Abstract
Ligustrum japonicum Thunb. (Oleaceae) has long been valued for the medicinal properties. Its fruits are traditionally utilized, while the leaves and branches are generally discarded after fruit harvest. These aerial parts therefore represent underutilized by-products whose phytochemical profiles remain insufficiently characterized. To elucidate the organ-specific chemical diversity and assess the potential value of these underutilized parts, a comparative analysis of the fruits, leaves, and branches was performed using HPLC-MS/MS combined with GNPS-based molecular networking, with a particular focus on secoiridoids, the characteristic metabolites of the Oleaceae family. This approach revealed substantial overlap as well as distinct variations in secoiridoid profiles among the three plant organs. Chromatographic separation yielded 14 secoiridoid derivatives shared across all organs. In addition, four previously undescribed secoiridoids were isolated and identified through spectroscopic analyses: secoligunosides A (1) and B (2) from the leaves and secoligunosides C (3) and D (4) from the branches. Among the major identified secoiridoids, oleuropein (10), 8Z-nüezhenide (17), and GL-3 (18) exhibited weak proliferative activity, showing an approximately 10-20% increase compared to control, on human dermal papilla cells. Collectively, these findings demonstrate that the leaves and branches not only contain key secoiridoids found in the fruits but also harbor unique metabolites, highlighting their value as alternative or complementary medicinal resources. The underutilized parts of L. japonicum therefore represent promising sources of natural products and warrant further investigation for future therapeutic applications.