Proceedings of the American Society of Animal Science,
1999 © 2000 American Society of Animal Science
Excerpts from P. R. Cheeke report
Actual and potential applications of schidigera saponins in human and animal nutrition
Saponins are natural detergents (surfactants) found in a variety of plants. The two major commercial sources of saponins are desert plants:Schidigera from Mexico and Quillaja saponaria from Chile.Schidigera saponins have a steroid nucleus, whereas Quillaja saponins are triterpenoid in structure. Saponins contain a lipophylic nucleus (steroid or triterpenoid) and one or more water-soluble carbohydrate side chains. Thus, the surfactant activity is a result of both fat-soluble and water-soluble moieties in the same molecule. Saponins have membranolytic properties; they complex with cholesterol in protozoal cell membranes, causing cell lysis. They have antibacterial activity and modify ruminal fermentation by suppressing ruminal protozoa and selectively inhibiting some bacteria. Ruminal ammonia concentrations are reduced. Schidigera extract is used for prevention and treatment of arthritis in horses, although convincing evidence of its efficacy has not been reported. Saponins influence absorption of lipids, through formation of micelles with bile salts and cholesterol in the intestine. There is evidence that oral administration of saponins may stimulate the immune system and increase resistance to a disease challenge. Schidigera extract has been shown to reduce neonatal pig mortality when fed to sows in late pregnancy.Thus, dietary saponin sources have several beneficial properties in animal production.
Saponins are natural detergents found in many plants.
Saponins have detergent or surfactant properties because they contain both water-soluble and fat-soluble components. They consist of a fat-soluble nucleus, having either a steroid or triterpenoid structure, with one or more side chains of water-soluble carbohydrates. Certain desert plants are especially rich in saponin content. One of the major commercial sources of saponins is Schidigera extract, which grows in the arid Mexican desert.
Production Schidera Extracts
Schidigera is native to the southwestern United States and Mexico. Currently, most commercial production of Schidigera products takes place in Mexico. The Schidigera plants are harvested by Mexican farmers and transported to processing plants. The trunk of the plant is the part used. The logs are mechanically macerated and the macerated material is subjected to mechanical squeezing in a press, producing Schidigera juice. The juice is concentrated by evaporation, with the concentrated product referred to as extract.
The term “Schidigera extract” is slightly misleading, in that the plant juice is removed by mechanical means, rather than by solvent extraction.Their antifungal and antibacterial properties are also important in cosmetic applications, in addition to their emollient effects.
Saponins and Protozoal Diseases
As discussed above, saponins suppress ruminal protozoa by the action of complexing with cholesterol in protozoal cell membranes. Antiprotozoal activity against ruminal protozoa raises the question of whether saponins would be effective against protozoal diseases that afflict humans, livestock, and poultry. Those protozoal diseases in which part of the life cycle occurs in the gastrointestinal tract would be expected to be responsive to antiprotozoal activity of saponins. An example is the disease giardiasis, caused by the protozoan Giardia lamblia (also known as G. duodenalis). It is one of the most common intestinal pathogens in humans and animals throughout the world (Olson et al., 1995). Schidigera saponins are effective in killing the giardia tropozoites in the intestine (McAllister et al., 1998). The effect of saponins on other common livestock protozoal diseases such as coccidiosis is an area that should be investigated.
In horses, various ciliated protozoa cause colitis and diarrhea (Manahan, 1970; Love, 1992; Gregory et al., 1986; French et al., 1996). There may be potential for use of Schidigera saponins to control protozoal diseases in horses. In the United States,Schidigera products are used in the horse feed industry to relieve symptoms of arthritis in horses. This use is based on work with humans (Bingham et al., 1975), suggesting that Schidigera saponins have antiarthritic effects, which Bingham (1976) speculated were due to antiprotozoal activity.
Citing evidence from other researchers that protozoa in the intestine may contribute to arthritis, Bingham (1976) suggested “that a reduction in protozoal infestation of patients’ intestines may be a Schidigera extract action.” He quotes Roger Wyburn-Mason of England on the “protozoal theory of the cause of rheumatoid arthritis.” Bingham (1976) states that “in 1964, Dr. Wyburn-Mason discovered a free living protozoan, an amoeba of the Naegleria genus of parasites in cases of active rheumatoid arthritis. It is a very fragile amoeba organism which can live indefinitely in the tissues of its host. He found it in all living tissues in patients with rheumatoid arthritis.” Bingham (1976) further states: “Along with treatment using the antiprotozoal drugs it is important to carry out an intensive routine of nutritional vitamin and mineral therapy to help the body restore the damaged joints as much as possible.”
