Network Pharmacology: Exploring the Resources and Methodologies

Abstract

Multi-target and combinatorial therapies have been focused for the past several decades. These approaches achieved considerable therapeutic efficacy by modulating the activities of the targets in complex diseases such as HIV-1 infection, cancer and diabetes disease. Most of the diseases cannot be treated efficiently in terms of single gene target, because it involves the cessation of the coordinated function of distinct gene groups. Most of the cellular components work efficiently by interacting with other cellular components and all these interactions together represent interactome. This interconnectivity shows that a defect in a single gene may not be restricted to the gene product itself, but may spread along the network. So, drug development must be based on the network-based perspective of disease mechanisms. Many systematic diseases like neurodegenerative disorders, cancer and cardiovascular cannot be treated efficiently by the single gene target strategy because these diseases involve the complex biological machinery. In clinical trials, many mono-therapies have been found to be less effective. In mono-therapies, the long term treatment, for the systematic diseases make the diseases able to acquired resistance because of the disease nature of the natural evolution of feedback loop and pathway redundancy. Multi-target drugs might be more efficient. Multi-target therapeutics might be less vulnerable because of the inability of the biological system to resist multiple actions. In this study, we will overview the recent advances in the development of methodologies for the identification of drug target interaction and its application in the poly-pharmacology profile of the drug.

Determining the Balance Between Drug Efficacy and Safety by the Network and Biological System Profile of Its Therapeutic Target

“…For example, the lower value of average closeness centrality of target was reported to demonstrate a less lethality risk (Chen et al, 2011 ), which was consistent with the findings of this study (a much higher average closeness centrality of the targets of NTI drugs was observed compared with that of NNTI ones, shown in Figure 1 ). Moreover, the higher level (lower value) of interconnectivity was frequently observed in lethal diseases such as cardiovascular disorder and cancer (Muhammd et al, 2018 ). Oncological and cardiovascular disorder had been recognized as life-threatening diseases, and the majority of their drugs were reported to be NTI ones (Muller and Milton, 2012 ; Yu et al, 2015 ).…”

Veratrilla baillonii Franch Could Alleviate Lipid Accumulation in LO2 Cells by Regulating Oxidative, Inflammatory, and Lipid Metabolic Signaling Pathways

“…Many studies have shown that the effectiveness of TCM in the complex diseases depends on the synergistic effects of multiple compounds and their targets. Network pharmacology and system biology can explain the effects of drugs on biological network destruction from the perspective of macro or global regulation and provide new research ideas and technical means for studying the mechanism of ethnic drug compounds ( Muhammad et al., 2018 ; Zhang Y. et al., 2018 ). In this study, the complexity of the active ingredients in V. baillonii and the diversity of potential regulatory targets in diseases were studied through network pharmacology analysis.…”

High-dimensionality Data Analysis of Pharmacological Systems Associated with Complex Diseases

“…The ability accurately to appreciate and predict a global somatic impact of pharmacological signaling will likely create a greater understanding of disease etiology and eventual network-level precision drugbased disease remediation (Prill et al, 2011;Hasan et al, 2012;Janssens et al, 2014;Muhammad et al, 2018). The appreciation of a network hypothesis for biologic activity presents many important new avenues for pharmacological research, especially in the aspect of prioritizing the most crucial factors/tissues within a hypercomplex signaling system.…”