Artemisia abrotanum L. (Southern Wormwood)—History, Current Knowledge on the Chemistry, Biological Activity, Traditional Use and Possible New Pharmaceutical and Cosmetological Applications

1. Introduction

The awarding of the 2015 Nobel Prize in Medicine for the discovery of artemisinin [1,2], a sesquiterpenoid lactone, in Artemisia annua (annual mugwort) and proving its effectiveness in the treatment of malaria sparked a huge interest in the world of science in the chemistry and biological activity of other Artemisia species [3,4,5,6,7]. One of the better-known medicinal species of this genus in Europe and Asia is Artemisia abrotanum L. (Asteraceae). This species occurs in the south-eastern part of Europe and in the countries of Central and North-Western Europe. This species also has its natural habitats in Asia Minor, Central Asia, and on the Arabian Peninsula [8]. The herb of this species—Abrotani herba— occupies an important position in the traditional medicine of European countries [8,9,10,11]. It is recommended most often for the treatment of diseases of the liver and the biliary tract. It is also used as an effective anthelmintic in children, and as an antipyretic. Recent professional studies have proven previously unknown biological activities of extracts from the herb and/or the leaves, and/or the distilled-off essential oil, namely antibacterial, antifungal, antioxidant, anticancer, and antiallergic properties [8,12]. Apart from the essential oil, the coumarins, phenolic acids and flavonoids present in the chemical composition of the plant are also responsible for the abovementioned biological effects. This species is also traditionally an object of interest of the food industry [13]. A recent development was its approval by the European CosIng (Cosmetic Ingredients) database for use in the production of cosmetics and its growing role as a cosmetic plant [14]. The aim of this article is to present the current state of knowledge regarding the position of A. abrotanum in the history of medicine, its importance in modern traditional medicine, the chemical composition, new directions of biological activity and the resulting possible new therapeutic applications and prospects for use in cosmetology. The aim was also presentation of biotechnological studies of this species and its position in the food industry.

2. Position in the History of European and Asian Medicine

A. abrotanum is one of those medicinal herbs that can be found already in the first herbals of our civilization. Descriptions of it were included in both Dioscorides and Pliny the Elder [15,16]. Noteworthy is the origin of the name “abrotanum”, which, according to Theophrastus of Eresos, may refer to a certain constitution of the body, namely to very thin and frail people (αβρος (abrós) in Greek means ‘slim, delicate’) [17]. This reference is significant because it corresponds exactly to the constitution of patients who were originally recommended to use this herb, namely those suffering from chronic respiratory ailments. Of the lung diseases, the most difficult to treat over the millennia had been tuberculosis, leading to persistent wasting of the body, but chronic bronchitis or asthma may have clinically manifested themselves in this way as well. In holistic Traditional Chinese Medicine (TCM), this condition is called “Lung-Qi weakening, with particular weakening of the Yin of the lungs”, and is the dominant indication for TCM treatment with this herb to this day [18]. Apart from bronchopulmonary ailments, A. abrotanum was also used in a number of other diseases, and its effects were widely known. In the Arab world, Avicenna, citing Galen among others, recommended its use in the absence of appetite, ulcers, and skin diseases, for hair growth, and as an amulet against evil spirits [19]. The Slavs considered A. abrotanum to be a cult “church herb”, used, for example, for making wreaths, hence its Polish name “boże drzewko” (“God’s little tree”) [20]. In the Middle Ages, applications from antiquity were adopted, and in Germanic areas in the 10th century, the spectrum of treatments with Artemisia abrotanum included broadly understood difficulty in breathing, pain from the liver, spleen, bladder and uterus, anthelmintic treatment, wound healing, to assist the stomach, intensify diuresis, and deter evil spirits [21]. A hundred years later, Hildegard of Bingen insisted on using this herb in compresses for leg pain [22]. In the Renaissance era, due to the warming and drying properties of A. abrotanum, it was recommended for use in ailments caused by cold and humidity, which mainly concerned the female genital tract and the functional circuits of the liver and spleen, according to the holistic nomenclature. This view was shared by the “Fathers of Botany”—Otto Brunfels [23], Hieronymus Bock [24], and Leonhart Fuchs [25], and half a century later also by their worthy successor—Jacobus Tabernaemontanus [26]. At the apex of the development of holistic thought in Western medicine, the following secondary properties were attributed to A. abrotanum: “dispersing, diluting, (surface) opening and cleansing effects” [27]. One of the most important Polish renaissance herbals—“Zielnik” by Simon Syrenius, also mentions the plant’s drying and warming effects as well as its effectiveness as a remedy against “venoms and poisons” (after Dioscorides and Pliny), repelling “venomous animals”, and in diseases of the lungs and the digestive system, and in women’s diseases [28]. A. abrotanum was also used as an antipyretic, against internal parasites and externally in the treatment of scalp and hair diseases, and as an anti-inflammatory medication in eye diseases and ulcers of various origins. The plant was used to prepare an oil with analgesic and diuretic properties, wine stimulating the appetite and effective against jaundice, and vodka for respiratory ailments [28]. In 19th-century folk medicine, the herb A. abrotanum was known as a medicine for skin diseases (added to baths), for throat and ear ailments, for sprains (in the form of compresses), and for women’s and childhood diseases [29].

