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

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.

Discovery of Natural Compounds for Cardiac Fibrosis by a Transcriptome-Based Functional Gene Module Reference Approach

“…3 Although useful, they fail to detect biological processes that are distributed across an entire fibrogenic network. In the present study, following our previous work, 27 a transcriptome-based approach, TFGMR, was proposed to systemically investigate the effects of natural products on CF.…”

Functional Gene Module–Based Identification of Phillyrin as an Anticardiac Fibrosis Agent

“…The ES values within [−1 1] could evaluate the overrepresentation of CFGM at the extremes (bottom or top) of each transcriptional profile. The significance of ES values was estimated by comparing these with a set of ES NULL values calculated randomly ( Li et al., 2019 ).…”

Systems pharmacology approaches in herbal medicine research: a brief review

“…TCM102 database is also widely utilized in research to discover new indications of herbal compounds based on the systems-based approach (18,19). For example, Li et al (18) have identified several vasodilators from TCM102 database.…”

“…TCM102 database is also widely utilized in research to discover new indications of herbal compounds based on the systems-based approach (18,19). For example, Li et al (18) have identified several vasodilators from TCM102 database. They first generated two gene signatures that involved in positive and negative regulation of blood vessel diameter by using databases GO and SEEK (search-based exploration of expression compendia) (112).…”

“…It has been widely utilized in research to retrieve drug repositioning candidates and to elucidate drug’s MOA in modern and herbal medicine ( 15 , 16 ). With a similar concept, drug-induced transcriptome data from MCF-7 breast cancer cell line treated with each of 102 TCM components (TCM102) have been published ( 17 ), enabling researchers to explore the activity of TCM ingredients at the molecular and cellular levels ( 18 , 19 ). As more and more herbal medicine studies conducting high-throughput transcriptome profiling have been published, numbers of gene expression data sets of herbs/ingredients generated in various experimental settings have been accumulated.…”