- What is chicory root
- Chicory Traditional Uses
- Chicory root extract
- Chicory root benefits
- Chicory root side effects
What is chicory root
Chicory (Cichorium intybus L.), a member of the Asteraceae family, is a well-known herb possessing various biological activities. Chicory is an erect fairly woody perennial herb, around 1 m in height with a fleshy taproot of up to 75 cm in length and large basal leaves 1). Historically, chicory was grown by the ancient Egyptians as a medicinal plant, coffee substitute, and vegetable crop and was occasionally used for animal forage. In the 1970s, it was discovered that chicory root contained up to 40% inulin, a polysaccharide similar to starch, which has a negligible impact on blood sugar and thus is suitable for diabetics 2). Inulin is mainly found in the plant family Asteraceae as a storage carbohydrate (for example Jerusalem artichoke, dahlia, yacon, etc.). It is used as a sweetener in the food industry with a sweetening power 1⁄10 that of sucrose and is sometimes added to yogurts as a prebiotic. Inulin is also gaining popularity as a source of soluble dietary fiber and functional food. To date, chicory is grown for the production of inulin on an industrial scale 3).
Chicory root (Cichorium intybus var. sativum) has also been cultivated in Europe as a coffee substitute 4). The roots are baked, roasted, ground, and used as an additive, especially in the Mediterranean region (where the plant is native). As a coffee additive, it is also mixed in Indian filter coffee, and in parts of Southeast Asia, South Africa, and southern United States, particularly in New Orleans. It has been more widely used during economic crises such as the Great Depression in the 1930s and during World War II in Continental Europe. Chicory, with sugar beet and rye, was used as an ingredient of the East German Mischkaffee (mixed coffee), introduced during the “East German coffee crisis” of 1976-79.
Chicory was grown by ancient Egyptians as a medicinal plant, vegetable crop, and animal feed 5). Chicory is native to Europe and Asia and has been widely used in traditional therapy for the medication gastrointestinal and inflammatory disorders 6). Important phytochemicals are distributed throughout the plant; however, the primary contents are present in the root. Chicory root extracts have been stated to have antimicrobial 7), antihyperglycemic 8), immunostimulant 9), antioxidative effect 10), antiinflammatory 11), and tumor-inhibitory activities 12).
Figure 1. Chicory root
Some beer brewers use roasted chicory to add flavor to stouts (commonly expected to have a coffee-like flavour). Others have added it to strong blond Belgian-style ales, to augment the hops, making a witlofbier, from the Dutch name for the plant.
Chicory root extract is a dietary supplement or food additive produced by mixing dried, ground chicory root with water, and removing the insoluble fraction by filtration and centrifugation. Other methods may be used to remove pigments and sugars. It is used as a source of soluble fiber. Fresh chicory root typically contains, by dry weight, 68% inulin, 14% sucrose, 5% cellulose, 6% protein, 4% ash, and 3% other compounds. Dried chicory root extract contains, by weight, about 98% inulin and 2% other compounds 13). Fresh chicory root may contain between 13 and 23% inulin, by total weight 14).
Chicory Traditional Uses
Chicory is a medicinally important plant in Eurasia and in parts of Africa. Despite its long tradition of use, the plant is not described in the European Pharmacopoeia or in any official Pharmacopoeia of a European Union member state 15). However, due to its prevalent distribution, different parts of the plant have been used in traditional medicines globally 16). Important phytochemicals are distributed throughout the plant, but the main contents are present in the root 17).
Medicinal plants have been used for centuries and numerous cultures still rely on indigenous medicinal plants to meet their primary health care needs. It is likely that the insightful knowledge of plant-based remedies in traditional cultures advanced through trial and error and that the most important cures were carefully passed from one generation to another 18). Historically, chicory was grown by the ancient Egyptians as a medicinal plant 19) and it has had a long history of therapeutic use both in areas where it is indigenous and in areas where it has been introduced. The various common or local names describing this plant may be ascribed to the widespread use by different folkloric groups.
Different preparations of this plant are employed to treat various symptoms and ailments (Table 1). The juice is said to be a folk remedy for cancer of the uterus and for tumors 20). In South Africa, although it is considered a widespread weed, leaves, stems, and roots are made into a tea for jaundice and chicory syrup is used as a tonic and purifying medicine for infants 21). In Turkey, an ointment is made from the leaves for wound healing 22). Decoction refers to a preparation that is made by adding cold water to the plant material which is then boiled and allowed to simmer for 5–10 min after which it is strained 23). Chicory decoctions are traditionally made from individual plant parts and/or from the plant as a whole (see Table 1).
According to the European monograph, traditional use of chicory roots includes the relief of symptoms related to mild digestive disorders (such as feeling of abdominal fullness, flatulence, and slow digestion) and temporary loss of appetite 24).
