Artemisia absinthium L. | Encyclopedia MDPI

Artemisia absinthium L.: Comparison

Please note this is a comparison between Version 2 by Catherine Yang and Version 1 by Agnieszka Szopa.

Artemisia absinthium – wormwood (Asteraceae) – is a very important species in the history of medicine, formerly described in medieval Europe as “the most important master against all exhaustions”. It is a species known as a medicinal plant in Europe and also in West Asia and North America. The raw material obtained from this species is Artemisiae herba and Artemisiae absinthium aetheroleum. The main substances responsible for the biological activity of the herb are: the essential oil, bitter sesquiterpenoid lactones, flavonoids, another bitterness-imparting compounds, azulenes, phenolic acids, tannins and lignans. In the official European medicine, the species is used in both allopathy and homeopathy. In the traditional Asian and European medicine, it has been used as an effective agent in gastrointestinal ailments and also in the treatment of helminthiasis, anaemia, insomnia, bladder diseases, difficult-to-heal wounds, and fever. Today, numerous other directions of biological activity of the components of this species have been demonstrated and confirmed by scientific research, antiprotozoal, antibacterial, antifungal, anti-ulcer, hepatoprotective, anti-inflammatory, immunostimulatory, cytotoxic, analgesic, neuroprotective, antidepressant, procognitive, neurotrophic, and cell membrane stabilizing activities. A. absinthium is also making a successful career as a cosmetic plant. In addition, the importance of this species as a spice plant and valuable additive in the alcohol industry (famous absinthe and vermouth-type wines) has not decreased. The species has also become an object of biotechnological research.

wormwood
significance in the history of medicine
traditional applications
position in official medicine
phytochemical and pharmacological studies
safety of use
cosmetical applications

1. Introduction

Over the past few years, there has been an increase in interest in research on the chemistry and biological activities of Artemisia species. This is undoubtedly connected with the awarding of the Nobel Prize in Medicine in 2015 for the discovery of artemisinin―a sesquiterpenoid lactone effective in the treatment of malaria, found in Artemisia annua (annual mugwort). A commonly known species of the genus Artemisia, with an important place in the history of medicine, is Artemisia absinthium L.

The aim of this work was the review of the latest literature reports on A. absinthium in order to evaluate the importance of this species in the traditional phytotherapy, as well as in the modern medicine. The emphasis was put on the latest biological activities confirmed by scientific studies. The applications in the cosmetology and in the food industry were also announced. Moreover, the studies on the safety of use as well as the biotechnological researches were reported.

The information about A. absinthium was collected collected from various sources such as official websites e.g., The Plant List, GBIF (Global Biodiversity Information Facility), WHO (World Health Organization), FDA (Food and Drug Administration), EFSA (European Food Safety Authority), EMA (European Medicines Agency), CosIng (Cosmetic Ingredient database), classical books, databases of scientific journals (e.g., Scopus, PubMed, Google Scholar), on-line books, and pharmacopoeias. In addition, professional historical descriptions of this species were also analyzed.

A. absinthium has its natural habitats in Europe, West Asia, and North Africa. The species has been used for centuries as effective in various gastrointestinal ailments and in the treatment of helminthiases. Contemporary pharmacological studies have focused on confirming and determining the mechanisms of these traditional directions of activity. They have also demonstrated new, previously unknown possible therapeutic applications resulting from proven antiprotozoal, antibacterial, antifungal, anti-ulcer, hepatoprotective, anti-inflammatory, immunomodulatory, cytotoxic, analgesic, neuroprotective, anti-depressant, procognitive, neurotrophic, cell membrane stabilizing, and antioxidant effects.

Furthermore, A. absinthium has today an important place in the production of cosmetics. It also has an established position in the food industry, as a base for alcoholic beverages and as a spice. It has also become an object of biotechnological research.

Recent years have seen publication of review articles on this species. However, they present the existing, broad knowledge on its therapeutic values in a very general way [1,2]^[1][2].

2. Applications in Cosmetology

In addition to the undeniable therapeutic properties, A. absinthium has also found application in cosmetics used for scalp, face, and hair care.

CosIng (Cosmetic Ingredient database)—a European database gathering data on cosmetic ingredients, allows the use of Artemisia absinthium in five forms. Among them there are skin care products, fragrances, and substances with antibacterial activity (Table 41) [110]^[3].

Table 41.

Use of

A. absinthium

in cosmetology as recommended by CosIng database.

CosIng Data	Description	Functions

Artemisia absinthium	extract		extract from the whole wormwood herb	skin conditioning
Artemisia absinthium	herb extract		extract from the blooming herb of wormwood	perfuming
Artemisia absinthium	oil		volatile oil obtained from the whole wormwood plant	antimicrobial
Artemisia absinthium	herb oil		essential oil obtained from the blooming wormwood herb	perfuming
Lactobacillus	/	Artemisia absinthium	leaf extract ferment filtrate	filtrate of the product obtained by fermentation of wormwood leaves by bacteria of the genus Lactobacillus	skin conditioning

Raw materials obtained from the plant are used as components of cosmetic products such as shampoos, face serums, masks, essences, tonics, moisturizing creams with an SPF filter, and under-eye patches. These forms of cosmetics are used to protect, cleanse, and moisturize the skin, as well as to remove skin imperfections. They are produced mainly with extracts of the herb of the plant or distilled oil; also included is the filtrate obtained after fermentation of the leaves by Lactobacillus sp.

