted using TCMSP, SwissTargetPrediction, and STITCH databases. The putative AD-related target proteins were identified from Therapeutic Target Database (TTD), GeneCards, and MalaCards database. The compound-target-disease network interactions were established to obtain the key targets about PLP acting on AD by network topology analysis. Then, the function annotation and signaling pathways of key targets were performed by GO and KEGG enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking using SystemsDock tools. Results There were 7 active compounds involving in 151 predicted targets identified in PLP. Besides, a total of 160 AD-related targets were identified. Among these targets, 30 shared targets of PLP and AD were acquired. After topological analysis of the PLP potential target-AD target network, 33 key targets that were highly responsible for the therapeutic effects of PLP on AD were obtained. Further GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in cell apoptosis and inflammatory response and maintained the function of neurons to accomplish the anti-AD activity. The molecular docking analysis verified that the 7 active compounds had definite affinity with the key targets. Conclusions The ameliorative effects of PLP on AD were predicted to be associated with regulating neural cell apoptosis, inflammatory response, and neurotrophy via various pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, and neurotrophin signaling pathway.
Highlights
Alzheimer’s disease (AD) is one of the commonest neurodegenerative diseases with high incidence and intricate pathogenesis
Further Gene Ontology (GO) and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in cell apoptosis and inflammatory response and maintained the function of neurons to accomplish the anti-AD activity. e molecular docking analysis verified that the 7 active compounds had definite affinity with the key targets
According to the characteristics of oral bioavailability, half-life, and drug likeness of the compounds, 7 compounds were screened out as the potential active ingredients including β-sitosterol, kaempferol, lactiflorin, mairin, paeoniflorigenone, paeoniflorin, and palbinone, which are listed in Table 1. e characteristics of the 85 compounds in Paeonia lactiflora Pall. (PLP) are shown in Stable 1
Summary
Alzheimer’s disease (AD) is one of the commonest neurodegenerative diseases with high incidence and intricate pathogenesis. There is no efficacious treatment options for AD patients. The current mainstream treatments for AD such as acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists show limited efficacy. The clinical trials showed that new drugs targeting Aβ or tau failed to improve cognitive ability and clinical outcomes of AD patients, and they were discontinued. It suggested that the efficacy of singletarget drug was limited and hard to meet clinical needs [5,6,7]. It is important and necessary to develop novel drugs with multitargets for AD treatment
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