Table 1. Traditional medicinal uses of Chicory (Cichorium intybus)
|Country||Traditional use(s)||Plant part(s)||Preparation(s)||Reference|
|Bosnia and Herzegovina||Diarrhea, strengthening the prostate and other reproductive organs, pulmonary cancer, hangover, and purification of biliary tract||Aerial part, flowers, roots||Not stated||26)|
|Liver disorders, spasmolytic,|
for gastric secretion,
|Roots, aerial parts||Decoction||28)|
|Diabetes||Whole plant||Not stated||30)|
|Jaundice, liver enlargement, gout, and rheumatism||Root||Decoction||31)|
|Cough relief||Not stated|
|Iran||Eupeptic, stomachic, depurative, choleretic, laxative, hypotension, tonic, and antipyretic||Whole plant||Not stated||32)|
|Italy||Blood cleansing||Leaves||Not stated||33)|
|High blood pressure||Leaves||Decoction||34)|
against jaundice, mild
|Leaves||Decoction, squashed fresh leaves||37)|
|Jordan||Internal hemorrhage, sedative in typhoid||Whole plant||Cooking||38)|
|Morocco||Renal disease||Aerial/roots||Not stated||39)|
|Kidney disorders, diabetes||Whole plant||Decoction||40)|
|Poland||Digestive complaints and lack of appetite||Roots||Tea||42)|
|Diuretic, digestive, laxative, anti-inflammatory, liver complaints, reducing blood sugar||Roots||Decoction/tea||44)|
|Cholagogue, digestive, hypoglycemic||Aerial part/root||Not stated||45)|
|South Africa||Jaundice, tonic||Leaves, stems, roots||46)|
|Turkey||Cancer, kidney stones||Roots||Decoction||47)|
|Hemorrhoids, urinary disorders||Aerial||Tea||49)|
Chicory root extract
Chicory presents a little investigated plant in terms of phytochemistry and pharmacology. Over 100 individual compounds have been isolated and identified from this plant (see Table 2), the majority of which are from chicory roots. Most of the pharmacological studies on this plant document the testing of aqueous and/or alcoholic extracts only. Apart from the pharmacologically important activities, the use of chicory (hairy root cultures) has also been implicated in the phytoremediation of DDT 50).
Chicoric acid has been identified as the major compound in methanolic extracts of chicory (Table 2). Aliphatic compounds and their derivatives comprise the main fraction while terpenoids comprise minor constituents of the plant. The flowers of chicory contain saccharides, methoxycoumarin cichorine, flavonoids, essential oils and anthocyanins contributing to the blue colour of the perianth. Table 2 provides a summary of the compounds isolated and identified from chicory. Octane, n-nonadecane, pentadecanone, hexadecane, and a tentatively identified compound have been found as principal volatile components 51). A list of volatile compounds is given in Table 3.
Table 2. Compounds isolated and identified from Chicory (Cichorium intybus)
|(7S, 8R)-3′-Demethyl-dehydrodiconiferyl alcohol-3′-O-β-glucopyranoside|
|Dimethoxycinnamoyl shikimic acid|
|Dicaffeoyltartaric acid (chicoric acid)|
|3-O-p-Coumaroyl quinic acid|
Table 3. Volatile constituents of Chicory (Cichorium intybus)
|(5E, 9E)-Farnesyl acetone|
Chicory root benefits
Two clinical studies on chicory roots are reported in the literature, both of which are pilot studies and are therefore considered to be insufficient to support a well-established use indication for chicory root 54). The first study, a phase 1, placebo-controlled, double-blind, dose-escalating trial, was conducted to determine the safety and tolerability of a proprietary bioactive extract of chicory root in patients with osteoarthritis 55). In general, the treatment was well tolerated. Only one patient who was treated with the highest dose of chicory had to discontinue treatment due to an adverse event. The results of the pilot study suggested that a proprietary bioactive extract of chicory root has a potential role in the management of osteoarthritis and merits further investigation. The second pilot study was conducted to assess whether chicory coffee consumption might confer cardiovascular benefits; thus, a clinical intervention was performed with 27 healthy volunteers, who consumed 300 mL chicory coffee daily for one week 56). Depending on the inducer used for the aggregation test, the dietary intervention showed variable effects on platelet aggregation. Whole blood and plasma viscosity were both significantly reduced, along with serum MIF levels, after a week of chicory coffee intake. It was concluded that the full spectrum of the effects was unlikely to be attributed to a single phytochemical; nevertheless, the phenolics (including caffeic acid) are expected to play a substantial role. The study offered an encouraging starting-point to describe the antithrombotic and anti-inflammatory effects of phenolic compounds found in chicory coffee.
In the European Union, there is currently only one registered/authorized herbal medicinal product containing C. intybus as single ingredient whilst there are several combination products on the market 57). The efficacy of herbal medicine Liv-52 consisting of Mandur bhasma, Tamarix gallica, and herbal extracts of Capparis spinosa, C. intybus, Solanum nigrum, Terminalia arjuna, and Achillea millefolium on liver cirrhosis outcomes was compared with the placebo for 6 months in 36 cirrhotic patients. The study concluded that Liv-52 possessed a hepatoprotective effect in cirrhotic patients. This protective effect of Liv-52 can be attributed to the diuretic, anti-inflammatory, anti-oxidative, and immunomodulating properties of the component herbs 58).
The antibacterial activity of the organic acid-rich extract of fresh red chicory (C. intybus var. sylvestre) was tested against periodontopathic bacteria including Streptococcus mutans, Actinomyces naeslundii, and Prevotella intermedia. The compounds identified from the active extract include oxalic acid, succinic acid, quinic acid, and shikimic acid. All of the organic acids were found to decrease biofilm formation and adhesion of bacteria to the cells, with different levels of efficacy. These compounds also induced biofilm disruption and detachment of dead cells for the cultured substratum 59). In other reports on the antimicrobial activity of C. intybus, the crude aqueous and organic seed extracts were found to be active against four pathogenic microorganisms, namely, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, and root extracts had pronounced effects on Bacillus subtilis, S. aureus, Salmonella typhi, Micrococcus luteus, and E. coli 60). The leaf extract of C. intybus also showed a moderate activity against multidrug resistant S. typhi 61). Guaianolides-rich root extracts of C. intybus have shown antifungal properties against anthropophilic fungi Trichophyton tonsurans, T. rubrum, and T. violaceum 62). A sesquiterpenoid phytoalexin cichoralexin isolated from chicory exhibited potent antifungal activity against Pseudomonas cichorii 63).
