Herbs in History: Wormwood

Wormwood

Artemisia absinthium


CONTENTS

By Alain Touwaide & Emanuela Appetiti | March 2023

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Malaria?

Artemisia absinthium (Oleg Marchak)

Illustration 1: Artemisia absinthium
 

The genus Artemisia raised to world notoriety in 2015 thanks to the Nobel Prize for physiology or medicine awarded to the Chinese scientist Tu Youyou for the research she performed over the previous 45 years on the species A. annua L. (Asteraceae) as an antimalarial agent. Interestingly, she started from the Chinese tradition, specifically ancient texts where she located references to sweet wormwood in correlation with intermittent fevers.
 
In the Mediterranean world, one of the most frequent species of the genus Artemisia is A. absinthium L., traditionally known as Absinth or Wormwood, which grows in temperate Eurasia and Northern Africa.
 
The Chinese historical indication of A. annua for the treatment of malaria authorizes to investigate whether the cognate species A. absinthium was already used or not for the same medical condition (Illustration 1). The question is even more legitimate because malaria was persistently present in the Mediterranean region until not so long ago and Wormwood probably was—and still is—ubiquitous. A screening of the ancient literature points in another direction.

 

Fits & Starts?

No botanical description of Wormwood appears in the ancient scientific literature before the 1st century CE, in De materia medica by Dioscorides, which is the largest compilation of Antiquity about the natural substances used for therapeutic purposes. There, we discover that ancient botanists distinguished three species of the plant. Of the first, Dioscorides wrote that it was well known and did not describe it in any precise way, specifying however that its best quality was found in the area of the Black Sea and in Cappadocia (present-day central Turkey), in the region of the mountain called Tauros (now called Aladağlar), in the Taurus chain which separates the central Cappadocia plateau from the Mediterranean coastal region. The second species too was growing in the Taurus Mountain of Cappadocia, in addition to Taphosiris in Egypt, close to Alexandria on the Mediterranean coast. The third one, which grew in Gaul on the slopes of the Alps, was called Santonikon, according to the name of the region corresponding to present-day Saintonge and around the city of Saintes, in Southern France. Though considered three species, they are more likely to be three different populations of the same species. Whatever the case, judging from its frequent mentions in the ancient literature, medical or other, Wormwood was most probably ubiquitous.
 
Whereas Wormwood appeared only recently in the botanical literature, it is abundantly mentioned in the medical literature as early as the most ancient treatises attributed to the Father of Medicine, Hippocrates (5th-4th cent. BCE). In its most ancient citation in mid-fifth century, it is indicated for the treatment of jaundice. During the following decades it then specialized in the treatment of gynecological conditions, mostly as a tampon, for affections of the womb (including excessive moisture), for the treatment of hysteria (supposed internal movements of the womb provoking severe troubles to women), dysmenorrhea, and sterility. In one case, however, it is prescribed against sore throat.
 

Artemis of Ephesus

Illustration 2: Artemis of Ephesus (copy of the statue of Artemis in Ephesus, upper part, Jona Lendering, Museum Selçuk, Museum of Ephesus)

This intense gynecological use was probably ancient, going way back in time before the Hippocratics, as the very name of the plant indicates through the link it creates with the goddess of Greek mythology Artemis. A daughter of the god of the gods, Zeus, and a twin brother of the god of light, the arts, and medicine, Apollo, Artemis was the goddess of life and vital force of nature, of chastity and childbirth, of the animal world and vegetation. In substance: the wildness of life in all its forms, its indomitable nature. This personification of life sometimes took an extreme form as, for example, a multi-breasted Artemis representing her in a very graphic and, at the same time, very symbolic way (Illustration 2).
 
Strangely enough, in the subsequent literature, Wormwood lost this original gynecological specialization and became the bitter plant par excellence in a radical change that could hint at a new start in the therapeutic history of Wormwood, as a result of experiments, trials and investigations aimed to diversify—and possibly expand—its range of uses.
 