3. General Information on the Species

A. abrotanum has many synonymous Latin names, including Abrotanum alpestre Jord., A. ambiguum Jord. & Fourr., A. brachylobium Jord. & Fourr., A. congestum Jord. & Fourr., A. incanescens Jord. & Fourr., A. mas Garsault, A. pauciflorum Jord. & Fourr., A. pedunculare Jord. & Fourr., A. platylobum Jord. & Fourr., A. pulverulentum Jord. & Fourr., A. rhodanicum Jord. & Fourr., A. suave Jord. & Fourr., A. virgatum Jord. & Fourr., A. viridulum Jord. & Fourr., A. xerophilum Jord. & Fourr., Artemisia abrotanifolium Salisb., A. altissima Ehrh., A. altissima Ehrh. ex DC. A. anethifolia Fisch., A. anethifolia Fisch. ex DC. [30,31,32]. The species is also known by numerous common names, for example: lad’s love, lemonwood, old man, slovenwood, southern wormwood, and southernwood (in English), and nayqatamisa (ajmara), abrotone, armoise aurone, armoise citronnelle, aurone mâle, aurone, citronelle aurone, citronnelle (in French). In German, there are only two names—Eberraute and Stabwurz [31,32,33,34,35,36]. In Polish, the species is customarily called “boże drzewko” (literally “God’s little tree”, a counterpart of the English name “Our Lord’s wood”) [33]. The pharmaceutical raw material is Artemisiae abrotani herba—the herb of the A. abrotanum plant—the flowering tips of its shoots. The dry herb has a grey-green colour, a slightly bitter taste and a citrusy, spicy aroma [33,37]. In traditional medicine, the leaves of the plant—Artemisiae abrotani folium, also constitute the raw material [11]. A. abrotanum is a semi-shrub reaching a height of 0.7–1.5 m [38]. The shoots of this species grow upright and have soft twigs. Young twigs are blue-green and older ones are brown. The stem is covered with secretory hairs [39]. The stems are highly branched with dense foliage. The grey-green leaves have numerous covering hairs on the upper side; the underside of the leaves is smooth. The leaves growing in the lower part of the stem are doubly pinnate and have ensiform sections, while in the upper parts they take on a singly pinnate, tripartite, and also ensiform shape. The whole plant has a strong distinctive lemon-like aroma [5,33,37,40,41].

The tiny yellow tubular flowers are gathered in spherical or ovoid-spherical hanging heads that form panicles. In Central Europe, flowering of the plant begins in August and lasts until September. Due to the climatic conditions, the plant in this region does not bear fruit. The fruits are small oblong achenes [5,33,37,40,41]. Cariological studies of the plant have shown that its specimens are most often diploid (2n = 2x = 18), less often tetraploid (2n = 4x = 36) [38]. A. abrotanum is a species native to Central Asia—in particular Armenia, Iran and Russia, and also to Asia Minor—Turkey and Europe, including Albania and Croatia [36]. The species also occurs in Central and North-Western Europe [42].

