Computational Evaluation of Phenolics and Flavonoids from Bryophyllum Pinnatum as Potential Inhibitors for Dipeptidyl Peptidase-4 and Sodium-Glucose Cotransporter-2

ABSTRACT Bryophyllum pinnatum, a medicinal plant known for its diverse pharmacological properties, has been explored in this study for its potential to inhibit dipeptidyl peptidase 4 (DPP-4) and sodium-glucose co-transporter 2 (SGLT2), two critical targets in the management of type 2 diabetes mellitus. The bioactive compounds of Bryophyllum pinnatum were screened using GC-MS Analysis. The GCMS analysis revealed the presence of 7 flavonoids and 10 phenolic compounds from Bryophyllum pinnatum. Molecular docking was performed by maestro Schrödinger generation module 11.5. and visualized in Biovia Discovery Studio and PyMol, respectively and the 10 phenolic and 7 flavonoid compounds present in Bryophyllum pinnatum were evaluated for their binding affinity and inhibitory potential against DPP-4 and SGLT2. Molecular docking studies revealed the binding affinity of the flavonoids and phenolic compounds to range between -8.723 to -2.522 Kcal/mol and -9.346 to -5.088 Kcal/mol for Dipeptidyl peptidase -4 and sodium glucose co-transporter 2 respectively. Myricetin-3- glucoside, Cyanidin -3- glucosidase, Quercetin -3-O-B-D- glucosidase and Cyanidin showed higher binding affinity compared to the standard drugs, Alogliptin, Vildaglitpin and Sitagliptin for dipeptidyl peptidase 4 while 2,3,4- trihydroxybenzoic acid has a lower binding affinity when compared to the standard drugs canagliflozen, dapagliflozin and empagliflozin. The interactions between the plant-derived compounds and the active sites of both enzymes, suggesting a promising inhibitory effect for dipeptidyl peptidase 4 than sodium glucose co-transporter 2. These Key compounds demonstrated high binding energies and favorable interactions, indicating their potential as inhibitors. This computational evaluation highlights the therapeutic promise of Bryophyllum pinnatum constituents in management of diabetes, warranting further experimental validation and development of these compounds into effective antidiabetic agent