In his treatise on plant physiology (De causis plantarum), the Father of Botany, Theophrastus (4th/3rd cent. BCE), limited himself to mention its bitterness. Dioscorides, instead, was more prolix. After he characterized it as an astringent and warming plant, he described no less than 33 different uses, none of which is gynecological in nature. Wormwood was mostly recommended for the treatment of conditions affecting the digestive system: stomach and liver ache, flatulence, jaundice, bile excess, ascarids, and round worms. It was also considered efficacious against anorexia and drunkenness nausea, in addition to dropsy, headache, and earache, pain in the eyes and amblyopy, sore throat, and dysmenorrhea. Finally, it was administered against poisoning by hemlock, spine thistle, and mushrooms, and against envenomation by the greater weever and shrew mouse.
 
Finally, Dioscorides added that the plant repels clothes moths. More intriguing because unexpected, he also mentioned that ink mixed with Wormwood prevents from mice eating books (made of papyrus in Dioscorides’ time). And he added that the plant was also used as a fly repellent.
 
Galen (2nd/early 3rd cent. CE) confirmed this change of route of Wormwood in repeating that it is astringent, adding that it is bitter and pungent, and has therefore a warming, cleaning, tonic, and desiccative action in an interesting association of properties and actions. According to the original system he created to precisely define and measure the action of natural remedies, Wormwood is warming at the 1st degree and desiccative at the 3rd. Thanks to this, it eliminates the excess of bile in the digestive and circulatory systems.
 

A Difficult Choice

Representation of Wormwood in a manuscript of Tractatus de herbis (London, British Library, MS Sloane 4016, folio 1 recto)

Illustration 3: Representation of Wormwood in a manuscript of Tractatus de herbis (London, British Library, MS Sloane 4016, folio 1 recto)
 

In front of this radical shift from gynecology to the digestive system, which might reflect attempts to explore new possible applications and diversify their range of applications of Wormwood, subsequent medico-botanists were facing a choice, particularly because they had access to all the previous literature, from the Hippocratic treatises to those by Galen.
 
In the Arabic World, where ancient Greek scientific and medical treatises became available thanks to translations from their original language into Arabic from the late 8th century onward, scientists summed up ancient knowledge and expanded it with new data of their own or from other traditions. One such new work—possibly the most significant—resulting from this scientific enterprise was the Qanun (Canon) by ibn Sina (980-1037), best known in the West and the historiographical tradition as Avicenna, which is a vast compilation on materia medica that can be aptly compared to its Greek equivalent, Dioscorides’ De materia medica.
 
Avicenna devoted a long chapter to Wormwood in the Canon in which he assembled data from both his Greek predecessors and Hunyan ibn Ishaq (808-873 CE), a physician who translated numerous Greek scientific works into Arabic in the early times of the Arabic Empire and also wrote original work. On this basis, Avicenna listed several oriental species of Wormwood not previously described in the literature, with a distribution up to Khorasan (covering parts of present-day Afghanistan, Turkmenistan and Iran).
 
Beyond this variety of species, he treated Wormwood in a unitary way, describing it as similar to Oregano, and considering it bitter and even acrid, and astringent. For him, it is warming at the 1st degree as did Galen, and drying at the 2nd, instead of the 3rd according to Galen. However, its juice is warming at the 3rd degree. As for its therapeutic uses, Avicenna mostly repeated those found in Dioscorides and Galen, and not those of the Hippocratic tradition, in addition to three new, cosmetic ones: the treatment of alopecia and of dark circles under the eyes, and the improvement of the skin color, giving it a good appearance.
 
In a further movement of circulation of knowledge all around the Mediterranean, the legacy of the past arrived in Italy in a clockwise movement, thanks to translations from Arabic into Latin. There, the translated texts were assimilated in the medical practices, compiled in all-encompassing encyclopedias, and also re-arranged in handy compendia. One of them is the so-called Tractatus de herbis (Treatise on Herbs, that is, Treatise on Medicinal Plants) probably dating back to the 13th century (Illustration 3).
 
At first glance, the compiler of the Tractatus followed the Greek tradition and stated that Wormwood is warming and desiccative in a combination of the information provided by both Dioscorides and Galen. He nevertheless differed from tradition in considering that these properties are of the 2nd degree of intensity.
 
