Thonningia sanguinea extract: Antioxidant and cytotoxic activities supported by chemical composition and molecular docking simulations

Abstract

The current study was designed to investigate the antioxidant and cytotoxic activities of Thonningia sanguinea whole‐plant extract. The total phenolic content was determined using Folin– Ciocalteu reagent and found to be 980.1 mg/g, calculated as gallic acid equivalents. The antioxidant capacity was estimated for the crude extract and the phenolic portion of T. sanguinea, whereupon both revealed a dose‐dependent scavenging rate of DPPH• with EC50 values of 36.33 and 11.14 μg/mL, respectively. Chemical profiling of the plant extract was achieved by LC‐ESI‐TOF‐MS/MS analysis, where 17 compounds were assigned, including ten compounds detected in the negative mode and seven detected in the positive mode. The phenolic portion exhibited promising cytotoxic activity against MCF‐7 and HepG2 cells, with IC50 values of 16.67 and 13.51 μg/mL, respectively. Phenolic extract treatment caused apoptosis in MCF‐7 cells, with total apoptotic cell death 18.45‐ fold higher compared to untreated controls, arresting the cell cycle at G2/M by increasing the G2 population by 39.7%, compared to 19.35% for the control. The apoptotic investigation was further validated by the upregulation of proapoptotic genes of P53, Bax, and caspases‐3,8 9, and the down-regulation of Bcl‐2 as the anti‐apoptotic gene. Bcl‐2 inhibition was also virtualized by good binding interactions through a molecular docking study. Taken together, phenolic extract exhibited promising cytotoxic activity in MCF‐7 cells through apoptosis induction and antioxidant activation, so further fractionation studies are recommended for the phenolic extract for specifying the most ac-tive compound to be developed as a novel anti‐cancer agent.