Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy

• Main Authors: Jerath, G. (Author), Kartha, C.C (Author), Kumar, V. (Author), Rai, A. (Author), Ramakrishnan, V. (Author)
• Format: Article
• Language: English
• Published: Nature Research 2021
• Subjects: Amalakirasayana; animal; Animals; biological model; cardiomegaly; Cardiomegaly; Chromatography, Liquid; clinical pharmacology; drug development; Drug Development; drug effect; drug potentiation; Drug Synergism; human; Humans; liquid chromatography; mass spectrometry; Mass Spectrometry; metabolism; Models, Biological; molecular docking; Molecular Docking Simulation; Pharmacology, Clinical; plant extract; Plant Extracts; procedures; protein analysis; Protein Interaction Maps; proteomics; Proteomics; signal transduction; Signal Transduction; systems biology; Systems Biology
• Online Access: View Fulltext in Publisher

 Advancements in systems biology have resulted in the development of network pharmacology, leading to a paradigm shift from “one-target, one-drug” to “target-network, multi-component therapeutics”. We employ a chimeric approach involving in-vivo assays, gene expression analysis, cheminformatics, and network biology to deduce the regulatory actions of a multi-constituent Ayurvedic concoction, Amalaki Rasayana (AR) in animal models for its effect in pressure-overload cardiac hypertrophy. The proteomics analysis of in-vivo assays for Aorta Constricted and Biologically Aged rat models identify proteins expressed under each condition. Network analysis mapping protein–protein interactions and synergistic actions of AR using multi-component networks reveal drug targets such as ACADM, COX4I1, COX6B1, HBB, MYH14, and SLC25A4, as potential pharmacological co-targets for cardiac hypertrophy. Further, five out of eighteen AR constituents potentially target these proteins. We propose a distinct prospective strategy for the discovery of network pharmacological therapies and repositioning of existing drug molecules for treating pressure-overload cardiac hypertrophy. © 2021, The Author(s).