SAPONINS Mills, S. 1991, “The Essential Book of Herbal Medicine”, Penguin Pengelly, A.1996, “The Constituents of Medicinal Plants: An Introduction to the Chemistry & Therapeutics of Herbal Medicines”, Sunflower Herbals Wohlmuth, H.1998, “Pharmacognosy and Medicinal Plant Pharmacology”, Southern Cross University Saponins are water-soluble phytochemicals which are characterised by having detergent properties and produce a foam when dissolved in water – they are soaps (sapo = soap in Italian). They are often referred to as triterpene glycosides or steroidal alkaloids. These detergent properties have been used in the past where saponin rich plants have been used as soap substitutes. Such plants are still being used today, especially in the cleansing of sensitive fabrics e.g. Saponaria officinalis (soapwort) Like other detergent compounds, saponin molecules possess a water-loving polar (hydrophilic) and a water-hating non-polar (hydrophobic) or fat-loving (lipophilic) end of the molecule. The polar end makes the molecule soluble in water while the non-polar end enables it to dissolve grease and other non-polar substances. The aglycone of a saponin is often referred to as the sapogenin. 3 TYPES On the basis of the chemical structure of the sapogenin, saponins are divided into two groups steroidal saponins and triterpenoid saponins STEROIDAL SAPONINS The sapogenin of steroidal saponins is steroidal in nature, with the glycone attached to carbon number 3. These have a close structural relationship with steroid hormones, cardioactive glycosides and vitamin D, and this makes these saponins of commercial interest as starting points for the synthesis of a number of drugs. 4 The effect on the female reproductive system of fenugreek containing the sapogenin, diosgenin inflammatory conditions of wild yam with dioscin and sarsaparilla (sarspogenin and smilogenin) the reproductive system of bethroot (trillium) suggests that the steroidal nature of their saponins may be interacting with steroidal receptors in the body as the triterpenoids do, or even may act as precursors to the steroidal hormones. 5 The toxic effects of the nightshade family (e.g. the problems with greening in potatoes), are due to steroidal saponins with alkaloid properties. Cholesterol is a common precursor to steroidal saponins in plants Steroidal saponins are most common in monocotyledons but are also found in some dicotyledons. Some examples of families and genera containing this type of saponin are: Monocotyledons Dicotyledons Dioscoraceae Dioscoria Liliaceae Trillium, Ruscus, Yucca Amaryllidaceae Agave Fabaceae Trigonella Scrophulariaceae Digitalis Apocynaceae Strophanthus Wild Yam (Dioscorea villosa): Some Dioscorea species contain steroidal saponins, including dioscin, which yields the sapogenin diosgenin. This aglycone was the raw material used in early semi-synthetic production of steroidal hormones and other steroidal compounds of pharmaceutical interest. Diosgenin is still used in hormone production. Galenical preparations of Dioscorea are used as spasmolytics and anti-inflammatories, particularly in the GIT and the female reproductive tract. It is also a visceral relaxant and a mild peripheral vasodilator. Dioscorea is used in rheumatic inflammatory conditions (including rheumatoid arthritis), colitis, cramps, dysmenorrhoea and ovarian and uterine pain. Sarsaparilla (Smilax officinalis): Contains 1 – 3% steroidal saponins, including sarsaponin and smilasaponin, based on the two very similar aglycones sarsasapogenin and smilagenin. Saponins may bind bacterial endotoxins in the intestines, preventing their absorption into the bloodstream. The German Commission E states that taking Sarsaparilla preparations lead to gastric irritations and temporary impairment of the kidneys. Smilax does not contain testosterone and there is no evidence of any anabolic action. Fenugreek (Trigonella foenum-graecum): Contains saponins which yield about 1.5% diosgenin and other sapogenins when hydrolysed. The content of steroidal saponins may be reflected in actions such as anti-inflammatory, galactagogue and hypoglycaemic. Saponin rich extracts have been shown to be anti-diabetic and to reduce blood cholesterol levels. Butcher’s broom (Ruscus aculeatus): Contains about 10% of steroidal saponins, known as ruscogenin and neo-ruscogenin. Ruscogenin is the aglycone of ruscin. Ruscus tones the venous system and reduces capillary fragility. Clinical trials have shown ruscogenins to be vasoconstricting and antiinflammatory. Triterpenoid saponins: Most of these saponins contain at least one carboxylic (-COOH) group. The common saponin actions described earlier are also evident in this group, that is, anti inflammatory and reflex actions. 