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Prediction and Characterisation of the System Effects of Aristolochic Acid: A Novel Joint Network Analysis towards Therapeutic and Toxicological Mechanisms.

Nie W, Lv Y, Yan L, Chen X, Lv H - Sci Rep (2015)

Bottom Line: However, the molecular mechanisms of AA systems effects remain poorly understood.Here, we employed a joint network analysis that combines network pharmacology, a protein-protein interaction (PPI) database, biological processes analysis and functional annotation analysis to explore system effects.Thirdly, the pathway-based functional enrichment analysis was manipulated using WebGestalt to identify the mostly significant pathways associated with AA.

View Article: PubMed Central - PubMed

Affiliation: Chongqing University Innovative Drug Research Centre, School of Chemistry and Chemical Engineering, Chongqing 401331, P.R. China.

ABSTRACT
Aristolochic acid (AA) is the major active component of medicinal plants from the Aristolochiaceae family of flowering plants widely utilized for medicinal purposes. However, the molecular mechanisms of AA systems effects remain poorly understood. Here, we employed a joint network analysis that combines network pharmacology, a protein-protein interaction (PPI) database, biological processes analysis and functional annotation analysis to explore system effects. Firstly, we selected 15 protein targets (14 genes) in the PubChem database as the potential target genes and used PPI knowledge to incorporate these genes into an AA-specific gene network that contains 129 genes. Secondly, we performed biological processes analysis for these AA-related targets using ClueGO, some of new targeted genes were randomly selected and experimentally verified by employing the Quantitative Real-Time PCR assay for targeting the systems effects of AA in HK-2 cells with observed dependency of concentration. Thirdly, the pathway-based functional enrichment analysis was manipulated using WebGestalt to identify the mostly significant pathways associated with AA. At last, we built an AA target pathway network of significant pathways to predict the system effects. Taken together, this joint network analysis revealed that the systematic regulatory effects of AA on multidimensional pathways involving both therapeutic action and toxicity.

No MeSH data available.


Related in: MedlinePlus

AA target pathway network mode.A red square denotes AA, blue circles denote genes, and green triangles denote KEGG pathways.
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f6: AA target pathway network mode.A red square denotes AA, blue circles denote genes, and green triangles denote KEGG pathways.

Mentions: To better understand the biological functions of AA-related targets, we carried out pathway-based functional enrichment analyses via WebGestalt. Ninety-one genes were significantly enriched, and 79 significant pathways with cut off P-values <0.05 were systematically enriched. Collectively, an AA target pathway network was constructed in Cytoscape that included 171 nodes and 1299 edges (Fig. 6). Furthermore, the AA target pathway network was divided into approximately 6 parts according to the pathway information.


Prediction and Characterisation of the System Effects of Aristolochic Acid: A Novel Joint Network Analysis towards Therapeutic and Toxicological Mechanisms.

Nie W, Lv Y, Yan L, Chen X, Lv H - Sci Rep (2015)

AA target pathway network mode.A red square denotes AA, blue circles denote genes, and green triangles denote KEGG pathways.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664954&req=5

f6: AA target pathway network mode.A red square denotes AA, blue circles denote genes, and green triangles denote KEGG pathways.
Mentions: To better understand the biological functions of AA-related targets, we carried out pathway-based functional enrichment analyses via WebGestalt. Ninety-one genes were significantly enriched, and 79 significant pathways with cut off P-values <0.05 were systematically enriched. Collectively, an AA target pathway network was constructed in Cytoscape that included 171 nodes and 1299 edges (Fig. 6). Furthermore, the AA target pathway network was divided into approximately 6 parts according to the pathway information.

Bottom Line: However, the molecular mechanisms of AA systems effects remain poorly understood.Here, we employed a joint network analysis that combines network pharmacology, a protein-protein interaction (PPI) database, biological processes analysis and functional annotation analysis to explore system effects.Thirdly, the pathway-based functional enrichment analysis was manipulated using WebGestalt to identify the mostly significant pathways associated with AA.

View Article: PubMed Central - PubMed

Affiliation: Chongqing University Innovative Drug Research Centre, School of Chemistry and Chemical Engineering, Chongqing 401331, P.R. China.

ABSTRACT
Aristolochic acid (AA) is the major active component of medicinal plants from the Aristolochiaceae family of flowering plants widely utilized for medicinal purposes. However, the molecular mechanisms of AA systems effects remain poorly understood. Here, we employed a joint network analysis that combines network pharmacology, a protein-protein interaction (PPI) database, biological processes analysis and functional annotation analysis to explore system effects. Firstly, we selected 15 protein targets (14 genes) in the PubChem database as the potential target genes and used PPI knowledge to incorporate these genes into an AA-specific gene network that contains 129 genes. Secondly, we performed biological processes analysis for these AA-related targets using ClueGO, some of new targeted genes were randomly selected and experimentally verified by employing the Quantitative Real-Time PCR assay for targeting the systems effects of AA in HK-2 cells with observed dependency of concentration. Thirdly, the pathway-based functional enrichment analysis was manipulated using WebGestalt to identify the mostly significant pathways associated with AA. At last, we built an AA target pathway network of significant pathways to predict the system effects. Taken together, this joint network analysis revealed that the systematic regulatory effects of AA on multidimensional pathways involving both therapeutic action and toxicity.

No MeSH data available.


Related in: MedlinePlus