DPP-IV Inhibitory Activity of the Ethanolic Extract of Red Gedi Leaves Abelmoschus manihot L. Medic

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BACKGROUND: At present, there are many drugs used to manage diabetes including dipeptidyl peptidase-4 (DPP-IV) inhibitors which target insulin secretion. Abelmoschus manihot L. Medic, an endemic species of Minahasa, Indonesia, has been used as an antidiabetic herbal medicine. AIM: In this study, we studied its metabolites activities, in silico and in vitro, as inhibitor for DPP-IV, thus regulating insulin secretion. RESULTS: Of 38 identified metabolites, when docked into the catalytic site DPP-IV, 10 showed good binding energy within range of the standard gliptin drugs, that is, hibiscetin, gossypentin, gossypetin - 3-glucoside, myricetin, myricetin 3-glucoside, alpha spinasterol, quercetin, syringaresinol, stigmasterol, and isoquercetin. Three of those ten metabolites showed Ki within standard drugs values, that is, gossypetin, alpha spinasterol, and stigmasterol. The profile of molecular dynamic simulation, total energy and root mean square deviation of those metabolites were all similar with the standard gliptin drugs and predicted good stability of the complexes. The subsequent in vitro assay determining DPP-IV activity of the red Gedi leaves extract demonstrated that indeed the extract inhibited DPP-IV activity with IC50 860.67 μg/mL. Further studies are ongoing to prove the antidiabetic properties of the whole as well as isolated single compounds of the extract in particular gossypetin, alpha spinasterol, and stigmasterol as DPP-IV inhibitors. CONCLUSION: Our in silico studies showed that the compounds of ethanolic extract of red Gedi leaves potentially serve as DPP-IV inhibitors. Based on computed binding affinity, Ki, total energy, RMSD, and stability, the most potent compounds of the extract to inhibit DPP-IV activity are probably gossypetin, alpha spinasterol, and stigmasterol.