Several studies have been conducted on grazing animals to determine the anthelmintic potential of secondary metabolites present in chicory. Grossly, it has been concluded that the animals grazing on chicory have a higher performance index and lower incidence of gastrointestinal nematode infestations. In the majority of the experiments, the condensed tannins and sesquiterpene lactones were responsible for anthelmintic activity 64). Anthelmintic activity of chicory has also been noticed in the case of lambs wherein the total number of abomasal helminths was found to be lesser in the lambs grazing on this plant 65). The condensed tannin and sesquiterpene-rich extracts of chicory were evaluated for their efficacy against the larvae of deer lungworm, Dictyocaulus viviparous and other gastrointestinal nematode larvae using a larval migration inhibition assay. A dose-dependent decrease in the larval motility was observed in both lungworm and gastrointestinal nematodes 66). The sesquiterpene lactone-rich extracts of C. intybus were also found to inhibit egg hatching of Haemonchus contortus 67).
The infusion of fresh chicory roots has a history of use as a remedy for malarial fevers in some parts of Afghanistan. The bitter compounds in the plant, namely, lactucin, lactucopicrin, and the guaianolide sesquiterpenes, isolated from aqueous root extracts of chicory were concluded to be the antimalarial components of the plant. Lactucin and lactucopicrin completely inhibited the HB3 clone of strain Honduras-1 of Plasmodium falciparum at concentrations of 10 and 50 μg/mL, respectively 68).
The folkloric use of chicory as a hepatoprotectant has been well documented. It is one of the herbal components of Liv-52, a traditional Indian tonic used widely for hepatoprotection. In a randomized, double-blind clinical trial conducted on cirrhotic patients, Liv-52 medication reduced the serum levels of hepatic enzymes, namely, alanine aminotransferase and aspartate aminotransferase. It also reduced the Child-Pugh scores and ascites significantly 69). Another polyherbal formulation, Jigrine, contains the leaves of C. intybus as one of its 14 constituents. Jigrine was evaluated for its hepatoprotective activity against galactosamine-induced hepatopathy in rats. The pretreatment of male Wistar-albino rats with jigrine significantly reduced the levels of aspartate transaminase, alanine transaminase, and urea and increased the levels of blood and tissue glutathione. Histopathological examination of the liver revealed that jigrine pretreatment prevented galactosamine toxicity and caused a marked decrease in inflamed cells 70).
The aqueous-methanolic extract of chicory seeds has been investigated for the hepatoprotective activity against acetaminophen and carbon tetrachloride-induced liver damage in mice. It was found to decrease both the death rate and the serum levels of alkaline phosphatase, glutamyl oxaloacetate transaminase, and glutamyl pyruvate transaminase 71). In analogous studies, the antihepatotoxic activity of the alcoholic extract of the seeds and aqueous extracts of the roots and root callus of C. intybus was estimated. The oral administration of these extracts in albino rats led to a marked decrease in the levels of hepatic enzymes. Also, histopathological examination of the liver showed no fat accumulation or necrosis after the treatment 72). Similar studies have established the hepatoprotective effect of esculetin, a phenolic compound, and cichotyboside, a guaianolide sesquiterpene glycoside reported from chicory 73).
Chicory has reported antidiabetic activity 74). Based on the traditional use of chicory in diabetes mellitus, the hypoglycemic and hypolipidemic properties of the ethanol extract of the whole plant were investigated. Diabetes was induced by intraperitoneal administration of streptozotocin in male Sprague-Dawley rats. The ethanol extract, at a dose of 125 mg/Kg body weight, significantly attenuated the serum glucose levels in the oral glucose tolerance test. A marked decrease in the serum triglycerides and cholesterol was also observed in the extract-treated rats. Hepatic glucose-6-phosphatase activity was found to be reduced in extract-treated diabetic rats as compared to untreated diabetic rats 75). The antidiabetic effect of the aqueous seed extract of C. intybus has also been investigated. Early-stage and late-stage diabetes were differently induced in male Wistar albino rats by streptozotocin-niacinamide and streptozotocin alone, respectively. The treatment with chicory extract prevented weight loss in both early-stage and late-stage diabetic rats. Chicory-treated diabetic animals resisted excessive increase in fasting blood sugar (assessed by glucose tolerance test). Grossly, normalization of blood parameters, namely, alanine aminotransferase, triacylglycerol, total cholesterol, and glycosylated heamoglobin, was seen in these animals. In early-stage diabetic rats, chicory treatment led to the increase in insulin levels pointing toward the insulin-sensitizing action of chicory 76).
Feeding the diabetic Wistar rats with chicory leaf powder led to a decrease in blood glucose levels to near normal value. Chicory administration also decreased the malondialdehyde (formed by thiobarbituric acid) levels and increased glutathione content. Anticholinesterase activity was restored to near normal, brain lipopolysaccharide decreased, and catalase activity increased 77). Caffeic acid and chlorogenic acid have been described as potential antidiabetic agents by increasing glucose uptake in muscle cells. Both compounds were also able to stimulate insulin secretion from an insulin-secreting cell line and islets of Langerhans. Another compound, chicoric acid, is also a new potential antidiabetic agent exhibiting both insulin-sensitizing and insulin-secreting properties 78).
