Malonylginsenosides with Potential Antidiabetic Activities from the Flower Buds of Panax ginseng

LC-MS-guided phytochemical isolation of malonylginsenosides, featuring neutral elimination of CO₂ and C₃H₂O₃ by the negative mode collision-induced dissociation, from the flower buds of Panax ginseng led to the isolation of 19 malonyl-substituted triterpenoid saponins. They include 15 new malonylginsenosides, malonylfloralginsenosides-Re₁-Re₃ (1-3), -Rb₁ and -Rb₂ (4, 5), -Rd₁-Rd₆ (6-11), and -Rc₁-Rc₄ (12-15), and the known m-Rb₁, m-Rc, m-Rb₂, and m-Rd (16-19). Compound 11 represents the first dimalonyl saponin isolated from the Panax genus, while 2-4, 9, and 10 are five ginsenosides with single malonylation at the C-20 sugar chain. The antidiabetic activities of nine of these malonyl-substituted ginsenosides (1, 3, 4, 8, 13, and 16-19) and five of the corresponding non-malonyl ginsenosides (Re, Rb₁, Rb₂, Rc, and Rd) were evaluated by L6 myotubes' glucose consumption and AMPKα2β1γ1 activation. Ginsenoside Rb₂, 1, and 18 promoted glucose consumption of differentiated L6 myotubes, while ginsenosides Rb₁, Rb₂, and Rd and the malonylginsenosides 4, 8, 13, 16, 17, and 19 activated AMPKα2β1γ1 (EC₅₀: 0.0168-2.8 μM, fold: 1.7-4.7).