Gymnetipregosides A-G, C₂₁ steroidal glycosides from Gymnema tingens and their glucose uptake bioactivities

Seven new C₂₁ steroidal glycosides, gymnetipregosides A - G (1-7), along with six known analogues, 12-O-cinnamoyl-20-O-nicotinoyl(20S)-pregn-6-ene-3β,5α,8β,12β,14β,17β,20-heptaol (8), 20-O-benzoyl-12-O-cinnamoyl-3β,5α,8β,12β,14β,17β,20-hepta-hydroxy-(20S)-pregn-6-ene (9), sylvepregoside A (10), gymnepregoside L (11), prosapogenin (12), and penupogenin-6-deoxy-3-O-methyl-β-D-allopyranosyl-(1 → 4)-oleandropyranosyl-(1 → 4)-β-D-cymaropyranosyl-(1 → 4)-β-D-cymaropyranoside (13) were isolated from the ethyl acetate fraction of the roots and stems of Gymnema tingens. Their structures were elucidated on the basis of extensive spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and comparison with the reported data. All isolated compounds were evaluated for their effects on glucose uptake in L6 myotubes. At a concentration of 50 μM, compounds 1, 5, 7-9, 11, and 13 significantly increased glucose uptake by 1.39- to 1.89-fold. Subsequent cytotoxicity assays indicated that compounds 1, 5, 7, 8, 11, and 13 exhibited minimal cytotoxic effects. Further dose-response experiments demonstrated that compounds 8 and 11 showed the most potent activities at a concentration of 25 μM, increasing glucose uptake by 2.06- and 2.02-fold, respectively.