C. intybus has been used in Turkish folklore for its antiulcerogenic potency. The aqueous decoction of C. intybus roots was orally administered to Sprague-Dawley rats 15 minutes before the induction of ulcerogenesis by ethanol. More than 95% inhibition of ulcerogenesis was observed in the test group 79).
The inhibition of TNF-α mediated cyclooxygenase (COX) induction by chicory root extracts was investigated in the human colon carcinoma (HT 29) cell line. The ethyl acetate extract inhibited the production of prostaglandin E2 (PGE2) in a dose-dependent manner. TNF-α mediated induction of COX-2 expression was also suppressed by the chicory extract 80).
Lactucin, lactucopicrin, and 11β, 13-dihydrolactucin exhibited analgesic action in mice in hot plate and tail-flick tests. In the hot plate test, all three compounds exerted an analgesic effect, with lactucopicrin being the most potent compound. In the tail-flick test, the antinociceptive effects of all the tested compounds (30 mg/kg dose) were comparable to that of ibuprofen (60 mg/kg dose). Lactucin and lactucopicrin were also established to have some sedative action as evident from the decreased spontaneous locomotor activity in mice 81).
The DPPH radical scavenging activity of a polyphenols-rich fraction of chicory has been investigated 82). The anti- and prooxidant activities of Cichorium species were studied in chemical as well as biological systems. In the case of chemical systems, the antioxidant activity of water-soluble compounds in C. intybus var. silvestre was established in the coupled model of linoleic acid and β-carotene. A pro-oxidant activity of some of the chemical components was recorded initially which notably diminished with time and/or thermal treatment. Thereafter, the antioxidant activity of the raw juice and its fractions persisted. The molecular weight ranges of the antioxidant fractions of raw juice were also identified based on dialysis 83). Two varieties of chicory, namely, C. intybus var. silvestre and C. intybus var. foliosum, have been investigated for their antioxidant (antiradical) activities in two distinct biological systems. The lipid peroxidation assay has been carried out on microsome membranes of rat hepatocytes after the induction of oxidative damage by carbon tetrachloride. The antiradical activity was expressed as the protective activity against lipid peroxidation and calculated as the percentage decrease in hydroperoxide degradation products. The second biological system used was the cultures of S. aureus after treatment with cumene hydroperoxide. The percentage increase of growth of bacteria was noted after the treatment with juices of chicory varieties. In both systems, the juices of chicory varieties showed strong antiradical activities 84).
Red chicory (C. intybus var. silvestre) was studied for its polyphenol content and the antioxidant activity was evaluated by using the synthetic 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl radical and three model reactions catalyzed by pertinent enzymatic sources of reactive oxygen species, namely, xanthine oxidase, myeloperoxidase, and diaphorase. Total phenolics were significantly correlated with the antioxidant activity evaluated with both the synthetic radical and the enzyme-catalyzed reactions. On a molar basis, red chicory phenolics were as efficient as Trolox (reference compound) in scavenging the synthetic radical 85). The aqueous-alcoholic extracts of the aerial parts of C. intybus also inhibited xanthine oxidase enzyme dose dependently 86). In another study, along with DPPH radical scavenging activity, C. intybus also exhibited inhibition of hydrogen peroxide and chelation of ferrous ion 87).
The crude ethanolic chicory roots extract caused a significant inhibition of Ehrlich tumor carcinoma in mice. A 70% increase in the life span was observed with a 500 mg/kg/day intraperitoneal dose of the tested extract 88). The aqueous-alcoholic macerate of the leaves of C. intybus also exerted an antiproliferative effect on amelanotic melanoma C32 cell lines 89). Magnolialide, a 1β-hydroxyeudesmanolide isolated from chicory roots, inhibited several tumor cell lines and induced the differentiation of human leukemia HL-60 and U-937 cells to monocyte or macrophage-like cells 90).
The aqueous chicory root extract inhibited the mast cell-mediated immediate allergic reactions in vitro as well as in vivo. This extract restrained the systemic anaphylactic reaction in mice in a dose-dependent manner. It also significantly inhibited passive cutaneous anaphylactic reaction caused by anti-dinitrophenyl IgE in rats. Other markers of allergic reaction, namely, plasma histamine levels and histamine release from rat peritoneal mast cells, decreased significantly whereas the levels of cAMP increased after the treatment with chicory root extract 91).
Other Pharmacologically Important Activities
The ethanol extract of the roots of chicory is reported to prevent the immunotoxic effects of ethanol in ICR mice. It was noted that body weight gains were markedly decreased in mice administered with ethanol. However, the body weight was not affected when ethanol was coadministered with the ethanol extract of chicory. Similarly, the weights of liver and spleen were not affected when ethanol extract was given along with ethanol. A considerable restoration in the other markers of immunity, namely, hemagglutination titer, plaque forming cells of spleen, secondary IgG antibody production, delayed-type hypersensitivity reaction (in response to subcutaneous administration of sheep red-blood cells to paw), phagocytic activity, number of circulating leucocytes, NK cell activity, cell proliferation, and production of interferon-γ, was registered 92). The immunoactive potential of an aqueous-alcoholic extract of the roots was established by a mitogen proliferation assay and mixed lymphocyte reaction (MLR). The extract showed an inhibitory effect on lymphocyte proliferation in the presence of phytohemagglutinin and a stimulatory effect on MLR 93).
