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

Abstract

Tribulus terrestris L. (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 terrestris L. 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 terrestris L. that can act as putative lead compounds to treat cardiac diseases. A total of 55 putative compounds were identified using methanolic extract of Tribulus terrestris L. 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 silico molecular 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 vivo and in vitro studies for better understanding and strong assertion.

Communicated by Ramaswamy H. Sarma

Keywords:

• Tribulus terrestris L.
• HPLC-QTOF-MS/MS
• network pharmacology
• molecular docking
• pathway analysis
• cardiac diseases

Authors contributions

Work and concept were initiated by PSR; literature search, data interpretation, and the manuscript were written by CMV. CB and AK for the collection of plant material. MBJ for his guidance to perform mass spectrometry experiments. CHM performed molecular docking and molecular dynamics using the Schrodinger suite. PSR, BP, and UYN critically reviewed and PSR approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the Department of Biotechnology, Government of India (BT/PR15963/TRM/120/83/2016) for the research grant to Dr. Padmalatha S Rai, KSTePS, DST, Government of Karnataka for granting PhD Fellowship (DST/KSTePS/Ph.D. Fellowship/LIF-05:2020-21) to Mr. Chigateri M Vinay and Manipal Academy of Higher Education, Manipal for providing us with the infrastructure facilities at Manipal School of Life Sciences and Manipal College of Pharmaceutical Sciences. Department of Biotechnology, Ministry of Science and Technology, India.