Analytical conditions of UPLC-MS

The Acquity UPLC system (Waters, Milford, MA, United States) was used for chromatographic separations, which was equipped with an Acquity UPLC BEH C18 analytical column (I.D. 2.1 mm × 100 mm, particle size 1.7 μm, pore size 130 Å). MS detection was performed with a mass spectrometer, which was equipped with an electrospray ionization source, using the negative ion electrospray mode. The nitrogen drying gas was set at a velocity of 600 L/h, and the temperatures of source and desolvation were 120 °C and 350 °C, respectively. The cone gas velocity was 50 L/h. The sampling cone voltage was set at 40.0 and the capillary voltage at 3.0 kV; the collision gas was argon, and the collision energy was set at 5.0 eV. According to the stability of the individual metabolites, tandem MS (MS/MS) analyses were performed with the mass spectrometer set at various collision energies, ranging from 30 to 80 eV.