Products of Taraxacum officinale Reduce Human Health Risk

Taraxacum officinale is predominantly cultivated and produced in Bulgaria, Romania, Hungary, and Poland. Dandelion occurs in the tropics, in cool highlands (1,200-1,500 m of altitude) and in warm sub-temperate and temperate zones around the northern hemisphere. It is able to tolerate drought and frost. Tea prepared from T. officinale has been used against fever, insomnia, jaundice, rheumatism, eczema and other skin diseases, and constipation (Barnes and Anderson, 2003). Extracts of T. officinale has inhibitory effect on tumor necrosis factor-alpha production from rat astrocytes. Sesquiterpene glucosides isolated from fractionation of the extract of T. officinale have anti-leukotriene activity. Luteolin and luteolin-7-O-glucoside from flower of T. officinale has suppressive effect on iNOS and COX-2 in RAW264.7 cells. T. officinale has been reported to have protective effect against cholecystokinin-induced acute pancreatitis in rats.

Dandelion includes potential bioactive components such as sesquiterpene lactones, taraxasterol (TS), taraxerol, chlorogenic acid (CGA), and CRA. These components are non-toxic and can be ex-ploited for their potentially anti-inflammatory, anti-oxidative, anti-rheumatic, and chloretic properties. However, dandelion has been shown to have a high content of these components compared to other plants; it contains a broad range of interest-ing bioactive components relevant to T2D that are likely to exert synergistic actions.The bitterness resulting from sesquiterpene lactones is due to components such as tarax-acolide, dihydro-lactucin, ixerin D, taraxinic acids, phenyl propanoids, and ainslioside, which have anti-inflammatory properties. These compo-nents are often present as glycosides. The bitter taste receptor (TAS2R16) on the cells of the tongue has a protective property to prevent the ingestion of toxic substances, eliciting an aversive sensory response (Bufe et al., 2002). However, there are flaws to this evolutionary system as a large proportion of sub-stances beneficial to health taste bitter. The health-promoting benefits of dandelion can be attributed to the presence of these bitter substances and of phenolic components, which possess anti-oxidative and anti-inflammatory activities. 

Similar to coffee, dandelion roots and flowers contain bioactive anti-oxidant components such as CGA that regulate the function of β-cells.The in cretin hormone glucagon-like peptide-1 (GLP-1) is secreted by intestinal L-cells as a result of the inhibition of glucose absorption by CGA. Dandelion leaf extract has anti-inflammatory properties, which may protect against cholecystokinin-induced acute pancreatitis in rats. TS is a component of TO, and has anti-carcinogenic and anti-tumor properties, as it was shown to cause a dose-dependent reduction in tu-mor cell viability by 26%. TS inhibits nitric oxide (NO), prostaglandin E2, TNF-α, IL-1β, and IL-6 in lipopoly-saccharide-induced macrophages and prevents LPS-induced nuclear factor κB (NF-κB) translocation from the cytoplasm to the nucleus. These results emphasize the anti-inflammatory effect of TS, as it was shown to block the NF-κB pathway that regulates protein-inflammatory gene expres-sion. Similarly, to other medicinal plants (e.g., Bidens pilosa L, Allium sativum, Gymnema syl-vestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia, and Ficus benghalensis), TS may modulate β-cell dysfunction and increase insulin gene expression, which pro-motes insulin secretion from the granules and in-hibits β-cell degradation.

Taraxacum officinale with other herbs treat hepatitis. Tea prepared from T. officinale has been used against fever, insomnia, jaundice, rheumatism, eczema and other skin diseases, and constipation [Barnes and Anderson, 2003]. T. officinale and other Taraxacum species have also been used against warts, cancers, and tumors [Anonyms, 2003]. Taraxacin or taraxinic acid or lactucopicrin [Kristo et al., 2001], lactucin [23] and cichorin [24] are chief bitter principles and belong to the guaianolide class. Taraxacoside, a type of acylated gamma-butyrolactone glycoside has been reported from the plant [Kisiel and Barszcz, 2000]. Eudesmanolides including tetrahydroridentin-B and taraxacolide-O-β-glucopyranoside are reported [Mizushina et al., 2003]. Phenylpropanoid glycosides:  dihydroconiferin, syringin, and dihydrosyringin [Cho et al., 2000] have been reported [Kashiwada et al., 2001]. The extracts of T. officinale have demonstrated antitumor, hypoglycemic, diuretic [Trojanova et al., 2004], antibacterial and nitric oxide regenration activity [Kitts and Hu, 2004 and Weeney and Vora, 2005]. We need to focus on other pharmacological investigations particularly antioxidant activity and anti-inflammatory activities, which might explain use of T. officinale in liver diseases [Kim et al., 2000]. Extracts of T. officinale has inhibitory effect on tumor necrosis factor-alpha production from rat astrocytes [Hu and Kitts, 2005]. Sesquiterpene glucosides isolated from fractionation of the extract of T. officinale have anti-leukotriene activity [Mizushina et al., 2003]. 

