A member of the daisy family (Asteraceae), the genus Cynara is small, and the classification of species in this genus continues to evolve. In the 18th and 19th centuries, it was believed that there were three Cynara species.1 In a 1992 study, a taxonomic revision of the genus proposed the recognition of eight Cynara species and four subspecies.2 Presently, the Plants of the World Online (POWO) database of the Royal Botanic Gardens, Kew, includes 10 accepted Cynara species.3 Although much of the literature has treated C. cardunculus and C. scolymus as separate species, the latter is now considered a synonym of C. cardunculus.3 Cynara cardunculus is a species complex that contains three taxa: globe artichoke (var. scolymus), cultivated or leafy cardoon (var. altilis), and wild perennial cardoon (var. sylvestris),4 the latter believed to be the wild progenitor of both varieties altilis and scolymus.5,6 There are also two accepted subspecies, C. cardunculus subsp. flavescens and C. cardunculus subsp. zingaroensis.3 The Jerusalem artichoke (Helianthus tuberosus, Asteraceae), native to parts of Canada and the United States, should not be confused with artichoke or cardoon and is outside the scope of this article.
Cynara cardunculus is a perennial plant with a rosette of large pinnate leaves that are green above, white below, and strongly veined. From the second year of growth, large flowerheads of tubular purple flowers bloom on branched stalks. The fleshy floral receptacle at the base of the inflorescence bracts is edible and constitutes the popular food item known as artichoke heart.7 This article focuses mainly on the medicinally used substances from this plant, including “Cynarae folium,” described in the European Pharmacopoeia as the whole or cut dried leaf of Cynara cardunculus (syn. C. scolymus), containing minimum 0.7% chlorogenic acid,8 and “Cynarae flos,” defined in the Pharmacopée Africaine as the fresh lower part of the capitula (involucral bracts [leaf-like bracts that surround the base of a capitulum] and receptacle), containing minimum 0.1% cynarin.9
The native range of C. cardunculus lies within Mediterranean southern Europe (Portugal, Spain, France, Italy, and the Western Balkans), the Balearic Islands of Spain, parts of Macaronesia (i.e., Canary Islands of Spain and Madeira archipelago of Portugal), and northern Africa (Morocco, Algeria, Tunisia, and Libya).3 The subspecies flavescens is native to much of the same range, while the subspecies zingaroensis is native to Sicily.3 Recent research suggests that the center of origin of C. cardunculus is likely southern Italy and probably the island of Sicily.6 Evidence also suggests that the globe artichoke (var. scolymus) was domesticated in Sicily about 2,000 years ago,10 although the first known attempts at selective breeding reportedly took place in Italian monastery gardens in the 15th century.11
Recently, several European regulations have been enacted for market promotion of distinct artichoke ecotypes (genetically distinct subpopulations that are especially adapted to particular environmental conditions) with protected geographical indication (PGI) or protected designation of origin (PDO) specifications. For example, in Italy, Carciofo Spinoso di Sardegna, of the local Spinoso Sardo ecotype, is a PDO with specifications for its physical and chemical characteristics, organoleptic properties, and specific production steps that must occur in a defined geographical area, among other requirements.12 In Spain, Alcachofa de Benicarló of the globe artichoke variety Blanca de Tudela has a PGI designation and is grown in specified municipalities near the coastal region of Baix Maestrat, Castellón province, Comunidad Valenciana.13 Outside of its native range, C. cardunculus is an invasive species (e.g., in South America, Oceania, and the western United States), releasing allelochemicals into the environment that inhibit germination or growth of potentially competitive native plants in the invaded range.14
The main countries for production of the immature flowers (buds) of C. cardunculus for the fresh food trade in terms of hectares harvested in 2019, in order of predominance, were Italy, Egypt, Spain, China, Peru, Algeria, France, Argentina, Tunisia, Turkey, Morocco, and the United States.15 The 2019 global export trade of the fresh flower buds for food use was dominated by six countries: Spain, Egypt, France, Tunisia, Italy, and the United States.16 However, the supply of artichoke leaf for medicinal use comes mainly from cultivation in European countries, namely Italy,17,18 France,19 Germany,20 Poland,21 Portugal,22 Romania,23,24 Serbia,25 and the United Kingdom.26 While there are about 300 varieties of C. cardunculus worldwide, mostly originating from Italy, France, and Spain,11 some registered cultivars are used specifically for medicinal artichoke cultivation in Europe including Saluschocke®, bred by SALUS Haus (Bruckmühl, Germany), Cynamed™, owned by Martin Bauer GmbH (Vestenbergsgreuth, Germany), and Green Globe and Imperial Star, both marketed by N.L. Chrestensen (Erfurt, Germany) and Pharmasaat (Artern, Germany),27 among others.
