Saponins immunostimulant activity

Two acylated saponins, tram- and cw-/ -methoxycinnamoyl triterpene glycosides, have recently been isolated from Silene jenisseensis (Caryophyllacea) [71]. Since these saponins contain quillaic acid as their aglycone (Fig. 11), they should be expected to have immunostimulating properties. However, no apparent immunostimulating activity was detected by an in vitro chemiluminescent granulocyte assay [4,71]. 

One of the forces driving interest in saponins as vaccine adjuvants is the industry s need for agents with improved performance. Currently, the most commonly used adjuvants are aluminum salt-based that produce only humoral immunity with limited antibody response. While these adjuvants were frequently adequate for first generation vaccines, new vaccines are now based on antigenic recombinant proteins that are poorly immunogenic. These newer vaccines require adjuvants with greater immunostimulating activity than that offered by alum. 

It is marketed as, and has been described to be, a potent adjuvant which has found widespread use in veterinary vaccines against, for example, foot and mouth disease, rabies, and in a number of experimental vaccines and in preclinical trials. Unfortunately its hemolytic activity and local counter reactions make it unsuitable for human vaccines [5]. Furthermore, Quil A is used for production of ISCOMs (immunostimulating complexes, typically composed of 0.5 % Quillaja saponins, 0.1% cholesterol, 0.1% phospholipid and antigen dissolved in PBS). Although side effects of Quil A were almost absent when incorporated into ISCOM, this form of vaccine is only used for veterinary vaccines and has not been approved for humans. Quil A is still a heterogeneous mixture, consisting of up to 23 different individual saponins detectable by HPLC [8]. Later, it was observed that not all saponins were active as adjuvants. A saponin termed QS III was purified from of a methanol extract of Quillaja bark by several chromatographic steps, it has, however, not been tested for adjuvant activity [12]. 

A new acylated gypsogenin heptaglycoside (9) from Acanthophyllum squarrosum showed a concentration-dependent immunomodulatory effect in the in vitro lymphocyte transformation test [54]. At high concentrations (10 Xg/ml), the saponin showed an immunosuppressive effect (60%) whereas the same compound displayed immunostimulating activity at very low concentrations (10 pg/ml). In the concentration range of 100 pg/ml-1 pg/ml, compound 9 exerted a synergic effect on ConA. 

The in vivo antitumoral effect of Virgaureasaponin E (34) in the mouse tumor models (sarcoma 180 and DBA2/MC.SC-1 fibrosarcoma models) could be due, at least in part, to an immunostimulant activity [69]. The ability of virgaureasaponin E (34) to reduce the tumor size by stimulating the immune system could be a consequence of stimulated immune parameters detected in ex vivo assays (proliferation and phagocytosis of bone marrow macrophage cells, release of TNFa in the blood of mice treated with the saponin after EPS induction) [69]. 

The main chemical constituents isolated from Chinese traditional drugs and herbs with immunoregulation or immunostimulating activity are listed in Table 4. Among them the polysaccharides and saponins are predominant. 

Protection of rats from devl. of Pseudomonas aeruginosa infections Activation of multiple effector pathwaye (Tcells, Bcells, macrophages) Protection of mice from devl. of C. albicans infection (macrophages) Polysaccharides as antineoplastic immunostimulators (NK cells) Proliferative responses of blood lymphocytes Protection of ginseng saponins of immunosuppression in mice Inhibition on bacterial endotoxin-induced embryolethality in rats Induction of neutrophil accumulation in mice... 

The pharmacologically active constituents of these Astragalus belong to two different kinds of chemical compounds, polysaccharides and saponins, and the most interesting pharmacological properties are hepatoprotective, immunostimulant and antiviral. 

Many saponins have been proven to be able to modify non-specific (both humoral and cellular) immune functions in vitro in a non-antigen-dependent manner. Here we will present a brief review on their influence on lymphocytes, macrophages, and granulocytes together with their influence on the liberation of cytokines and the activation of NK cells. Few in vivo studies have been performed in order to prove the significance of saponins as immunostimulants. 

Saponins have additionally been reported to exhibit adjuvant-active properties. An open cage-like immunostimulating complex of cholesterol, lipid, immunogen, and saponins from bark of Quillaja saponaria MOL. (soap bark tree) has found successful application as an active adjuvant for vaccinatiMi [16]. 

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