Nobiletin as a Neuroprotectant against NMDA Receptors: An In Silico Approach
Sadaf Jahan,
Neeru Singh Redhu,
Arif Jamal Siddiqui,
Danish Iqbal,
Johra Khan,
Saeed Banawas,
Mohammed Alaidarous,
Bader Alshehri,
Shabir Ahmad Mir,
Mohd Adnan,
Aditya Bhushan Pant
Affiliations
Sadaf Jahan
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
Neeru Singh Redhu
Department of Molecular Biology, Biotechnology and Bioinformatics, Chaudhary Charan Singh Haryana Agricultural University, Hisar 125004, Haryana, India
Arif Jamal Siddiqui
Department of Biology, College of Science, University of Hail, P.O. Box 2440, Hail 55476, Saudi Arabia
Danish Iqbal
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
Johra Khan
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
Saeed Banawas
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
Mohammed Alaidarous
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
Bader Alshehri
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
Shabir Ahmad Mir
Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Al-Majmaah 11952, Saudi Arabia
Mohd Adnan
Department of Biology, College of Science, University of Hail, P.O. Box 2440, Hail 55476, Saudi Arabia
Aditya Bhushan Pant
System Toxicology & Health Risk Assessment Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhavan, 31, Mahatma Gandhi Marg, P.O. Box No. 80, Lucknow 226001, Uttar Pradesh, India
Excitotoxicity is a type of neurodegenerative disorder. It caused by excessive glutamate receptor activation, which leads to neuronal malfunction and fatality. The N-methyl-D-aspartate (NMDA) receptors are found in glutamatergic neurons, and their excessive activation is primarily responsible for excitotoxicity. They are activated by both glutamate binding and postsynaptic depolarization, facilitating Ca2+ entry upon activation. Therefore, they are now widely acknowledged as being essential targets for excitotoxicity issues. Molecular docking and molecular dynamics (MD) simulation analyses have demonstrated that nobiletin efficiently targets the binding pocket of the NMDA receptor protein and exhibits stable dynamic behavior at the binding site. In this study, five potential neuroprotectants, nobiletin, silibinin, ononin, ginkgolide B, and epigallocatechin gallate (EGCG), were screened against the glutamate NMDA receptors in humans via computational methods. An in silico ADMET study was also performed, to predict the pharmacokinetics and toxicity profile for the expression of good drug-like behavior and a non-toxic nature. It was revealed that nobiletin fulfills the criteria for all of the drug-likeness rules (Veber, Lipinski, Ghose, Muegge, and Egan) and has neither PAINS nor structural alerts (Brenks). In conclusion, nobiletin demonstrated a possible promising neuroprotectant activities compared to other selected phytochemicals. Further, it can be evaluated in the laboratory for promising therapeutic approaches for in vitro and in vivo studies.
