Parinari curatellifolia (PC), an indigenous African plant has numerous nutritional, and medicinal benefits, including hepatoprotection. Following the established approach of using plant metabolites as prototype drugs, flavonoids from PC were investigated as potential hepatoprotective therapeutics using in silico approach. Initially, the flavonoids were identified by high performance liquid chromatography (HPLC), afterwards, their drug-likeness, biological activities, and toxicity were predicted using different algorithms and softwares. HPLC revealed 3-methylquercetin, chrysin, kaempferol, quercetin, pinocembrin, tricetin, apigenin, baicalein, genistein, isorhamnetin, and myricetin as prominent flavonoids in PC extract. Furthermore, all the compounds fulfilled Lipinski’s rule of five, were predicted to be non-toxic, and were also shown by prediction of activity spectra for substances to demonstrate probable hepatoprotection mechanisms. Molecular docking of the Parinari flavonoids and Cytochrome P450 1A1 showed binding energy scores ranging from −8.7 to −10.2 kcal/mol, while molecular dynamic simulation confirmed the stability of the complexes formed with ΔGbind ranging from −35.85 to –32.00. Hence, this study establishes the hepatoprotective effect of the natural PC compounds and proposes the activation of Cytochrome P450 1A1 as a major mechanism of action. In addition, a successful effort has been made to validate previously reported flavonoid activities of PCs using a comprehensive computational approach.
Key words: Flavonoids, Hepatoprotective, Molecular dynamic simulation, Parinari curatellifolia, Plant metabolites, Toxicity
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