Isolation of D Pintol from Glycin Max L Merr Plant and Evaluation of its Effects on Doxorubicin Induced Genotoxicity and Cytotoxicity in Normal Cells Via Induction of p53 Pathway

Abstract

The present research was intended to isolate D-P from young Soybean plants in a simple, convenient, less time-consumable, and economically profitable method. This objective was achieved by isolating D-P from Glycine max L. Merr. plants using the Vacuum Liquid Chromatography technique after being extracted with the Soxhlet apparatus. 2.079 g of D-P was isolated from 2.2 Kg of powder material of the aerial parts of Soybean plant. As a result, the VLC technique tends to be the ideal technique for isolating D-P from Soybean plants. The present investigation revealed the protective effect of the Isolated D-P against DOX-mediated genotoxicity and cytotoxicity in normal cells through the activation of p53 expression. In the in silico molecular docking work, the docking score obtained from Autodoc 4.0 software revealed that the compound of interest, D-P (Ligand), had good glide scores for binding affinity with the proteins p53 and NF-and#954;B (p65). Hence the D-P was reported to have a strong binding affinity for the proteins p53 and NF-and#954;B (p65). As a result, D-P could be considered as an excellent activator for signaling these proteins. Furthermore, Western blot analysis revealed that D-P activated p53 expression while suppressed NF-and#954;B (p65) expression in kidney, liver, and heart tissues. In vivo antioxidant assays of different enzymes and lipid peroxidation assay revealed that the antioxidant action of D-P significantly decreased DOX-induced free radical generation and oxidative stress. In in vitro and in vivo genotoxicity tests, D-P showed protection against DOX-mediated oxidative DNA damage, chromosomal aberration, and sperm shape abnormalities. In conclusion, the current study proved D-P s protective role against DOX-induced genotoxicity and cytotoxicity through its antioxidant and anti-inflammatory property and stimulation of the p53 signaling pathway for antioxidant activity; D-P could be used as adjuvant therapy for DOX chemotherapy to mitigate DOX-mediated genotoxicity and cytotoxicity.