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Bioinformatics investigation of therapeutic mechanisms of Xuesaitong capsule treating ischemic cerebrovascular rat model with comparative transcriptome analysis.

ABSTRACT: BACKGROUND:Xuesaitong soft capsule (XST) which consists of panax notoginseng saponin (PNS) has been used to treat ischemic cerebrovascular diseases in China. The therapeutic mechanism of XST has not been elucidated yet from prospective of genomics and bioinformatics. METHODS:A transcriptome analysis was performed to review series concerning middle cerebral artery occlusion (MCAO) rat model and XST intervention after MCAO from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were compared between blank group and model group, model group and XST group. Functional enrichment and pathway analysis were performed. Protein-Protein interaction network was constructed. The overlapping genes from two DEGs sets were screened out and profound analysis was performed. RESULTS:Two series including 22 samples were obtained. 870 DEGs were identified between blank group and model group, and 1189 DEGs were identified between model group and XST group. GO terms and KEGG pathways of MCAO and XST intervention were significantly enriched. PPI networks were constructed to demonstrate the gene-gene interactions. The overlapping genes from two DEGs sets were highlighted. ANTXR2, FHL3, PRCP, TYROBP, TAF9B, FGFR2, BCL11B, RB1CC1 and MBNL2 were the pivotal genes and possible action sites of XST therapeutic mechanisms. CONCLUSION:MCAO is a pathological process with multiple.

SUBMITTER: Liao J

PROVIDER: S-EPMC4891458 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Bioinformatics investigation of therapeutic mechanisms of Xuesaitong capsule treating ischemic cerebrovascular rat model with comparative transcriptome analysis.

Liao Jiangquan J Wei Benjun B Chen Hengwen H Liu Yongmei Y Wang Jie J

American journal of translational research 20160515 5

<h4>Background</h4>Xuesaitong soft capsule (XST) which consists of panax notoginseng saponin (PNS) has been used to treat ischemic cerebrovascular diseases in China. The therapeutic mechanism of XST has not been elucidated yet from prospective of genomics and bioinformatics.<h4>Methods</h4>A transcriptome analysis was performed to review series concerning middle cerebral artery occlusion (MCAO) rat model and XST intervention after MCAO from Gene Expression Omnibus (GEO) database. Differentially ...[more]

PMID: 27347353

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Project description:Guanxin-Shutong capsule (GXSTC), a combination of Mongolian medicines and traditional herbs, has been clinically proven to be effective in treating cerebrovascular diseases (CBVDs). However, the underlying pharmacological mechanisms of GXSTC in CBVDs remain largely unknown. In this study, a combination of systems pharmacology and experimental assessment approach was used to investigate the bioactive components, core targets, and possible mechanisms of GXSTC in the treatment of CBVDs. A total of 15 main components within GXSTC were identified using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) and a literature research. Fifty-five common genes were obtained by matching 252 potential genes of GXSTC with 462 CBVD-related genes. Seven core components in GXSTC and 12 core genes of GXSTC on CBVDs were further determined using the protein-protein interaction (PPI) and component-target-pathway (C-T-P) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results predicted that the molecular mechanisms of GXSTC on CBVDs were mainly associated with the regulation of the vascular endothelial function, inflammatory response, and neuronal apoptosis. Molecular docking results suggested that almost all of core component-targets have an excellent binding activity (affinity < -5 kcal/mol). More importantly, in middle cerebral artery occlusion (MCAO) -injured rats, GXSTC significantly improved the neurological function, reduced the infarct volume, and decreased the percentage of impaired neurons in a dose-dependent manner. Western blotting results indicated that GXSTC markedly upregulated the expression of vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS), while downregulating the expression of cyclooxygenase-2 (COX-2) and transcription factor AP-1 (c-Jun) in MCAO-injured rats. These findings confirmed our prediction that GXSTC exerts a multi-target synergetic mechanism in CBVDs by maintaining vascular endothelial function, inhibiting neuronal apoptosis and inflammatory processes. The results of this study may provide a theoretical basis for GXSTC research and the clinical application of GXSTC in CBVDs.

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Project description:BACKGROUND: The naked mole rats (NMRs) are small-sized underground rodents with plenty of unusual traits. Their life expectancy can be up to thirty years, more than seven times longer than laboratory rat. Furthermore, they are resistant to both congenital and experimentally induced cancer genesis. These peculiar physiological and pathological characteristics allow them to become a suitable model for cancer and aging research. RESULTS: In this paper, we carried out a genome-wide comparative analysis of rat and NMR using the recently published genome sequence of NMR. First, we identified all the rat-NMR orthologous genes and specific genes within each of them. The expanded and contracted numbers of protein families in NMR were also analyzed when compared to rat. Seven cancer-related protein families appeared to be significantly expanded, whereas several receptor families were found to be contracted in NMR. We then chose those rat genes that were inexistent in NMR and adopted KEGG pathway database to investigate the metabolic processes in which their proteins may be involved. These genes were significantly enriched in two rat cancer pathways, "Pathway in cancer" and "Bladder cancer". In the rat "Pathway in cancer", 9 out of 14 paths leading to evading apoptosis appeared to be affected in NMR. In addition, a significant number of other NMR-missing genes enriched in several cancer-related pathways have been known to be related to a variety of cancers, implying that many of them may be also related to tumorigenesis in mammals. Finally, investigation of sequence variations among orthologous proteins between rat and NMR revealed that significant fragment insertions/deletions within important functional domains were present in some NMR proteins, which might lead to expressional and/or functional changes of these genes in different species. CONCLUSIONS: Overall, this study provides insights into understanding the possible anti-cancer mechanisms of NMR as well as searching for new cancer-related candidate genes.

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Bioinformatics investigation of therapeutic mechanisms of Xuesaitong capsule treating ischemic cerebrovascular rat model with comparative transcriptome analysis.

Publications

Bioinformatics investigation of therapeutic mechanisms of Xuesaitong capsule treating ischemic cerebrovascular rat model with comparative transcriptome analysis.

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