Michael Clanahan Introduction
Artemisia absinthium L., commonly known as wormwood,
green ginger, or wermot, has been used for thousands of years in a variety of fashions. Although most famous for its role in the production of the alcoholic drink Absinthe, wormwood has played a major part in traditional medical practices in multiple cultures. A few main components of the plant that have been isolated include thujone, absinthin, caffeoylquinic acids, phenols, and select flavonoids, all of which have different physiological effects and in some cases, beneficial health properties.
Traditionally, this plant has been used to treat many different ailments from diabetes to stomachaches to tuberculosis. Used all over the world, this powerful plant has faded in and out of popularity, but continues to have significant medicinal value in many areas.
Botanical Description
Morphologically, wormwood is very similar to other plants in the Asteraceae family. This herb has a perennial root system, and has characteristic firm, branched stems that are woody at the base (Grieve, 2011). Typically, the plant reaches no more than two to three feet, as it is found mainly in arid climates (Arnold, 1989). The leaves of the plant are whitish on both sides, but also contain silvery gray sheen due to short, fine hairs on the indented outside. This sheen can be seen in Figure 1. Wormwood is a flowering plant, identifiable by its small globular flower bundles of greenish-yellow tint, mainly
Figure 1. Characteristics sheen of Artemesia absintium L. leaves. (Source: http://www.flowertropes.com/index/tag/kevin-kline)
between the months of July and October. (Grieve, 2011). Unlike many other plants of the Asteraceae family, the small wormwood fruits do not contain a crown of hairs, also called “pappus” (Grieve, 2011). Although the leaves and flowers of the plant taste very bitter, the roots have a characteristic aromatic taste. The flowers smell of thujone, an important compound with medicinal values will be discussed. (Grieve, 2011).
Closely related plants include Roman wormwood (Artemisia
pontica), A. judaica, Sea Wormwood (A. maritima), as well as 83 | M e d i c i n a l P l a n t M o n o g r a p h s
the herb Tarragon (A. dracunculus) which is also known commonly as dragon’s-wort (Grieve, 2011). Tarragon is found in many spice gardens, and Southernwood (A. abrotanum) is found primarily in border habitats between fields. The entire family is characterized not just by physical likeness, but most importantly the intense bitterness contained in all parts of the plant (Grieve, 2011).
Traditional Uses
Wormwood is one of the oldest known herbs to be used in traditional medicine, with evidence tracing its usage back to ancient Egyptians. Wormwood’s appearance in the Ebers Papyrus dating from 1550 B.C. support this claim and indicate not only medicinal value, but also religious significance (Arnold, 1989). Another important historical medical document, Historia Naturalis, written by Pliny in the first century A.D. mentions wormwood in a medical context that shines light on the common name of the plant. The encyclopedia describes wormwood extract as having powerful effects on gastrointestinal worms, often ridding the human of a large part of the parasitic load (Arnold, 1989). Dioscorides’
De Materia Medica, completed around 65 A.D., also mentioned
wormwood’s anthelmintic properties, but included many more applications. These include applications such as a natural insect repellant and a natural antidote to poisoning by hemlock and toadstools (Grieve, 2011). The leaves were commonly dried and stored with garments and furs to protect them from moths (Arnold, 1989). De Materia Medica’s authority for over 1500 years is illustrated by the fact that John Gerard, a highly revered Elizabethan herbalist in the 1500s, mentions in his book Herball that “wormewood voideth away the wormes of the guts” (Mann, 2009).
Wormwood was utilized by other cultures, such as traditional practices in modern day Turkey. In the Kirklareli Province, wormwood is known locally by many names, including pelinotu and pelin. People in this particular area would use almost all of the parts of the plant to treat different ailments. For example, the arial parts, when prepared as an infusion could be used as an abortifacient, a cure for stomach ache, and appetizer, or a blood depurative. However, when prepared as a decoction and consumed 1-2 times a day for 7-8 days, it could be used to treat diabetes, uterine cysts, and tuberculosis. Also, by cutting the shoots into small pieces and eaten two times a day for 8 days, it is believed to treat malaria (Kültür, 2007). In traditional Caribbean medicine, the plant is used primarily for women’s health. This includes treatment for menstrual cramps and vaginitis (Lans, 2007). Wormwood even plays a part in traditional Chinese medicine (TCM) as a treatment for bacillary dysentery (Zhang, 2005).