Luteolin and luteolin-7-O-glucoside from flower of T. officinale has suppressive effect on iNOS and COX-2 in RAW264.7 cells [Seo et al., 2005]. T. officinale has been reported to have protective effect against cholecystokinin-induced acute pancreatitis in rats [Rana and Sumanth, 2006] Hydro-alcoholic acid of T. officinale roots demonstrated anti-oxidant activity in rats. Extract of T. officinale, in the dose of 100 mg/kg, p.o., improved the superoxide dimutase, catalase, glutathione, and peroxidase levels decreased by CCl4 treatment [Hu and Kitts, 2003].  It is predominantly cultivated and produced in Bulgaria, Romania, Hungary, and Poland [Brock, 2004]. Dandelion occurs in the tropics, in cool highlands [1,200-1,500 m of altitude] and in warm sub-temperate and temperate zones around the northern hemisphere. It is able to tolerate drought and frost [Honek et al., 2009 and Mingarro et al., 2015]. In subarctic and Northern temperate regions, there are around 2800 known species [Kirschner et al., 2014]. The species Taraxacum officinale WEBER WIGG originates from Europe, and is used for medicinal purposes, while Taraxacum platycarpumis used as a Chinese traditional medicine to treat T2D and hepatic diseases [Petlevski et al., 2003]. As a perennial weed, dandelion produces a stout taproot with an average length of 15-30 cm [Beguin et al., 2001]. They are often sown between April and June in northern Europe [Lee, 2011]. It is often consumed as a food [salads] as it is a rich source of micronutrients such as minerals and vitamins [Escudero et al., 2003]. Dandelion is used as a popular traditional medicine in Turkey and Mexico for the control of T2D [Onal et al., 2005]. Tandem liquid chromatography and mass spectrometry analysis of dandelion have revealed rich sources of β-carotene, which protects cells from oxidation and cellular damage [Khoo et al., 2011]. Recently, bio-chemical analysis identified chicoric acid [CRA] as the most abundant component of dandelion; with a polyphenolic amount of 34.08 ± 1.65 g/kg in Taraxacum officinale leaves and stems [Schütz et al., 2005; Kenny et al., 2015 and Fraisse et al., 2011]. Besides its use as a coffee substitute and flavor enhancer in drinks, the leaf extracts are known to be effective against obesity and cardiovascular disease [Choi et al., 2010]. Dandelion includes potential bioactive components such as sesquiterpene lactones, taraxasterol [TS], taraxerol, chlorogenic acid [CGA], and CRA. These components are non-toxic and can be ex-ploited for their potentially anti-inflammatory, anti-oxidative, anti-rheumatic, and chloretic properties [Arpadjan et al., 2008]. However, dandelion has been shown to have a high content of these components compared to other plants; it contains a broad range of interest-ing bioactive components relevant to T2D that are likely to exert synergistic actions [Sharma and Zafar, 2014]. The bitterness resulting from sesquiterpene lactones is due to components such as tarax-acolide, dihydro-lactucin, ixerin D, taraxinic acids, phenyl propanoids, and ainslioside, which have anti-inflammatory properties [Soares et al., 2013]. These compo-nents are often present as glycosides. The bitter taste receptor [TAS2R16] on the cells of the tongue has a protective property to prevent the ingestion of toxic substances, eliciting an aversive sensory response [Bufe et al., 2002]. However, there are flaws to this evolutionary system as a large proportion of sub-stances beneficial to health taste bitter. The health-promoting benefits of dandelion can be attributed to the presence of these bitter substances and of phenolic components, which possess anti-oxidative and anti-inflammatory activities [Schütz et al., 2006]. 

