Defining the Role of Isoeugenol from <i>Ocimum tenuiflorum</i> against Diabetes Mellitus-Linked Alzheimer’s Disease through Network Pharmacology and Computational Methods
Reshma Mary Martiz,
Shashank M. Patil,
Mohammed Abdulaziz,
Ahmed Babalghith,
Mahmoud Al-Areefi,
Mohammed Al-Ghorbani,
Jayanthi Mallappa Kumar,
Ashwini Prasad,
Nagendra Prasad Mysore Nagalingaswamy,
Ramith Ramu
Affiliations
Reshma Mary Martiz
Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India
Shashank M. Patil
Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India
Mohammed Abdulaziz
Department of Environmental Health, Faculty of Public Health and Health Informatics, Umm Al-Qura University, Makkah 21955, Saudi Arabia
Ahmed Babalghith
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
Mahmoud Al-Areefi
Department of Health Information Management & Technology, Faculty of Public Health and Health Informatics, Umm Al-Qura University, Makkah 21955, Saudi Arabia
Mohammed Al-Ghorbani
Department of Chemistry, College of Science and Arts, Ulla, Taibah University, Madina 41477, Saudi Arabia
Jayanthi Mallappa Kumar
Department of Pharmacology, JSS Medical College, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India
Ashwini Prasad
Department of Microbiology, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India
Nagendra Prasad Mysore Nagalingaswamy
Department of Biotechnology, JSS Science and Technology University, JSS Technical Institutional Campus, Mysore 570006, Karnataka, India
Ramith Ramu
Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru 570015, Karnataka, India
The present study involves the integrated network pharmacology and phytoinformatics-based investigation of phytocompounds from Ocimum tenuiflorum against diabetes mellitus-linked Alzheimer’s disease. It aims to investigate the mechanism of the Ocimum tenuiflorum phytocompounds in the amelioration of diabetes mellitus-linked Alzheimer’s disease through network pharmacology, druglikeness and pharmacokinetics, molecular docking simulations, GO analysis, molecular dynamics simulations, and binding free energy analyses. A total of 14 predicted genes of the 26 orally bioactive compounds were identified. Among these 14 genes, GAPDH and AKT1 were the most significant. The network analysis revealed the AGE-RAGE signaling pathway to be a prominent pathway linked to GAPDH with 50.53% probability. Upon the molecular docking simulation with GAPDH, isoeugenol was found to possess the most significant binding affinity (−6.0 kcal/mol). The molecular dynamics simulation and binding free energy calculation results also predicted that isoeugenol forms a stable protein–ligand complex with GAPDH, where the phytocompound is predicted to chiefly use van der Waal’s binding energy (−159.277 kj/mol). On the basis of these results, it can be concluded that isoeugenol from Ocimum tenuiflorum could be taken for further in vitro and in vivo analysis, targeting GAPDH inhibition for the amelioration of diabetes mellitus-linked Alzheimer’s disease.