Wormwood is traditionally most famous for its role in the production of the alcoholic beverage, absinthe. Although used medicinally all over the world for centuries, its narcotic effects did not become significant until around 1790 in Switzerland. Pierre Ordinaire, a French refugee and physician, created an extract of wormwood for use as a stomach tonic. Due to its characteristic green tint and reported hallucinogenic properties, the drink quickly became known as La Fée Verte, or The Green Fairy (Lainer, 1995). Early in the 19th century,
the drink recipe was acquired by a Frenchmen named Major Dubied and his son-in-law, Henry-Louis Pernod. Pernod would eventually take over the company, and his name became historically attached to absinthe (Lainer, 1995). At this point, the drink became associated more with social functions than the medical world. Because of its high price originally, only those in certain circles could afford it, and this included the world of the artists (Lainer, 1995). A few artists known to
have partaken in the consumption of absinthe were Baudelaire, Rimbaud, Picasso, and most famously, Vincent Van Gogh (Ashcraft, 2011). Van Gogh may have been addicted to absinthe in his lifetime. Evidence also suggests that this addiction aggravated his psychosis and that the hallucinations he witnessed stemming from thujone may have caused him to commit suicide (Arnold, 1989). Other artists couldn’t get enough. Oscar Wilde once wrote, “What difference is there between a glass of absinthe and a sunset?” (Ashcraft, 2011). As the drink became more accessible, the general public began to take part. The French public consumed an estimated 700,000 liters of absinthe in 1874. However, due to increased popularity and a severely decreased wine-grape harvest (phylloxera infestation), by 1900, the number of liters consumed surpassed 36 million (Ashcraft, 2011).
Absinthism emerged as a serious disease around this time due to excessive public consumption. Characterized by dazed victims, as well as incredibly vivid hallucinations, absinthism became a serious problem towards the end of the 19th century,
and also became a point of attack for those opposing the absinthe business (Arnold, 1989). Some suggested raising the taxes on absinthe to reduce addictions within the population. When this proposal failed, another bill was brought forward and ultimately passed in 1908 that increased the amount of alcohol in absinthe. The explanation for this was that absinthe with a higher degree of alcohol was healthier and that the requirement for higher alcohol content would eliminate those producers who used artificial essences with lower standards of purity,” as this was thought to be the reason for some of the addictions (Lanier, 1995). It would not be for another 6 years until the sale absinthe was banned on August 16th, 1914. This
was done as an “emergency measure” to stem alcoholism, but absinthe continued to circulate in the public. In January 1915, a presidential decree was issued, explicitly banning absinthe
Figure 2. Chemical structure of thujone. (Source:
http://www.rdchemicals.com/chemicals.php?mode=details&mol_id=8286)
(Lanier, 1995). Although the fear of alcoholism and absinthism was greatest in France, several countries banned absinthe before France, including Switzerland in 1908, The United States in 1912, and Italy in 1913 (Lanier, 1995).
In 2007, the effective ban was lifted when the Alcohol and Tobacco Tax and Trade Bureau (TTB) redefined the restrictions on the drink. Today, one can buy absinthe in liquor stores, but with one major difference: it is thujone-free. The FDA requires that all thujone be filtered out of the final product before distribution to the public. In order for absinthe to be “thujone-free,” it must test for lower than 10ppm (CFR, 2007).
Chemistry and Pharmacology
Wormwood has a rich variety of present compounds. The major constituent is thujone (absinthol), a terpene, which is toxic if ingested in sufficient quantities. Thujone, characterized by its menthol-like odor, is commonly credited with causing the convulsion episodes anecdotally reported to be associated with Absinthe consumption. The structure of thujone can be seen in Figure 2.
Figure 3. Chemical Structure of 5-caffeoylquinic acid.
(Source: http://www.39kf.com/cooperate/qk/American-Society-for- Nutrition/037804/2008-12-28-551072.shtml)
Wormwood’s overpowering bitter taste can be directly attributed to its absinthin content. This sesquiterpene lactone has a bitterness threshold of one part per 70,000. In other words, a single ounce can be detected in 524 gallons of water (Arnold, 1989). Interestingly, the King James Bible mentions the bitterness of wormwood a few times. This occurs a few times in the Old Testament, most notably in the book of Proverbs: “But her end is bitter as wormwood, sharp as a two- edged sword” (AV Prov.5:4). Wormwood is again specifically mentioned by name in The Book of Revelations as part of the rapture: “And the third angel sounded, and there fell a great star from heaven, burning as it were a lamp, and it fell upon the third part of the rivers, and upon the fountains of waters; And the name of the star is called Wormwood: and the third part of the waters became wormwood; and many men died of the waters, because they were made bitter” (AV Apoc. 8:10- 11). Although the biblical source is accurate in depicting wormwood’s intrinsic bitterness, there is no evidence to support its lethality.
