Saponin lowers iron. glucose, uric acid, cholesterol: key factors in malaria

Most research work on Artemisia annua has ignored saponins and polysaccharides because these are only soluble in water and in the search of the golden fleece or the exceptional antimalarial molecule most extracts are obtained with organic solvents.
Saponins are found in many plants, often in desert plants and are also present in some marine organisms. Most medicinal plants are rich in saponins, which to a large extent are responsible for their bitterness. In fact saponins protect plants from phytopathogenic microorganisms, phytophagous mammalian and insects.
The major commercial sources of saponins are yucca, soya, alfalfa. Saponins are widely distributed secondary plant metabolites. They are amphiphilic like soaps combining a lipophilic chain with an hydrophilic attachment, a sugar moiety linked to a hyrophobic aglycone. The great complexity of saponin structure arises from the variability in the aglycone structure and the nature of the side chains. This renders a quantitative determination by spectroscopy very difficult and their presence or concentration is generally assessed by the froth test based on the foaming properties. Saponins are used to increase the foaming of beer !
Most saponins are highly surface-active, and many form addition-complexes with sterols, including those of fungal, plant and animal cells. This leads to membrane destabilization and cell lysis. The ability of many saponins to cause hemolysis in vitro is a property that is widely used in the design of quantitative bioassays. For the same reason saponins are used as adjuvants in vaccines. The uses of saponins as adjuvants in vaccines may also be related to the activation of lymphocytes (SR Chavali et al., Int J Immunopharmacol 1987, 9, 673-83). In 2010 we noticed (personal communication) a much stronger activation of lymphocytes by Artemisia annua tea from Luxembourg than from Cameroon. As per the froth test the tea from Luxembourg contains much more saponins.
A British study (IT Johnson et al., J Nutr 116, 1986, 2270-2277) shows that the saponins from three different plants increase the permeability of the small intestinal mucosal cells, facilitating the uptake of material to which the gut would normally be impermeable. A study on medicinal plants from Iran containing saponins Artemisia dracunculus, Heracleum persicum, Cuminum cynimum shows that the aqueous extract from Artemisia dracunculus has the highest hemolytic effect (G D Noudeh et al., Afr J Biotechnol, 2010, 9, 110-116).
A German research paper (E Baumann et al., Acta Histochem, 2000, 102, 21-35) shows that the incubation of cells and tissues with saponin makes the lipid bilayer permeable to macromolecules, by affecting the interaction between transmembrane proteins and the cytoskeleton. This will admit the access of antibodies to the cytoplasmic surface of cells. Saponin from medicinal herbs also activates calcium-dependent potassium channels (OB McManus et al., Biochemistry, 1993, 32, 6128-33). They modulate the sodium pump and ATPase ( A de Souza et al., Zeitung Naturforschung, 59c 2003 432-436). In the Chinese pharmacopeia plant mixtures rich in saponins have been used to enhance the bioavailability of artemisinin (G Brown, Molecules, 2010,15,7603-7698).
The nutritional significance of saponins for humans stems largely from their hypocholesterolemic action, which has been extensively studied in laboratory animals. (Br J Nutr. 1988 May;59(3):389-96). Saponins bind with cholesterol. Cholesterol is continually secreted into the intestine via the bile, with much of it subsequently reabsorbed. Saponins cause a depletion of body cholesterol by preventing its re-absorption, thus increasing its excretion in much the same way as other cholesterol-lowering drugs do.

Saponins from Medicago sativa (lucerne) and Gypsophila (Southon S1, et al., Br J Nutr 1988, 59, 389-96) reduced Fe absorption from a single meal rich in iron by 17%. Iron forms very stable complexes with saponins and that is why iron absorption is reduced (Samina Siddiqi. PhD Thesis, Univ Karachi 1994).

