Protein tyrosine phosphatase 1B and α-glucosidase inhibitory activities of Pueraria lobata root and its constituents

Ethnopharmacological relevance Pueraria lobata root was used to treat wasting-thirst regarded as diabetes mellitus and was included in the composition of Okcheonsan, which is prescribed for thirst-waste in traditional Chinese medicine. Aim of the study The objective of this study was to evaluate the anti-diabetic potential of the root of Pueraria lobata and its constituents via protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase inhibitory activities. Materials and methods In this study, anti-diabetic activities of the 70% ethanolic (EtOH) extract from P. lobata roots and its solvent soluble fractions with the isolated compounds were investigated by evaluating in vitro PTP1B and α-glucosidase inhibitory activities. We also examined the potentials of active compounds as PTP1B and α-glucosidase inhibitors via enzyme kinetics and in silico molecular docking simulation between the enzymes and active compounds. Results Triterpenoids lupeol and lupenone were potent PTP1B inhibitors with IC₅₀ values of 38.89±0.17 and 15.11±1.23 μM. Kinetic study using the Lineweaver-Burk and Dixon plots demonstrated that these compounds showed a noncompetitive-type inhibition against PTP1B with respective K_i values of 13.88 μM and 21.24 μM. In addition, molecular docking simulation showed lupeol and lupenone has negative binding energy values of −8.03 and −8.56 kcal/mol. Considering the α-glucosidase inhibitory potential, daidzein, genistein, and calycosin exhibited the most potent α-glucosidase inhibition with IC₅₀ values of 8.58±0.94, 2.37±0.52 and 6.84±1.58 μM, respectively. Kinetic study demonstrated that these 3 compounds showed a noncompetitive-type inhibition against α-glucosidase with respective K_i values of 17.64 μM, 5.03 μM and 13.83 μM. Moreover, molecular docking simulation showed daidzein, genistein and calycosin has more lower binding energy (−7.16 kcal/mol, −7.42 kcal/mol and −7.31 kcal/mol) with higher binding affinity and tight binding capacity in the molecular docking studies than standard ligand α-D-glucose (−6.74 kcal/mol). Conclusion Our results of the present study clearly demonstrate the potential of P. lobata extract and its constituents to inhibit PTP1B and α-glucosidase, contributing to the development of therapeutic or preventive agents that can be used in the treatment of diabetes.