Identification of the Hypoglycemic Active Components of Lonicera japonica Thunb. and Lonicera hypoglauca Miq. by UPLC-Q-TOF-MS

<i>Lonicera japonica</i> Thunb. and <i>Lonicera hypoglauca</i> are famous Chinese medicines used for hyperglycemia; however, the specific compounds that contributed to the hypoglycemic activity and mechanism are still unknown. In this study, the antidiabetic activity of <i>L. japonica</i> buds and <i>L. hypoglauca</i> buds, roots, stems, and leaves extracts was primarily evaluated, and the <i>L. japonica</i> buds and <i>L. hypoglauca</i> buds, roots, and stems extracts displayed significant hypoglycemic activity, especially for the buds of <i>L. hypoglauca</i>. A total of 72 high-level compounds, including 9 iridoid glycosides, 12 flavonoids, 34 organic acids, and 17 saponins, were identified by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) combined with the fragmentation pathways of standards from different parts of <i>L. japonica</i> and <i>L. hypoglauca</i> extracts. Among them, 19 metabolites, including 13 saponins, were reported for the first time from both medicines. Seven high-content compounds identified from <i>L. hypoglauca</i> buds extract were further evaluated for hypoglycemic activity. The result indicated that neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, and isochlorogenic acid C displayed significant antidiabetic activity, especially for isochlorogenic acid A and isochlorogenic acid C, which demonstrated that the five chlorogenic-acid-type compounds were the active ingredients of hypoglycemic activity for <i>L. japonica</i> and <i>L. hypoglauca</i>. The potential mechanism of hypoglycemic activity for isochlorogenic acid A and isochlorogenic acid C was inhibiting the intestinal α-glucosidase activity to block the supply of glucose. This study was the first to clarify the hypoglycemic active ingredients and potential mechanism of <i>L. japonica</i> and <i>L. hypoglauca</i>, providing new insights for the comprehensive utilization of both resources and the development of hypoglycemic drugs.