Bioactive compound identification and in vitro evaluation of antidiabetic and cytotoxic potential of Garcinia atroviridis fruit extract

With a continuous threat of type 2 diabetes mellitus (T2DM) worldwide, efforts to discover new alternatives are ongoing for its management. Therefore, the use of natural herbal products is promising to achieve this goal as it has been reported to have fewer side effects compared to synthetic drugs. Garcinia atroviridis is one of the plants that has been reported to have various therapeutic functions, including antioxidant, antimicrobial, anticancer, anti-inflammatory, and antihyperlipidemic. This study aimed to identify the bioactive compounds and evaluate the antidiabetic and cytotoxic potential of G. atroviridis fruit aqueous crude extract. The G. atroviridis fruit extract demonstrated promising inhibitory potential against the alpha-amylase and alpha-glucosidase enzymes with half -maximal inhibitory concentration (IC50) of 211 +/- 0.74 mu g/ml and 963 +/- 0.85 mu g/ml, respectively. While the IC50 cytotoxicity concentrations of G. atroviridis extract on L6 cells for 24 h, 48 h, and 72 h, are 0.96 +/- 0.11 mg/ ml, 0.63 +/- 0.5 mg/ml and 0.45 +/- 0.3 mg/ml, respectively. It was noted that the IC50 for alpha-glucosidase inhibition was higher than the IC50 of L6 cells cytotoxicity for 48 h, and 72 h, however the extract still proved to be viable to help in managing diabetes at lower concentration since there are other properties in the extract that can potentially help in targeting other diabetic therapeutic candidates, such as alpha-glucosidase. Further, through LCMS chromatographic analysis, a library of 62 chemical constituents was generated. These were put up for further pharmacological screening and molecular docking analyses, and we short-listed 18 potent antidiabetic bioactive compounds. Besides, molecular dynamics (MD) simulation was performed, which showed stable ligand-protein complexes. In conclusion, the findings of this research demonstrated that G. atroviridis fruit extract could be an excellent source of bioactive compounds with promising antidiabetic potential.