Establishing network pharmacology between natural polyphenols and Alzheimer’s disease using bioinformatic tools – An advancement in Alzheimer’s research
Arunkumar Subramanian, T. Tamilanban, Vetriselvan Subramaniyan, Mahendran Sekar, Vipin Kumar, Ashok Kumar Janakiraman, Saminathan Kayarohanam
Abstract
Alzheimer’s disease (AD) is a major cause of disability and one of the top causes of mortality globally. AD remains a major public health challenge due to its prevalence, impact on patients and caregivers, and the current lack of a cure. In recent years, polyphenols have garnered attention for their potential therapeutic effects on AD. The objective of the study was to establish network pharmacology between selected polyphenols of plant origin and AD. Insilico tools such as SwissADME, ProTox3.0, pkCSM, Swiss Target Prediction, DisGeNET, InterActiVenn, DAVID database, STRING database, Cytoscape/CytoHubba were employed to establish the multi-target potential of the polyphenolic compounds. The present study revealed that out of 17 polyphenols, 10 ligands were found to possess a drug-likeness nature along with desirable pharmacokinetic parameters and a lesser toxicity profile. Also, the results highlighted the possible interactions between the polyphenols and the disease targets involved in AD. Further, this study has shed light on the mTOR pathway and its impact on AD through the autophagic mechanism. Overall, this study indicated that polyphenols could be a better therapeutic option for treating AD. Hence, the consumption of polyphenolic cocktails as a part of the diet could produce more effective outcomes against the disease. Additional studies are warranted in the future to explore additional pathways and genes to provide a comprehensive understanding regarding the usage of the shortlisted polyphenols and their derivatives for the prevention and treatment of AD. • The study identified 10 out of 17 polyphenols with favorable drug-likeness and lower toxicity, indicating their potential as therapeutic agents for Alzheimer's disease (AD). • A range of in silico tools, including SwissADME, ProTox3.0, Swiss Target Prediction, and others, were used to establish the network pharmacology of polyphenols, revealing their multi-target potential in AD treatment. • The study highlighted the mTOR pathway's role in AD and its impact through the autophagic mechanism, providing a deeper understanding of the disease's pathology and potential intervention points. • The findings suggest that incorporating polyphenolic cocktails into the diet could enhance therapeutic outcomes against AD, offering a practical approach to disease management. • The study calls for further research to explore additional pathways and genes to comprehensively understand the efficacy and mechanisms of polyphenols and their derivatives in preventing and treating AD.