Pursuing the reading, however, we discover that the author behind the Tractatus did not have an exact knowledge of either the plant or the classical texts. And we may wonder whether he was a scientist with knowledge of the matter or a compiler. When discussing the different species of Wormwood, he distinguished indeed the Pontic and the whitish species. About the Pontic, he explained its name in two different ways: first, as a reference to the region called Pontos in Greek (which is the Black Sea) where it grew particularly, in a way recalling Dioscorides. But then, he added that the name of the species indicated that it has a marine taste. In so doing, it misinterpreted the term Pontic, considering that it meant marine since pontos in ancient Greek was the term for the sea. But the adjective Pontic in ancient Greek designated one specific sea, the one now identified as the Black Sea.
 
Pursuing the analysis, the Tractatus specified that the plant is extremely bitter, and of a green color. Going on along these lines, it attributed two properties to the plant: cathartic because of its warming nature and bitter taste, and astringent because of the thickness of its matter and its marine nature. On this basis, it identified the pontic species as a thick species. In so doing, it explained its cathartic action by its warming properties (it dissolves thick humors) and its astringency by its thick nature. Having made these theoretical considerations, the compiler of the treatise reproduced the uses of the plant found in the previous literature, including the preservation of clothes and books. If he thus confirmed the non-gynecological line of uses, he also generated interferences that might have required to revise the whole topic.
 

Diversification & Continuity

The geography of science then changed. The conquest of the capital of the Byzantine Empire, Constantinople, by the Turks in 1453, was followed by a massive emigration of population from the Eastern Mediterranean to the West. Among these migrants were scholars and scientists who brought with them their books and science, including the founding text of Dioscorides and the theorization of Galen, making them available to Western medico-botanists. Determining and possibly understanding the uses of Wormwood attested by the tradition was again on the agenda of medical botany.
 
In 1542, the German classicizing botanist Leonhart Fuchs (1501-1566) published the monumental Historia stirpium (Inquiry into medicinal plants), in which he mostly translated into Latin the Greek texts of Dioscorides and Galen. After he distinguished two species (the Pontic and the marine ones), he wrote that the former was the common species and that it grew in Germany. He then briefly added a third species (the one growing in the Alps according to Dioscorides). For the rest he exactly reproduced the data provided by his ancient Greek predecessors, in addition to material taken from the Latin encyclopedist Pliny (1st cent. CE), author of Natural History (Historia Naturalis).
 
Twelve years later (1554), the Belgian botanist and physician Rembert Dodoens (1517-1585) published his Kruideboeck (Book of Herbs, that is, Book on Medicinal Plants), which was not written in Latin as was current practice then, but in the vernacular and, more specifically, in Flemish. About Wormwood, he distinguished five different species:
 

  • the first having large leaves (latifolium), which corresponded to the Pontic species of Dioscorides, and was found in some cold mountains of Switzerland according to Dodoens;

  • the second species is the marine one, with narrow leaves. It is called Seriphon, and it is the second species of Dioscorides. According to Dodoens, it grew on the shores of Holland, Zeeland, and Flanders (that is, on the shores of the North Sea), and in France and Italy;

  • the third species is the Egyptian one, of which Dodoens received an individual;

  • the fourth is the narrow-leaf species, which grew, according to him, in Mysia (that is, in Asia Minor), Thracia (north-east Greece), and Pannonia (north-eastern Greece and Bulgaria), and also in Bohemia, Germany, Belgium, and England. It was commonly designated as the Roman Absinth. This species is in fact the same as the Pontic of Galen;

  • the fifth is a scented and tasteless species.

Further species are not Absinth, but other genera that have been erroneously confused with Absinth. As for their uses, they are mostly the same as those in Dioscorides and Galen.
 