Thiol groups such as cysteine protein residues are known to be the pri-mary target group of sesquiterpene lactones [Schmidt, 2006]. Sesquiterpene lactones do not exert direct anti-oxidant activity, which is attributable to their structure, but could show greater efficacy as a direct anti-oxidant due to the presence of allylic alcohol [Graziani et al., 2015 and Chadwick et al., 2013].

Taraxasterol [TS] is a pentacyclic-triterpene, which is highly present in dandelion roots throughout the year [Koh et al., 2010]. It is common in esculent plants such as legumes, cereals, nuts, and seeds as well as plant oils [Xu et al., 2004]. It is also extracted from the flowers of Carthamus tinctorius, Chry-santhemum morifolium, and Helianthus annuus. According to Zhang et al. [2012], TS has anti-inflammatory properties, and is considered a therapeutic agent for the treatment of inflamma-tory diseases. It is known as a monohydroxy triterpene, which is found in burdock, arnica, and chicory, and which displays several biological activities [Ovesna et al., 2004]. It is a naturally occurring sterol derived from hydroxylated poly-cyclic isopentenoid that has the structure of 1,2-cyclopentanophenanthrene. Apart from their importance in agricultural products for the food industry, sterols have a wide range of diverse bio-logical activities, representing an economic value for the pharmaceutical industry [Abidi, 2001]. Other studies using liquid chromatography with [photo] diode array detection [LC-DAD] indicated that the concentration in leaf extracts amounts to 0.85 mg/g, with 0.22% dry weight [Dw]; HPLC-UV analysis showed concentrations to be 8 mg/g in leaf extracts. LC-DAD analysis indicated CRA at 0.09-0.51% DW in roots and 0.77% DW in the leaves [Kenny et al., 2014; Davaatseren et al., 2013; Colle et al., 2012 and Chkhikvishvili and Kharebava, 2001]. CGA consists of major phenolic components which generate the natural anti-oxidant property, possibly by binding to enzymes or multi-subunits of proteins, thereby altering their biological activities [Kang et al., 2004]. Thus, CGA may be used as an anti-diabetic, anti-oxidant, and anti-carcinogenic agent, which is based on its 5-0-caffeoylquinic acid structure and its scavenger activity for reactive oxygen and nitrogen species [Nakatani et al., 2000]. CRA is the most abundant component found in the roots, leaves, and stems of dandelion. This was revealed by the analysis of thirty phenolic components of dandelion juice, using liquid chromatography, mass spectrometry, and HPLC.2,3-dicaffeoyltartaric acid is a phenolic component from Chichorium intybus, which is known to be a strong anti-diabetic agent [Tousch et al., 2008]. CGA and CRA originate from plants of the same family [Chichorium intybus], and have been used as raw materials for the generation of coffee substitutes [Kim, 2001]. Dandelion is also rich in vitamins [A, C, D, E, and B], inositol, lecithin, and minerals such as iron, magnesium, sodium, calcium, silicon, copper, phosphorus, zinc, and manganese [Ata et al., 2011]. The bioactive components in dandelion have demonstrated a series of anti-diabetic effects, which are due to the pharmacological actions of components such as sesquiterpene lactones, triter-penes/phytosterols [taraxasterol], phenols, flavonoids, and phenolic acids [Gonzalez-Castejon et al., 2012]. Metformin is currently the first choice and most used anti-diabetic drug treatment, and was obtained originally from galegine discovered in Galega officinalis [Bailey and Day, 2004]. Similarly, acarbose, used as an anti-diabetic drug for the inhibition of alpha glucosidase, was discovered from a bacterium [Brunkhorst and Schneider, 2005]. The main factor in T2D is the dysregulation of insulin secretion and insulin sensitivity that leads to increased blood sugar levels [hyperglycemia] and T2D, which can later cause the development of vascular diseases [Xiao et al., 2013]. This complex carbohydrate, can help to normalize blood sugar levels. According to Amin et al. [2015], it reduces hyperglycemia when used in high levels of water extract [Mir et al., 2015]. CGA has been a potential compound for preventing obesity and inflammation. It also impacts on insulin secretion and sensitivity, making it an attractive option for use as future anti-diabetic drugs [Resnick and Howard, 2002]. Insulin resistance, which occurs in several key tissues such as liver, muscles, and adipose tissue, is the primary cause of hyperglycemia and a hall-mark in T2D pathogenesis [Hamden et al., 2008]. This process may cause an increase in the production of lipid peroxide which in turn decreases the anti-oxidative defense [Gonzalez-Castejon et al., 2012], thus supporting the development of β-cell dysfunction. β-cell dysfunction impairs insulin secretion as a result of glucotoxicity and lipotoxicity, which negatively influences the conversion of pro insulin to insulin [Kaneto et al., 2007]. Studies on dandelion extracts revealed that it may stimulate the release of insulin in pancreatic β-cells, which consequently counteracts the effects of hyperglycemia [Hussain et al., 2004]. Seo et al. [2005] showed that dandelion leaf extract has anti-inflammatory properties, which may protect against cholecystokinin-induced acute pancreatitis in rats [Seo et al., 2005]. TS is a component of TO, and has anti-carcinogenic and anti-tumor properties, as it was shown to cause a dose-dependent reduction in tu-mor cell viability by 26% [Koo et al., 2000]. Zhang et al. [2012] showed that TS inhibits nitric oxide [NO], prostaglandin E2, TNF-α, IL-1β, and IL-6 in lipopoly-saccharide-induced macrophages and prevents LPS-induced nuclear factor κB [NF-κB] translocation from the cytoplasm