Review Fagopyrum Tataricum

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Review

Fagopyrum tataricum (L.) Gaertn.: A Review on its Traditional Uses, Phytochemical and Pharmacology

2 3 1 1 1 4* 1,5* Lijuan Lv , Yuan Xia , Dezhi Zou , Huarui Han , Yingli Wang , Huiyong Fang and Minhui Li

1Baotou Medical College, Baotou, Inner Mongolia 014060, China 2Department of Basic Science, Tianjin Agricultural University, Tianjin 300384, China 3Inner Mongolia Medical University, Hohhot, Inner Mongolia 010110, China 4Traditional Chinese Medicine College, Hebei University, Hebei, 071002, China 5Inner Mongolia Institute of Traditional Chinese Medicine, Hohhot, Inner Mongolia 010000, China

Received March 4, 2016 ; Accepted March 25, 2016

Fagopyrum tataricum (L.) Gaertn. is an effective medical plant, and is also used as a healthy and adjuvant therapy functional food. Although a considerable amount of scientific research was reported on F. tataricum in the last decades, it is currently scattered across various publications. The present review comprises the traditional uses and ethnobotanical, phytochemical and pharmacological research on F. tataricum in the last decades. A large number of chemical studies and pharmacological during the last decades have demonstrated the vast medicinal potential of F. tataricum. The objective of this review is to bring together most of the scientific research available on F. tataricum and evaluate its effects and mechanisms.

Keywords: Fagopyrum tataricum (L.) Gaertn., medical plant, functional food

Introduction and can be used for combating symptoms such as fatigue (Zhang et Fagopyrum tataricum (L.) Gaertn., also known as tartary al. 2008; Guo et al. 2010; Lee et al. 2013). For these reasons, F. buckwheat, is a member of the Polygonaceae family. The annual tataricum plays an important role in healthcare as an adjuvant herbaceous plant is ecologically adaptable and grows in diverse therapy and as a healthy functional food for the prevention of environments, spanning the mountainous regions of Inner disease (Zhang et al. 2008). Mongolia (altitude of 500 _ 3900 m), Sichuan, Hebei, Shanxi, The aim of this article is to review the traditional uses of the F. Gansu, and other provinces in China. It is widely cultivated in tataricum, and summarize its ethnobotanical, phytochemical, and Europe and North America, and has been introduced in pharmacological characteristics. Through this review, the authors Kazakhstan, Russia, and other countries because of increasing hope to attract the attention of natural product researchers demand (Li & Zhang 2001; Wu et al. 2003; Xuan & Tsuzuki throughout the world to focus on the unexplored potential of 2004). Fagopyrum tataricum possesses an abundance of medicinal plants, investigating them systematically so they can be compounds with medicinal properties, such as flavonoids and further developed. phenylpropanoids, and a number of essential amino acids and minerals. It has beneficial effects such as antioxidant, anti-aging, History of ethnomedicinal uses anti-tumour, antibacterial, hypoglycaemic, and hypotensive effects, Plants have been used as a source of medicine by humankind

*To whom correspondence should be addressed. E-mail: Minhui Li; [email protected] Huiyong Fang; [email protected] 2 L. Lv et al. since ancient times. Fagopyrum tataricum, called ‘Ku Qiao Mai’ in 5,7,3’,4’-tetramethylquercetin-3-O-rutinoside (8), kaempferol-3-O- Chinese folklore, is a medicinal plant with a history spanning more rutinoside (9), and quercetin-3-O-rutinoside (10) (Saxena & than 2000 years. The roots and rhizomes are widely used in Samaiya 1987; Bao et al. 2003a),and quercetin-3-O-rutinoside is traditional Chinese medicine for alleviating pain (including concentrated in the leaves (>33.41 mg/g) (Xu et al., 2002; Ren et stomach pain and lumbocrural pain), invigorating the spleen, and al., 2013). Quercetin-3-rhamnoside (11) and 3’,4’,5,7-4-O-methyl treating indigestion and