In a 2014 survey of 2,359 adult consumers from Finland, Germany, Italy, Romania, Spain, and the United Kingdom, artichoke supplements ranked as the third most frequently used herbal food supplement product overall. In Spain, artichoke ranked first, and in Germany, second.28,29 In the United States, for reasons that are not totally clear, artichoke herbal supplement sales are relatively low, and artichoke supplements have not been listed among the 20 top-selling herbal dietary supplements in the natural health food or mainstream retail channels since at least the early 2000s, according to annual HerbalGram Herb Market Reports.30-33
HISTORY AND CULTURAL SIGNIFICANCE
Pictorial images of artichoke on temple walls and tombs of pharaohs demonstrate its use and importance in ancient Egypt.11 Greek medical botanist Pedanius Dioscorides (ca. 40–ca. 90 CE), in his De Materia Medica, described the use of the root as a deodorant and also to benefit stomach, liver, bladder, and kidney health.1 The genus name Cynara comes from the Greek Κυνάρα, meaning “artichoke.”34 The English common name artichoke stems from the Arabic ḥaršuf, which led to alcachofa in Spanish, artichaut in French, and articiocco in Italian, from which the name Articoca was first used in 1542 by German botanist Leonhart Fuchs (1501–1566), afterwards named Artischock by Dutch physician Gemma Frisius (1508–1555).35 The Syriac word ‘akkūḇā, referring to C. cardunculus, can best be translated as “cardoon,” comparable to the Jewish Aramaic ‘akkōḇīṯā, meaning “a thistle sting” and Arabic ‘akkūb, meaning “globe-thistle.”36
In his 1737 work Genera Plantarum, Swedish botanist Carl Linnaeus (1707–1778) assigned the genus name Cynara,37 and in his 1753 work Species Plantarum, he described three species: C. cardunculus with habitat stated as Crete, C. humilis with habitat of Tingatano (present-day northern Morocco) and Baetica (present-day Andalusia, southern peninsular Spain), and C. scolymus with habitat of Italy (in particular Sicily) and Gallia Narbonensis (Gaul of Narbonne),38 which today encompasses the regions of Languedoc and Provence in southern France. Linnaeus described three varieties of C. scolymus and listed C. cardunculus as a distinct species derived from one parent and not a hybrid.39
A 2004 ethnopharmacognostic survey on remedies used in central Lucania in southern Italy reported that aerial parts of wild C. cardunculus are decocted together with aerial parts of dog figwort (Scrophularia canina, Scrophulariaceae) and creeping cinquefoil (Potentilla reptans, Rosaceae) as an anti-rheumatic preparation and applied as a compress.40 In a 2000 ethnobotanical survey of medicinal plants grown in home gardens in Catalonia, Spain, 14% of respondents reported using C. cardunculus (plant part and mode of administration not reported) as an abortive, and 5% reported using C. scolymus as a hepatoprotective.41 Published in 2012, another ethnobotanical survey in Salamanca province, Spain, that looked at remedies used against witches and the “evil eye,” described traditional cheese-making by curdling milk with artichoke flowers and lamb rennet. However, if the milk did not set properly, this was attributed to having made contact with the evil eye of a witch in the village. To remedy this, the cheese-maker would smoke the milk by burning the flowering aerial parts of mastic thyme (Thymus mastichina, Lamiaceae) and Magydaris panacifolia (Apiaceae) with a few drops of olive (Olea europaea, Oleaceae) fruit oil.42
In Greek folk medicine, the pulverized fresh leaves of C. cardunculus, covered with olive oil, are applied topically to relieve infant teething pain.43 The flowers are also processed into a vegetal rennet for cheese making in several regions.4 For example Djben, a traditional fresh cheese, is made in Algeria with the raw milk of ewe, cow, or goat, coagulated with dried flowers of wild C. cardunculus without the use of starter culture.44 Djben may be made by macerating the flowers of different species (C. cardunculus, C. cardunculus var. scolymus, or C. humilis) in different milks, depending on which is available in different regions of the Maghreb countries (Algeria, Libya, Mauritania, Morocco, Tunisia) and Western Sahara, where this cheese is a specialty.45
In the early 20th century, the Sicily-born Mafioso Ciro “The Artichoke King” Terranova (1888–1938) ran an artichoke extortion racket in New York City, pocketing an estimated $1 million annually through the monopoly.46 In December 1935, New York City Mayor Fiorello La Guardia (1882–1947) went to the Bronx Terminal Market and, as a tactic to break up the Mafia monopoly, issued an emergency proclamation prohibiting the sale, display, and possession of artichokes in all public places until it was possible to purchase artichokes freely without unlawful restraint, restriction or racketeering, coercion, or duress. Three days after the mayor’s proclamation, the baby artichoke extortion racket was broken up, and the ban was lifted.47 In 1948, at the age of 22, Marilyn Monroe (1926–1962) was selected as the inaugural “Artichoke Queen” in Castroville, California, the location of the first artichoke cultivation in the United States and annual Artichoke Festival.48
