Saponins toxic properties

The toxic properties of quillaja saponins limit their use as adjuvants in vaccine development. For example, Quil-A a commercial preparation of... 

Some steroidal alkaloids are nitrogen analogues of steroidal saponins, and display similar properties such as surface activity and haemolytic activity, but these compounds are toxic when ingested. These types of compound, e.g. solasonine (Figure 5.88) (aglycone solasodine),... 

Saponins are widely distributed in plants and are a particular form of glycosides. They are so-called because of their soaplike effect, which is due to their surfactant properties. They also have hemolytic properties and, when injected into the bloodstream, are highly toxic. When taken by mouth, saponins are comparatively harmless. According to the structure of the aglycone or sapo-genin two kinds of saponin are recognized, the steroidal and triterpenoid type. 

Many alkaloids are infamous for their strong toxicity towards animals and humans. Most of the deadly alkaloids fall into the class of neurotoxins (see above). The others have cytotoxic properties (Table 1.2). A cytotoxic effect can be generated when cell membranes are made leaky (as by saponins or steroidal alkaloids), or when elements of the cytoskeleton are inhibited. The spindle poisons vinblastine, vincristine, colchicine, and taxol are particularly famous. Actin filament formation is blocked by fungal poisons such as phalloidin from Amanita phalloides. 

Fabaceae and Plantaginaceae. When dissolved in water, saponins form soapy solutions and can therefore be used as detergents in the preparation of galenicals and cosmetics. Saponins can increase the permeability of biomembranes and may thus exhibit cytotoxic, haemolytic and antiviral properties most of them are highly toxic for fish. Moreover, steroid saponins are important starting materials for the commercial production of steroid hormones. 

This group involves a considerable number of physiologically active compounds whose activity is largely dependent on the complete stmcture, including the glycosidic moiety. A number of these compounds have detergent properties, e. g., saponins, and such physicochemical properties are partly responsible for their toxicity, e. g. the hemolytic activity of some saponins is caused by the damage of the erythrocyte membrane. 

The toxicity of starfishes may be derived from the saponins. The biological activities of these compounds were reported, including haemolytic properties, and antitumour [104] and antibacterial activities [105]. Inhibition activities for influenza virus multiplication, and anti-inflammatory activity towards contraction of the rat phrenic nerve diaphragm preparation, were also reported [106]. Saponins are chemical defence agents in starfishes, and they also induce escape reactions in bivalve molluscs [107]. It is of interest to note that the sperm agglutination substance in the egg jelly of starfish is similar to asterosaponin A [108]. 

In a continuing search for adjuvants with enhanced adjuvanticity and low toxicity, some authors have prepared new chemical semi-synthetic saponins and had compared their adjuvant properties with original saponins. 

ADJUVANTICnr, TOXICITY AND PHYSICAL PROPERTIES OF QUILLAJA SAPONINS... 

It is evident that aldehyde-containing saponins, particularly those from Quillaja saponaria Molina, have unique features which provide them with particular immune stimulating properties. However, some of their chemical properties cause instability and toxicity which interfere with their utility as adjuvants. A better understanding of the underlying relationships between the saponin s chemical structure and biological functions, such as immune system modulation and toxicity, would allow the future development of semi-synthetic and synthetic molecules having the advantages but not the liabilities of these natural products. 

Deacylated quillaja saponins were modified by incorporation of a Cn alkyl chain at the carboxyl group of the glucuronic acid residue to yield a family of saponin analogs referred to as GPI-OIOO. These stable derivatives, when compared by reverse phase HPLC to the acylated or deacylated forms of quillaja saponins, are more hydrophobic. The presence of the alkyl chain in GPI-OIOO is expected to increase the selfassociating properties of these derivatives in water, as well as their capacity to form complexes with proteins that are held by hydrophobic interactions. These analogs are similar to the deacylated quillaja saponins in that they appear to be devoid of toxicity in mice at a dose up to 1 mg. 

Many of the biological properties for which saponins are known are due to this hydrophobic/hydrophilic asymmetry and consequent ability to lower surface tension (Gershenzon and Croteau, 1991 Hostettmann et al., 1991). In general, both the sugar and the aglycone are necessary for activity. Saponins have soap-like properties in aqueous solutions. This is a major reason for acute toxicity when they are injected intravenously. These compounds have been used to capture fish (as piscicides) since ancient times (Howes, 1930). Saponins in the diet are more toxic to cold-blooded than to warm-blooded animals. Most saponins hemolyze red blood cells (Marston and Hostettmann, 1991). 

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