These comments are very interesting in view of what we now know about Schidigera saponins. They are very effective in killing protozoa (Wallace et al., 1994; Klita et al., 1996; Wang et al., 1997, 1998). If the hypothesis of Bingham is correct, then Schidigera extract may have beneficial effects on arthritis in horses by way of its antiprotozoal activity. As previously discussed, saponins react with cholesterol in protozoal cell membranes, causing the membrane to break down and the protozoal cell to lyse and die.
There are well-known interactions between rheumatoid arthritis, chronic inflammatory disease, and food and nutrition (Parke et al., 1996; Martin , 1998). Of particular importance are nutrients that stimulate formation of oxidants and peroxides (e.g., unsaturated fatty acids, iron), which promote inflammatory disease, and antioxidants (e.g., vitamin E) and omega-3 fatty acids (fish oils), which protect against auto-oxidation.
Schidigera saponins are known to reduce iron absorption (Southon et al., 1988) and may reduce fatty acid absorption by sequestering bile acids that are necessary for micelle formation and fat absorption (Oakenfull and Sidhu, 1989).
An interesting possibility is that Schidigera saponins may control the protozoa that cause the fatal disease equine protozoal myeloencephalitis (EPM). This disease has been reported from throughout North America (Bentz et al., 1997; Blythe et al., 1997; Saville et al., 1997). The protozoal organism involved has been isolated and named Sarcocystis neurona (Dubey et al., 1991). The protozoa invade the tissues of the central nervous system (CNS), causing fatal neurologic damage.
Horses ingest the protozoal sporocysts in contaminated feed and pasture. The sporocysts sporulate in the intestine, producing sporozoites that enter the intestinal epithelial cells, where they undergo asexual reproduction to produce merozoites. These invade CNS tissue, causing disruption of function and, ultimately, fatal neurologic disease. Clinical signs include weakness, lameness, muscle atrophy, blindness, and seizures. A major source of infection is opossum feces, contaminating feed and pasture (Fenger et al., 1995).
Lending support to the saponin suppression of intestinal protozoa theory is that saponins have been investigated as potential antiprotozoal agents against human disease.
Saponin-containing plant extracts have protective activity against the human disease leishmaniasis (McClure and
Nolan, 1996), which is second in importance only to malaria among the protozoal diseases of humans. Another significant point is that saponins stimulate the immune system (Maharaj et al., 1986) and produce an array of antigen-specific and nonspecific immune responses (Chavali and Campbell, 1987). Saponins are used as adjuvants in antiprotozoal vaccines (Bomford, 1989). Thus, it is possible that dietary Schidigera saponins will not only have protective effects against EPM by killing sporozoites in the intestine, but they may also stimulate the immune system to give horses increased resistance against any protozoa that do invade their tissues.
As discussed in a later section (Saponins, Surfactants, and Intestinal Function), saponins increase intestinal permeability by causing microlesions of the intestinal mucosa. It is possible, regarding interactions with gut protozoa, that high doses of saponins could increase the ability of infective protozoal life stages (e.g., sporozoites, tropozoites, and merozoites) to invade the intestinal mucosa. Much research is needed on saponin effects on protozoal diseases.
Cholesterol-Saponin Interactions
It has been known for many years that saponins form insoluble complexes with cholesterol (Lindahl et al., 1957).
Saponins form micelles with sterols, such as cholesterol and bile acids. The hydrophobic portion of the saponin (the agly-cone or sapogenin) associates (lipophilic bonding) with the hydrophobic sterol nucleus, in a stacked micellar aggregation (Oakenfull and Sidhu, 1989).
Interactions of saponins with cholesterol and other sterols account for many of the biological effects of saponins, particularly those involving membrane activity. Implications of the roles of saponins in reducing blood cholesterol levels in humans will be discussed later. Oakenfull and Sidhu (1989) reviewed the effects of dietary saponins on blood and tissue cholesterol levels in poultry. It was demonstrated over 40 yr ago that dietary saponin reduces blood cholesterol levels in chickens (Newman et al., 1957; Griminger and Fisher, 1958).
This effect is likely a result of saponins binding to cholesterol in the bile in the intestine, and preventing its reabsorption.
