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

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.

Automated summary

Advancements in systems biology have led to the development of network pharmacology, shifting from traditional one-target, one-drug approaches to targeting networks and multi-component therapeutics. This study utilizes a combination of in-vivo assays, gene expression analysis, cheminformatics, and network biology to identify potential pharmacological co-targets for cardiac hypertrophy in a multi-constituent Ayurvedic concoction. The research proposes a novel prospective strategy for the discovery of network pharmacological therapies and repositioning of existing drug molecules for treating pressure-overload cardiac hypertrophy.