Phenylpropanoids from the Nitraria tangutorum fruit as glycerol phosphate dehydrogenase inhibitors through in vitro, in silico and in vivo studies

The fruit of Nitraria tangutorum, often known as "desert cherry", has been proven to have hypoglycemic effect, but its chemical composition and hypoglycemic mechanism remain unclear. In this study, phenylpropanoids in N. tangutorum were rapidly and efficiently discovered by UPLC-MS guided separation. Through multi-chromatographic separation and NMR identification, a total of fifteen phenylpropanoids were identified, which were mono-phenylpropanoids (1-3), phenylpropanoid glycosides (4-11), and di-phenylpropanoids (12-15), respectively. All the compounds (1-15) were obtained from this species for the first time. In order to verify the target of N. tangutorum for its hypoglycemic effect, a target network of "phenylpropanoids-type 2 diabetes (T2DM)" was constructed by network pharmacology method. The results showed that glycerol phos-phate dehydrogenase inhibitory experiment (GPDH, PDB: 1WPQ) was the most likely hypoglycemic target of the compounds. Therefore, GPDH inhibitory experiment and molecular docking simulation were used to verify its effect. The results showed that phenylpropanoids had good inhibitory activities, especially di-phenylpropanoid compound 13. The same results also appeared in HFD induced T2DM model mice. The above studies demon-strated that phenylpropanoids, especially di-phenylpropanoids, were the chemical basis for the glucose regu-lating effects of N. tangutorum, and its target may be GPDH, from in vitro, molecular simulation and in vivo perspectives. This study provided a basis for the development of N. tangutorum fruit as a hypoglycemic functional food.