Efforts to reduce egg cholesterol levels by feeding sources of saponins to laying hens have generally not been successful (Nakaue et al., 1980; Sim et al., 1984). The main source of egg cholesterol is endogenous synthesis in the ovary, so reductions in blood cholesterol in laying hens do not result in lowered egg cholesterol.
Dietary saponins also reduce blood cholesterol levels in mammals (Oakenfull and Sidhu, 1989). In livestock species, a possible application might be the use of dietary saponin to reduce meat cholesterol levels. However, because cholesterol in meat is an integral component of muscle cell membranes, it is not likely to be possible to lower meat cholesterol levels by dietary manipulations.
Cholesterol-lowering properties of saponins in humans are of obvious interest. There is little clinical trial information. Bingham et al. (1978) observed a reduction in serum cholesterol levels in human patients receiving Schidigera tablets for arthritis relief. This seems to be the only study reported in which a saponin product has been given directly to human subjects.
The Masai people of East Africa have low serum cholesterol levels despite a diet rich in animal fat. Chapman et al. (1997) attribute the low cholesterol levels to the Masai diet, in which saponin-rich herbs are added to milk and meat-based soups.
A number of studies, such as those of Malinow et al. (1977), have shown that alfalfa saponins have hypocholesterolemic activity in nonhuman primates. A number of synthetic saponins have been shown to be cholesterol absorption inhibitors (Harwood et al., 1993; Morehouse et al., 1999), causing reduction in plasma non-high-density-lipoprotein cholesterol fractions.
Although it is generally accepted that the principal action of saponins on blood cholesterol is by sequestration of cholesterol and bile acids in the intestine, another possible mode of action is via increased intestinal cell turnover rate. An increased rate of exfoliation of intestinal cells caused by the membranolytic action of saponins could result in increased loss of cell membrane cholesterol contained in the exfoliated cells (Gee and Johnson, 1988; Milgate and Roberts, 1995).
Saponins, Surfactant Activity, and Intestinal Function
Saponins affect the permeability of intestinal cells by forming addition complexes with sterols (e.g., cholesterol) in mucosal cell membranes (Johnson et al., 1986). These authors found that saponins increase the permeability of intestinal mucosal cells, inhibit active nutrient transport, and may facilitate the uptake of substances to which the gut
would normally be impermeable. This was confirmed in a more recent study (Gee et al., 1997), in which it was demonstrated that exposure of rats to saponin increased the trans-mucosal uptake of the milk allergen â -lactoglobulin.
Saponin-exposed rats developed antigen-specific antibody responses to administration of ovalbumin (Atkinson et al., 1996), indicating that saponins may increase the sensitivity of animals to dietary antigens. Saponins from various food sources, such as oats (Onning et al., 1996) and quinoa (Gee et al., 1993), increase intestinal cell permeability.
Saponins, being both fat- and water-soluble, have surfactant and detergent activity. Thus, they would be expected to influence emulsification of fat-soluble substances in the gut, including the formation of mixed micelles containing bile salts, fatty acids, diglycerides, and fat-soluble vitamins.
Saponins form micelle-like aggregates in water (Oaken-full and Sidhu, 1989). They have a critical micelle concentration (CMC); below the CMC the molecules remain unassociated and make an abrupt change in physical properties as they make the transition to the micellar state at the CMC.
Increased temperature or pH increases the CMC, and increased salt concentration decreases it (Mitra and Dungan, 1997). In the digestion and absorption of fats, both emulsification and micelle formation are involved. Dietary lipids, mainly triglycerides, are emulsified by bile acids in the duo-denum. Free fatty acids, released by lipase action, form mixed micelles with bile acids, transporting the fatty acids through an aqueous medium to the intestinal mucosal surface for absorption. Saponins would be expected to influence both fat emulsification and micelle formation.
Formation of micelles containing bile acids and saponins has been described by Oakenfull and Sidhu (1989). Bile acids and saponins form a stacked structure with the hydrophobic nuclei stacking together like a pile of coins, with the hydrophilic carbohydrate side chains of the saponin molecules extending out from the interior core. Many hundreds of saponin and bile acid molecules may aggregate in this manner, with the physical characteristic determined by the particular chemical structure of the saponin involved.
Saponins act as emulsifiers, stabilizing the oil/water inter-face (Barla et al., 1979; Oakenfull and Sidhu, 1989). Saponins have a high capacity for solubilizing monoglycerides (Barla et al., 1979). Based on these activities, it can be speculated that dietary saponins could improve fat emulsification and digestion. However, the opposite seems to be true, with several studies finding that dietary saponin reduces fat digestibility. For example, Reshef et al. (1976) found that dietary alfalfa saponins reduced fat digestibility in mice, although there was no effect in quail.