Wormwood also contains important compounds called phenols, which have been linked to antioxidant activities. According to Mahmoudi group, wormwood contains 194.9 ± 9.7 mg gallic acid equivalent/g of extract. Polyphenols, or more specifically flavonoids, have also been shown to exhibit antioxidant activities. Total flavonoid levels in A. absinthium are 12.4 ± 0.6 mg quercetin equivalent/g of extract, a promising value (Mahmoudi, 2009). It is thought that the antioxidant properties of many phenols and flavonoids may decrease incidence of certain human diseases when the consumption of foods rich in these compounds is increased (Mahmoudi, 2009).
Caffeoylquinic acids contained within wormwood are a relatively new discovery in the scientific community. 5- caffeoylquinic acid is one of the most abundant within A.
absinthium, and also goes by the name of chlorogenic acid
(Fiamegos, 2011). Figure 3 depicts the structure of 5- caffeoylquinic acid. Studies suggest 5-caffeoylquinic acid is a potent antimicrobial compound, as well as an effective biofilm reducer (Fiamegos, 2011).
Biological Activity
Thujone may be the most important, as well as controversial compound contained within wormwood. Its method of action is thought to be a reduction of GABAA receptor activity, thereby reducing serotonergic responses (Deiml, 2004). Because thujone reduces GABAA receptor activity, neuron- firing inhibition is reduced, allowing neurons to fire more frequently. This is thought to cause the convulsions anecdotally and scientifically reported (Höld, 2000). As stated before, wormwood was traditionally used as an anathematic. Thujone is the compound responsible for this anti-parasitic activity. Although thujone is a toxic substance, and can be
lethal as high doses, ethanol appears to protect against lethal effects of thujone, which may have implications for thujone content in the popular drink, Absinthe (Höld, 2000).
As discussed before, the phenolic and flavonoidic contents of
A. absinthium exhibit important antioxidant properties.
Oxidizing compounds, such as H2O2 (hydrogen peroxide) and
NO (nitric oxide), can cause severe damage within the human body due to the propagation of free radicals. Although not fully understood, flavonoids exhibited strong reducing potential. When compared to a known reducing (antioxidant) compound, in this case Vitamin C, a methonalic extraction of wormwood flavonoids showed no significant difference in absorbance levels (Mahmoudi, 2009).
Phenolics, including quercetin, may have a direct effect on H2O2 scavenging, thereby resulting in the termination of the
free radical chain reaction (Mahmoudi, 2009). The structure of quercetin, a polyphenolic, is shown in Figure 4. Quercetin showed high antioxidant activity, or high H202 scavenging
activity, as its IC50 was 17.01 ± 0.03µg/ml. Hydrogen peroxide
as a compound does not have a high rate of activity, but can sometimes create hydroxyl radicals within the body (Mahmoudi, 2009). Wormwood phenolics were also extremely effective in chelating Fe2+, a transition metal capable of free
radical generation from peroxides, with an IC50 value of 419 ±
20.95µg/ml (Mahmoudi, 2009).
A study from the Ahmad group showed that methanolic wormwood extractions exhibited strong analgesic properties using the tail immersion method in mouse model. Analgesic properties were detectable in all three tested dose levels (300, 500, and 1000 mg/kg), of which the results were dose dependent (Ahmad, 1992). When compared to the standard acetylsalicylic dose of 300 mg/kg, the wormwood extract showed a significantly faster onset of analgesic effects, but
Figure 4. Chemical structure of quercetin.(Source: http://www.worldofmolecules.com/antioxidants/quercetin.htm)
ultimately this analgesia was less potent overall (Ahmad, 1992). This same group then studied anti-inflammatory effects of the methanolic extract to conclude that it was effective, but also dosage-dependent. The 1000 mg/kg dose was tested using the hind paw edema method in a mouse model, and again exhibited significant activity. Results showed a peak activity at 3 hours after administration, and a resulting 41% inhibition in increased paw volume (Ahmad, 1992). Again, however, this activity was much less intense and lasted a shorter period of time, as well as a delayed response in anti- inflammation (Ahmad, 1992). Although these effects were exhibited, the exact compounds responsible for the medicinal actions are unknown.