traumatic injury. It has been documented quercetin-3-O-α-L-pyran rhamnose-(1-6)-O-β-D-pyranglucoside in many well-known works, such as Shennong Bencao Jing (Pre- (12) has been isolated from whole plants and leaves of F. tataricum Qin, Eastern Han Dynasty), Qimin Yaoshu (the last year of the (Saxena & Samaiya 1987; Ren et al. 2013). Quercetin-3-O-β-D- Northern Wei Dynasty, A.D. 533-544), Beiji Qianjin Yaofang glucoside (13), quercetin-3-O-β-D-galactoside (14) and quercetin- (Tang Dynasty, A.D. 652), Yinshan Zhengyao (Song Dynasty), 3-O-α-L-rhamnoside (15) are found in whole plants (Ren et al., Compendium of Materia Medica (Ming Dynasty, A.D. 1590) and 2013). Quercetin-3-O-β-D-xylosyl-(1→2)-α-L-rhamnoside (16) is Qun Fang Pu·Gupu (Ming Dynasty). Fagopyrum tataricum ‘is also found in F. tataricum at high levels (0.44 _ 0.85 mg/g) relative bitter in taste,’ according to Shennong Bencao Jing. It improves to other flavonoids in various parts of the plant (Ren et al., 2013). listening and speaking abilities, as well as promoting immunity and Kaempferol-3-O-β-D-galactoside (17) and kaempferol-3-O-β-D- digestive function, per the Compendium of Materia Medica (Tian glucoside (18) are present in whole plants (Ren et al. 2013). & Ren 2007). In Korea, F. tataricum is known as the ‘food of the Quercetin-3-dirhamnoside (19), quercetin-3-rhamnodiglucoside gods.’ In Japan, it is ‘panacea.’ (20), quercitin-3-rutinoglucoside (21), and quercetin-3- Fagopyrum tataricum not only has medicinal effects, it also rutinodiglucoside (22) have been detected by high performance possesses rich nutritional value. The plant can be eaten on a long- liquid chromatography-mass spectrometry (HPLC-MS) (Sato et al., term basis: its leaves and seeds used as a key ingredient in wine, 1980). Only four flavone C-glycosides-vitexin (23), orientin (24), soy sauce, buckwheat vinegar, bitter-buckwheat tea, and buckwheat isoorientin (25), and isovitexin (26) have been isolated from the ice cream, etc. (Zhao et al. 2002); its seeds processed into sprouts of F. tataricum (Kim et al., 2007). nutritional powder and made into biscuits, packaged noodles, Phenylpropanoids Sixteen phenylpropanoids have been found macaroni and tofu (Wang et al., 2011). In essence, F. tataricum is in F. tataricum (Fig. 2). 3’,5’-Dimethoxy-4’-O-β-D-glucopyranosyl- an excellent plant resource that concomitantly functions as both cinnamic acid (27) has been isolated from the seeds of F. tataricum medicine and foodstuff. (Wang et al., 2009). cis-2,4-Dihydroxycinnamic acid (28), 3-(3,4-dihydroxycinnamoyl) quinic acid (29), and Phytochemical compounds 7-hydroxycoumarin (30) have been obtained from the seeds of F. Many compounds have been isolated from Fagopyrum tataricum (Xu et al. 2002; Sun et al. 2008; Zheng et al. 2012). tataricum, primarily from its seeds and roots. They include Coumarin (31) has been obtained from the roots of F. tataricum flavonoids, phenylpropanoids, phenolic acids and their derivatives, (Hu et al. 2012). Four phenlypropanoid glycosides, 1,3,6-tri-p- sterols, terpenoids, and quinonoids, etc. The structures of primarily coumaroyl-6’-feruloyl sucrose (32), 3,6-di-p-coumaroyl-1,6’-di- active substance are illustrated in the figures (Fig. 1-4). feruloyl sucrose (33), 1,6,6’-tri-feruloyl-3-p-coumaroyl sucrose Flavonoids Flavonoids are the main chemical constituents of (34), and 1,3,6,6’-tetra-feruloyl sucrose (35) have been isolated F. tataricum in previous phytochemical investigations in which the from whole plants of F. tataricum (Ren et al. 2013). Seven content of flavonoids is greater than 4% as determined by phenylpropanoid glycosides, (3,6-O-di-p-coumaroyl-1-O-acetyl)- ultraviolet-visible spectroscopy (Shi et al., 2012). To date, twenty- β-D-fructofuranosyl-(2→1)-(2’,6’-O-diacetyl)-α-D- six flavonoids have been isolated and categorized from F. glucopyranoside (36), (3,6-O-di-p-coumaroyl-1-O-acetyl)-β-D- tataricum (Fig. 1), including flavonols, flavanones, flavone