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 Hydrangea macrophylla var. acuminata leaves, resulting in the isolation of 41 secondary metabolites, including four new compounds: one phenolic (3) and three bis-iridoid glycosides (30–32). The inhibitory activities of these compounds against PTP1B and α-glucosidase were evaluated. Among them, compound 12 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 8 and 9 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 H. macrophylla var. acuminata 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.