Identification of α-glucosidase inhibitors in Machilus litseifolia by combined use of high-resolution α-glucosidase inhibition profiling and HPLC-PDA-HRMS-SPE-NMR

TY - JOUR

T1 - Identification of α-glucosidase inhibitors in Machilus litseifolia by combined use of high-resolution α-glucosidase inhibition profiling and HPLC-PDA-HRMS-SPE-NMR

AU - Li, Tuo

AU - Kongstad, Kenneth Thermann

AU - Stærk, Dan

PY - 2019/2/22

Y1 - 2019/2/22

N2 - Type 2 diabetes is a chronic multifactorial disease affecting more than 425 million people worldwide, and new selective α-glucosidase inhibitors with fewer side effects are urgently needed. In this study, a crude ethyl acetate extract of Machilus litseifolia was fractionated by solid-phase extraction using C 18 cartridges to give a fraction enriched in α-glucosidase inhibitors. Subsequent microfractionation and bioassaying of the eluate by high-performance liquid chromatography (HPLC) using a complementary pentafluorophenyl column allowed construction of a high-resolution α-glucosidase inhibition profile (biochromatogram). This was used to target high-performance liquid chromatography-photodiode array detection-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-PDA-HRMS-SPE-NMR) analysis toward α-glucosidase inhibitors. This led to the identification of 13 dicoumaroylated flavonol rhamnosides, of which seven (8, 10, 12a, 12b, 16, 17, and 18) are reported for the first time, and two lignans, of which one (5) is reported for the first time. IC 50 values of isolated compounds toward α-glucosidase range from 5.9 to 35.3 μM, which is 8 to 91 times lower than the IC 50 value of 266 μM measured for the reference compound acarbose.

AB - Type 2 diabetes is a chronic multifactorial disease affecting more than 425 million people worldwide, and new selective α-glucosidase inhibitors with fewer side effects are urgently needed. In this study, a crude ethyl acetate extract of Machilus litseifolia was fractionated by solid-phase extraction using C 18 cartridges to give a fraction enriched in α-glucosidase inhibitors. Subsequent microfractionation and bioassaying of the eluate by high-performance liquid chromatography (HPLC) using a complementary pentafluorophenyl column allowed construction of a high-resolution α-glucosidase inhibition profile (biochromatogram). This was used to target high-performance liquid chromatography-photodiode array detection-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-PDA-HRMS-SPE-NMR) analysis toward α-glucosidase inhibitors. This led to the identification of 13 dicoumaroylated flavonol rhamnosides, of which seven (8, 10, 12a, 12b, 16, 17, and 18) are reported for the first time, and two lignans, of which one (5) is reported for the first time. IC 50 values of isolated compounds toward α-glucosidase range from 5.9 to 35.3 μM, which is 8 to 91 times lower than the IC 50 value of 266 μM measured for the reference compound acarbose.

U2 - 10.1021/acs.jnatprod.8b00609

DO - 10.1021/acs.jnatprod.8b00609

M3 - Journal article

C2 - 30668111

SN - 0163-3864

VL - 82

SP - 249

EP - 258

JO - Journal of Natural Products

JF - Journal of Natural Products

ER -