fructofuranosyl-(2→1)-(2’-O-acetyl-6’-O-feruloyl)-α-D- C-glycosides, and O-glycosides. Three flavonols, kaempferol 1( ), glucopyranosi-de (37), (3,6-O-di-p-coumaroyl-1-O-acetyl)-β-D- isokaempferol (2), and quercetin (3), have been isolated from an fructofuranosyl-(2→1)-(2’,4’-O-diacetyl-6’-O-feruloyl)-α-D- alcohol extraction of F. tataricum (Bao et al. 2003a; Bao et al. glucopyranoside (38), (3-O-p-coumaroyl -6-O-feruloyl)-β-D- 2003b). One flavanone, (-)-liquiritigenin (4), has been isolated from fructofuranosyl-(2→1)-(2’-O-acetyl-6’-O-p-coumaroyl)-α-D- the roots of F. tataricum (Hu et al., 2012). One flavanol, glucopyranoside (39), (3,6-O-di-p-coumaroyl-1-O-acetyl)-β-D- (-)-epicatechin (5), has been found in F. tataricum seeds (Zhang et fructofuranosyl-(2→1)-(2’-O-acetyl)-α-D-glucopyranoside (40), al., 2011). Twenty-one types of flavone glycosides from F. (1-O-p-coumaroyl-3,6-O-diferuloyl)-β-D-fructofuranosyl-(2→1)- tataricum have been isolated or identified, including flavone (6’-O-p-coumaroyl)-α-D-glucopyranoside (41), and (1,6-O-di-p- O-glycosides and flavone C-glycosides. Most of them are flavone coumaroyl-3-O-feruloyl)-β-D-fructofuranosyl-(2→1)-α-D- O-glycosides isolated from seeds, including quercetin-3-O- glucopyranoside (42) have been isolated from the roots of F. rutinoside-7-O-galactoside (6) and quercetin-3-O-rutinoside-3’-O- tataricum (Zheng et al. 2012). The phenylpropanoid glycoside glucoside (7) (Saxena & Samaiya 1987; Li & Ding 2001), content varies among different parts of the same plant (roots > The Traditional Uses, Phytochemical and Pharmacology of Fagopyrum tataricum (L.) Gaertn 3 stems > leaves) (Zheng et al. 2012). and 5-hydroxymethyl-2-furfuraldehyde (95) are found in the roots Phenolic acids and their derivatives Thirteen phenolic acids (Samiya & Saxena 1986; Ren et al. 2013). and their derivatives have been obtained from F. tataricum (Fig. 3). In addition, minerals such as magnesium, potassium, copper, p-Hydroxybenzoic acid (43), vanillic acid (44), gallic acid (45), selenium, and zinc, are also present in F. tataricum (Zhang et al. syringic acid (46), ferulic acid (47), caffeic acid (48), 2,4-dihyroxy- 2008). cinnamic acid (49), p-coumaric acid (50), O-coumaric acid (51), and protocatechuic acid (52) have been identified from the seeds of F. Pharmacological effects tataricum (Xu et al., 2002; Sun et al., 2008). p-Hydroxybenzaldehyde An increasing number of researchers are focusing on the (53) and vanillin (54) have been obtained from the roots (Hu et al., pharmacological activity of F. tataricum. This section describes the 2012), and chlorogenic acid (55) has been isolated from the sprouts primary pharmacological effects studied in recent decades. of F. tataricum (Kim et al., 2007). In addition, p-hydroxybenzoic Anti-tumour effects Flavonoids from F. tataricum can acid, vanillic acid, gallic acid, syringic acid, ferulic acid, caffeic acid, decrease the production of intracellular peroxide, remove the p-coumaric acid, O-coumaric acid, and protocatechuic acid have intracellular superoxide anions, and significantly inhibit cancer cell been detected in F. tataricum using reverse-phase high-performance growth (Liu et al., 2007). The primary biological flavonoid in liquid chromatography (RP-HPLC), with ferulic acid present at the tartary buckwheat is quercetin, present at a concentration of about highest concentration (1014.36 mg/kg). 