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Four new cardenolide monoglycosides, cardenolides N-1 (1), N-2 (2), N-3 (3), and N-4 (4), were isolated from Nerium oleander, together with two known cardenolides, 5 and 12, and seven cardenolide monoglycosides, 6-11 and 13. The structures of compounds 1-4 were established on the basis of their spectroscopic data. The in vitro anti-inflammatory 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 1, 5, 6, and 11-13 were active at an IC50 value of less than 1 microM. The cytotoxicity of compounds 1-13 was evaluated against three human cell lines, normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). Compounds 1, 4, 6, and 11-13 were active toward V-13 cells, and compounds 1, 11, and 12 were active toward HepG2 cells at IC50 values of less than 1 microM. Compounds 4, 5, 10, and 12 showed selective cell growth inhibitory activity toward V-13 tumor cells compared with that of parental normal WI-38 cells. The MDR-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. Compounds 4, 9, and 10 showed significant effects on calcein accumulation, compound 4 showing stronger activity than that of verapamil.

Three new pregnanes, 21-hydroxypregna-4,6-diene-3,12,20-trione (1), 20R-hydroxypregna-4,6-diene-3,12-dione (2), and 16beta,17beta-epoxy-12beta-hydroxypregna-4,6-diene-3,20-dione (3), were isolated from Nerium oleander, together with two known compounds, 12beta-hydroxypregna-4,6,16-triene-3,20-dione (neridienone A, 4) and 20S,21-dihydroxypregna-4,6-diene-3,12-dione (neridienone B, 5). The structures of compounds 1-3 were established on the basis of their spectroscopic data. The anti-inflammatory activity in vitro of compounds 2-4 was examined on the basis of inhibitory activity against the induction of intercellular adhesion molecule-1 (ICAM-1), and compound 4 was active. The cytotoxic activity of compounds 1-5 was evaluated against four human cell lines, normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), human liver tumor cells (HepG2), and human lung carcinoma cells (A-549). Compound 4 showed significant cell growth inhibition of VA-13 and HepG2 cells. The MDR-reversal activity of compounds 1-5 was evaluated on the basis of the amount of calcein accumulated in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 1, 2, and 5 showed significant effects on calcein accumulation.

Two new taraxasterane-type triterpenes, 20beta,28-epoxy-28alpha-methoxytaraxasteran-3beta-ol (1) and 20beta,28-epoxytaraxaster-21-en-3beta-ol (2), were isolated from an ethyl acetate extract of the leaves of Nerium oleander, together with ursane-type triterpenes, 28-nor-urs-12-ene-3beta,17beta-diol (3) and 3beta-hydroxyurs-12-en-28-aldehyde (4). The structures of 1 and 2 were established on the basis of their spectroscopic data. Anti-inflammatory activity of 1-4 was examined on the basis of inhibitory activity against the induction of intercellular adhesion molecule-1 (ICAM-1). Cytotoxic activity of 1-4 was evaluated against four human cell lines, A-549, WI-38, VA-13, and HepG2 cells.

New ursane-type triterpene 1, oleanane-type triterpene 2, and dammarane-type triterpene 15 were isolated from the leaves of Nerium oleander together with 12 known triterpenes, 3beta-hydroxy-12-ursen-28-oic acid (ursolic acid, 3), 3beta,27-dihydroxy-12-ursen-28-oic acid (4), 3beta,13beta-dihydroxyurs-11-en-28-oic acid (5), 3beta-hydroxyurs-12-en-28-aldehyde (6), 28-norurs-12-en-3beta-ol (7), urs-12-en-3beta-ol (8), urs-12-ene-3beta,28-diol (9), 3beta-hydroxy-12-oleanen-28-oic acid (oleanolic acid, 10), 3beta,27-dihydroxy-12-oleanen-28-oic acid (11), 3beta-hydroxy-20(29)-lupen-28-oic acid (betulinic acid, 12), 20(29)-lupene-3beta,28-diol (betulin, 13), and (20S,24R)-epoxydammarane-3beta,25-diol (14). On the basis of their spectroscopic data, the structures of the new compounds 1, 2, and 15 were established as 3beta,20alpha-dihydroxyurs-21-en-28-oic acid, 3beta,12alpha-dihydroxyoleanan-28,13beta-olide, and (20S,24S)-epoxydammarane-3beta,25-diol, respectively. The anti-inflammatory activity of the seven isolated compounds and methyl esters of ursolic acid and oleanoic acid in vitro was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). The anticancer activity of the 14 isolated compounds, including 1, 2, 15, and methyl esters of ursolic acid and oleanolic acid in vitro was examined on the basis of the cell growth inhibitory activities toward three kinds of human cell lines.