Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 195, Issue -, Pages 127-136Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2016.10.020
Keywords
Herbal medicine; Polypharmacological effects; RNA-seq; Transcriptome-based inference method; Target identification
Categories
Funding
- National Natural Science Foundation of China [81522051, 81530100]
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Ethnopharmacological relevance: Herbal medicine is a concoction of numerous chemical ingredients, and it exhibits polypharmacological effects to act on multiple pharmacological targets, regulating different biological mechanisms and treating a variety of diseases. Thus, this complexity is impossible to deconvolute by the reductionist method of extracting one active ingredient acting on one biological target. Aim of the study: To dissect the polypharmacological effects of herbal medicines and their underling pharmacological targets as well as their corresponding active ingredients. Materials and methods: We propose a system-biology strategy that combines omics and bioinformatical methodologies for exploring the polypharmacology of herbal mixtures. The myocardial ischemia model was induced by Ameroid constriction of the left anterior descending coronary in Ba-Ma miniature pigs. RNA-seq analysis was utilized to find the differential genes induced by myocardial ischemia in pigs treated with formula QSKL. A transcriptome-based inference method was used to find the landmark drugs with similar mechanisms to QSKL. Results: Gene-level analysis of RNA-seq data in QSKL-treated cases versus control animals yields 279 differential genes. Transcriptome-based inference methods identified 80 landmark drugs that covered nearly all drug classes. Then, based on the landmark drugs, 155 potential pharmacological targets and 57 indications were identified for QSKL. Conclusion: Our results demonstrate the power of a combined approach for exploring the pharmacological target and chemical space of herbal medicines. We hope that our method could enhance our understanding of the molecular mechanisms of herbal systems and further accelerate the exploration of the value of traditional herbal medicine systems.
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