Evaluation of the Antidiabetic Potential of Selected Bioactive Compounds from Yam Bean (Pachyrhizus erosus): A preliminary in silico study

Abstract

Diabetes mellitus is one of the most significant global public health challenges, with a steadily increasing prevalence, particularly in low- and middle-income countries. Despite the availability of several therapeutic options, their limitations and adverse effects underscore the urgent need for the discovery of novel antidiabetic agents. Natural products remain a valuable source of bioactive compounds with considerable potential for drug development. This study aimed to evaluate the antidiabetic potential of seven bioactive compounds isolated from yam bean (Pachyrhizus erosus) using an in silico approach combining physicochemical characterization, pharmacokinetic and toxicological profiling, and molecular docking analysis. The selected compounds, dolineone, daidzin, daidzein, genistein, gentisic acid, neodulin, and erosone were initially assessed for their physicochemical properties and drug-likeness using SwissADME. Their pharmacokinetic and toxicity profiles (ADMET) were subsequently predicted using pkCSM and ADMETlab 2.0. Molecular docking simulations were then performed against α-glucosidase (PDB ID: 3W37), a key therapeutic target involved in carbohydrate digestion and postprandial glucose regulation. The results demonstrated that most of the investigated compounds possessed physicochemical properties consistent with good oral bioavailability and exhibited favorable pharmacokinetic profiles. Toxicological predictions indicated a low risk of toxicity, including the absence of predicted hepatotoxicity for all compounds. Molecular docking analysis showed that all seven compounds interacted with the active site of α-glucosidase. Among them, daidzin exhibited the strongest binding affinity (−8.3 kcal/mol), surpassing that of the reference inhibitor acarbose (−8.0 kcal/mol). Furthermore, daidzin formed multiple interactions with key catalytic amino acid residues, suggesting a high inhibitory potential against α-glucosidase. Overall, these findings highlight the potential of bioactive compounds from Pachyrhizus erosus, particularly daidzin, as promising candidates for the development of novel α-glucosidase inhibitors for diabetes management. However, further in vitro and in vivo studies are warranted to validate their biological activity, elucidate their mechanisms of action, and assess their therapeutic efficacy and safety.