Chicoric acid has shown vasorelaxant activity against nor-epinephrine-induced contractions in isolated rat aorta strips 94). A pronounced anticholinesterase activity of the dichloromethane extract of chicory roots was seen in the enzyme assay with Ellman’s reagent. Two sesquiterpene lactones, namely, 8-deoxylactucin and lactucopicrin, also exhibited a dose-dependent inhibition of anticholinesterase 95). The methanolic extract displays wound healing effect and β-sitosterol was determined as the active compound responsible for the activity, possibly due to its significant anti-inflammatory and antioxidant effects, as well as hyaluronidase and collagenase inhibition 96).
Chicory root side effects
Although chicory has a long history of human use, the high levels of secondary metabolites have shown potential toxicological effects. To evaluate the safety of chicory root extract, Ames test and subchronic toxicity assessment were conducted. The sesquiterpene-rich extract was evaluated for potential mutagenic properties (Ames test) using Salmonella typhimurium strains TA97a, TA98, TA100, and TA1535 and Escherichia coli strain WP2 uvrA. Though cytotoxicity was observed at high extract doses in some strains, mutagenicity was not noted. A 28-day (subchronic) oral toxicity study, conducted in CRL:CD (SD) IGS BR rats, concluded that there was no extract-related mortality or any other signs of toxicological significance 97). The toxicity evaluation of chicory root extracts has also been done by Vibrio fischeri bioluminescence inhibition test (Microtox acute toxicity test). This bacterial test measures the decrease in light emission from the marine luminescent bacteria V. fischeri when exposed to organic extracts. The tested extracts showed less than 20% inhibition of bioluminescence and hence were concluded to be safe for human use 98). However, toxicological data on chicory is currently limited; moreover, considering that the Asteraceae family is a known source of allergic problems, a contraindication for hypersensitivity should be included in the safety data 99). Recent studies suggest the use of chicory as a biomonitor for heavy metals 100); considering that chicory enters the food chain, this plant should be used with caution.
References [ + ]
|1, 17.||↵||Bais HP, Ravishankar GA. Cichorium intybus L.—cultivation, processing, utility, value addition and biotechnology, with an emphasis on current status and future prospects. Journal of the Science of Food and Agriculture. 2001;81(5):467–484.|
|2, 20, 51, 53.||↵||Judžentienė A, Būdienė J. Volatile constituents from aerial parts and roots of Cichorium intybus L. (chicory) grown in Lithuania. Chemija. 2008;19:25–28.|
|3.||↵||Sink filling, inulin metabolizing enzymes and carbohydrate status in field grown chicory (Cichorium intybus L.). van Arkel J, Vergauwen R, Sévenier R, Hakkert JC, van Laere A, Bouwmeester HJ, Koops AJ, van der Meer IM. J Plant Physiol. 2012 Oct 15; 169(15):1520-9. https://www.ncbi.nlm.nih.gov/pubmed/22795678/|
|5.||↵||Alloush GA, Belesky DP, Clapham WM. Forage chicory: a plant resource for nutrient-rich sites. J Agron Crop Sci. 2003;189: 96–104. doi: 10.1046/j.1439-037X.2003.00014.x|
|6.||↵||Cichorium intybus: Traditional Uses, Phytochemistry, Pharmacology, and Toxicology. Street RA, Sidana J, Prinsloo G. Evid Based Complement Alternat Med. 2013; 2013():579319. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860133/|
|7.||↵||Chicory extracts from Cichorium intybus L. as potential antifungals. Mares D, Romagnoli C, Tosi B, Andreotti E, Chillemi G, Poli F. Mycopathologia. 2005 Aug; 160(1):85-91. https://www.ncbi.nlm.nih.gov/pubmed/16160773/|
|8.||↵||Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic rats. Pushparaj PN, Low HK, Manikandan J, Tan BK, Tan CH. J Ethnopharmacol. 2007 May 4; 111(2):430-4. https://www.ncbi.nlm.nih.gov/pubmed/17197141/|
|9.||↵||Effects of the ethanol extract of Cichorium intybus on the immunotoxicity by ethanol in mice. Kim JH, Mun YJ, Woo WH, Jeon KS, An NH, Park JS. Int Immunopharmacol. 2002 May; 2(6):733-44. https://www.ncbi.nlm.nih.gov/pubmed/12095163/|
|10.||↵||Antioxidative effects of cichorium intybus root extract on LDL (low density lipoprotein) oxidation. Kim TW, Yang KS. Arch Pharm Res. 2001 Oct; 24(5):431-6. https://www.ncbi.nlm.nih.gov/pubmed/11693546/|
|11.||↵||Inhibition of the expression and activity of cyclooxygenase-2 by chicory extract. Cavin C, Delannoy M, Malnoe A, Debefve E, Touché A, Courtois D, Schilter B. Biochem Biophys Res Commun. 2005 Feb 18; 327(3):742-9. https://www.ncbi.nlm.nih.gov/pubmed/15649409/|
|12.||↵||Tumour inhibitory activity of chicory root extract against Ehrlich ascites carcinoma in mice. Hazra B, Sarkar R, Bhattacharyya S, Roy P. Fitoterapia. 2002 Dec; 73(7-8):730-3. https://www.ncbi.nlm.nih.gov/pubmed/12490244/|
