In Silico, In Vitro and Ex Vivo Evaluation of the Antihyperglycaemic, Antioxidant and Cytotoxic Properties of Coccinia grandis L. Leaf Extract

Research background. Coccinia grandis (L.) is traditionally used for the management of diabetes mellitus. Since, scientific evidence and the mechanism of action have yet to be investigated extensively, this study aimed to evaluate the antidiabetic and cytotoxic effects together with the optimization and development of a scale-up process design for higher yields of bioactive phytocompounds from C. grandis. Experimental approach. The in silico study was performed to predict the binding affinity of phytocompounds of C. grandis for α-amylase and α-glucosidase enzymes involved in the pathophysiology of diabetes with pharmacokinetic assessment. Response surface methodology was employed to determine the optimum values for TPC, TFC, TTC and antioxidant activities (DPPH and FRAP) across 17 separate experimental runs that varied microwave-assisted extraction parameters like temperature (50–70 °C), power (400–1000 W) and time (15-45 min). The purification and identification phytocompounds were done by column chromatography, TLC, UV-Visible, FTIR and LC-MS spectral analysis, respectively. The in vitro antidiabetic activity was done by α-amylase and α-glucosidase enzymatic inhibitory assay while cytotoxic investigations were done by percentage hemolytic activity, MTT and CAM assay. Results and conclusions. The reported major bioactive compounds have demonstrated an excellent binding affinity for α-amylase and α-glucosidase enzymes in the range of 3.7 to 8.6 kcal/mol with good pharmacokinetic properties and toxicities ranging from low to medium. The bioactive constituents such as TPC, TFC, TTC and antioxidant activities like DPPH and FRAP were found to be high and depend on the microwave-assisted optimized extraction parameters like temperature, time and power: 55 °C, 45 min, and 763 W, respectively. Sixteen compounds were identified by their FTIR and LC-MS spectra in the plant sample after preliminary identification, purification and TLC. The percentage enzyme inhibition was dependent on the concentration of the extract (7.81–125 µg/mL), and was found to be higher than acarbose. The hemolytic activity was found to be compatible with ISO standards and in MTT and CAM assay, low toxicity was observed in the range 7.81−125 µg/mL, which supports its potential use as antidiabetic drug formulation as well as functional food development. Novelty and scientific contribution. Researchers, scientists, and businesspeople in the food and pharmaceutical sectors will have new opportunities due to the study's findings to develop antidiabetic food formulations and medications to help diabetics for better control their condition and maintain overall health.