Phytochemical constituents of <i>Hydrangea macrophylla</i> var. <i>acuminata</i> leaves and their inhibitory activity against PTP1B and α-glucosidase

This study presents the first comprehensive phytochemical analysis of <i>Hydrangea macrophylla</i> var. <i>acuminata</i> leaves, resulting in the isolation of 41 secondary metabolites, including four new compounds: one phenolic (<b>3</b>) and three bis-iridoid glycosides (<b>30</b>-<b>32</b>). The inhibitory activities of these compounds against PTP1B and α-glucosidase were evaluated. Among them, compound <b>12</b> exhibited the most potent dual inhibition, with IC₅₀ values of 8.0 ± 1.1 µM for PTP1B and 3.4 ± 0.2 µM for α-glucosidase. Compounds <b>8</b> and <b>9</b> showed notable α-glucosidase inhibitory activity, with IC₅₀ values of 21.9 ± 0.4 µM and 43.8 ± 2.1 µM, respectively. Enzyme kinetics and molecular docking studies revealed their inhibition mechanisms and binding interactions. This study is the first detailed phytochemical investigation of <i>H. macrophylla</i> var. <i>acuminata</i> and highlights its potential as a natural source of PTP1B and α-glucosidase inhibitors. These findings underscore the plant's promise for developing antidiabetic agents targeting PTP1B and α-glucosidase.