|13.||↵||The water-soluble extract of chicory reduces glucose uptake from the perfused jejunum in rats. J Nutr. 1996 Sep;126(9):2236-42. https://www.ncbi.nlm.nih.gov/pubmed/8814212|
|14.||↵||Chicory Root Yield and Carbohydrate Composition is Influenced by Cultivar Selection, Planting, and Harvest Date. https://dl.sciencesocieties.org/publications/cs/abstracts/44/3/748|
|15, 42, 54, 57, 99.||↵||European Medicines Agency. Assessment report on Cichorium intybus L., radix. EMA/HMPC/113041/2010, 2013.|
|16.||↵||Comparative evaluation of traditional prescriptions from Cichorium intybus L. for wound healing: stepwise isolation of an active component by in vivo bioassay and its mode of activity. Süntar I, Küpeli Akkol E, Keles H, Yesilada E, Sarker SD, Baykal T. J Ethnopharmacol. 2012 Aug 30; 143(1):299-309. https://www.ncbi.nlm.nih.gov/pubmed/22750434/|
|18, 23.||↵||Gurib-Fakim A. Medicinal plants: traditions of yesterday and drugs of tomorrow. Molecular Aspects of Medicine. 2006;27(1):1–93.|
|19.||↵||Wang Q, Cui J. Perspectives and utilization technologies of chicory (Cichorium intybus L.): a review. African Journal of Biotechnology. 2011;10(11):1966–1977.|
|21, 46.||↵||van Wyk BE, van Oudtshoorn B, Gericke N. Medicinal Plants of South Africa. Pretoria, South Africa: Briza Publications; 1997.|
|22, 48.||↵||Sezik E, Yeşilada E, Honda G, Takaishi Y, Takeda Y, Tanaka T. Traditional medicine in Turkey X. Folk medicine in Central Anatolia. Journal of Ethnopharmacology. 2001;75(2-3):95–115.|
|24.||↵||European Medicines Agency. Community herbal monograph on Cichorium intybus L., radix. EMA/HMPC/121816/2010, 2012.|
|25.||↵||Bischoff TA, Kelley CJ, Karchesy Y, Laurantos M, Nguyen-Dinh P, Arefi AG. Antimalarial activity of Lactucin and Lactucopicrin: sesquiterpene lactones isolated from Cichorium intybus L. Journal of Ethnopharmacology. 2004;95(2-3):455–457.|
|26.||↵||Šarić-Kundalić B, Dobeš C, Klatte-Asselmeyer V, Saukel J. Ethnobotanical survey of traditionally used plants in human therapy of east, north and north-east Bosnia and Herzegovina. Journal of Ethnopharmacology. 2011;133(3):1051–1076.|
|27.||↵||Hanlidou E, Karousou R, Kleftoyanni V, Kokkini S. The herbal market of Thessaloniki (N Greece) and its relation to the ethnobotanical tradition. Journal of Ethnopharmacology. 2004;91(2-3):281–299.|
|28, 37.||↵||Leporatti ML, Ivancheva S. Preliminary comparative analysis of medicinal plants used in the traditional medicine of Bulgaria and Italy. Journal of Ethnopharmacology. 2003;87(2-3):123–142.|
|29, 38.||↵||Ahmed B, Al-Howiriny TA, Siddiqui AB. Antihepatotoxic activity of seeds of Cichorium intybus . Journal of Ethnopharmacology. 2003;87(2-3):237–240.|
|30, 31, 75.||↵||Pushparaj PN, Low HK, Manikandan J, Tan BKH, Tan CH. Anti-diabetic effects of Cichorium intybus in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology. 2007;111(2):430–434.|
|32.||↵||Miraldi E, Ferri S, Mostaghimi V. Botanical drugs and preparations in the traditional medicine of West Azerbaijan (Iran) Journal of Ethnopharmacology. 2001;75(2-3):77–87.|
|33.||↵||Pieroni A. Medicinal plants and food medicines in the folk traditions of the upper Lucca Province, Italy. Journal of Ethnopharmacology. 2000;70(3):235–273.|
|34.||↵||Guarrera PM, Forti G, Marignoli S. Ethnobotanical and ethnomedicinal uses of plants in the district of Acquapendente (Latium, Central Italy) Journal of Ethnopharmacology. 2005;96(3):429–444.|
|35.||↵||Loi MC, Maxia L, Maxia A. Ethnobotanical comparison between the villages of Escolca and Lotzorai (Sardinia, Italy) Journal of Herbs, Spices & Medicinal Plants. 2005;11(3):67–84.|
|36.||↵||Pieroni A, Quave C, Nebel S, Heinrich M. Ethnopharmacy of the ethnic Albanians (Arbëreshë) of northern Basilicata, Italy. Fitoterapia. 2002;73(3):217–241.|
|39.||↵||Jouad H, Haloui M, Rhiouani H, El Hilaly J, Eddouks M. Ethnobotanical survey of medicinal plants used for the treatment of diabetes, cardiac and renal diseases in the North centre region of Morocco (Fez-Boulemane) Journal of Ethnopharmacology. 2001;77(2-3):175–182.|
|40.||↵||El-Hilaly J, Hmammouchi M, Lyoussi B. Ethnobotanical studies and economic evaluation of medicinal plants in Taounate province (Northern Morocco) Journal of Ethnopharmacology. 2003;86(2-3):149–158.|
|41, 77.||↵||Ahmad M, Qureshi R, Arshad M, Khan MA, Zafar M. Traditional herbal remedies used for the treatment of diabetes from district attock (Pakistan) Pakistan Journal of Botany. 2009;41(6):2777–2782.|
|43.||↵||Šavikin K, Zdunića G, Menković N, et al. Ethnobotanical study on traditional use of medicinal plants in South-Western Serbia, Zlatibor district. Journal of Ethnopharmacology. 2013;146(3):803–810.|