66.3 ± 1.14 mg/g (Wang et al. 2013). Augmenting quercetin and Sterols and Terpenoids Currently, six sterols have been extending treated time inhibits C6 cell growth and increases the isolated from F. tataricum (Fig. 4). β-Sitosterol (56) and ergosterol number of cells in G0/Gl phase. It also reduces the number of cells peroxide (57) have been obtained from the seeds and hulls. in S and G2/M phases, reduces the expression of Bcl-2 protein (an β-Sitosterol has been detected in the different parts of 34 tartary anti-apoptotic protein), and increases the expression of P53 protein buckwheat varieties using high-performance liquid (a tumour suppressor). Up-regulating P53 and down-regulating chromatography (HPLC). It is present in the range of Bcl-2 induces C6 cell apoptosis (Zhou et al. 2006). In addition, 4.1 mg/100 g _ 65.3 mg/100 g (Peng et al., 2012). Daucosterol (58), rutin inhibits the proliferation of the human hepatocellular liver β-sitosterol palmitate (59) stigmast-4-ene-3, 6-dione (60), and carcinoma HepG2 cells in a dose-dependent manner (Ma et al., 6-hydroxy stigmasta-4,22-dien-3-one (61) have been isolated from 2011). the seeds and roots of F. tataricum (Bao et al. 2003a; Bao et al. Studies of the mechanism by which flavonoids inhibit 2003b; Hu et al. 2012). Three terpenoids have been reported in F. proliferation and their potential application against tumours have tataricum (Fig. 4). Ursolic acid (62) has been detected in the seeds focused on microtubule stability (Takagi et al. 1998; Gupta & (Sun et al. 2008). α-Thujene (63) and α-terpineol (64) have been Panda 2002; Jackson & Venema 2006; Touil et al. 2009; Marone detected from the leaves of F. tataricum (Samiya & Saxena 1986). et al. 2011). These data demonstrate that some flavonoids, such as Two quinines were isolated from F. tataricum (Fig. 4). Emodin (65) quercetin from tartary buckwheat, influence tubulin polymerization has been obtained from the seeds of F. tataricum (Bao et al., and microtubule depolymerization in a manner similar to paclitaxel 2003a). 2,5-Dimethoxy benzoquinone (66) has been obtained from and colchicine (Gupta & Panda 2002; Xiao et al. 2006). Paclitaxel the roots of F. tataricum (Hu et al. 2012). is a well-established drug for the treatment of different types of Amino acids and proteins Sixteen amino acids have been cancers, while colchicine binds to soluble tubulin dimers to prevent identified from the seeds: glutamic acid (67), arginine (68), lysine dimer polymerization into microtubules (Gupta & Panda 2002; (69), threonine (70), valine (71), methionine (72), phenylalanine Xiao et al. 2006). Quercetin depolymerizes microtubules (Takagi (73), leucine (74), isoleucine (75), aspartic acid (76), serine (77), et al. 1998; Gupta & Panda 2002; Jackson & Venema 2006). proline (78), glycine (79), cystine (80), histidine (81), and tyrosine By using hormone refractory human prostate cancer cells in (82) (Zhang et al., 1998). Moreover, three proteins have also been culture, Takagi et al. (1998) determined that quercetin causes identified from the seeds: albumin 83( ), prolamin (84), and glutelin morphological changes, inhibits cell proliferation, and promotes (85) (Guo & Yao 2006). The protein content of tartary buckwheat disassembly of cellular α-microtubules. Immunofluorescence seed is 14.3%, which is higher than that in rice corn, wheat flour tubulin staining of bovine aortic endothelial cells clearly shows that and corn (Liu et al. 2007). The protein content of tartary buckwheat quercetin upsets normal mitotic and cytoplasmic microtubule leaves is 18.94% (Wang et al. 2003). polymerization and induces early M-phase cell cycle arrest Other compounds One aromatic ester, bis (2-ethylhexyl) (Jackson & Venema 2006). Quercetin binds to tubulin at the benzene-1,2-dicarboxylate (86), is found in the roots (Hu et al. colchicine site, stimulates the GTPase activity of soluble tubulin, 2012). One miazine, uracil (87), is found in the seeds (Bao et al., and inhibits microtubule polymerization by inducing 2003a). Nine aldehyde compounds N-trans-feruloyltyramine (88), conformational changes in tubulin. These findings suggested a (E,E)-2,4-decadienal (89), (E)-2-nonenal, 2-phenylethanol (90), novel mechanism of action for natural quercetin: It prevents (E,E)-2,4-nonadienal (91), hexanal (92), decanal (93), nonanal (94) proliferation by binding tubulin, which disrupts microtubule 4 L. Lv et al. polymerization (Gupta & Panda 2002). Researchers believe that 2006; Lee et al. 2013). Wistar rats fed high-fat diets and gavaged quercetin has