In-Silico Study of Bioactive Compounds from Moringa oleifera Fruit as Anti Premature Senescence Agents in Cardiac Cells: A Study on the p53 Protein

Abstract

Background: Cellular senescence, characterized by irreversible cell cycle arrest, contributes significantly to the pathogenesis of cardiovascular diseases through mechanisms involving oxidative stress and activation of p53-mediated signaling. Moringa oleifera, widely recognized for its antioxidant properties, has demonstrated anti-aging effects; however, the specific bioactive compounds within its fruit and their mechanisms of action remain poorly understood. Objective: This study aimed to investigate the potential of M. oleifera fruit-derived compounds as anti-premature senescence agents targeting the p53 protein using in-silico molecular docking approaches. Methods: Bioactive compounds from M. oleifera fruit were screened via molecular docking against the human p53 protein, with Nutlin-3 used as a positive control. Binding affinities, hydrogen bonding, and hydrophobic interactions were analyzed to determine ligand–receptor interactions. Results: Niacin and oxalic acid exhibited stronger binding affinities (–5.90 and –6.00 kcal/mol, respectively) compared to Nutlin-3 (–5.64 kcal/mol). Niacin formed stable hydrogen bonds and hydrophobic interactions with key residues within the p53 active site, suggesting a capacity to modulate p53 activity. Oxalic acid demonstrated the highest binding affinity but lacked hydrogen bonding, indicating potential instability despite strong interaction. These findings support previous studies highlighting M. oleifera’s role in ROS suppression and p53 modulation, pointing to its therapeutic relevance in mitigating cellular aging. Conclusion: Niacin and oxalic acid from M. oleifera exhibit promising binding characteristics as modulators of the p53 pathway. Their anti-senescence potential warrants further validation through molecular dynamics simulations and biological assays. This study supports the development of natural compound-based therapeutics for age-related cardiac degeneration.