In 1985, a monograph for “Flos Cynarae scolymus” entered volume one of the first edition of Pharmacopée Africaine, including tests for identification, composition, purity, and strength, and indicated its use for treating hepatic and renal dysfunctions, as a diuretic, and for arteriosclerosis.9 The German Commission E published a positive therapeutic monograph for “Cynarae folium” (Artischockenblätter) in 1988 (revised in 1990), in the form of cut, dried leaf, fresh-pressed plant juice, or other galenical preparations, indicated for use as a choleretic (promoting bile secretion) drug for dyspeptic problems.49
The World Health Organization (WHO) published a “Cynarae folium” monograph in 2009, in volume four of the WHO Monographs on Selected Medicinal Plants, listing medical uses supported by clinical data including treatment of digestive complaints (e.g., dyspepsia, feeling of fullness, flatulence, nausea, stomach ache, and vomiting) and adjunct treatment of mild to moderate hypercholesterolemia.50 In 2011, and in its 2018 revision, the European Medicines Agency (EMA) published a labeling standards monograph for artichoke that superseded the German Commission E monograph for purposes of product marketing authorization in the European Union (EU).51 In Canada, a labeling standards monograph for licensed artichoke Natural Health Products (NHPs) was published in 2008 and revised in 2018.52 A quality monograph for the dried leaf was first published in the fifth supplement to the fifth edition of the European Pharmacopoeia (PhEur 5.5) in 2006.53 A corresponding monograph for the dry extract of artichoke leaf was admitted to PhEur 6.3 in 2009.54
In 2010, the European Food Safety Authority (EFSA) issued an opinion that a cause-and-effect relationship had not been established between the consumption of artichoke leaf or extract and a beneficial physiological effect related to an increase in renal water elimination (diuresis).55 In the same year, EFSA issued an opinion on proposed antioxidant health claims for dried artichoke leaf that no evidence had been provided to establish that having antioxidant activity/content and/or antioxidant properties is a beneficial physiological effect.56 In 2014, the German Federal Office of Consumer Protection and Food Safety (BVL) assessed and classified artichoke leaf as “not novel in food supplements,” but also as a medicinal plant on List B, meaning that restricted use in foods is recommended because pharmacological effects occur at or above the known therapeutic use dosage level.57
CURRENT AUTHORIZED USES IN COSMETICS, FOODS, AND MEDICINES
In the United States, artichoke leaf and extracts may be used in dietary supplements, which require Food and Drug Administration (FDA) notification within 30 days of marketing if a structure-function claim is made and product manufacturing that adheres to current Good Manufacturing Practices (cGMPs).58 The leaves are also classified as Generally Recognized as Safe (GRAS) by the FDA, but specifically for use as a natural flavoring substance in alcoholic beverages only.59
In Canada, the dried leaf is regulated as an active ingredient of licensed NHPs, which require pre-marketing authorization from the Natural and Non-prescription Health Products Directorate (NNHPD). Licensed NHPs prepared from pharmacopeial quality artichoke leaf may be labeled and marketed for uses including to help relieve digestive upset, such as indigestion, and as a choleretic to help increase bile flow, in dosage forms including dried leaf powder and non-standardized extracts (e.g., fluidextract, herbal tea decoction or infusion, tincture, or dry extract).52
In the EU, preparations of artichoke leaf may be used as an active ingredient of registered traditional herbal medicinal products (THMPs) labeled with the therapeutic indication “for the symptomatic relief of digestive disorders such as dyspepsia with a sensation of fullness, bloating and flatulence.” For this use, the artichoke leaf may be prepared in the forms of: (a) cut dried leaves for herbal tea, (b) powdered dried leaves, (c) aqueous dry extract of dried leaves (drug-to-extract ratio [DER] range 2-7.5:1), (d) aqueous dry extract of fresh leaves (DER 15-35:1), (e) aqueous soft extract of fresh leaves (DER 15-30:1), or (f) ethanol (20% VV) soft extract of dried leaves (DER 2.5-3.5:1).
