Systems pharmacology analysis of synergy of TCM: an example using saffron formula

Abstract

Traditional Chinese medicine (TCM) follows the principle of formulae, in which the pharmacological activity of a single herb can be enhanced or potentiated by addition of other herbs. Nevertheless, the involved synergy mechanisms in formulae remain unknown. Here, a systems-based method is proposed and applied to three representative Chinese medicines in compound saffron formula (CSF): two animal spices (Moschus, Beaver Castoreum), and one herb Crocus sativus which exert synergistic effects for cardiovascular diseases (CVDs). From the formula, 42 ingredients and 66 corresponding targets are acquired based on the ADME evaluation and target fishing model. The network relationships between the compounds and targets are assembled with CVDs pathways to elucidate the synergistic therapeutic effects between the spices and the herbs. The results show that different compounds of the three medicines show similar curative activity in CVDs. Additionally, the active compounds from them shared CVDs-relevant targets (multiple compounds-one target), or functional diversity targets but with clinical relevance (multiple compounds-multiple targets-one disease). Moreover, the targets of them are largely enriched in the same CVDs pathways (multiple targets-one pathway). These results elucidate why animal spices and herbs can have pharmacologically synergistic effects on CVDs, which provides a new way for drug discovery.

An Integrated Approach Exploring the Synergistic Mechanism of Herbal Pairs in a Botanical Dietary Supplement: A Case Study of a Liver Protection Health Food

“…ch/) (prediction probability > 0:5 was selected) [52], and DrugBank (https://www.drugbank.ca/). All acquired targets were limited to Homo sapiens and mapped to UniProt (https://www.uniprot.org/), CTD (http://www.ctdbase.org/), and Database and Therapeutic Targets Database (https://db .idrblab.org/ttd/) for normalization [6], removing redundant and erroneous targets to guarantee the accuracy of the targets. A text mining of PubMed Gene (https://www.ncbi.nlm.…”

“…System Pharmacology can describe the complex interaction between phytochemicals and biological systems which makes it an ideal tool for identifying potential mechanisms of action and rationale for TCM formulas [4]. Previous studies have successfully interpreted the synergistic mechanisms of herbal combinations at the molecular level using System Pharmacology [5,6]. The identification of chemical composition in herbs plays a key step during the process of System Pharmacology analysis.…”

Computational methods and applications for quantitative systems pharmacology

“…Systems pharmacology methods are frequently used in exploration of pharmacodynamic material basis and MoA of traditional Chinese medicine (TCM) [130][131][132][133][134][135][136][137][138][139]. The recent applications of these QSP methods in TCM are summarized in Table 2 Erigeron breviscapus ADME pharmacokinetic screening, target fishing, protein-protein interaction network analysis and in vitro experiments verification [141] Eucommia ulmoides Oliv.…”

Crude polysaccharide from a wild mushroom enhances immune response in murine macrophage cells by TLR/NF-κB pathway

“…As for example, in China, Sijunzi decoction, a clinically active fraction comprising of four crude drugs has been traditionally prescribed as immunomodulators and expectedly it also can be used as immune‐adjuvant cancer therapy . Usually the crude form manifest synergistic effect of mixture of active constituents, that offers an alternative of the concept one drug → one target → one disease . Several researchers have also been demonstrated the similar theory for development of natural prebiotics from mushroom's crude polysaccharides .…”

“…one disease. [4] Several researchers have also been demonstrated the similar theory for development of natural prebiotics from mushroom's crude polysaccharides. [5,6] Therefore, such potentials of crude fraction should be employed for prevention of many incurable complex diseases with the application of one drug for multiple targets.…”