title: Prediction and Characterisation of the System Effects of Aristolochic Acid: A Novel Joint Network Analysis towards Therapeutic and Toxicological Mechanisms.
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.
authors.affiliation: Chongqing University Innovative Drug Research Centre, School of Chemistry and Chemical Engineering, Chongqing 401331, P.R. China.
authors.forename: Wenna
authors.initials: W
authors.lastname: Nie
authors.affiliation: Yunnan Branch, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, P.R China.|Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Jinghong 666100, P.R. China.
authors.forename: Yana
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Chongqing University Innovative Drug Research Centre, School of Chemistry and Chemical Engineering, Chongqing 401331, P.R. China.
authors.forename: Leyu
authors.initials: L
authors.lastname: Yan
authors.affiliation: Yunnan Branch, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Jinghong 666100, P.R China.|Key Laboratory of Dai and Southern Medicine of Xishuangbanna Dai Autonomous Prefecture, Jinghong 666100, P.R. China.|Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Chongqing University Innovative Drug Research Centre, School of Chemistry and Chemical Engineering, Chongqing 401331, P.R. China.|Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD 4059, Australia.
authors.forename: Haitao
authors.initials: H
authors.lastname: Lv
mesh_terms: D034341:Aristolochic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D030541:Databases, Genetic; D053263:Gene Regulatory Networks / Q000187:drug effects*; D006801:Humans
chemical_list: D034341:Aristolochic Acids