Dataset Information

Computational Prediction of Antiangiogenesis Synergistic Mechanisms of Total Saponins of Panax japonicus Against Rheumatoid Arthritis.

ABSTRACT: Objective: To investigate the anti-angiogenesis mechanisms and key targets of total saponins of Panax japonicus (TSPJ) in the treatment of rheumatoid arthritis (RA). Methods: RStudio3.6.1 software was used to obtain differentially expressed genes (DEGs) by analyzing the differences in gene expression in the synovial tissue of RA and to predict the potential targets of active compounds from TSPJ by the PharmMapper and SwissTargetPrediction databases. We evaluated the overlapping genes by intersectional analysis of DEGs and drug targets. Based on the overlapping genes, we used Cytoscape 3.7.2 software to construct a protein-protein interactions (PPI) network and applied Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to determine the mechanisms of the treatment. Finally, the correlations with angiogenesis-related genes were explored. Collagen-induced arthritis (CIA) model was established and treated with different doses of TSPJ. The manifestations of CIA were determined by evaluation of arthritis index and histology score. Serum levels of vascular endothelial growth factor (VEGF) and the hypoxia-inducible factor 1 (HIF-1) were tested by ELISA. The mRNA levels of IL-1? and IL-17A were detected by real time-quantitative PCR. Results: Altogether, 2670 DEGs were obtained by differential analysis, and 371 drug targets were predicted for four active components (Araloside A, Chikusetsusaponin IVa, Ginsenoside Rg2, and Ginsenoside Ro). A total of 52 overlapping genes were included in the PPI network and the KEGG analysis. However, only 41 genes in the PPI network had protein interactions. The results of the KEGG enrichment analysis were all related to angiogenesis, including VEGF and HIF-1 signaling pathways. Seven genes with negative correlations and 16 genes with positive correlations were obtained by correlational analysis of DEGs in the VEGF and HIF-1 signaling pathways. SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), and the signal transducer and activator of transcription 3 (STAT 3) had a higher value of degree and showed a significant correlation in the pathways; they were regarded as key targets. Compared with the model group, TSPJ significantly relieved the symptoms and decreased the expression of VEGFA, HIF-1?, IL-1?, and IL-17A in serum or spleens of CIA mice. Conclusion: In the current study, we found that antiangiogenesis is one of the effective strategies of TSPJ against RA; SRC and STAT 3 may be the key targets of TSPJ acting on the VEGF and HIF-1 signaling pathways, which will provide new insight into the treatment of RA by inhibiting inflammation and angiogenesis.

SUBMITTER: Guo X

PROVIDER: S-EPMC7723436 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Computational Prediction of Antiangiogenesis Synergistic Mechanisms of Total Saponins of Panax japonicus Against Rheumatoid Arthritis.

Guo Xiang X Ji Jinyu J Jose Kumar Sreena Goutham Sanker GS Hou Xiaoqiang X Luo Yanan Y Fu Xianyun X Mei Zhigang Z Feng Zhitao Z

Frontiers in pharmacology 20201029

Objective: To investigate the anti-angiogenesis mechanisms and key targets of total saponins of Panax japonicus (TSPJ) in the treatment of rheumatoid arthritis (RA). Methods: RStudio3.6.1 software was used to obtain differentially expressed genes (DEGs) by analyzing the differences in gene expression in the synovial tissue of RA and to predict the potential targets of active compounds from TSPJ by the PharmMapper and SwissTargetPrediction databases. We evaluated the overlapp ...[more]

PMID: 33324204

Similar Datasets

Project description:The Panax genus has been a source of natural medicine, benefitting human health over the ages, among which the Panax japonicus represents an important species. Our understanding of several key pathways and enzymes involved in the biosynthesis of ginsenosides, a pharmacologically active class of metabolites and a major chemical constituents of the rhizome extracts from the Panax species, are limited. Limited genomic information, and lack of studies on comparative transcriptomics across the Panax species have restricted our understanding of the biosynthetic mechanisms of these and many other important classes of phytochemicals. Herein, we describe Illumina based RNA sequencing analysis to characterize the transcriptome and expression profiles of genes expressed in the five tissues of P. japonicus, and its comparison with other Panax species. RNA sequencing and de novo transcriptome assembly for P. japonicus resulted in a total of 135,235 unigenes with 78,794 (58.24%) unigenes being annotated using NCBI-nr database. Transcriptome profiling, and gene ontology enrichment analysis for five tissues of P. japonicus showed that although overall processes were evenly conserved across all tissues. However, each tissue was characterized by several unique unigenes with the leaves showing the most unique unigenes among the tissues studied. A comparative analysis of the P. japonicus transcriptome assembly with publically available transcripts from other Panax species, namely, P. ginseng, P. notoginseng, and P. quinquefolius also displayed high sequence similarity across all Panax species, with P. japonicus showing highest similarity with P. ginseng. Annotation of P. japonicus transcriptome resulted in the identification of putative genes encoding all enzymes from the triterpene backbone biosynthetic pathways, and identified 24 and 48 unigenes annotated as cytochrome P450 (CYP) and glycosyltransferases (GT), respectively. These CYPs and GTs annotated unigenes were conserved across all Panax species and co-expressed with other the transcripts involved in the triterpenoid backbone biosynthesis pathways. Unigenes identified in this study represent strong candidates for being involved in the triterpenoid saponins biosynthesis, and can serve as a basis for future validation studies.

Project description:BackgroundPanax notoginseng saponins (PNS) have been deemed effective herb compounds for treating ischaemic stroke (IS) and improving the quality of life of IS patients. This study aimed to investigate the underlying mechanisms of PNS in the treatment of IS based on network pharmacology.MethodsPNS were identified from the Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible targets were predicted using the PharmMapper database. IS-related targets were identified from the GeneCards database, OMIM database, and DisGeNET database. A herb-compound-target-disease network was constructed using Cytoscape, and protein-protein interaction (PPI) networks were established with STRING. GO enrichment and KEGG pathway analysis were performed using DAVID. The binding of the compounds and key targets was validated by molecular docking studies using AutoDock Vina. The neuroprotective effect of TFCJ was substantiated in terms of oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde) and the levels of IGF1/PI3K/Akt pathway proteins.ResultsA total of 375 PNS targets and 5111 IS-related targets were identified. Among these targets, 241 were common to PNS, and IS network analysis showed that MAPK1, AKT1, PIK3R1, SRC, MAPK8, EGFR, IGF1, HRAS, RHOA, and HSP90AA1 are key targets of PNS against IS. Furthermore, GO and KEGG enrichment analysis indicated that PNS probably exert therapeutic effects against IS by regulating many pathways, such as the Ras, oestrogen, FoxO, prolactin, Rap1, PI3K-Akt, insulin, PPAR, and thyroid hormone signalling pathways. Molecular docking studies further corroborated the experimental results.The network pharmacology results were further verified by molecular docking and in vivo experiments.ConclusionsThe ameliorative effects of PNS against IS were predicted to be associated with the regulation of the IGF1-PI3K-Akt signalling pathway. Ginsenoside Re and ginsenoside Rb1 may play an important role in the treatment of IS.

Dataset Information

Computational Prediction of Antiangiogenesis Synergistic Mechanisms of Total Saponins of Panax japonicus Against Rheumatoid Arthritis.

Publications

Computational Prediction of Antiangiogenesis Synergistic Mechanisms of Total Saponins of <i>Panax japonicus</i> Against Rheumatoid Arthritis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets