Explicating the property and action of traditional Chinese medicine (TCM) in the perspectives of modern science deepens the insight into the property of TCM, and provides the basis for new drug discovery and clinical therapy. In this study, we investigated the relationship between transient receptor potential melastatin 8 (TRPM8) and pungent flavor using three-dimensional pharmacophores based on virtual screening methods.

Firstly, an inhouse database was established to identify the related pharmacological action according to the traditional Chinese herbs expressing an action of promoting blood circulation. Then, several therapeutic targets, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), cholesteryl ester transfer protein (CETP), Niemann-Pick C1-Like 1 (NPC1L1) and platelet-activating factor receptor (PAFR), were selected to screen traditional Chinese herbs, and the common virtual screening hits with various hit scores providing data to reveal the correlation among TRPM8 and therapeutic targets.

According to the screening results, TRPM8 agonists were able to identify the effective components of pungent herbs and TRPM8, which shares the common virtual screening hits with the therapeutic targets, was considered to be related to the action of pungent taste.

The novel ideas and methods in this study are beneficial to unveil the scientific relationship between a TCM property and its action.

Used extensively to treat cardiovascular disease, Danqi analogous formulas (DQAF) include prescriptions for Danqi (DQ), Fufang Danshen (FFDS) and Qishen Yiqi (QSYQ). Differences in prescription compatibility result in varying emphases of DQAF in clinical application.

Based on network analysis in this study, common and distinct mechanisms of DQAF actions on cardiovascular disease were analyzed at a systemic level. Components–targets–pathways models were developed by Cytoscape (http://www.cytoscape.org/); whereby, target information for active compounds was obtained based on the PharmMapper database (http://59.78.96.61/pharmmapper/), which was further used to search pathways using the Kyoto Encyclopedia of Genes and Genomes database (http://www.genome.jp/kegg/). Based on target and network analyses, we discovered RBP4 is a potential common target of DQAF, while mitogen-activated protein kinase 1 (MAPK1) and glutathione S-transferase P were potential targets of FFDS and QSYQ, respectively. Furthermore, the potential of DQAF to treat cardiovascular disease occurs through effects on the endocrine, immune, and digestive systems, in addition to lipid, sugar and amino acid metabolic pathways. Whereas FFDS exhibits effects on Toll-like receptor, transforming growth factor beta and MAPK signaling pathways; QSYQ exerts effects on cyclic adenosine monophosphate signaling, as well as metabolism of glutathione and arachidonic acid.

This study not only reflects the formulas-effect modality of multiple compounds, targets and pathways, but also provides clues to better understand physiological mechanisms of DQAF.