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Santonin from Artemisia campestris: a famous forgotten anthelmintic.

September 18, 2015 - 06:04 -- Pierre Lutgen

200 years ago, in 1830 the anthelmintic properties of santonin were discovered , simultaneously by Dr Kahler in Düsseldorf and Dr Alms in Mecklenburg in a plant from Turkestan, Artemisia cina. Its presence, although at lower concentrations, was later found in Artemisia maritima, Artemisia campesris, Artemisia gallica, Artemisia absinthium, Artemisia sieberi. (Berichte der Deutschen Chemischen Gesellschaft , 1867, Vol 6, 875-1670). Stanislao Cannizzaro is known widely for his , "Sunto di un corso di filosofia chimica", on santonin which he presented at the Karlsruhe Congress of 1860. In his PhD thesis of 1843 in Heilbronn Dr Kleiner writes: „ Omnibus aliis anthelminticus Santoninum maxime praevalet, ac ullo medicamento nequaquam compensator“. In other words, santonin is really the best anthelmintic.

But the German pharmacists rediscovered what Dioscorides had described in the year 17 : that Artemisia was a vermifuge. And we rediscosvered by serendipity what was common knowledge and practice 50 years ago. But santonin has been banned form pharmacopeia and research, and there are no papers available in PubMed on this molecule over the last 20 years. The only recent paper concerning santonin is on calves. Capsules containing herbal powder of Artemisia maritima and Brassica nigra were given at 5g/calf daily to 20 cattle for 7 days. Compared with the 6 animals left untreated the preparation was 100% active with faecal examination for helminths (LK Sharma Indian Veterinary Journal, 1993, 70, 459-469). Another study showed that santonin in a 15 mg/kg dose has an efficacy similar to piperazine given at the 88 mg/kg dose level for the treatment of ascariasis in buffalo calves without significant side effects (MS Akhtar et alJ Vet Pharmacol Ther. 1982 Mar;5(1):71-6)

Santonin was used extensively as an anthelmintic against nematodes, particularly Ascaris, in the last two centuries. It was generally given as infusion of 5-10 g herb in 500ml water. To children it was given in the form of candies (Journal für Kinderkrankheiten, 1843). A very generally employed specific against round worms was the blossom of Artemisia maritima, popularly called worm-seed. At the dose of a spoonfull two or three times a day, in syrup or honey. Several weeks after the cure, the stools must be again examined for the eggs of the ascarides. In the US Dr.Hobson’s laxative Santonin was in every house pharmaacy cabinet. In 1938 Dr C Williams concludes that santonin is undoubltly the most suitable drug to be given at home if the parents are properly instructed (Arch Dis Child 1938, 13, 235-240).

In Artemisia cina the concentration of santonin in the dry matter may attain 2-3%. In plants of Artemisia maritima from Thuringia the content is 0.21-0.83 in the second year of this perennial plant (T Kawatani et al., Bull Nat Inst Hyg Sci,Tokyo, 1960, 78, 49-53).

For many years the mechanism of santonin was a mystery. It did not show any in vivo toxic effect on nematodes. In fact santonin does not kill worms in the host organism, but stimulates the muscles of the worms, causes convulsions, therefore expelling them alive from the bowels. This process is facilitated by using a laxative like castor oil. The disturbance of locomotion of Ascaris sulla and lumbricoides is well described in a paper from Tokyo. The drug operates in the nanomolar range. (Y Kobayashi et al., Jap J Pharmacol. 1962, 1, 130). To observe the locomotion of these nematodes they were placed in a glass tube. By adding a santonin solution in 1: 5000 dilution the locomotion of the worm immediately ceased entirely and then, after a while, its body began to curl around itself. It remains alive in this condition. The motionless worm will be driven down by the peristaltic movements of small intestine and colon to be expelled finally.

Artemisia campestris and santonin are also active against Giardia lamblia (IN-AlKaissi, al AnBar J Vet Sci 3 2010 48-52), against Haemonchus contortus  in bullock (CR Jangde et al. Indian Vet Journal, FAO) and event against nematode infestation in hibiscus roots (NC Sukul et al., Homeopathy, 2006,95, 144-147).

Santonin was also famous for its antipyretic properties (ML Martin et al., J Ethnopharmacol, 1988, 23, 285-90). It has strong antiinflammatory and analgesic properties (MM Al-Harbi et al., Jpn J. Pharmacol. 1994, 64, 135-139). No reports on negative effects for the consumption of santonin or Artemisia maritima infusions are known, nor for any other Artemisia variety. But as santonin was not very soluble in water it was extracted by organic solvents and administred in the form of pills. And the daily doses prescribed were in the range of 1-3 grams which was at the limit of toxicity. Similar effects of hepatotoxicity, cytotoxicity, embryotoxicity, splenotoxicity cardiotoxicity, genotoxicity are described in the scientific literature for artemisinin and its derivatives. Artemisinin, a drug efficient in the nanomolar range like santonin, if used at doses of 1000 mg/day in monotherapy is also at the limit of toxicity.

No negative health effects can be found in the literature for the regular consumption of Artemisia maritima tea. But high concentrations of santonin may indeed lead to xanthopsia or „yellow vision“. While absinthe is unduly infamous for its content of thujone, Artemisia absinthium also contains santonin (N Perez-Souto et al., J Chromatogr 192, 593, 209-15). And Van Goghs artwork after excessive quantities of absinthe may have been inspired not by thujone but by santonin

Artemisia campestris and Artemisia absinthium are perennial plants : a tremendous advantage for access in case of need for poor African families if they have these plants in their garden. Not only as anthelmintic but also as antimalarial. Saponin has been banned. The chemical drug recommended by WHO and generally used against nematodes is Albendazole. The price of one pill is 0,5-1.0 euro. Common side effects Albendazole include nausea, abdominal pain, headaches, potentially bone marrow suppression, liver inflammation and harm to pregnant women.

Clinical trials with Artemisis campestris against nematodes have started in several African countries with M4L and IFBV-BELHERB. Lets hope that others will join us and that research on santonin and Artemisia campestris will be resumed and that the ban on santonin be lifted.