Saponins have ammonia-binding activity. When ammonia is processed by the liver, uric acid is created. Saponins cause notable delays in uric acid crystallization. They accelerate the excretion of uric acid. (G L Chen, Am J Chin Med 34,01, 2006). Similar effects were observed in the presence of a surfactant, lauryl sulfate. Whitaferin, a saponin, which is called Indian ginseng, or Smilax riparia, in China also alleviates gout (EP Sabines et al, J Pharm Pharmaceut Sci 11:4, 45-56.2008, WU XH et al., Am J Chin Med 2014, 42, 257-9)
Saponins inhibit the intestinal permeability of glucose and may consequently inhibit the growth of Plasmodium falciparum which uses glucose as food.
Uric acid, glucose, iron and cholesterol are key factors in malaria. An excess of each one exacerbates the disease.
There are many anecdotical claims that Artemisia annua stems are more efficient against several diseases than leaves. The problem is that it is very difficult, even impossible to find quantitative data on saponins in any Artemisia species
In the plant Mimosa pudica saponin concentration in aqueous extracts is higher in stems than in leaves (1.55% versus 1.30%). All other constituents like alkaloids, flavonoids, tannins, glycosides are lower in stems (I Ibrahim et al., Am J Biol Chem 2014, 2, 8-16). The ethanolic extract of the leaves even doesn’t contain any saponin, while that of the stems does.
The pharmacological activity of Centella asiatica is attributed mainly to saponins like hinokinin (Viola Müller, Thesis, 2013, Universität, Bonn). The plant contains up to 4% of saponins on dry weight and is used in China against leprosy.
The anti-inflammatory effect of the saponin extracts of 5 Nigerian plants rich in saponin : Schwenkia americana (2.74% saponin), Asparagus africanus (3.59%), Dichrostachys cinerea (1.62%), Ficus iteophylla (=,81%), and Indigofera pulchra (1.57%) has been described and is equivalent to Ketoprofen (HS Hassan et al., Afr J Complement Altern Med, 2012, 9, 250-255). An extensive study has been run on the antioxidant activity of saponins isolated from Ivy Hedera helix. At the concentration of 75 mg/L they showed 85% inhibition on lipid peroxidation. Their DPPH, superoxide radical and H2O2 scavenging properties were equivalent to alpha-tocopherol and butylated hydroxytoluene (I Gülçin et al., Planta Med, 2004, 70, 561-563). Ginsengoside, the saponin of ginseng, has strong wound healing properties (Young Sao Kim et al., J Ginseng Res 2011, 35, 360-367) through the promotion of anti-oxidant and anti-inflammatory , the promotion of matrix synthesis and re-epithelization.
Saponin as coadjuvant was very efficient in a vaccine against hemorrhagic septicemia in mice and buffalo calves, increasing CD4 and CD8 cell populations and improving the humoral immune response (S Kumar et al., Indian J Animal Sc. 2012, vol 82 No 9). Similar effects have been described by M-A Lacaille-Dubois (Immunomodulatory Agents from Plants, ed Paniham, 1999).
The University of Al Quds in Palestine found that saponin inhibits beta-hematin crystallization (Personal communication from Mutaz Akkawi).
Saponin is anthelmintic and inhibits hepatitis C virus propagation (Jihye Lee et al., PLOSone.June 2012, Vol 7-6)
The stems of the medicinal plant Cissus populnea from Niger are rich in saponins and are used by the Fulanis to feed their cattle, ostensibly to increase milk production (M Soladoye et al., Phytologia Balcanica, 2012, 18, 149-153). The plant Achyrantus bidentata rich in saponins has strong analgesic and anti-inflammatory properties Gao C.Ket al., 2003 Anhui Mel. Pharm. J. 7, 248–249) In Brazil the Brachiara bizantha grass is used in cattle feeding. In this plant the concentration of saponins decreases from 3 % in spring to 0.6% in autumn (F Lima et al., Federal University of Goias)
The most complete study for the plant Achyrantus bidentata on accumulation and dynamics of saponins in vegetative organs has been run in China (Jinting Li et al., J Integrative Plant Biology 2008) over the months from August to November. In the leaves the saponin decreases from 4.09% in August to 0.06% in November, but in the stems it only decreases from 4.13 to 1.47. This may explain to some extent why leaves of Artemisia annua harvested in October have lost a lot of their efficiency, for example in the beta-hematin inhibition test.
The average saponin content in vegetables is 0.4%, except for asparagus and beans where it is higher. In mate tea in Argentina it is 1%.
Based on all these data on vegetables and medicinal plants our best estimate for saponins in Artemisia plants is around 1%. Which is a lot compared to other constituents like individual terpenes or coumarins.
This definitely deserves more research: hidden treasures in the jungle!
Pierre Lutgen
28 April 2015


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