Safety assessment of Detarium microcarpum Guil. & Perr. (Leguminosae) root bark extract in rats: Acute, sub-acute toxicity, ADMET, molecular docking, and molecular dynamics simulations approach

Since the last decades, Detarium microcarpum have been used and studied due to the significant properties to threat various ailments. It is therefore crucial to ascertain the safety properties of is phytoconstituents. The present study was taken up to investigate the oral acute toxicity, 28 days repeated oral sub-acute toxicity study of D. microcarpum root bark extract in Albino Wistar rats, molecular docking, and molecular dynamic simulation. Based on acute oral toxicity, the LD₅₀ value of the extract was considered “non-toxic” up to a 5000 mg/kg b.w. The regular administration of the extract post 28-day treatment was also qualified as safe based on the body and organ weight, hematological, biochemical, and histopathological results in the sub-acute toxicity assay. The majority of the previous identified and isolated compounds passed the ADMET analysis, and the molecular docking identified 1,7-dihydroxy-6-methylxanthone (15) as the top one candidate with an effective binding affinity of −8.1, and − 7.5 (kcal/mol), for P450 and UGT2B7 proteins respectively. This compound was then further assessed using MD simulation, which verified the molecule's stability and binding to the targeted protein. Collectively these data build the foundation of support demonstrating that D. microcarpum root bark extract could be considered as a promising medicinal drug and concluded its suitable used for pharmacological purposes.