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

LC-MS-guided pliytocheinical 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 malonylsubstituted triterpenoid saponins. They include 15 new malonylginsenosides, malonylfloralginsenosides-Re-1-Re-3 (1-3), -Rb-1 and -Rb-2 (4, 5), -Rd(1)-Rd(6) (6=11), and -Rc(1)-Rc(4) (12-15); and the known m-Rb-1, m-Rc, m-Rb-2, and m-Rd (16-19). CompOund 11 represents the first dimalunyl saponin isolated from the Panax genus, while 2-4, 9, :and TO 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) arid five of the corresponding non-malonyl ginsenosides (Re, Rb-1, Rb-2, Rc, and Rd) were evaluated by L6 myotubes' glucose consumption and AMPK alpha 2 beta 1 gamma 1 activation. Ginsenoside Rb-2, 1, and 18 promoted glucose consumption of differentiated L6 imyotubes, while ginsenosides Rb-1, Rb-2, and Rd and the malonylginsenosides 4, 8, 13, 16, 17, arid 19 activated AMPK alpha 2 beta 1 gamma 1 (EC50: 0:0168-2.8 mu M, fold: 1.7-4.7).