A. abrotanum likes warm, sunny, and humus-rich sites, with well-drained, not too moist soils [33,43]. In Central and North-Western Europe, the species reproduces only vegetatively by division or from hardwood and softwood cuttings. In other parts of the world, if the species grows in a warm climate, it reproduces by seed. The first harvest takes place in the second year after planting. During the flowering period, the tips of the shoots are collected, which are then dried in shaded and airy natural drying enclosures. Larger batches of the raw material are dried in drying rooms with the temperature increased to 35 °C. It is also advisable to trim annually the lower, lignified parts of the plant. This treatment improves the branching and ‘bouncing-back’ of the herb, and increases the yield [33,43]. After drying, the woody parts are discarded and the non-lignified herb is placed in airtight packages and stored in the dark [39,41,43].

4. Chemical Composition

Analyses of the compounds present in A. abrotanum have focused primarily on the essential oil present in the herb of the species [9,11,40]. The composition and concentration of A. abrotanum essential oil are variable and dependent on the cultivation site, among other things [9]. The dominant fraction of the oil are compounds with a monoterpenoid structure. The remaining fractions are compounds of sesquiterpenoid, diterpenoid, triterpenoid, or spiroterpenoid structures, and phenylpropanoid derivatives (Table 1).

In 2020, Lithuanian researchers determined the composition of the essential oil obtained from the herb of A. abrotanum plants growing in Lithuania, which were at various stages of plant development. The compound that was present in the highest amounts was piperitone. The remaining substances isolated in large amounts were: 1,4-cineole, lavandulyl butanoate, aromadendrene, and isogermacrene D. The essential oil content in the herb of the plant was the highest at the stage of flower-bud setting (38.48%), and the lowest at the stage of leaf growth and development (20.38%) [9].

Egyptian researchers conducted a study in 2020 evaluating an influence of trace elements on productivity of A. abrotanum. The main components isolated from essential oil of A. abrotanum aerial parts were: 2-hydroxy-1,8-cineole, β-eudesmol, and camphor. In the experiment the scientists treated A. abrotanum with foliar spray containing iron (Fe), magnesium (Mg) or manganese (Mn). The foliar application of Fe (3 g/L), Mg (8 g/L) or Mn (300 mg/L) significantly increased values of growth, yield, major constituents of essential oil and chemical composition of the plant in comparison with control [46].

Romanian scientists have reported that the main component of the essential oil of A. abrotanum herb was davanone and its derivatives. The researchers also isolated, in small amounts, 1-terpineol, trans-piperitol, and estragole [47]. In contrast, the dominant compound in the essential oil of plants harvested in Cuba was trans-sabinyl acetate [44], and in the essential oil from plants harvested in Iraq borneol [48]. The main components in plants harvested in Crimea were 1,8-cineole and camphor [49]. The chemical structures of the most abundant compounds in A. abrotanum essential oil are shown in Figure 1.

In addition to the essential oil, the herb of A. abrotanum also contains compounds with phenolic structures. The research conducted at JSS University in Mysore (India) has documented the presence of phenolic compounds in the amount of 9.35 mg/g dry weight in terms of gallic acid, and the presence of flavonoids in the amount of 11.0 mg/g dry weight in terms of rutoside [34]. Another study has proven the presence of phenolic acids. This group of compounds, present in the leaves of A. abrotanum plants growing in Saudi Arabia, was dominated by rosmarinic, chlorogenic, caffeic and isochlorogenic acids [40]. The structures of the compounds are shown in Figure 2. Other studies, in turn, identified the flavonoids present in the plant, including apigenin, hyperoside, quercetin, quercitrin, kaempferol, luteolin, myricetin, rutoside, and also lactone - artemisinin [33,37,40]. Among other compounds isolated from the herb of A. abrotanum were also coumarins, including isofraxidine, umbelliferone, scopoletin, herniarin, and esculetin [33,37,47,50,51]. Moreover, the herb has been found to contain the next sesquiterpenoid lactone—santonin [50], an alkaloid—abrotine [33,37], tannins, organic acids [44], sterols [52], and resin [33,37,53,54]. The chemical composition of the A. abrotanum plant is shown in Table 2.

