Novel gurmarin-like peptides from Gymnema sylvestre and their interactions with the sweet taste receptor T1R2/T1R3.

Gymnema sylvestre (GS) is a traditional medicinal plant known for its hypoglycemic and hypolipidemic effects. Gurmarin (hereafter Gur-1) is the only known active peptide in GS. Gur-1 has a suppressive sweet taste effect in rodents but no or only a very weak effect in humans. Here, 8 gurmarin-like peptides (Gur-2 to Gur-9) and their isoforms are reported in the GS transcriptome. The molecular mechanism of sweet taste suppression by Gur-1 is still largely unknown. Therefore, the complete architecture of human and mouse sweet taste receptors T1R2/T1R3 and their interaction with Gur-1 to Gur-9 were predicted by AlphaFold-Multimer (AF-M) and validated. Only Gur-1 and Gur-2 interact with the T1R2/T1R3 receptor. Indeed, Gur-1 and Gur-2 bind to the region of the cysteine-rich domain (CRD) and the transmembrane domain (TMD) of the mouse T1R2 subunit. In contrast, only Gur-2 binds to the TMD of the human T1R2 subunit. This result suggests that Gur-2 may have a suppressive sweet taste effect in humans. Furthermore, AF-M predicted that Gα-gustducin, a protein involved in sweet taste transduction, interacts with the intracellular domain of the T1R2 subunit. These results highlight an unexpected diversity of gurmarin-like peptides in GS and provide the complete predicted architecture of the human and mouse sweet taste receptor with the putative binding sites of Gur-1, Gur-2, and Gα-gustducin. In addition, gurmarin-like peptides may serve as promising drug scaffolds for the development of antidiabetic molecules.

Suppression of Oral Sweet Sensations during Consumption of Sweet Food in Humans: Effects on Gastric Emptying Rate, Glycemic Response, Appetite, Food Satisfaction and Desire for Basic Tastes.

Suppression of oral sweet sensation (OSS) acutely reduces intake of sweet-tasting food due to lower liking. However, little is known about other physiological responses during both the prandial and postprandial phase. Here, we explored the effects of Gymnema sylvestre (GS)-based suppression of OSS of several types of sweet-tasting food (muffin, sweet yogurt, banana) on gastric emptying, blood glucose (BG), plasma insulin (PI), appetite indices (hunger, fullness and prospective consumption), satisfaction and desire for tastes. Fifteen healthy subjects (22 ± 3 years, 9 women) took part in the study. Subjects rinsed their mouth with either GS solution or distilled water before eating the sweet-tasting food. Subjects felt decreased sweet taste intensity and reduced taste liking associated with GS rinsing after consuming each food, compared with rinsing with distilled water (p < 0.05). Gastric emptying, BG, PI and appetite indices during and after the prandial phase did not significantly change with GS rinsing compared to rinsing with distilled water (p > 0.05). Higher desire for sweet taste as well as lower satisfaction (p < 0.05) in the postprandial phase were observed with GS rinsing. These results suggest that the suppression of OSS does not affect gastric emptying, glycemic response and appetite during and after consumption of sweet-tasting food.