Products containing A. absinthium can be found in the offers of foreign companies worldwide. South Korean, Russian and American cosmetics producers are leaders among them.

3. Applications in the Food Industry

A. absinthium is the main ingredient in absinthe, which is a high-proof alcoholic beverage that was particularly popular in the 19th and 20th centuries because of its psychoactive properties due to the high α- and β-thujone content [15,111]^[4][5]. Information on the safety and mechanism of action of both compounds is presented later in this review.

Dried aerial parts of the plant are used to produce absinthe. In a traditional recipe, wormwood, along with other herbs, is macerated. The obtained macerate of a greenish colour with a slightly stinging, strongly bitter taste is subjected to distillation, leading to a reduction in the amount of bitter compounds. In the last stage, the distillate is diluted with water and the product has a characteristic light green colour [15]^[4].

The European Food Safety Authority (EFSA) states that in the European Union, the α- and β-thujone content in alcoholic beverages, including absinthe, must not exceed 10 mg/kg for spirits with an ethanol content higher than 25%, or it must not exceed 35 mg/kg in bitter spirits [112]^[6].

Wormwood is also added to wines to give them aroma and bitterness. Vermouths are a popular type of wine containing A. absinthium. The whole herb together with A. absinthium roots is used for their production; also used are other aromatic or bitter herbs (e.g., Salvia officinalis, Coriandrum sativum, Citrus aurantium var. amara) and spices (e.g., Syzygium aromaticum, Cinnamomum zeylanicum, Zingiber officinale). In the United States, vermouths are used to make cocktails, while in Europe they are served without any admixtures [113]^[7].

In small quantities, A. absinthium is recommended for seasoning meat, vegetable soups and fresh vegetables. It is also used as a dye and flavouring in the traditional Korean rice cake “green songpyeon”, which is an integral part of the celebration of the “chuseok” thanksgiving festival. In Morocco, A. absinthium is added to mint tea [31]^[8].

4. Safety of Use

It is worth pointing out the dangers of drinking absinthe. Its consumption initially causes the feeling of well-being and hallucinations, slowly leading to a depressive stage. Chronic abuse of the spirit has been described as absinthism, characterized by blindness, tremors, hallucinations, and significant deterioration of the mental state. The degeneration that is observed in the advanced stage causes convulsions and can even lead to death.

Currently, however, the influence of the substances present in A. absinthium herb on the development of absinthism is being questioned. The most probable hypothesis is that absinthism is misdiagnosed alcoholism because all the symptoms characteristic of absinthism can be attributed to ethanol itself [114]^[9].

A. absinthium is a species rich in compounds that show toxic effects. These are α- and β-thujone, with α-thujone being thought to be two to three times more harmful. The likely mechanism of action of these compounds is interaction with the GABA receptor of chloride channels [15]^[4]. The compounds exhibit neurotoxic activity leading to hyperactivity, tremors and tonic convulsions [16]^[10]. These symptoms have been confirmed in studies on laboratory animals (mice). Intraperitoneal injection of α-thujone into rodents induced tremors. Convulsions did not occur if diazepam or phenobarbital was administered prophylactically [115]^[11].

EFSA emphasizes, however, that the α- and β-thujone content in the essential oil of the plant ranges from 0% to 70.6%, which will also result in the occurrence or absence of side effects [31]^[8].

Wormwood should not be used if the patient has gastric or duodenal ulcers, biliary obstruction, liver disease, or if he is allergic to plants of the family Asteraceae. This species should not be used during pregnancy and breastfeeding because, as shown in experiments on pregnant rats, Absinthii herba hinders embryo implantation and reduces the number of births. An overdose of preparations containing the plant may result in vomiting, diarrhoea and urinary retention [11,30]^[12][13].

The potential effect of skin irritation and potential acute toxicity of the essential oil of the plant were investigated in 2014. After testing in healthy volunteers, researchers found no skin irritation after applications of undiluted A. absinthium oil. Acute toxicity tests in a group of mice did not show increased animal mortality after oral application of the essential oil; however, neurological, muscular and gastrointestinal problems were observed [20]^[14].

As potentially dangerous compounds, EFSA lists α- and β-thujone, absinthin, and anabsinthin. The summarizing conclusions regarding A. absinthium contain the information that the plant can be safely used as a basic substance. It has a known toxicological profile, and the compounds that were previously considered harmful are currently being investigated as medicinal substances [31]^[8].

The FDA (U.S. Food and Drug Administration) lists A. absinthium as an allergenic species. The source of allergens is the pollen, which can also be present in extracts of the plant [116]^[15].

5. Biotechnological Research

Although there are no problems with obtaining A. absinthium from natural habitats or by cultivation, attempts are being made at finding biotechnological solutions. They can undoubtedly bypass the problems associated with the chemical variability of the raw materials derived from the plant—the herb and the essential oil. Biotechnological research to date has been concerned with endogenous production of secondary metabolites and the development of micropropagation protocols.

