Structure–Activity Relationship of Oleanane Disaccharides Isolated from Akebia quinata versus Cytotoxicity against Cancer Cells and NO Inhibition

Abstract

In order to further determine the nature of structure–activity relationship on the cytotoxicities of saponins with 1→2 and 1→3 linkages of disaccharides, we isolated guaianin N, collinsonidin, kalopanaxsaponin A and hederoside D₂ as disaccharides, and patrinia glycoside B-II as a trisaccharide, from the n-BuOH extract of Akebia quinata (Lardizabalaceae). Complete acid hydrolysis of the extract afforded oleanolic acid (1) and hederagenin (2). By sulforhodamine B (SRB) assay, kalopanaxsaponin A containing an α-L-rhap-(1→2)-α-L-arap moiety exhibited distinctly higher cytotoxicity (IC₅₀ 1.8—2.7 μg/ml) against all of the tested cell lines than the other saponins (IC₅₀, 4—8 μg/ml). These results suggest that the α-L-rhap-(1→2)-α-L-arap moiety has a unique structural significance in terms of its cell biochemistry, compared to those oleanane glycosides with other sugar linkages. On the other hand, kalopanaxsaponin A exhibited a significant inhibitory effect on nitric oxide production by lipopolysaccharide (LPS)-activated macrophage 264.7, whereas other saponins had weaker activities.