| Traditional Chinese medicine(TCM)adheres to the principle of formulae,in which the pharmacological activities of one herb can be potentiated or prolonged by addition of other herbs.However,the involved synergistic mechanisms in formulae remain elusive.Here,a novel systems pharmacology approach is proposed and applied to three representative Chinese medicine in compound saffron formula(CSF): two animal spices(Moschus,Beaver Castoreum),one herb Crocus sativus which exert synergistic effects for cardiovascular disease(CVD).The results show that 42 potential ingredients and 66 corresponding targets are acquired based on ADME evaluation and target fishing model.Then,to elucidate the synergistic mechanism between them,we systematically elaborated the mechanism of action of these three drugs on CVDs from the molecular level,target level,pathway level and tissue/organ level.Moreover,the network relationships and CVDs pathways are assembled to elucidate the synergistic therapeutic effects between the spices and herbs.The results show that the different molecules of the three drugs show similar curative activity in CVDs.Additionally,the active compounds of them shared CVDs-relevant targets(multiple compounds-one target),or the functionally diverse targets but with potentially clinically relevant associations(multiple compounds-multiple targets-one disease)in network level.Moreover,various potential targets from them potentially act on the same CVDs pathways(multiple targets-one pathway).These modes of interaction elucidate why animal spices and herb with pharmacological synergy on CVDs.Based on the above findings,we conducted molecular docking of the relevant compounds,the results confirmed that the high affinity of the compound and the corresponding target,further confirmed that the reliability of the three drugs for the treatment of CVDs.which provide a potential way for drug discovery and novel research ideas and approaches for compound optimization. |
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