Integrated LC-MS/MS and network pharmacology approach for predictingactive ingredients and pharmacological mechanisms of Tribulus terrestrisL. against cardiac diseases

AbstractTribulus terrestrisL. (Gokshura) is a medicinal herb used for treating cardiac diseases and several other diseases. However, the active ingredients and the possible mechanism of action for treating cardiac diseases remain unclear. Hence, the study was designed to identify the active ingredients and to explore the potential mechanism of action of Tribulus terrestrisL. for treating cardiac diseases by an integrated approach of metabolomics and network pharmacology. We performed HPLC-QTOF-MS/MS analysis to identify putative compounds and network pharmacology approach for predictive key targets and pathways. Using molecular docking and molecular dynamics simulation, we identified the active ingredients in Tribulus terrestrisL. that can act as putative lead compounds to treat cardiac diseases. A total of 55 putative compounds were identified using methanolic extract of Tribulus terrestrisL. using HPLC-QTOF-MS/MS analysis. Network pharmacology analysis predicted 32 human protein targets from 25 secondary metabolites, which have shown direct interaction with cardiac diseases. Based on the degrees of interaction, the hub targets such as TACR1, F2, F2R, ADRA1B, CHRM5, ADRA1A, ADRA1D, HTR2B, and AVPR1A were identified. In silicomolecular docking and simulation resulted in the identification of active ingredients such as Kaempferol 3-rutinoside 7-glucuronide, Keioside, rutin, moupinamide, aurantiamide, quercetin-3-o-α-rhamnoside, tribuloside, and 3ˈˈ,6ˈˈ- Di-O-p-coumaroyltrifolin against hub protein targets. Hence, these compounds could be potential lead compounds for treating cardiac diseases. A further assessment of its efficacy can be made based on in vivoand in vitrostudies for better understanding and strong assertion.Communicated by Ramaswamy H. Sarma