|44.||↵||Jarić S, Popović Z, Mačukanović-Jocić M, et al. An ethnobotanical study on the usage of wild medicinal herbs from Kopaonik Mountain (Central Serbia) Journal of Ethnopharmacology. 2007;111(1):160–175.|
|45.||↵||Kokoska L, Polesny Z, Rada V, Nepovim A, Vanek T. Screening of some Siberian medicinal plants for antimicrobial activity. Journal of Ethnopharmacology. 2002;82(1):51–53.|
|47, 96.||↵||Süntar I, Akkola EK, Kelesb H, Yesiladac E, Sarkerd SD, Baykala T. Comparative evaluation of traditional prescriptions from Cichorium intybus L. for wound healing: stepwise isolation of an active component by in vivo bioassay and its mode of activity. Journal of Ethnopharmacology. 2012;143(1):299–309.|
|49.||↵||Tetik F, Civelek S, Cakilcioglu U. Traditional uses of some medicinal plants in Malatya (Turkey) Journal of Ethnopharmacology. 2013;146(1):331–346.|
|50.||↵||Uptake and degradation of DDT by hairy root cultures of Cichorium intybus and Brassica juncea. Suresh B, Sherkhane PD, Kale S, Eapen S, Ravishankar GA. Chemosphere. 2005 Dec; 61(9):1288-92. https://www.ncbi.nlm.nih.gov/pubmed/15885743/|
|52.||↵||Street RA, Sidana J, Prinsloo G. Cichorium intybus: Traditional Uses, Phytochemistry, Pharmacology, and Toxicology. Evidence-based Complementary and Alternative Medicine : eCAM. 2013;2013:579319. doi:10.1155/2013/579319. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3860133/|
|55.||↵||Olsen NJ, Branch VK, Jonnala G, Seskar M, Cooper M. Phase 1, placebo-controlled, dose escalation trial of chicory root extract in patients with osteoarthritis of the hip or knee. BMC Musculoskeletal Disorders. 2010;11, article 156 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912794/|
|56.||↵||Schumacher E, Vigh É, Molnár V, et al. Thrombosis preventive potential of chicory coffee consumption: a clinical study. Phytotherapy Research. 2011;25(5):744–748.|
|58, 69.||↵||Fallah Huseini H, Alavian SM, Heshmat R, Heydari MR, Abolmaali K. The efficacy of Liv-52 on liver cirrhotic patients: a randomized, double-blind, placebo-controlled first approach. Phytomedicine. 2005;12(9):619–624.|
|59.||↵||Gazzani G, Daglia M, Papetti A, Gregotti C. In vitro and ex vivo anti- and prooxidant components of Cichorium intybus . Journal of Pharmaceutical and Biomedical Analysis. 2000;23(1):127–133.|
|60.||↵||Shaikh T, Rub RA, Sasikumar S. Antimicrobial screening of Cichorium intybus seed extracts. Arabian Journal of Chemistry. 2012|
|61.||↵||Rani P, Khullar N. Antimicrobial evaluation of some medicinal plants for their anti-enteric potential against multi-drug resistant Salmonella typhi . Phytotherapy Research. 2004;18(8):670–673.|
|62.||↵||Mares D, Romagnoli C, Tosi B, Andreotti E, Chillemi G, Poli F. Chicory extracts from Cichorium intybus L. as potential antifungals. Mycopathologia. 2005;160(1):85–91|
|63.||↵||Monde K, Oya T, Shirata A, Takasugi M. A guaianolide phytoalexin, cichoralexin, from Cichorium intybus . Phytochemistry. 1990;29(11):3449–3451.|
|64.||↵||Miller MC, Duckett SK, Andrae JG. The effect of forage species on performance and gastrointestinal nematode infection in lambs. Small Ruminant Research. 2011;95(2-3):188–192.|
|65.||↵||Marley CL, Cook R, Keatinge R, Barrett J, Lampkin NH. The effect of birdsfoot trefoil (Lotus corniculatus) and chicory (Cichorium intybus) on parasite intensities and performance of lambs naturally infected with helminth parasites. Veterinary Parasitology. 2003;112(1-2):147–155.|
|66.||↵||Molan AL, Duncan AJ, Barry TN, McNabb WC. Effects of condensed tannins and crude sesquiterpene lactones extracted from chicory on the motility of larvae of deer lungworm and gastrointestinal nematodes. Parasitology International. 2003;52(3):209–218.|
|67.||↵||Foster JG, Cassida KA, Turner KE. In vitro analysis of the anthelmintic activity of forage chicory (Cichorium intybus L.) sesquiterpene lactones against a predominantly Haemonchus contortus egg population. Veterinary Parasitology. 2011;180(3-4):298–306.|
|68.||↵||Leclercq E. Determination of lactucin in roots of chicory (Cichorium intybus L.) by high-performance liquid chromatography. Journal of Chromatography A. 1984;283:441–444.|
|70.||↵||Najmi AK, Pillai KK, Pal SN, Aqil M. Free radical scavenging and hepatoprotective activity of jigrine against galactosamine induced hepatopathy in rats. Journal of Ethnopharmacology. 2005;97(3):521–525.|
|71.||↵||Zafar R, Mujahid Ali S. Anti-hepatotoxic effects of root and root callus extracts of Cichorium intybus L. Journal of Ethnopharmacology. 1998;63(3):227–231.|
|72.||↵||Gilani AH, Janbaz KH, Shah BH. Esculetin prevents liver damage induced by paracetamol and CCL4 . Pharmacological Research. 1998;37(1):31–35.|