potential clinical use in the treatment of various with total flavonoids in F. tataricum bran extracts in three dose forms of cancers in combination with known anticancer drugs groups _1.0 g/kg, (high dose), 0.5 g/kg (medium dose), and 0.2 g/ (Takagi et al. 1998; Gupta & Panda 2002; Jackson & Venema kg (low dose) – have significantly lower serum triglycerides total 2006; Xiao et al. 2006; Marone et al. 2011). cholesterol compared to the high-fat control group, (P < 0.01). A Anti-oxidation effects Fagopyrum tataricum has strong anti- low dose is associated with elevated serum glutathione peroxidase oxidant activity because it is rich in rutin, quercetin, polyphenols, and higher anti-atherogenic index, as well as lower serum and many other substances. The shell extract of F. tataricum malondialdehyde levels and atherogenic index (Wang et al., 2006). 2+ significantly inhibits spontaneous lipid peroxidation and Fe /H2O2 Anti-atherosclerosis effects Flavonoids from tartary induced hepatic lipid peroxidation in mice livers, with inhibition buckwheat inhibit the oxidation of low-density lipoprotein (LDL), rates of 38.1% and 24%, respectively (Zhang, 2004). An preventing atherosclerosis by scavenging free radicals, inhibiting experiment on the anti-oxidative activities of total flavonoids of endogenous vitamin E, chelating metal ions, and affecting the tartary buckwheat flour (TFTBF), quercetin, and rutin on rat liver activity of related enzymes (Wang et al. 2006). They may also and red blood cell models revealed that quercetin is one of the most prevent atherosclerosis by inhibiting the secretion of various pro- important anti-oxidant components in TFTBF, and the inhibition of inflammatory cytokines or by suppressing gene expression 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical of quercetin (Préstamo et al. 2003). Other possible mechanisms include the was 72% higher than TFTBF and rutin (53%, 66%, 69%, 63%) inhibition of lipoxygenase, generation of oxidized LDL, regulation (Wang et al. 2006). The DPPH elimination rate is as high as 70% of macrophages, and the protective effects of paraoxonase when the concentration of flavonoid extracted from tartary (Préstamo et al. 2003; Li & Guo 2003). buckwheat seedlings is 47 µg/mL, significantly higher than seen Regulation role of capillary permeability and fragility The with vitamin C and vitamin E. These results indicate that the flour and leaves of tartary buckwheat are rich in flavonoids and flavonoids of F. tataricum strongly inhibit oxidation and can be vitamins, especially rutin (0.8% _ 1.5%). Rutin and bioflavonoids used as natural antioxidants (Zhou et al. 2006). have synergistic effects on vitamin C, reducing capillary fragility The flavonoids from F. tataricum also have strong superoxide and permeability. Thus, it can be used as adjuvant therapy agent dismutase (SOD) activity. This promotes antagonistic effects for the prevention and treatment of hypertension and against nonylphenol (which damages cells through lipid atherosclerosis (Lan et al. 2005). peroxidation) and eliminates oxide free radicals from the body Lowing blood pressure effects Because it is rich in bioflazzvonoids, (Quan et al., 2005) in a manner similar to SOD activity against Fagopyrum tataricum can be used to lower blood pressure. Nitric oxide active oxygen, except flavonoids from F. tataricum are chemically generation and the abnormal apoptosis of vascular smooth muscle cells more stable than SOD (Zhang et al. 2001). At pH 6.0 _ 10.6, have bidirectional regulation effects (Li & Guo 2003). Antihypertensive especially in alkaline condition, the SOD activity in flavonoids is peptides can be created through enzymatic hydrolysis of proteins in F. more stable than SOD activity in human blood erythrocytes. tataricum bran (Wang & Li 2004). Flavonoid SOD activity is optimally stable at 40℃ and pH 8.0. Anti-thrombotic effects Flavonoids from F. tataricum have an Hypoglycaemic effects Fagopyrum tataricum