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

Abstract 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, cheminformat...

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Autores principales:	Aparna Rai, Vikas Kumar, Gaurav Jerath, C. C. Kartha, Vibin Ramakrishnan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6f53b632952146e7b40af56c91c87711
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spelling	oai:doaj.org-article:6f53b632952146e7b40af56c91c877112021-12-02T12:11:50ZMapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy10.1038/s41540-021-00171-z2056-7189https://doaj.org/article/6f53b632952146e7b40af56c91c877112021-02-01T00:00:00Zhttps://doi.org/10.1038/s41540-021-00171-zhttps://doaj.org/toc/2056-7189Abstract 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.Aparna RaiVikas KumarGaurav JerathC. C. KarthaVibin RamakrishnanNature PortfolioarticleBiology (General)QH301-705.5ENnpj Systems Biology and Applications, Vol 7, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Aparna Rai Vikas Kumar Gaurav Jerath C. C. Kartha Vibin Ramakrishnan Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
description	Abstract 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.
format	article
author	Aparna Rai Vikas Kumar Gaurav Jerath C. C. Kartha Vibin Ramakrishnan
author_facet	Aparna Rai Vikas Kumar Gaurav Jerath C. C. Kartha Vibin Ramakrishnan
author_sort	Aparna Rai
title	Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
title_short	Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
title_full	Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
title_fullStr	Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
title_full_unstemmed	Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
title_sort	mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/6f53b632952146e7b40af56c91c87711
work_keys_str_mv	AT aparnarai mappingdrugtargetinteractionsandsynergyinmultimoleculartherapeuticsforpressureoverloadcardiachypertrophy AT vikaskumar mappingdrugtargetinteractionsandsynergyinmultimoleculartherapeuticsforpressureoverloadcardiachypertrophy AT gauravjerath mappingdrugtargetinteractionsandsynergyinmultimoleculartherapeuticsforpressureoverloadcardiachypertrophy AT cckartha mappingdrugtargetinteractionsandsynergyinmultimoleculartherapeuticsforpressureoverloadcardiachypertrophy AT vibinramakrishnan mappingdrugtargetinteractionsandsynergyinmultimoleculartherapeuticsforpressureoverloadcardiachypertrophy
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Mapping drug-target interactions and synergy in multi-molecular therapeutics for pressure-overload cardiac hypertrophy

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