Characterization of the sweetness of natural plant-derived sweeteners mogroside IV and V and their interactions with human sweet taste receptor.

Mogrosides are an important type of natural plant-derived sweeteners, which are used in foods and medicines. However, their sweetness and structure-activity relationship, especially those for the representative members mogrosides IV and V, have been rarely reported. In the present study, we characterized the sweet taste properties (threshold values, etc) of mogrosides IV and V with a cell-based calcium mobilization assay, showing that mogrosides represent a category of primitive sweet compounds which are edible by primates as well as other mammals. Furthermore, it was demonstrated that the sweetness of mogrosides can be inhibited by a classical sweet taste modulator, lactisole. Moreover, the binding site of mogroside IV in human Tas1R2 Venus flytrap domain was identified with the method of molecular docking, which was further validated by functional mutagenesis analysis. These results provide helpful guidelines for further exploring the structure-activity relationship and molecular design of mogrosides.