A method of action is unknown for the methanolic wormwood extraction resulting in antidepressant effects in the mouse model. For this experiment, a forced swimming test (FST) was used. The results showed a remarkable decrease in duration of immobility, and were dose dependent (Mahmoudi, 2009). These results can be seen in Table 1. The results for the 1000 mg/kg wormwood extraction dose are very similar to the 5
Table 1. Effect of methanol extract of Artemisia absinthium L. on the duration of immobility during forced swimming test and tail suspension test (Mahmoudi, 2009).
mg/kg dose of the antidepressant imipramine, a known seratonin (HT-5) and norepinephrin reuptake inhibitor (Mahmoudi, 2009).
As mentioned before, A. absinthium extracts contain a significant amount of 5-caffeoylquinic acid (5-CQA). Recent developments in antimicrobial studies have pointed towards bacterial efflux pumps. Efflux pump inhibitors (EPIs) effectively stop bacteria from expelling antibiotics taken up from the surroundings, therefore effectively allowing the antibiotics to kill the bacteria. Although the effective compounds from A. absinthium extracts have not been completely identified, 5-CQA plays a key part in the antimicrobial actions as an EPI by docking with the efflux pump and changing its conformation, effectively cutting off any flow (Fiamegos, 2011).
Clinical Studies
One of the most interesting clinical studies conducted on wormwood involves its usage in treating Crohn’s Disease. This disease, characterized by intense abdominal pain and frequent diarrhea, is thought to be an autoimmune disorder, but there is existing evidence pointing towards a viral cause (Smith, 1993). Wormwood extracts contain caffeoyl and dicaffeoylquinic acids that have been shown in vitro to inhibit HIV-1 integrase. HIV-1 integrase is responsible for the integration of reversibly transcribed viral DNA into the host genome (Fiamegos, 2011). Another study conducted by Karim et al. (1996), produced evidence suggesting that aqueous extracts of A. absinthium are capable of protecting cells against herpes virus (Karim, 1996). The Omer group (2007) conducted a study administering wormwood capsules to Crohn’s Disease patients being regularly treated with 5- aminosalicylates and select steroids. For standardization, the wormwood capsules contained 250mg wormwood powder, and a filler consisting of 100mg rose, 40mg cardamom, and 10mg mastic resin, whereas the placebo capsule only contained the filler (Omer, 2007). The results showed that at week 10, 65% of the test group exhibited little to no symptoms of the disease. Even more interesting is that these patients did not need to restart steroid treatment, as there is no remission of the disease (Omer, 2007). Another interesting point is that those patients that benefited from the treatment also experienced a higher quality of life and better mood than those who didn’t, according to Hamilton’s Depression Scale (Omer, 2007).
Contraindications
As stated before, because thujone reduces GABAA receptor activity, neuron-firing inhibition is reduced, allowing neurons
to fire more frequently. This is thought to cause the convulsions anecdotally and scientifically reported (Höld, 2000). These convulsions were also reported in other sources, along with a possible connection to kidney failure (Ashcraft, 2005). Another source reported thujone as hepatotoxic, as well as damaging to the brain. Other reported side effects include anxiety and sleeplessness (Naser, 2005). Thujone’s interactions with other drugs has not been well documented. Current Use in Allopathic and CAM Therapies
Artemisia absinthium is not used currently in allopathic
medicine the United States. However, it is commonly used in CAM therapies as a tea or tincture, and there are claims that it aids in many common ailments, including appetite promotion, anti-anxiety, as well as hastening the child birthing process. Wormwood has even been reported as an effective agent in treating dropsy, as it is believed to be a powerful diuretic (Grieve, 2011). However, because of the negative aura surrounding wormwood from previous centuries, natural supplements and use is relatively low.
Discussion
Artemisia absinthium is an incredibly important historic herb,
used for thousands of years for its medical benefits, abused for its hallucinogenic and euphoric properties, and in modern times, studied for its beneficial compounds that aid in fighting disease. Although in past centuries it was abused and consequently received negative light, current applications of incredibly important compounds contained within wormwood (phenols, flavonoids, caffeoylquinic acids, etc.) show a promising future for the plant.
Currently, wormwood’s promise in treating Crohn’s Disease and other viral diseases is attracting the attention of the scientific community. As stated previously, A. absinthium contains large amounts of 5-caffeoylquinic acid (5-CQA), which is being investigated as a compliment to antibiotics. This may have larger implications in the medical community’s struggle to keep up with antibiotic-resistant strains of bacteria. If 5-CQA is investigated further in its mechanism and effectiveness against bacteria, it may grant the medical community more time to develop stronger antibiotics.
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