The dried leaf used for production of registered THMPs must conform to the quality standards monographs of the European Pharmacopoeia (Cynarae folium PhEur or Cynarae folii extractum siccum PhEur).8 Furthermore, use of an extract of the leaves in cosmetic products is authorized in the EU specifically for skin-conditioning function.60 New potential uses for extracts of the leaves as an “active” component of food packaging to help increase shelf life have been proposed recently.4
Artichoke leaf preparations have a longstanding use as a traditional medicine for digestive disturbances (e.g., dyspepsia), as a choleretic, and for their lipid-lowering, hepatoprotective, antioxidant, diuretic, and anti-atherogenic effects.9,49-52,61-63 These health benefits have been reported in multiple studies, including animal models, pre-clinical, phytochemical, laboratory, and human clinical studies.
Artichoke leaf’s antioxidant properties and characteristic lipid-lowering and hepatoprotective activities have been attributed to mono- and dicaffeoylquinic acids (cynarin and chlorogenic acid), caffeic acid, sesquiterpene lactones, and flavonoids (including the glycosides luteolin-7-O-rutinoside, luteolin-7-O-glucoside, and luteolin-4-O-glucoside).64-66 Other constituents in the phytochemical profile include phytosterols, tannins, glycolic and glyceric acids, sugars, inulins, and enzymes.67 The natural bitter taste of artichoke leaf is attributed to cynaropicrin, a sesquiterpene lactone.66,68 This profile is focused on the artichoke leaf (Cynarae folium), but the high-inulin profile of other Cynara plant parts, mostly the inflorescence and external bracts, is also noteworthy. Currently, inulin is researched for its benefits as a prebiotic, which may promote beneficial bacteria found in the gastrointestinal system.69,70
Specifically, recent human clinical trials of artichoke preparations have documented health benefits associated with artichoke’s lipid-lowering effects,71-74 hepatoprotective effects,64 and improvement of gastrointestinal symptoms related to functional dyspepsia75,76 and irritable bowel syndrome (IBS).77,78 Table 1 summarizes selected clinical studies and the effects of artichoke preparations on these health states.
Multiple meta-analyses and systematic reviews have assessed the effects of artichoke preparations on cardiovascular health and related parameters. Sahebkar et al (2018)79 performed a meta-analysis and systemic review on the effects of artichoke leaf extract (ALE) on human lipid profiles. From the total of nine trials reviewed and 702 subjects, Sahebkar et al reported significant decreases in total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels in those taking ALE. No significant effects were reported for triglycerides and high-density lipoprotein-cholesterol (HDL-C) levels. The reviewed studies showed differing dosage levels, durations of treatment, and standardization of the extracts.
A systematic review and dose-response meta-analysis of clinical trials by Hemati et al (2021)80 found that artichoke supplementation decreased waist circumference. The data sets, however, did not show significant changes in body weight or body mass index (BMI), with the exception of hypertensive patients in a subgroup analysis that showed significant body weight reduction. Panahi et al (2018)64 studied the effects of ALE supplementation on nonalcoholic fatty liver disease and found that both BMI and waist circumference were reduced significantly in the ALE group compared to placebo. Jalili et al (2020)81 conducted a systematic review and meta-analysis of nine randomized controlled trials (RCTs) and reported that artichoke supplementation correlated with significantly decreased fasting blood sugar.