to the nucleus. These results emphasize the anti-inflammatory effect of TS, as it was shown to block the NF-κB pathway that regulates protein-inflammatory gene expres-sion [Zhang et al., 2012]. Similarly, to other medicinal plants [e.g., Bidens pilosa L, Allium sativum, Gymnema syl-vestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia, and Ficus benghalensis], TS may modulate β-cell dysfunction and increase insulin gene expression, which pro-motes insulin secretion from the granules and in-hibits β-cell degradation [Patel et al., 2012]. ROS include hydroxyl radicals, superoxide radicals, singlet oxygen, and peroxyl radicals, which con-tribute to several forms of human cancer and other severe diseases [Hu and Kitts, 2005]. Recently, CGA found in the roots of dandelion has been identified as a potent anti-oxidant, which may suppress oxidative stress markers such as malondialdehyde and glutathione [Del Rio et al., 2005]. It has also been shown that glucose may generate ROS in β-cells, implying that glucose-induced oxidative stress is a mechanism of glucose toxicity [Robertson et al., 2007]. The process of ROS formation involves auto-oxidation, oxidative phosphorylation, glycosylation, and glucosamine pathways [Robertson et al., 2004]. Excess ROS production requires anti-oxidant defense, which is provided by dandelion extract, as is known from several studies conducted both in vitro and invivo [You et al., 2010].  Their leaf extracts are effective hydrogen donors, hydrogen peroxide scavengers, and reducing agents [Czinner et al., 2001]. Several studies have demonstrated the anti-oxidative effect of dandelion. According to Hagymasi et al. [2000], extracts from dandelion leaf and root are hydrogen-donating, ROS formation-inhibiting, and radical-scavenging [Hu and Kitts, 2005]. In an-other recent study of dandelion flower extracts, ethyl acetate fraction scavenged ROS by preventing DNA from ROS-induced damage. The prevention of oxidative stress was due to the presence of bioactive components including luteolin and luteo-lin 7-O-glucoside [Hagymasi et al., 2000]. This results in a decrease of glucose transportation into the muscle cells, thereby in-creasing levels of glucose and fat in the blood plasma, eventually causing hyperglycemia and lipid oxidation, which can be controlled by the anti-oxidative property of dandelion [Tfayli et al., 2009]. In a study evaluating the effects of anti-oxidant on C57BL/6J mice fed a high-fat and -cholesterol diet using leafy mixed vegetable extracts [including dandelion], a significant drop in lipid peroxidation in various organs including the liver was observed [Kim et al., 2009]. This was due to the anti-oxidative activities expressed by enzymes present in the leafy ex-tracts, including glutathione peroxidase, glu-tathione reductase, and superoxide dismutase [Kim et al., 2009]. Therefore, a possible explanation for the effects and mechanisms of dandelion on T2D could be its interaction with factors involved in the metabolic syndrome [lipid metabolism, glucose metabolism, protein metabolism, α- and β-cells dysfunction] [Grundy et al., 2004]. The mechanisms of plant polyphenolic components against T2D involve the stimulation of cAMP that increases exocytosis in β-cells, inhibition of insulin degradative processes, prevention of oxidative stress, regeneration of β-cells, reparation and cellular hypertrophy, and cellular prolifera-tion in the islets of Langerhans [Eddouks et al., 2002; Prabhakar and Doble, 2008; Mukherjee et al., 2006; Bnouham et al., 2006 and Jarald et al., 2006]. During digestion, most enzymes in the mouth and small intestines of humans, including α-amylase and α-glucosidase, facilitate the cleavage of carbohydrates to produce glucose which is absorbed through the walls of the small intestines into the blood stream [Kumar et al., 2011]. Their dysfunction may cause the accumulation of fat in muscle tissue and subsequently the decrease of adenosine triphosphate [ATP] in membrane transport [Perk et al., 2013]. The pathways involved are the glycolytic cycle and Krebs cycle, in addition to other pathways involved in the release of insulin from β-cells. CGA and CRA may activate glu-cokinase in glycolysis, which catalyzes the phosphorylation of glucose to glucose-6-phosphate [G6P] [Coman et al., 2012 and Vessal et al., 2003]. Studies have shown that plants rich in CGA can improve the functional activities of these crucial enzymes [phosphofructokinase, hexokinase, and pyruvate kinase] [Prabhakar and Doble, 2008]. Before insulin is released from the granules that are assembled within the trans-Golgi network in the cytoplasm of β-cells, two processes take place:1] closure of the ATP-gated potassium channel and 2] activation of the voltage-gated calcium channel take place [Bratanova-Tochkova et al., 2002]. Jensen et al. [2008] proposed that insulin exocytosis is controlled by the intracellular ATP/ADP ratio of β-cells, followed by an elevation in glucose metabolism [Jensen et al., 2008]. The enhanced ATP/ADP ratio induces plasma membrane depolarization by the closure of β-cells KATP-sensitive channels. The resultant influx of Ca2+ causes insulin export through fusion of a readily releasable pool containing vesicles within the plasma membrane [Jensen et al., 2011]. The effect of dandelion-derived compounds on PKA and PKC also helps to provide elevated Ca2+levels. Similar to coffee, dandelion roots and flowers contain bioactive anti-oxidant components such as CGA that regulate the function of β-cells [McCarty, 2005]. The in-cretin hormone glucagon-like peptide-1 [GLP-1] is secreted by intestinal L-cells as a result of the inhibition of glucose absorption by CGA [McCarty, 2005]. 