|73.||↵||Ahmed B, Khan S, Masood MH, Siddique AH. Anti-hepatotoxic activity of cichotyboside, a sesquiterpene glycoside from the seeds of Cichorium intybus . Journal of Asian Natural Products Research. 2008;10(3-4):223–231|
|74.||↵||Hardeep FM, Pandey DK. Anti-diabetic activity of methanolic extract of chicory roots in streptozocin induced diabetic rats. International Journal of Pharmacy. 2013;3(1):211–216.|
|76.||↵||Ghamarian A, Abdollahi M, Su X, Amiri A, Ahadi A, Nowrouzi A. Effect of chicory seed extract on glucose tolerance test (GTT) and metabolic profile in early and late stage diabetic rats. DARU Journal of Pharmaceutical Sciences. 2012;20:56–65.|
|78.||↵||Tousch D, Lajoix A-D, Hosy E, et al. Chicoric acid, a new compound able to enhance insulin release and glucose uptake. Biochemical and Biophysical Research Communications. 2008;377(1):131–135.|
|79.||↵||Gürbüz I, Üstün O, Yeşilada E, Sezik E, Akyürek N. In vivo gastroprotective effects of five Turkish folk remedies against ethanol-induced lesions. Journal of Ethnopharmacology. 2002;83(3):241–244.|
|80.||↵||Cavin C, Delannoy M, Malnoe A, et al. Inhibition of the expression and activity of cyclooxygenase-2 by chicory extract. Biochemical and Biophysical Research Communications. 2005;327(3):742–749.|
|81.||↵||Wesołowska A, Nikiforuk A, Michalska K, Kisiel W, Chojnacka-Wójcik E. Analgesic and sedative activities of lactucin and some lactucin-like guaianolides in mice. Journal of Ethnopharmacology. 2006;107(2):254–258.|
|82.||↵||Heimler D, Isolani L, Vignolini P, Romani A. Polyphenol content and antiradical activity of Cichorium intybus L. from biodynamic and conventional farming. Food Chemistry. 2009;114(3):765–770.|
|83, 84.||↵||Papetti A, Daglia M, Grisoli P, Dacarro C, Gregotti C, Gazzani G. Anti- and pro-oxidant activity of Cichorium genus vegetables and effect of thermal treatment in biological systems. Food Chemistry. 2006;97(1):157–165.|
|85.||↵||Lavelli V. Antioxidant activity of minimally processed red chicory (Cichorium intybus L.) evaluated in xanthine oxidase-, myeloperoxidase-, and diaphorase-catalyzed reactions. Journal of Agricultural and Food Chemistry. 2008;56(16):7194–7200.|
|86.||↵||Pieroni A, Janiak V, Dürr CM, Lüdeke S, Trachsel E, Heinrich M. In vitro antioxidant activity of non-cultivated vegetables of ethnic Albanians in southern Italy. Phytotherapy Research. 2002;16(5):467–473.|
|87.||↵||El SN, Karakaya S. Radical scavenging and iron-chelating activities of some greens used as traditional dishes in Mediterranean diet. International Journal of Food Sciences and Nutrition. 2004;55(1):67–74.|
|88.||↵||Hazra B, Sarkar R, Bhattacharyya S, Roy P. Tumour inhibitory activity of chicory root extract against Ehrlich ascites carcinoma in mice. Fitoterapia. 2002;73(7-8):730–733.|
|89, 98.||↵||Conforti F, Ioele G, Statti GA, Marrelli M, Ragno G, Menichini F. Antiproliferative activity against human tumor cell lines and toxicity test on Mediterranean dietary plants. Food and Chemical Toxicology. 2008;46(10):3325–3332.|
|90.||↵||Lee K-T, Kim J-I, Park H-J, Yoo K-O, Han Y-N, Miyamoto K-I. Differentiation-inducing effect of magnolialide, a 1β-hydroxyeudesmanolide isolated from Cichorium intybus, on human leukemia cells. Biological and Pharmaceutical Bulletin. 2000;23(8):1005–1007.|
|91.||↵||Kim HM, Kim HW, Lyu YS, et al. Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus . Pharmacological Research. 1999;40(1):61–65.|
|92.||↵||Kim J-H, Mun Y-J, Woo W-H, Jeon K-S, An N-H, Park J-S. Effects of the ethanol extract of Cichorium intybus on the immunotoxicity by ethanol in mice. International Immunopharmacology. 2002;2(6):733–744.|
|93.||↵||Amirghofran Z, Azadbakht M, Karimi MH. Evaluation of the immunomodulatory effects of five herbal plants. Journal of Ethnopharmacology. 2000;72(1-2):167–172.|
|94.||↵||Sakurai N, Iizuka T, Nakayama S, Funayama H, Noguchi M, Nagai M. Vasorelaxant activity of caffeic acid derivatives from Cichorium intybus and Equisetum arvense . Yakugaku Zasshi. 2003;123(7):593–598.|
|95.||↵||Rollinger JM, Mock P, Zidorn C, Ellmerer EP, Langer T, Stuppner H. Application of the in combo screening approach for the discovery of non-alkaloid acetylcholinesterase inhibitors from Cichorium intybus . Current Drug Discovery Technologies. 2005;2(3):185–193.|
|97.||↵||Schmidt BM, Ilic N, Poulev A, Raskin I. Toxicological evaluation of a chicory root extract. Food and Chemical Toxicology. 2007;45(7):1131–1139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3836359/|
|100.||↵||Yakupoğlu D, Güray T, Yurtsever Sarica D, Kaya Z. Determination of airborne lead contamination in Cichorium intybus L. in an urban environment. Turkish Journal of Botany. 2008;32(4):319–324.|