title: Gymnemic acids inhibit sodium-dependent glucose transporter 1.
abstract: To evaluate the activity of botanicals used in Chinese Traditional Medicine as hypoglycemic agents for diabetes type II prevention and/or treatment, extracts prepared from 26 medicinal herbs were screened for their inhibitory activity on sodium-dependent glucose transporter 1 (SGLT1) by using two-electrode voltage-clamp recording of glucose uptake in Xenopus laevis oocytes microinjected with cRNA for SGLT1. Showing by far the strongest SGLT1 inhibitory effect, the phytochemicals extracted from Gymnema sylvestre (Retz.) Schult were located by means of activity-guided fractionation and identified as 3-O-β-D-glucuronopyranosyl-21-O-2-tigloyl-22-O-2-tigloyl gymnemagenin (1) and 3-O-β-D-glucuronopyranosyl-21-O-2-methylbutyryl-22-O-2-tigloyl gymnemagenin (2) by means of LC-MS/MS, UPLC-TOF/MS, and 1D/2D-NMR experiments. Both saponins exhibited low IC50 values of 5.97 (1) and 0.17 μM (2), the latter of which was in the same range as found for the high-affinity inhibitor phlorizin (0.21 μM). As SGLT1 is found in high levels in brush-border membranes of intestinal epithelial cells, these findings demonstrate for the first time the potential of these saponins for inhibiting electrogenic glucose uptake in the gastrointestinal tract.
authors.affiliation: Chair of Food Chemistry and Molecular Sensory Science, Technische Universitaet Muenchen , Lise-Meitner-Straße 34, D-85354 Freising, Germany.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Corinna
authors.initials: C
authors.lastname: Dawid
authors.forename: Gabor
authors.initials: G
authors.lastname: Kottra
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D031104:Gymnema sylvestre / Q000737:chemistry; D006801:Humans; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry*; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D004365:Drugs, Chinese Herbal; D012503:Saponins; D051269:Sodium-Glucose Transporter 1; D014315:Triterpenes; C007898:gymnemic acid; D005947:Glucose