Deciphering Antidiabetes Functional Foods Properties of Graptophyllum pictum via Integrated In Silico and In Vitro Study

The search for natural antidiabetic agents has highlighted Graptophyllum pictum (L.) Griff. (known also as Red African leaf) as a promising candidate due to its traditional medicinal use and emerging scientific evidence. This study integrates metabolomic profiling, in silico docking, and in vitro enzyme inhibition assays to explore the antidiabetic potential of Graptophyllum pictum L. Griff (G. pictum) leaf extracts. High-resolution LC–MS/MS analysis identified nine metabolites across polar, semipolar, and nonpolar fractions, including bicine, phloroglucinol, isorhamnetin, kaempferide, rhamnazin, astaxanthin, limonin, diosgenin, and stigmasterol. Structure– activity relationship (SAR) and ADMET analyses revealed bicine and phloroglucinol as strong insulysin (insulin-degrading enzyme, IDE) inhibitor (Pa >0.70) with acceptable drug-likeness and low toxicity. Molecular docking showed that limonin, stigmasterol, astaxanthin, and diosgenin displayed high binding affinities toward diabetes-related targets (GLP-1R, INSR, PPARγ, α-glucosidase, and α-amylase), often exhibiting stronger predicted binding affinities than metformin in silico. Consistently, in vitro assays demonstrated that polar (ALEP) and semipolar (ALESP) extracts exhibited potent, dose-dependent inhibition of α-amylase and α-glucosidase, respectively. The findings support G. pictum as a viable source of bioactive compounds for developing bioactive compound candidates with antidiabetic potential, warranting further in vivo and clinical validation. The findings of the proposed research paper position G. pictum as a viable reservoir of antidiabetic candidates that act via complementary mechanisms. However, these findings are preliminary and require further validation through in vivo and pharmacokinetic studies. Priority next steps include isolation and quantification of actives, mechanistic validation beyond docking, pharmacokinetics, and in vivo efficacy and safety to enable translational development.