Optimization of MAE for Carica papaya phytochemicals, and its in silico, in vitro, and ex vivo evaluation: For functional food and drug applications

Abstract

The present research aims to establish its scientific basis by proposing and validating the hypothesis that bioactive phytochemicals of Carica papaya can be an ideal functional food and drug compound for the management of diabetes mellitus. The in silico molecular docking and pharmacokinetic analysis of phytochemicals of C. papaya revealed that the phytochemicals have a high potential to inhibit α-amylase and α-glucosidase enzymes (−9.3 to −7.7 kcal/mol), responsible for post-prandial high blood glucose level and low to moderate level of absorption, distribution, metabolism and excretion (ADME) and toxicity. The experimental design was set up for industrial application for high-yield recovery of bioactive components from C. papaya leaf. The microwave-assisted extraction optimized response variables from 17 experimental runs, like total phenol content, total flavonoid content, total tannin content, and antioxidant activities (1,1-diphenyl-2-picrylhydrazyl and ferric-reducing antioxidant power) were obtained at a temperature of 61 °C at a microwave power level of 807 W and 45 min of processing. The phytochemical screening, thin-layer chromatography, Ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, and liquid chromatography-mass spectrometry spectral analysis revealed the presence of 18 out of 21 reported major phytochemicals of C. papaya. The in vitro enzymatic activity indicated high inhibition for α-amylase (IC50 40.03 ± 2.61 μg/mL) and α-glucosidase (IC50 66.52 ± 1.52 μg/mL) enzymes. The hemolytic activity was found to be less than 5% compatible with ISO standards for the intervention of biomaterials. Furthermore, the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and chorioallantoic membrane assay assays suggested low toxicity at the concentration of up to 62.5 μg/mL. This study will help food and pharmaceutical researchers, scientists, and industrialists produce antidiabetic food compositions and medications to help diabetics manage their diabetes and enhance their health.