is commonly inhibitory effect on platelet aggregation and thrombosis induced by used in traditional medicine as a treatment for diabetes. Its adenosine diphosphate, collagen, and thrombin. Hydroxyethyl rutin compounds affect blood glucose in experimental diabetic rats and could prevent thrombosis. However, the antithrombotic mechanism may prevent insulin resistance. At high concentrations (250 mg/L), of flavonoids is not clear. Previous studies report that buckwheat flavonoids and acarbose have glucosidase inhibition rates of 85% flour inhibits angiotensin-I converting enzyme (ACE) activity (Lin and 62.6%, respectively, with flavonoids stimulating peroxisome et al. 2004). Common hulls extracted using 50% (v/v) ethanol proliferator-activated receptor α and γ in a dose-dependent manner solvent have remarkable inhibitory activity against ACE, with a

(Xue et al. 2005; Berger et al. 2005). Moreover, rutin and its half maximal inhibitory concentration (IC50) of 30 μg/mL. Based metabolite inhibit advanced glycation end-products (AGEs) on the ferric reducing antioxidant power assay, the antioxidant (Campbell 2005). In fact, both ethanol extract of buckwheat (EEB) activity of common hulls extracted with 50% (v/v) ethanol solvent and rutin markedly attenuate the generation of AGEs in vitro. is superior to the extracts using deionized water solvent or 20% (v/ Treatment with EEB and rutin suppresses α-glucosidase and v) ethanol solvent (Tsai et al. 2012). α-amylase activity in a dose-dependent manner, suggesting that F. Protective effects on cerebral ischemia Canine renal artery tataricum can be used as glucosidase and amylase inhibitors occlusion experiments show that tartary buckwheat flavonoids have (Pashikanti et al. 2010). anti-ischemic effects and can significantly increase serum Lipid-lowering and cholesterol-lowering effects Fagopyrum creatinine in dogs (Lin et al., 2011). In mice with cerebral tataricum significantly lowers blood lipids and cholesterol, ischemia, tartary buckwheat flavonoids play a protective role preventing hyperlipidaemia induced by high-fat diets (Zhang et al. significantly reducing malondialdehyde levels in brain tissue, The Traditional Uses, Phytochemical and Pharmacology of Fagopyrum tataricum (L.) Gaertn 5 thereby reducing brain damage (Yan & Xu 2005). should be further investigated. Antibacterial activity Total flavonoids identified from F. tataricum generally have significant antibacterial effects. A 0.08% Acknowledgements This work was financially supported by the flavone solution from F. tataricum can eliminate 83%~85% of “Twelfth Five-year Plan” Program supported by the Ministry of Escherichia coli, Bacillus subtilis, and Staphylococcus aureus at Science and Technology (2012BAI28B02), Specific funds of 8 h, and 92% _ 93% at 48 h. Researchers believe even stronger Traditional Chinese Medicine industry (201407003) and “Supported antimicrobial activity may be achieved by adding phenolic groups By Program for Young Talents of Science and Technology in to naturally occurring flavonoids (Wanget al. 2003). Universities of Inner Mongolia Autonomous Region” (NJYT- Other activities An increasing number of pharmacology 13-B18). studies of F. tataricum are being conducted. The hot-plate test was used to observe analgesic effects of tartary buckwheat sprout References extracts on mice with dimethybenzene-induced ear edema. Results Bao TN, Peng SL, Zhou ZZ, et al. (2003a). Chemical Constituents of showed that tartary buckwheat sprout extract has analgesic effects Buckwheat. Nat. Prod. Res. Dev, 15, 24-26. (Hu et al. 2009; Lin et al. 2011). Quercetin has antitussive and Bao TN, Zhou ZZ, Zhang F, et al. (2003b). Chemical Constituents of anti-asthmatic effects. A study conducted to compare the Buckwheat Hulls. Nat. Prod. Res. Dev, 15, 116-117. oestrogen-like activity of flavonoid and daidzin and linseed lignans Berger JP, Akiyama TE, and Meinke PT. (2005). PPARs: therapeutic in tartary buckwheat bran found that