Nutritional Profiling, Antioxidant Activity, and <i>In vivo</i> Toxicological Evaluation of <i>Myristica fragrans</i> Seeds: Renal-Protective Insights from Molecular Docking

Abstract Medicinal plants are utilized in the pharmaceutical, nutraceutical, food, and beverage industries for their safety and health-promoting properties. The current study evaluates the nutritional composition, antioxidant activity, ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis, in vivo safety assessment, and the in silico renal-protective effect of Myristica fragrans seed powder and extract. The proximate composition and antioxidant potential of M. fragrans were evaluated by AOAC (Association of Official Agricultural Chemists), along with the TPC (Total Phenolic Contents), FRAP (Ferric Reducing Antioxidant Power), and DPPH (2,2-Diphenyl-1-picrylhydrazyl) methods. For safety assessment, Sprague-Dawley rats were supplemented with M. fragrans seed powder (MFSP) and hydroethanolic extract (MFS-HEE) for 28 days. Additionally, eugenol, Licarin A, and myristicin were assessed for ADMET properties and docked with 4E4D (Crystal structure of the mouse RANKL-OPG complex), using PyRx and Discovery Studio Visualizer. The results showed that M. fragrans seeds comprise fat (26.55%), fiber (12.23%), and protein (15.75%), and hydroethanolic extract exhibited maximum antioxidant activity in DPPH and FRAP assays. Furthermore, safety evaluation revealed no hematological and histopathological adverse effects. The lipid profile was reduced by 600 mg/kg body weight of dried M. fragrans seeds extract. Licarin A revealed the highest binding affinity (-7.6 kcal/mol) with the renal-injury related protein in molecular docking analysis; moreover, eugenol exhibited the highest predicted absorption and safety compared to other compounds in ADMET analysis. In conclusion, MFSP and MFS-HEE are safe and have renal protective potential.