The results of several studies suggest that artichoke leaf may help decrease gastrointestinal symptoms and improve quality of life in individuals with functional dyspepsia and IBS.75,77,78,82,83 Yoon et al (2011)83 and Rahimi et al (2012)82 both reviewed the same two studies of ALE for IBS management.
In a 2009 Cochrane systematic review, “Artichoke leaf extract for treating hypercholesterolaemia,” the authors concluded that only mild, transient, and infrequent adverse events (AEs) have been reported for short-term use of ALE.84 Authoritative herbal monographs include cautions and contraindications associated with artichoke leaf preparations for individuals with hypersensitivity to the Asteraceae plant family and individuals with hepatobiliary diseases.49-52,61-63
According to a 2012 survey of herbalists working in Marrakesh, Morocco, the roots of Kherchouf (C. cardunculus) are fairly commonly confused in the market with roots of Tasskra (Echinops spinosissimus subsp. fontqueri, Asteraceae).86 Artichoke leaf is found as an ingredient of certain types of food supplement products known to be adulteration targets (e.g., weightloss products), and deliberate substitution of other lower-cost ingredients or misidentification of other Cynara species is possible. Accordingly, a molecular approach based on real-time polymerase chain reaction (PCR) coupled to high-resolution melting (HRM) analysis was developed for rapid differentiation of Cynara species (C. cardunculus, C. cardunculus var. scolymus, C. humilis, and C. syriaca) that could be applied to the analysis of commercial products for authentication.87
Another study suggested that quantifying the variation in phenolic compounds in artichokes, relative to genetic and environmental factors, could also allow for authentication.88 In a study of herbal medicinal products labeled as containing ALE, 7.7% of tested samples (2 of 26) varied significantly from the reference product (i.e., they did not contain the marker chlorogenic acid, and the chromatograms also suggested the presence of synthetic drug substances). The results were inconclusive due to a lack of standards for identifying the synthetic drugs that could be used as adulterants in artichoke extract products.89
SUSTAINABILITY AND FUTURE OUTLOOK
The International Union for Conservation of Nature (IUCN) European Red List of Medicinal Plants assigns C. cardunculus to the conservation category of least concern (LC), meaning that it is not threatened overall in Europe.90 However, the species is classified as vulnerable in France.91 And while this species is not listed in the Red Book of Italy,92 C. cardunculus subsp. zingaroensis has been classified as regionally vulnerable in Sicily.93 North Tunisian germplasm of C. cardunculus var. sylvestris has reportedly been damaged by significant genetic erosion, pollution, urbanization, and poor farming practices.5 The main C. cardunculus germplasm collections are located in Italy, France, and Spain. However, the expansion of commercial cultivation of single uniform varieties has led to a reduction in diversity. In Italy and France, only a few varieties are cultivated over large areas. And, in Spain, a single ecotype, Blanca de Tudela, accounts for 90% of production.10 Genetic variation analysis of cultivated Cynara species and their wild relatives is important for biodiversity conservation, especially with regard to food security,94 as the artichoke reportedly ranks as the fourth most important food crop in Europe.10 Cynara tournefortii is classified as a vulnerable species in Portugal,95 extremely rare in Morocco,96 and critically endangered in Spain.97 Cynara baetica is extremely rare in Morocco96 and vulnerable in Spain, and C. algarbiensis is listed as a vulnerable species in Spain.97
A 2020 study suggested that C. cardunculus could become a model crop for climate change adaptation due to the species’ ability to grow in dry and marginal lands.98 Seed germination and seedling establishment of C. cardunculus typically are not negatively impacted by abiotic stresses (caused in plants by drought, flooding, extreme temperatures) that are further exacerbated by climate change. In a context of uncertainty for farmers due to climate change and environmental pollution, C. cardunculus appears to be a crop that can be grown on marginal lands that are predicted to be unsuitable for other crops, thus providing farmers with an economic crop to transition to in the future.99
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