Screening Ingredients from Herbs against Pregnane X Receptor in the Study of Inductive Herb-Drug Interactions: Combining Pharmacophore and Docking-Based Rank AggregationReportar como inadecuado




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BioMed Research International - Volume 2015 2015, Article ID 657159, 8 pages -

Research Article

Department of Bioinformatics, Tongji University, Shanghai 200092, China

Shanghai Center for Bioinformation Technology, Shanghai, China

School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, Liaoning, China

Received 4 September 2014; Revised 22 December 2014; Accepted 27 December 2014

Academic Editor: Feng Luo

Copyright © 2015 Zhijie Cui et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The issue of herb-drug interactions has been widely reported. Herbal ingredients can activate nuclear receptors and further induce the gene expression alteration of drug-metabolizing enzyme and-or transporter. Therefore, the herb-drug interaction will happen when the herbs and drugs are coadministered. This kind of interaction is called inductive herb-drug interactions. Pregnane X Receptor PXR and drug-metabolizing target genes are involved in most of inductive herb-drug interactions. To predict this kind of herb-drug interaction, the protocol could be simplified to only screen agonists of PXR from herbs because the relations of drugs with their metabolizing enzymes are well studied. Here, a combinational in silico strategy of pharmacophore modelling and docking-based rank aggregation DRA was employed to identify PXR’s agonists. Firstly, 305 ingredients were screened out from 820 ingredients as candidate agonists of PXR with our pharmacophore model. Secondly, DRA was used to rerank the result of pharmacophore filtering. To validate our prediction, a curated herb-drug interaction database was built, which recorded 380 herb-drug interactions. Finally, among the top 10 herb ingredients from the ranking list, 6 ingredients were reported to involve in herb-drug interactions. The accuracy of our method is higher than other traditional methods. The strategy could be extended to studies on other inductive herb-drug interactions.





Autor: Zhijie Cui, Hong Kang, Kailin Tang, Qi Liu, Zhiwei Cao, and Ruixin Zhu

Fuente: https://www.hindawi.com/



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