Network pharmacology-based prediction of inhibiting leukocyte recruitment and angiogenesis of total glucosides of peony against rheumatoid arthritis

Abstract

Background: Total glucosides of peony (TGP) is extracted from Paeonia lactiflora Pallas, which has been approved for rheumatoid arthritis (RA) treatment. There were approximately 15 monoterpene glycosides identified in TGP. Pervious researches focused on the effects of TGP and the major ingredient paeoniflorin (PF), but the functions of other monoterpene glycosides and their interactions were not clear.Network pharmacology has been one of the new strategies for multi-target drug discovery. In this study, we investigate the functions of all components of TGP and their interactions in RA treatment based on network pharmacology methods. Methods:The components of TGP were searched out the Web of Science, PubMed, China National Knowledge Infrastructure databases; then we identified the potential targets based of chemical similarity in the Similarity Ensemble Approach. The molecular related with RA were obtained from DrugBank, GeneCards, DisGeNET and Online Mendelian Inheritance in Man (OMIM) databases. The componentstargets-disease network was constructed and analyzed with Cytoscape software; Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted with R for function analysis. The hub components-targets interactions were validated with Autodock Vina.Results: Twenty potential targets of TGP were predicted for RA treatment. The major components of TGP, PF and albiflorin (AF) had more predicted targets. Hub targets of TGP were LGALS3/9, VEGFA, FGF1, FGF2, IL-6, IL-2, SELP, PRKCA and ERAP1. These targets ameliorated RA mainly through inhibiting leukocyte recruitment and angiogenesis. Enriched pathways including VEGFR pathway, signaling by interleukins, PI3K-Akt signaling pathway, platelet activation, extracellular matrix organization, and so on. The combination of PF, AF and lactiflorin (LF) with the hub targets was further validated using docking program. Conclusions:We investigated the comprehensive mechanism of TGP for RA treatment. We analyzed the different targets of the components in TGP and predicted the new effects of TGP on inhibiting leukocyte recruitment and angiogenesis. This study provides a better understanding of TGP on the RA treatment.

Appearance of green tea compounds in plasma following green tea consumption is modulated by the gut microbiome in mice

“…60 Lactiflorin, a monoterpene glycoside, has been used in the treatment of rheumatoid arthritis via inhibiting leukocyte recruitment and angiogenesis via, potentially, the VEGFR and PI3K-Akt signaling pathways, interleukin signaling, and platelet activation. 61 Previous studies have focused on the health effects of green tea catechins, a subgroup of flavonoids with known antioxidant properties. 62 While several catechins, including epigallocatechin 3-p-coumarate, catechin 3-gallate, gallocatechin 3'-gallate, and epigallocatechin 3-cinnamate were found in green tea extract, these were not found at detectable levels in at least 3 mouse plasma samples and hence were not included in microbiome analyses.…”

Unraveling the Therapeutic Mechanism of Saussurea involucrata against Rheumatoid Arthritis: A Network Pharmacology and Molecular Modeling-Based Investigation

“…Additionally, in the biological process analysis, certain processes are associated with the regulation of cell-cell adhesion. Adhesion molecules are important regulators of leukocyte recruitment into the synovial tissue [60], while Leukocytes, which are aberrantly recruited and activated, are characteristic features of rheumatoid arthritis (RA), as they migrate out of the blood, cross the endothelium, and infiltrate inflamed tissues, triggering a cascade of pathological processes, particularly in the early stages of the disease [61].…”

Paeoniflorin inhibiting the angiogenesis via decreasing MEF2A level to downregulate the expression of LncRNA MALAT1 of exosomes in multiple myeloma

“…Furthermore, studies have revealed that PF enhances chemotherapy e cacy by increasing sensitivity to chemotherapeutic drugs and improving tumor response. Additionally, PF exerts its anti-tumor effects through modulation of various signaling pathways involved in tumorigenesis such as PI3K/Akt 15 , MAPK 16 , and NF-κB pathways 17 .Although there have been reports indicating that PF can improve neurons apoptosis 18 , suppress angiogenesis in rheumatoid arthritis 19 and in glioblastoma 20 ,effectively inhibit the expression of MMP-2 by up-regulating miR-29b, thereby exerting inhibitory effects on MM cell proliferation and promoting apoptosis 21 , no research has been conducted on the therapeutic potential of PF in exosome derived from multiple myeloma cells. Therefore, we designed the present study to explore the role of aberrant lncRNA in MM-derived exosomes on MM angiogenesis and the pharmacological mechanisms underlying PF regulation of MM tumor progression (Fig.…”