In 2013, one of Pakistani research groups proposed a method of producing A. absinthium secondary metabolites by cultures in vitro. In the first stage aimed at establishing the cultures, they tested the Murashige-Skoog (MS) medium enriched only with the addition of 0.5–5.0 mg/L thidiazuron (TDZ), or a combination of TDZ with 1.0 mg/L naphthalene-1-acetic acid (NAA), or with 1.0 mg/L indole-3-acetic acid (IAA). Thus prepared substrates were used to initiate cultures from leaf explants. Callus obtained on MS media supplemented with 1.0 mg/L TDZ and 1.0 mg/L NAA was passaged for biomass growth. Further experiments on the growth and production of secondary metabolites involved the use of suspension cultures established from 35-day callus cultures. Biomass was grown in Erlenmeyer flasks containing MS medium with 1.0 mg/L TDZ and 1.0 mg/L NAA. The biomass was taken for analysis at 3-day intervals during 42-day cultivation cycles. Phytochemical analysis was performed by HPLC. Seedlings from germinating seeds constituted the control sample. The amount of phenolic acids in the suspension was 3.57 mg/g (control: 2.75 mg/g), and the amount of flavonoid compounds was 1.77 mg/g (control: 1.20 mg/g). The results of the study showed that A. absinthium suspension cultures might be a good potential source of phenolic acids and flavonoids [35]^[16].

Scientists from the same research group also studied the effect of light and its absence on the accumulation of secondary metabolites in A. absinthium suspension cultures. The cultures were grown on MS medium supplemented with 1 mg/L TDZ and 1 mg/L NAA. The dynamics of biomass growth were measured during 39-day cultivation cycles. Cultures grown in the presence of continuous artificial light with a radiation intensity of 40 mol·m⁻²·s⁻¹ reached their maximum, 3.9-fold, increase in dry biomass on day 30, whereas cultures grown in the dark, a 3.7-fold increase, on day 27 of cultivation. In addition, in vitro cultures grown in the presence of light were found, using UV-VIS spectroscopy methods with the addition of Folin-Ciocalteu reagent, to have elevated levels of phenols, while those with the addition of aluminium chloride—elevated levels of flavonoids. The results of the study showed that appropriate lighting conditions for A. absinthium cultivation had a positive effect on the efficiency of secondary metabolite production [117]^[17].

A Hindu research group has developed a protocol for micropropagation of A. absinthium by indirect organogenesis. The most effective for callus growth was MS medium with 0.5 mg/L 2,4-dichlorophenoxyacetic acid (2,4-D) and 0.5 mg/L kinetin (Kin). Maximal induction of shoots from callus was found on a medium containing 4.5 mg/L BAP (6-benzylaminopurine) and 0.5 mg/L NAA. With a different quantitative combination of growth regulators, i.e., 1.5 mg/L BAP and 0.5 mg/L NAA, a pronounced induction of many shoots from nodal explants was observed. The most beneficial medium promoting rhizogenesis was one with the addition of 0.5 mg/L indole-3-butyric acid (IBA) [118]^[18].

6. Conclusions

A. absinthium is a species with a very important position in the history of Asian and European medicine; described in medieval Europe as “the most important master against all exhaustions”, it was mainly used to treat digestive tract diseases and worm infestations.

Nowadays, this species has the status of a pharmacopoeial species in the European allopathic as well as homeopathic therapies. Currently the species occupies an important place in the traditional European and Asian medicine.

In modern times, A. absinthium has been the object of numerous studies on the chemistry of raw materials derived from it—the herb and the essential oil, as well as numerous studies on the biological activity of extracts.

Research on the chemistry of the plant has identified a large number of compounds in the herb, including most of all the presence of essential oil with a very rich but variable chemical composition, bitter sesquiterpenoid lactones, flavonoids, other bitterness-imparting compounds, azulenes, phenolic acids, tannins and lignans.

Research on biologically active extracts from the herb and/or individual isolated compounds and/or essential oil has drawn attention to the mechanism of action of these raw materials in known classical applications. It has also provided evidence for numerous, very valuable, previously unknown, new directions of biological activity of the raw materials—antiprotozoal, antibacterial, antifungal, anti-ulcer, hepatoprotective, anti-inflammatory, immunomodulatory, cytotoxic, analgesic, neuroprotective, antidepressant, procognitive, neurotrophic, cell membrane stabilizing, and antioxidant effects.

Both phytochemical and pharmacological tests are carried out by research centres located all over the world.

The species is also used with great success as a source of cosmetic raw materials, in Southeast Asia, North America (USA) and Europe, in particular. The long-known significance of the species in the food industry, as a base in the production of alcoholic beverages (absinthe and vermouth wines) and as a valuable spice, is not decreasing. The species has also become the subject of biotechnological research on the production of bioactive compounds and the possibility of micropropagation using established in vitro cultures.

The proven new directions of the biological activity of extracts from the herb and of individual isolated compounds and the essential oil of wormwood substantiate the medieval claim that Artemisia absinthium is: “the most important master against all exhaustions”.

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