Pancreatic islets consist of four cells: insulin-secreting β-cell, glucagon-secreting α-cell, somatostatin secreting δ-cell, and polypeptide-secreting F-cell [Brissova et al., 2005]. GLP-1 production, resulting from the action of CGA, helps to modulate glucose-dependent insulin secretion from the β-cell. Eventually, there is a stimulation of membrane receptors which activates cAMP [Macdonald et al., 2002]. Other β-cell transcription factors that regulate insulin gene expression and β-cell function include PPAR, Nkx2-2, Nkx6.1, pdx1, Beta2, Pax6, and Foxa2 [Abudula and Hermansen, 2008]. 

Some plant forms of the genus Taraxacum, known as dandelion, have long been applied in folk medicine to treat liver disorders and some diseases of women, such as breast and uterine cancer, and as infants, choleretics, diuretics and anti-inflammatory drugs [Ahmad et al., 2000].This species is listed in the National List of Medicinal Plants of Interest to SUS [RENISUS]; a list with a list of phytotherapeutic plant forms that present potential to generate products of interest within the Unified Health System [SUS] and whose purpose is to conduct studies and research that will subsidize the design of a list of herbal and phytotherapeutic plants to be provided for use of the population, safely and effectively for the treatment of a particular disease [Brasil and Portal, 2014].

T. officinale is rich in minerals such as iron, copper and potassium, has the vitamins B1, PP and D12-14and contains many more vitamins A [14,000 IU / 100g] and C large majority of vegetables [Alonso and Tratado, 2000].