At the end of our journey, the Englishman John Gerard (ca 1545–1612), an herbalist who owned a large garden in London, published in 1597 a Herbal in which he collected much of the information available in his time about medicinal plants and their uses. Walking in the footsteps of Dodoens, he divided further the genus of Wormwood, introducing no less than ten different species: the one with large leaves or Pontic; the species with narrow leaves or Pontic according to Galen; the species with narrow leaves or Roman; the marine, white species; the marine species with large leaves; the Sementina or Holie Wormwood; and four foreign or bastard species: arborescens, white, Egyptian, and scentless. However, if he elaborated much on their description and names, he did not do so about their therapeutic applications, and repeated, instead, Dodoens’ information.
 

A Complex Genus, but a Single Taste

Strange history, thus, that of Wormwood in the Mediterranean World from Antiquity to the dawn of modern botany and botanical therapeutics. After it changed therapeutic profile, shifting from the gynecological to the digestive system in a way that was never revised, it became identified as the bitter plant in a unitary way, even though an increasing number of sub-species were distinguished.
 
Adding to these paradoxes, Wormwood does not seem to have been used for the treatment of malaria in the Mediterranean World, contrary to China, even though this medical condition was endemic in the region until not so long ago. Nevertheless, there might have been some awareness of the anti-parasitic action of Wormwood in Dioscorides’ statement that it avoided cloth to be infested by moths and books to be eaten by mice, in addition to be a fly repellent. Would it be that the Greeks were close to discover its anti-malarial action through its anti-parasitic property? Or that they did use Wormwood to this end, but did not record such use in writing?
 
Whatever the case, the foliage of the plant has a great many properties, mostly for the digestive system as the departure from the gynecological uses announced: anthelmintic, antiseptic, antispasmodic, appetizer, carminative, cholagogue, stomachic and vermifuge, in addition to some gynecological and other uses, emmenagogue, febrifuge, hypnotic, and stimulant, and also condiment in moderate doses. And, just as Dioscorides already stat, it does protect clothes from moth, and is an insect repellent.
 
It is toxic in high doses, and small quantities (even the scent) can provoke nervous disorders, convulsions, and insomnia, all of which recall the symptoms of the overconsumption of Absinthe, the anise-flavoured liquor particularly used in France during the 19th century among the Parisian circles of writers and artists, among whom one might count the painters Vincent Van Gogh and Pablo Picasso, and the writers Charles Baudelaire, Arthur Rimbaud, and Marcel Proust, also including James Joyce and Ernest Hemingway. Absenthism was characterized by hallucinations, sleeplessness and convulsions.


Tu Youyou’s Nobel Prize Discourse
https://www.nobelprize.org/uploads/2018/06/tu-lecture.pdf
 
Documents from the European Medicines Agency
 
Committee on Herbal Medicinal Products (HMPC)
European Union herbal monograph on Artemisia absinthium L., herbs Final
4 March 2020 EMA/HMPC/751490/2016 Corr. 1
https://www.ema.europa.eu/en/documents/herbal-monograph/final-european-union-herbal-monograph-artemisia-absinthium-l-herba-revision-1_en.pdf
 
Committee on Herbal Medicinal Products (HMPC)
Assessment report on Artemisia absinthium L., herba
30 May 2017 EMA/HMPC/751484/2016 Final
https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-artemisia-absinthium-l-herba-revision-1_en.pdf
 
Committee on Herbal Medicinal Products (HMPC)
List of references supporting the assessment of Artemisia absinthium L., herba Final
30 May 2017 EMA/HMPC/186849/2017
https://www.ema.europa.eu/en/documents/herbal-references/final-list-references-supporting-assessment-artemisia-absinthium-l-herba-revision-1_en.pdf
 
Articles (selection, chronological order)
 
Ekiert H. et l. 2021. Artemisia abrotanum L. (Southern Wormwood)-History, Current Knowledge on the Chemistry, Biological Activity, Traditional Use and Possible New Pharmaceutical and Cosmetological Applications. Molecules 26(9) (2021 Apr 25): 2503.
doi:  10.3390/molecules26092503
https://pubmed.ncbi.nlm.nih.gov/33923002/
 
Kshirsagar S.G., R.V. Rao 2021. Antiviral and Immunomodulation Effects of Artemisia. Medicina (Kaunas) 57(3) (2021 March): 217.
doi: 10.3390/medicina57030217  
https://www.mdpi.com/1648-9144/57/3/217
 