5. Application in Traditional European and Non-European Medicine

In European traditional medicine, Abrotani herba is used in diseases of the liver, such as atony, contractile states of the bile ducts and stagnation of or insufficient bile secretion. Herbal infusions are used to improve digestion, increase appetite, and also as an astringent in diarrhea. It is also recommended to use infusions as an aid in cases of anorexia, flatulence, and hypoacidity [14,33,37,39]. Extracts from the plant have also been used as a remedy for frostbite, lymphadenitis, and in the treatment of epilepsy [37,39,43]. The species has been used in the treatment of malaria [54].The leaves have been used to improve liver function, stimulate menstruation, and relax smooth muscles. Other indications have included cancer prophylaxis and therapy, and men have used the plant as a hair growth agent [55]. The plant is also used as an anthelmintic agent in the treatment of oxyurosis and ascariasis in children [33]. In Bosnia and Herzegovina, the species has also been used in the treatment of jaundice [58], and in Turkey in the treatment of fever [59]. In traditional Indian medicine, Siddha, A. abrotanum is used as a repellent to repel insects and parasites [60].

6. Application in Modern Phytotherapy and Position in Official European Medicine

The herb A. abrotanum can be found primarily in homeopathic medicines. The French Pharmacopoeia states that their production is based on a 65% mother tincture, prepared from fresh herb of A. abrotanum. The tincture should contain at least 0.1% m/m of ortho-dihydroxycinnamic acid derivatives, expressed in terms of chlorogenic acid [61,62]. These preparations are indicated for the treatment of inflammation of the colon, rosacea, frostbite, and inflammation of the lymph nodes and mucous membranes [37,43]. Homeopathic medicines from A. abrotanum are also indicated for people suffering from depression and anxiety [63]. The European Medicines Agency (EMA) has also authorized the use of homeopathic preparations from A. abrotanum in farm animals used for food production [11].

Artemisiae abrotani herba and Artemisiae abrotani folium do not have the status of pharmacopoeial raw materials in European countries. The species and the raw materials obtained from it are, however, successfully used in official European allopathic medicine. A good example is the research conducted at Havelhoehe Research Institute and Charite’ University Medical Centre in Berlin, and the University of Witten/Herdecke in Herdecke (Germany). For a period of two years (2004–2005), it was recorded the prescribing by primary care doctors and specialist doctors of preparations containing plant extracts from plants of the family Asteraceae. Over that time, preparations with A. abrotanum extracts were recommended to 202 patients. The preparations included both homeopathic remedies and herbal mixtures as well as medicines containing only A. abrotanum extract. The indications for the use of these medications were usually diagnosed non-infectious inflammations of the intestines or of the large intestine [45,61].

In official European medicine similar as in traditional medicine the most often the whole plant extracts are used [11]. They contain the mixture of flavonoids, coumarins, phenolic acids and essential oils. These groups of metabolites with polyphenolic structures are important plant components with among others antioxidant and antitumor activities. For documented antibacterial and antifungal properties the components of essential oil are responsible. Synergic action might be created between these groups of polyphenols. In the phytotherapy as the galenic formulation the infusions and tinctures from A. abrotanum herb are recommended. Moreover, this raw material is endorsed for use in choleretic and gastric mixtures, as well as for strengthening and soothing baths. A. abrotanum is also the subject of patents in the field of pharmacy in Europe [43,64]. The mechanisms of action of A. abrotanum extracts and/or essential oil are summarized in Table 3.

7. New Directions of Biological Activity of Extracts from the Herb and/or Leaves, and/or Essential Oil Confirmed by Scientific Research

8. Application in Cosmetology and in the Food Industry

A. abrotanum, like other Artemisia species, is also used in the production of cosmetics.The European CosIng database advises that A. abrotanum herb, leaf and stem extracts can be used as a protective, moisturizing, and caring agent for use on the skin [14]. Such extracts can be found in face and hand creams, serums, body lotions, scrubs, milks, and pedicure masks. Products containing A. abrotanum are offered by Polish companies such as Organic life, Perfecta, German: Dr Hauschka, English: Bulldog Natural, Lush, American: Jack Black, Physicians Formula, Aveeno, and French: Decléor [14]. Interestingly, according to a pilot study from 2021 A. abrotanum leaf extract offers promising results as an ingredient of nail gel used in patients with nail plate surface abnormalities [69]. Moreover, because of antibacterial activity against macrolides resistant Propionibacterium acnes strain, A. abrotanum extract has a potential as an active compound in cosmetics for acne-prone skin [12].

