Metabolic profiling, histopathological anti-ulcer study, molecular docking and molecular dynamics of ursolic acid isolated from Ocimum forskolei Benth. (family Lamiaceae)

Abstract Ocimum forskolei (Habak), Lamiaceae, is an endemic species from Yemen and KSA; where our present study was aimed at investigating the Metabolic profiling coupled with LC HR-MS analysis of the dichloromethane fraction from the aerial parts of that plant with a special emphasis on ursolic acid as the major predominating compound from this fraction. Histopathological evaluation of ursolic acid in different doses against indomethacin-induced ulcers in rats revealed a highly significant and dose dependent protection. With the dose level of 50 mg/kg b.w., Ursolic acid gave an ulcer index of 1.33 ± 0.33 and 97.8% inhibition, compared to cimetidine as a standard with 3.0 ± 0.58 and 95.2%. To rationalize this activity, docking on various macromolecular targets was performed, followed by molecular dynamics on the most promising target; the M3 receptor. A high binding energy of -344 kJ/mol is predicted between Ursolic acid and the protein indicating the stability of the predicted pose.