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How to explain the high solubility of artemisinin in Artemisia annua infusions?

October 20, 2015 - 08:37 -- Pierre Lutgen

A review paper published by Frank van der Kooy in 2013 (Journal of Ethnopharmacology, 150, 1-13) revived our interest in the question why the solubility of artemisinin is higher in Artemisia annua infusions than for the pure substance in distilled water.

We quote : « It is possible that the compounds responsible for the enhanced aqueous solubility of artemisinin only occur in the stems and not in the leaves…Furthermore, no studies have been conducted on the possible chemical reactions that can take place or the extraction efficiency of urine, as this was the common extraction solvent in ancient times.This interaction between common water ions and salts, and also common metabolites present in urine, should be further investigated and its effect on the various biological activities ascribed to Artemisia annua ».

Extraction efficiencies for artemisinin of greater than 70% have been noticed (K Räth et al., Am J Trop Med Hyg 2004, 70, 128-32) The authors proposed that the low water solubility of artemisinin is overcome by the action of other constituents present in Artemisia annua.

Along these lines a paper from Tehran studying the effect of surfactants on extraction of polyphenolic compounds (R Hosseinzadeh et al., PlosONE, 2013, 8(3) e57353) shows indeed that surfactants in water give a much higher extraction of polyphenols than methanol in water. The authors also studied the influence of ionic strength and pH. A 2% potassium chloride solution in water was determined to be the optimum salt concentration for the extraction. At higher concentrations the extraction of hydrophilic compounds is partially blocked. It is possible that osmotic pressure plays a role in the rupture of plant cells. This needs to be investigated.

More important even could be the work we have done in partnership with the University of Al Quds, Jerusalem, Palestine. For several medicinal herbs including Artemisia species, they find that when the extraction in done by hot water containing NaCl or sodium bicarbonate, the beta-hematin inhibition effect is strongly enhanced (M Akkawi et al., Med Aromat Plants, 2014, 3:1, 1000150; S Jaber et al., J Pharm Pharmacol, 2015, 63-72). The effect of sodium bicarbonate is negligable if is added to the infusion after extraction. This is the case for all salts dissolved in pure water: NaCl, KBr, NaNO3, KCl, ZnCl2, KI, K2HPO4) : they have no effect per se on beta-hematin inhibition (personal communication from M Akkawi).

The use of urine for efficient extraction of medicinal herbs may rely on similar elements. Urine contains 1% of chlorides. It also contains 1 gm per liter of sodium bicarbonate, or more if the pH of urine is > 7 (JL Gamble, 1922, 51, 299-310). Bicarbonate contents are much higher in roots and stems than in leaves (A Wallake, Plant aand Soil, 1979, 51, 431-435).

Artemisia plants are rich in the ambiphilic surfactant saponin. Based on literature data on vegetables and medicinal plants our best estimate for saponins in Artemisia plants is around 1% versus 0.4 % in vegetables. There are many anecdotical claims that Artemisia annua stems are richer in saponins than leaves. The problem is that it is very difficult, even impossible to find quantitative studies on saponins in any Artemisia species.

Among all the medicinal plants those of the Artemisia family have the highest potassium content. The first to report this were E Brisibe, P de Magalhaes, J Ferreira et al, (Food Chemistry, 2008, 115, 1240-46). Potassium concentrations in Artemisia annua are 10 to 100 times higher than those of other minerals, particularly sodium . A study in Morocco measured the potassium content of four medicinal plants. For Artemisia herba alba it is the highest (R Imelouane et al., J Mater Envir Si 2011, 2, 104-11). A more complete study in Pakistan, comparing 10 medicinal plants finds that potassium content in Artemisia annua is the highest (I Hussain et al., World Appl Sci J., 2011, 12, 1464-1468). Often the concentration of potassium is higher in stems than in leaves, in artichoke for example, in rice (RA Sperotto et al., Rice, 2012, 5 :27), in tomatoes (G Gary et al., J Exp Botany, 1998, 49, 49-57).

Why and how these constituents of Artemisia annua enhance the solubility of lipophilic constituents needs further investigation. The work of Frank van der Kooy (Planta Medica 011, 77, 1754-6) has shown that the extraction is up to 80% if the dried herb is in contact with boiling water for 2-5 minutes. The addition of a very small amount of salt or bicarbonate before pouring the boiling water will strengten the infusion.

A freshly prepared infusion probably contains all the constituants of the plant which have an antimalarial effect. A true polytherapy which explains why the cure rate in all trials in a dozen African countries is >95%. Much higher than for any kind of ACT (artemisinin combined therapy) which are not more than the combination of two monotherapies without synergy but with resistances.

For an African Artemisia tea is available in the home garden, efficient and inexpensive.

Pierre Lutgen

Mutaz Akkawi

Lucile Cornet Vernet


Smain CHEMAT's picture
Submitted by Smain CHEMAT on

That is a very interesting article. As an expert on extraction and purification of artemisinin, I allow myself to give some scientific explanations to the fact that the presence of bicarbonate salts enhances extraction.
First why boiling water gives more artemisinin, this is a causal effect not a direct one; artemisinin is dissolved in essential oil ducts present in the leaves, high temperature of boiling water enhances solubility of essential oil in it which in turn entrain artemisinin in water.
Addition of bicarbonates will cause dehydration of cell ducts by an osmose like effect, so ducts will dry then explode to release their content, so we will have more artemisinin and co-metabolites in the bulk medium. Although most artemisinin analogs present in the leaves have antimalarial activity but the main driver here is Artemisinin. Nonetheless, the synergy effect is definitely here.


Submitted by Chris Carlson (not verified) on

To clarify, I think I am to understand that higher concentrations of potassium can often be found in the stems vs. the leaves but levels of artemisinin is not at a higher concentration in stems or leaves per-say.