Eremophilane-type sesquiterpenes from Ligularia hodgsonii: isolation, structural characterization, and pro-angiogenic...

A comprehensive chemical investigation of the rhizomes and roots of Ligularia hodgsonii Hook. was undertaken, which resulted in the identification of 11 previously undescribed eremophilane-type sesquiterpenes (1-4, 7-12, and 14), in addition to five known analogues (5-6, 13, and 15-16). The structures of previously undescribed compounds were fully characterized through comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, single-crystal X-ray diffraction experiment, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculation. Compounds 1-12 represent six pairs of epimers at the C-11 position, and an empirical pattern to distinguish the C-11 stereochemistry was therefore established based on their characteristic Cotton effects in the ECD spectra, which was subsequently applied to revise the absolute configuration of the known compound 13. Furthermore, the pro-angiogenic activity of some isolated compounds was evaluated in human umbilical vein endothelial cells (HUVECs). Compound 14 exhibited potent effect by promoting HUVEC migration and facilitating the formation of capillary-like tubular networks, while compounds 7, 11, 13, and 15 interrupted wound healing in HUVECs. The findings provide the first insights into the bioactivity of eremophilane-type sesquiterpenes responsible for the wound-healing therapeutic effect of L. hodgsonii.