The major effect of saponins on lipid digestibility seems to be exerted via effects on bile acids. Saponins form micelles with bile acids (Oakenfull and Sidhu, 1989), reducing availability of bile acids for formation of micelles with fatty acids. The bioavailability of vitamins A and E may also be reduced by saponins, probably because of sequestration of bile acids (Jenkins and Atwal, 1994).
Primary bile acids are those excreted in the bile, and secondary bile acids are the result of microbial metabolism of primary bile acids. For example, cholic acid is a primary bile acid that is converted to deoxycholic acid by microbial activity in the hindgut. Saponins bind to primary bile acids, protecting them from bacterial action. Thus, with dietary saponin, formation of secondary bile acids is reduced in rats (Oakenfull et al., 1979), in pigs (Topping et al., 1980), and in humans (Potter et al., 1980).
The binding of primary bile acids by saponins may be significant in preventing colon cancer (Rao and Sung, 1995), by reducing their availability to form secondary bile acids via hindgut microbial activity. Secondary bile acids are cytotoxic and tumor-promoting. In addition to the bile acids, saponins also bind to cholesterol and prevent cholesterol oxidation in the colon. Oxidized cholesterol products are promoters of colon cancer (Koratkar and Rao, 1997). Thus, dietary saponins may have beneficial effects against two major human health problems: coronary heart disease (by hypocholes-terolemic activity) and colon cancer (by sequestering bile acids).
Digestibility of fats in ruminants is limited by the lack of emulsifying agents in the rumen. Ramirez et al. (1998) investigated whether the inclusion of schidigera extract in a high-fat diet for feedlot cattle would improve fat utilization. However, there were no effects on ruminal or postruminal digestion of fatty acids, although there was a tendency toward reduced postruminal digestibility of fatty acids.
Feed grains such as barley, wheat, and oats contain non-starch polysaccharides (NSP) such as â -glucans, which are viscous gums that are poorly water-soluble. They cause a “plugging-up” of the intestinal mucosa in poultry because of their high viscosity. Speculatively, saponins via their surfactant activity might be effective in improving the water-solubility of NSP, improving the feeding value of barley, wheat, and oats for poultry. However, preliminary studies (H.L. Classen, Univ. of Saskatchewan, personal communication; A. Skrede, Agricultural Univ. of Norway, As, personal communication) have not shown an improvement from the feeding of extract with NSP-containing grains.
Stillbirths in Swine
Cline et al. (1996) found that feeding a Schidigera extract-containing commercial feed additive to sows prior to farrowing resulted in a significant reduction in numbers of pigs born dead (stillbirths). Blood oxygen levels were higher in piglets at birth from sows fed the Schidigera extract. Cline et al. (1996) suggested that the reduction in stillbirths was a result of improved blood oxygen supply to the fetuses during birth. Pre-weaning mortality was also reduced. Piglets suffering from oxygen deprivation during birth are less viable and more likely to succumb to stress of postuterine life (Herpin et al., 1996). The results of Cline et al. (1996) were later confirmed (Herpin, unpublished observations), observing that dietary inclusion of whole Schidigera plant powder in sow diets caused a reduction in stillbirths and increased viability of neonatal pigs. However, there were no differences in blood oxygenation between control and Schidigera-fed pigs. Litters with stillbirths have a higher preweaning mortality than litters without stillbirths (Leenhouwers et al., 1999). The number of litters with no stillbirths was greater with the Schidigera treatment than in the control group (Herpin, unpublished observations).
Saponin-containing Schidigera extracts are currently used in the feed industry for control of ammonia and odor. The active components in this function are probably carbohydrates, rather than saponins. Specific roles of saponins may involve modification of gut microbes, particularly in ruminants. Saponins suppress ruminal protozoa by binding to cholesterol in the protozoal cell membrane, causing the organism to lyse and die. Saponins inhibit Gram-positive bacteria and have antifungal properties. Antiprotozoal activity against pathogenic protozoa such as giardia by saponins has been observed. When used as feed additives, saponins have multifaceted beneficial properties.
Literature Cited
P.R.Cheeke on a report at the Proceedings of the American Society of Animal Science, 1999 © 2000 American Society of Animal Science