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Detection of Vasodilators From Herbal Components by a Transcriptome-Based Functional Gene Module Reference Approach

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Detection of Vasodilators From Herbal Components by a Transcriptome-Based Functional Gene Module Reference Approach

Peng Li et al. Front Pharmacol.

Abstract

Vasodilatation is one of the key therapeutic strategies for the treatment of various cardiovascular diseases with high blood pressure. Therefore, development of drugs assisting blood vessel dilation is promising. It has been proven that many drugs display definite vasorelaxant effects. However, there are very few studies that systemically explore the effective vasodilators. In this work, we build a transcriptome-based functional gene module reference approach for systematic pursuit of agents with vasorelaxant effects. We firstly curate two functional gene modules that are specifically involved in positive and negative regulation of vascular diameter based on the known gene functional interaction knowledge. Secondly, a collection of gene expression profiles following herbal component treatment are collected from a public gene expression database. Then, the correlation of the gene modules is evaluated in each herbal component-induced gene expression profile by gene set enrichment analysis. The vasorelaxant effects of the candidate compounds can be predicted and ordered by the values of a defined index. Finally, the top 10 candidate compounds are experimentally tested for their vasorelaxant effects on vessel contraction induced by Phe in aortic rings. This strategy integrating different types of technologies is expected to help to create new opportunities for the development of novel vasodilators.

Keywords: drug discovery; gene expression profile; gene module; herbal component; vasodilator.

Figures

Figure 1
Figure 1
A transcriptome-based functional gene module reference (TFGMR) strategy to predict candidate vasodilators from herbal components based on specific function gene modules of regulating blood vessel diameter and herbal component–induced transcriptional profiles. GO, Gene Ontology; BP, biological process; PFGM, functional gene module that positively regulates blood vessel diameter; NFGM, functional gene module that negatively regulates blood vessel diameter; GSEA, gene set enrichment approach; ES, Enrichment Score.
Figure 2
Figure 2
Functional annotations for PFGM and NFGM members.
Figure 3
Figure 3
Vasorelaxant effects of various herbal components on rat thoracic aorta rings with endothelium (n = 8) precontracted with Phe. Relaxation (%) was calculated as a percentage of decrease in the maximal tension induced by Phe. Data are shown as the means ± SD. *P < 0.05 vs the control group.
Figure 4
Figure 4
Functional analysis for the genes regulated by the six compounds ferulic acid, borneol, daidzin, magnolol, chenodeoxycholic acid, and artemisinin. A link between a compound (red) and a function node (green) indicates that the regulated genes of the compound are significantly involved in the function annotation. The node size is correlated with the network degree of the node.

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