The leaves of A. abrotanum, due to their pleasant aroma, are used to flavour meats, salads, and cottage cheese. As flavourings, they are sometimes added to confectionery as well as to alcoholic beverages such as vermouths and liqueurs [13,33,41]. The herb of A. abrotanum can be found as an ingredient in teas [41].

9. Safety of Use

At Havelhoehe Research Institute and Charite’ University Medical Centre in Berlin, and the University of Witten/Herdecke in Herdecke (Germany), adverse effects associated with the use of preparations based on plants from the Asteraceae family had been documented for two years. Of the 236 patients taking homeopathic remedies, herbal mixtures, or single-ingredient preparations from A. abrotanum extracts, only two were found to produce side effects. The reported ailments, after taking a preparation composed of extracts of A. abrotanum and Matricaria recutita, included stomach pain and allergy. However, no serious side effects were reported [61].

10. Biotechnological Research

A review of the scientific literature has shown that A. abrotanum is a species that so far has sporadically been the object of research in the field of plant biotechnology. A protocol for the micro-propagation of this species has been only developed. Young leaves of the plant were sterilized and placed in the MS (Murashige and Skoog) medium supplemented with 4.44 µM 6-benzyladenine (BA) and 0.54 or 0.81 µM naphthyl-1-acetic acid (NAA). Abundant callus growth and shoot formation were achieved. With the addition of 4.44 μM BA and 0.54 μM of NAA, 3.61 shoots per explant were obtained (31 shoots in total), and with the addition of 4.44 μM BA and 0.81 μM NAA, 4.05 shoots per explant were obtained (total of 38 shoots). The obtained shoots were rooted using the MS medium without the growth regulators or supplemented with 0.49 µM indole acetic acid (IAA) or 0.54 µM NAA. Afterwards, the plants were transplanted into soil-filled pots [70].

11. Conclusions

Artemisia abrotanum is a species with an important position in the history of European, Middle-Eastern and Asian medicine (including especially Traditional Chinese Medicine (TCM)). Currently, it also has an important position in traditional European and Asian medicine (especially in the Middle East). The French Pharmacopoeia recommends the plant for use in official homeopathic medicine. In many European and Middle Eastern countries, this species is traditionally used in allopathic medicine. Recent phytochemical studies of this species have proven the variability of the chemical composition of its essential oil. Pharmacological studies, in turn, have provided evidence of new, previously unknown directions of biological activity of extracts from the herb and/or leaves, and/or essential oil of the plant—antimicrobial, antioxidant, anticancer, and antiallergic effects. Some studies also indicate the possibility of using the plant in the prevention of diseases spread by insects, due to the repellent properties of the essential oil. This creates prospects for the medicinal use of the plant to an even greater extent. This species is also invariably used in the food industry as a spice and as a flavouring additive to alcoholic beverages and teas. A novelty is the possibility of using extracts from various parts of the plant in the production of cosmetics. The species is approved by the European CosIng database to be used for this purpose. In the light of contemporary research, A. abrotanum appears to be an attractive species with valuable medicinal, culinary, and cosmetic qualities.

Author Contributions

Data collection: H.E., A.S., J.Ś., P.K., A.R., E.K.; design of the study: H.E.; analysis and interpretation of the data: A.S., H.E., E.K., P.K., J.Ś., A.R., M.T.; drafting the manuscript: H.E., A.S., P.K., A.R.; critical revision of the manuscript: H.E., A.S., M.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by grand numbers: N42/DBS/000010 and N42/DBS/000136 supported by the Polish Ministry of Science and Higher Education.

Conflicts of Interest

The authors declare no conflict of interest.