Physiological Actions of Formulas

Immunostimulation

The biomedical formulas contain naturally occurring triterpene glycosides (saponins) derived from Quillaja saponaria. Although produced by plants as a defense against infection, the unique chemical structures of Q. Saponaria saponins also make them exceptionally potent human immune stimulators. Oral administration of saponins has long been considered as a means of enhancing both systemic and mucosal immune responses. Unfractionated saponins administered to mice together with antigen, increased serum antibody titers by greater than tenfold.(i) Further effects include stimulation of high levels of antibody to T-dependent and T-independent antigens as well as induction of cytotoxic T lymphocyte (CTL) responses.(ii) The triterpene saponins stimulate a Th1 type immune response and are the only natural substances reported to date, that are capable of stimulating the production of CTL responses against exogenous proteins.(iii) This type of immune response is considered crucial in the body's fight against intracellular pathogens.

ANTI-HYPERCHOLESTEROLEMIC

The blood cholesterol lowering capabilities of saponins has been unequivocably demonstrated iv. Recent research in Canada and Africa has focused on the blood cholesterol levels of the Masai tribes of East Africa. Their apparent low cholesterol levels, despite a diet very high in animal products and saturated fats, are likely due to the consumption of saponin-rich herbs.

Cholesterol is continually secreted into the intestines as a constituent of bile. Much of it is subsequently reabsorbed. Saponins cause a depletion of body cholesterol by binding and preventing its reabsorption, thus increasing its excretion. This mechanism is similar to other cholesterol lowering drugs such as cholestyramine.

The binding of bile acids by saponins has other important implications. As the cholesterol-laden bile is metabolized in the colon by bacteria, secondary bile acids are formed. Some of these secondary metabolites have been demonstrated to promote the formation of colon cancer. Research at the University of Toronto has shown that feeding saponins to mice reduced the number of pre-neoplastic colon lesions. Saponins were also shown to provide a dose-dependent inhibitory effect on growth of human carcinoma cells in culture.

Saponins, by their chemical nature, are surface-active molecules. Because of their amphipathic structure, they form micelles in aqueous solution v. Saponins have been shown to intercalate into cell membranes forcing a lipid rearrangement. This binding is mediated by cholesterol vi. Electron micrographs of saponin treated cell membranes reveal an arrangement of hexagonal pores that form in the membrane vii. It is speculated that immunostimulant activity may be mediated through the introduction of antigens directly to the cytoplasm of the cell through these "saponin pores".

ANTIPARASITIC

The human immune response to infection with parasites is highly complex. Many protozoa enter the body via the digestive tract or cause their pathological effects in the gut. The mechanism of enhanced protection by saponins may be based on stimulation of TH1 type immune responses with the production of IgG2a antibody viii. Saponins also form strong, insoluble complexes with the cholesterol in the protozoal cell membrane. The pores then formed (by the mechanism described above) cause the cell to lyse and rupture. Giardiasis, for example, produces symptoms of severe diarrhea associated with the presence of the protozoa Giardia lamblia in untreated drinking water. Research has shown saponins as very effective in killing Giardia trophozoites, the infective stage released into the gut when the oocytes sporulate.

Selected References:

i Campbell, J.B., Maharaj, I., Roith, J. "Vaccine formulations for oral immunization" Kwert, E. and Merieux, C ed., Springer-Verlag, Berlin 1985

ii Charlotte Read Kensil "Saponins as vaccine adjuvants" Critical Reviews 1996; 13:1-55

iii Nord, L.I., Kenne; L. "Separation and structural analysis of saponins in a bark extract from Quillaja saponaria Molina"
Carbohydr. Res, 1999; 320: 70-81

iv Malinow, R. "Cholesterol lowering properties of saponins" Amer. Journal of Clinical Nutrition, 1997.

v Dalsgaard, K. "A stud of the isolation and characterization of the saponin Quil A" Acta Vet. Scand. Suppl, 1978; 69:1

vi Bomford, R. "Saponin and other haemolysins (vitamin A, allipathic amines, polyene antibiotics) as adjuvants for SRBC in the mouse" Int. Arch. Allergy Appl. Immun. 1980; 63:170

vii Bomford, R. "Saponin and other haemolysins (vitamin A, allipathic amines, polyene antibiotics) as adjuvants for SRBC in the mouse" Int. Arch. Allergy Appl. Immun. 1980; 63:170