Bisht D., D. Kumar, D. Kumar, K. Dua, D.K. Chellappan 2021. Phytochemistry and pharmacological activity of the genus artemisia. Archives of Pharmacal Research, 44(5) (2021 May):439-474.
doi: 10.1007/s12272-021-01328-4
 
Ivanov M et al. 2021. New Evidence for Artemisia absinthium L. Application in Gastrointestinal Ailments: Ethnopharmacology, Antimicrobial Capacity, Cytotoxicity, and Phenolic Profile. Evidence-Based Complementary and Alternative Medicines 2021 (2021 Jul 22): 9961089.
doi:  10.1155/2021/9961089   
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324356/
 
Batiha G.E. et al. 2020. Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Wormwood (Artemisia absinthium). Antibiotics 9(6) (2020 Jun 23):353.
doi: 10.3390/antibiotics9060353 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7345338/
 
Szopa A. et al. 2020. Artemisia absinthium L. Importance in the History of Medicine, the Latest Advances in Phytochemistry and Therapeutical, Cosmetological and Culinary Uses. Plants 9(9) (2020 Aug 19): 106.
Boudjelal A eet al. 2020.Phytochemical Profile, Safety Assessment and Wound Healing Activity of Artemisia absinthium L. Plants 9(12) (2020 Dec 10): 1744.
doi: 10.3390/plants9121744
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763807/
 
Hashimi A. et al. 2019. One for All - Artemisia absinthium (Afsanteen) “A Potent Unani Drug”. TANG 9(4) (2019 Nov 29): e5.
doi: http://dx.doi.org/10.5667/tang.2019.0020
Masoudi M., M. Saiedi. A Review study of Ethnopharmacology, Phytochemistry, and Anti-inflammatory, an 2017tioxidant, and anti-microbial effect of Artemisia absinthium. Der Pharmacia Lettre 9(4) (2017): 155–162.
 
Koulu M, S. Örmä. A. Liljeblad, P. Niemelä P. 2016. Artemisaiae as medicinal and herbal medicinal plants from ancient times to the present day. Duodecim. 132(19) (2016): 1763-1770.
https://pubmed.ncbi.nlm.nih.gov/29188968/
 
Bailen M. et al. 2013. Chemical composition and biological effects of essential oils from Artemisia absinthium L. cultivated under different environmental conditions. Industrial Crops and Products 49 (2013): 102–107.
https://www.sciencedirect.com/science/article/abs/pii/S0926669013002331?via%3Dihub
 
Nalbantsoy A. eet al. 2013. Viper venom induced inflammation with Montivipera xanthina (Gray, 1849) and the anti-snake venom activities of Artemisia absinthium L. in rat. Toxicon 65 (2013): 34–40.
doi: 10.1016/j.toxicon.2012.12.017
 
Jarić S. et al. 2011. Phytotherapy in medieval Serbian medicine according to the pharmacological manuscripts of the Chilandar Medical Codex (15–16th centuries). Journal of Ethnopharmacology 137(1) (2011): 601–619.
doi: 10.1016/j.jep.2011.06.016
 
Kundan Singh B., S. Anupam 2011. Evaluation of antioxidant and free-radical scavenging potential of Artemisia absinthium. Pharmaceutical Biology 49 (2011): 1216–1223.
doi: 10.3109/13880209.2011.578142
 
Lachenmeier D.W. Wormwood (Artemisia absinthium L.)-A curious plant with both neurotoxic and neuroprotective properties. Journal of Ethnopharmacology 131(1) (2010): 224–227.
doi: 10.1016/j.jep.2010.05.062
 
Basta A., O. Tzakou, M. Couladis, M. Pavlovic 2007. Chemical Composition of Artemisia absinthium L. from Greece. JEOR-Journal of essential oil research 19(4) (2007): 316-318.
doi: 10.1080/10412905.2007.9699291
 
Erdogrul, O.T. 2002. Antibacterial activities of some plant extracts used in folk medicine. Pharmaceutical biology 40(24) (2002): 267-273.
doi.org/10.1076/phbi.40.4.269.847

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