13 Triterpenoid saponins are mostly found in dicotyledons: Dicotyledons Fabaceae Glycyrrhiza Asteraceae Solidago Apiaceae Bupleurum Primulaceae Primula Phytolaccaceae Phytolacca Polygalaceae Polygala Caryophyllaceae Stellaria Licorice (Glycyrrhiza glabra): Glycyrrhiza contains over a dozen different triterpenoid saponins, the main one being glycyrrhizic acid at 2 – 6%, which occurs in the plant as a mixture of potassium and calcium salts. This mixture is known as glycyyrhizin, an intensely sweet compound, 50 times sweeter than sucrose. The saponin of glycyrrhizic acid is glycyrrhetinic acid. (figure 6.53, page 95) 15 The saponins of licorice have anti-inflammatory, demulcent, expectorant and antiviral (herpes virus) properties and also affect hormone levels and hormone like actions Mineral corticoid action (mimics aldosterone): increases Na+ and Cl- while decreasing K+, thus leading to fluid retention (and contraindications of oedema and hypertension Mimics ACTH stimulating glucocorticoid secretion from the adrenal cortex Inhibits the breakdown of glucocorticoid hormones (including cortisol), aldosterone and progesterone Clinical studies have shown that glycyyrhizic acid and glycyrrhetinic acid accelerate the healing time of gastric ulcers, apparently due to increased rate of mucous secretion. Licorice contains a variety of potentially active constituents apart from saponins , including isoflavones and other flavonoids. Oat seedling roots observed by fluorescence microscopy, showing the natural fluorescence of the saponin, avenacin. The left-hand image shows the tip of a main root axis; the right-hand image shows a root lateral emerging from a root axis. Properties of saponins Haemolysis, therefore, saponins are not for long term or high dose use. On injection, like all detergents, they cause lysis of the blood cells and are thus highly toxic. However, o Because saponins are hydrolysed in the GIT before any absorption takes place and the free sapogenins do not display haemolytic properties, there is little to no haemolytic risk associated with oral ingestion (with the possible exception of bleeding ulcer). o The haemolytic potential varies amongst saponins those found in Panax ginseng are practically devoid of haemolytic activity while the saponins of Phytolacca spp. are 19 potent haemolytic agents. Upper GIT irritation, and therefore, act as a reflex expectorant. This effect can be best described as a slight irritation of the mucous membrane. The action conveys two general actions of saponins: o Increased absorption, following increased blood supply to the mucosa o Reflex expectorant action, mediated by the embryonic neural link between the mucous membranes of the GIT and the respiratory tract. Important expectorant herbs containing saponins include Polygala senega, Verbascum thapsus, Viola odorata 20 o This reflex stimulation of the stomach wall is a result of the fact that most saponins, when taken in bulk, have an emetic effect – their detergent action promotes elimination on the part of the stomach. When taken in sub-emetic doses, the emetic action becomes a reflex stimulating expectoration as with such wellknown alkaloidal emetics as lobelia (Lobelia inflata) or ipecacuanha (Cephaelis ipecacuanha). 21 Other saponins have a less irritating effect on the digestive system, actually settling it and aiding the absorption of important minerals. The saponins of spinach, asparagus, beetroot, oats and many of the legumes are likely to have a useful action. 22 Facilitation of solubility and absorption of larger molecules Interruption of absorption of transport of small molecules gymnema disrupts the absorption and uptake of sugar Anti-inflammatory effects, other than that conveyed by the local effect in the GIT. Good examples of anti-inflammatory herbs containing saponins are Stellaria media, Aesculus hippocastanum, Solidago virgaurea, Scrophularia nodosa 23 Cholesterol-lowering effects by inhibiting absorption and stimulating bile excretion e.g. Trigonella foenum-graecum and Glycyrrhiza glabra. However, they need to be consumed in quite large amounts. There is also a group of saponins with prospects for vascular disorders, including varicose veins, thrombotic conditions, arteritis, phlebitis and arteriosclerosis. These are indications for the vascular remedy Aesculus hippocastanum, but could also include Achillea millefolium and Tilia spp. Anti-microbial effects, especially fungal 24 Anti-viral – topical and gut only Hepatoprotective effects – saikosaponins from Bupleurum spp (Apiaceae), ginsenosides from Panax ginseng Araliaceae) Saponins are highly toxic to fish and other cold blooded animals, and many cultures all over the world have exploited saponin containing plants as fish poisons. In this form they are harmless to humans. A number of common foods contain saponins e.g. tomatoes, asparagus, beetroot, oats and some legumes