Polar cardenolide monoglycosides from stems and twigs of Nerium oleander and their biological activities

Twelve polar cardenolide monoglycosides, 1, 2, 4–13, and oleagenin (3) were isolated from the methanol extract of stems and twigs of Nerium oleander. Among these, oleagenin (3) and cardenolide monoglycosides named cardenolide B-1 (1) and cardenolide B-2 (2) were isolated from natural sources for the first time. The in vitro antiinflammatory activity of compounds 1–13 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 4–7 were active at an IC50 value of less than 0.4 μM. The cytotoxic activity of compounds 1–13 was evaluated against three human cell lines: normal human fibroblast cells (WI-38), malignant tumor cells derived from WI-38 (VA-13), and human liver tumor cells (HepG2). Compounds 4, 6, and 7 were active toward these three cell lines at IC50 values of less than 0.7 μM, and compounds 5 and 8 were active toward the cell lines at IC50 values of less than 1.5 μM. The multidrug resistance (MDR) cancer-reversal activity of compounds 1–13 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compound 1 and 12 showed significant effects on calcein accumulation.