Ginsenoside Re and notoginsenoside R1: Immunologic adjuvants with low haemolytic effect

The further purification of the total saponins from the roots of Panax notoginseng (Burk.) F. H. Chen by ordinary and reversed-phase silica-gel, as well as Sephadex LH-20 chromatography afforded two adjuvant active dammarane-type saponins, ginsenoside Re (1) and notoginsenoside R1 (2). These two saponins were evaluated for haemolytic activities and adjuvant potentials on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA). The concentrations inducing 50% of the maximum haemolysis (HD50), using 0.5% red blood cell suspensions, were 469.6+/-16.9 and 420.4+/-22.9 microg/ml for 1 and 2, respectively. Compounds 1 and 2 significantly increased the concanavalin A (Con A)-, lipopolysaccharide (LPS)-, and OVA-induced splenocyte proliferation in the OVA-immunized mice (P<0.05, P<0.01, or P<0.001). The OVA-specific IgG, IgG1, and IgG2b antibody titres in serum were also significantly enhanced by 1 and 2 compared with OVA control group (P<0.05, P<0.01, or P<0.001). The results indicate that 1 and 2 showed a slight haemolytic activity and significant adjuvant effect on specific antibody and cellular immune response against OVA in mice, and that the type of the terminal sugar of the sugar chain at C(6) of protopanaxatriol could not only affect their haemolytic activities and adjuvant potentials, but have significant effects on the nature of the immune responses. The information about this structure-function relationship might be useful for developing semisynthetic dammarane-type saponin derivatives with immunological adjuvant activity.