Mega Sonia Pertiwi, Irmanida Batubara, Rizka Fatriani, Setyanto Tri Wahyudi, Wisnu Ananta Kusuma, Trivadila Trivadila, Bambang Pontjo Priosoeryanto
Neurodegenerative diseases are marked by the progressive loss of specific neurons, leading to cognitive and motor impairments. This neurodegeneration occurs gradually and silently over the years, with continuous neuronal cell death before clinical symptoms emerge. Neuroprotection, which seeks to prevent or minimize neuronal damage, has gained increasing attention—particularly through natural compounds—as potential therapeutic agents. Amaranthus has demonstrated antioxidant, neuroprotective, and antidepressant properties; however, further biochemical investigations are required. This study integrates protein–protein interaction network (PPIN) analysis, molecular docking-based virtual screening, and molecular dynamics to identify key neuroprotective targets and bioactive compounds in Amaranthus. PPIN analysis of 27 neuroprotection-related proteins identified key hub proteins, including Dopamine D2 receptor (D2), metabotropic glutamate receptor 2 (mGlu2), 5-hydroxytryptamine receptor 1A (5HT1A), γ-aminobutyric acid B receptor (GABAb), metabotropic glutamate receptor 3 (mGlu3), SERT (serotonin reuptake transporter), cannabinoid type 1 receptor (CB1), Milestones of Recovery Scales (MORs), and monoamine oxidase B (MAOB) that play critical roles in neuronal survival and neurotransmission. Molecular docking-based virtual screening identified 10 ligands targeting MAOB, mGlu2, mGlu3, and GABAb receptors exhibiting lower binding energies than control ligands, suggesting strong interactions. Among these, dihydrokaempferol showed the most favorable profile, combining high binding affinity, strong predicted bioactivity, and interaction stability in molecular dynamics simulations, despite some pharmacokinetic limitations” might better reflect the nature of the findings. These findings highlight the therapeutic potential of Amaranthus-derived compounds for neurodegenerative diseases. © 2025 Visagaa Publishing House.
Department of Chemistry, Faculty of Mathematics and Natural Sciences, IPB University, IPB Dramaga Campus, West Java, Bogor, 16680, Indonesia; Tropical Biopharmaca Research Center, International Research Institute of Food, Nutrition and Health, IPB University, West Java, Bogor, 16128, Indonesia; Biology Study Program, Faculty of Science, Sumatera Institute of Technology, Lampung, Indonesia; Departement of Physics, Faculty of Mathematics and Natural Sciences, IPB University, IPB Dramaga Campus, West Java, Bogor, 16680, Indonesia; Department of Computer Science, Faculty of Mathematics and Natural Sciences, IPB University, IPB Dramaga Campus, West Java, Bogor, 16680, Indonesia; School of Veterinary Medicine & Biomedical Sciences, IPB Dramaga Campus, West Java, Bogor, 16680, Indonesia