these three ingredients, targets for metabolic disease. Trends Pharmacol. Sci, 26, 244-251. including flavonoid of tartary buckwheat bran, have oestrogen-like Campbell IW. (2005). The clinical significance of PPAR gamma agonism. effects (Cao et al., 2006; Lin et al., 2011). Lastly, tartary Curr. Mol. Med, 5, 349-363. buckwheat is rich in vitamins, especially vitamin B1, which Cao HP, Fang ZQ, Wang XB, et al. (2006). Estrogen-like action of improves digestive function and prevents dermatophytosis (Wang flavonoid in tartary buckwheat bran on ovariectomized rats. Shanghai J. et al. 2011; Zhao et al. 2012). Tradit. Chin. Med, 3, 59-61. Toxicity/side-effects Tartary buckwheat capsule is not Guo XN, Zhu KX, Zhang H, et al. (2010). Anti-Tumor Activity of a Novel mutagenic in rats and mice fed tartary buckwheat extracts Protein Obtained from Tartary Buckwheat. Int. J. Mol. Sci, 11, 5201- continuously. It does not have a negative effect on their growth, 5211. development, hamatology, or biochemical and pathological indexes Guo XN and Yao HY. (2006). Fractionation and characterization of tartary (Wang et al. 2011). However, over-eating the seeds of F. tataricum buckwheat flour proteins.Food Chem, 98, 90-94. can affect digestive function (Tian et al. 2008). Gupta K and Panda D. (2002). Perturbation of microtubule polymerization Conclusion With dietary habits gradually focusing more on by quercetin through tubulin binding: a novel mechanism of its nutrition, health, and pure and natural products, functional foods antiproliferative activity. Biochemistry, 41, 13029-13038. are drawing increasingly more attention. Food processed from the Hu YB, Zhao G, Peng LX, et al. (2009). Tartary buckwheat spouts extract. seeds, roots, and rhizomes of Fagopyrum tataricum is being used J. Chengdu Univ. (Nat. Sci. Edn.), 28, 101-103. to treat chronic diseases (hypoglycaemia, cardiovascular diseases, Hu CL, Zheng CJ, Cheng RB, et al. (2012). Chemical constituents from and cancer) and to prevent illness through its anti-tumour and roots of Fagopyrum tataricum. Chin. Tradit. Herb. Drugs, 5, 866-868. antioxidant. Fagopyrum tataricum seeds and roots are added to Jackson SJ and Venema RC. (2006). Quercetin inhibits Enos, microtubule many health-related products including nutritional powder, health polymerization, and mitotic progression in bovine aortic endothelial protection tea, and others. In fact, the whole plant of F. tataricum cells. J. Nutr, 136, 1178-1184. has highly bioactive compounds could be considered appropriate as Kim SJ, Zaidul ISM, Maeda T, et al. (2007). A time-course study of a functional food. However, it is noteworthy that current studies on flavonoids in the sprouts of tartary (Fagopyrum tataricum Gaertn.) the chemical constituents of F. tataricum lack depth. buckwheats. Sci. Hortic, 115, 13-18. More studies on the phytochemistry and the mechanism of Lan Z, Zeng FJ, Zeng L, et al. 2005. Adjustive Effects and mechanism of action of the primary active components should be encouraged for bioflavonoids on heart and blood vessel system. Modern Prevent. Med, a fuller understanding. Studies on the constituents responsible for 32, 613-615. its pharmacological activities and the effects of therapy and are Lee CC, Lee BH, and Lai YJ. (2013). Antioxidation and antiglycation of needed. An investigation into its potential utilization in the Fagopyrum tataricum ethanol extract. J. Food Sci. Technol (2015) 52, prevention and treatment of chronic diseases (such as type II 1110-1116, 44-45. diabetes) may yield great advances. Li D and Ding XL. (2001). Study on Antioxidant Effect of Tartary In addition, the safety and toxicity of the roots, leaves, and Buckwheat Flavonoid. CNKI Journal Food Sci, 22-23. shells of F. tataricum have not been fully explored. Limited data Li SQ and Zhang QH. (2001). Advances in the Development of Functional show overeating the seeds can affect digestive function. It follows Foods from Buckwheat. Crit. Rev. Food Sci. Nutr, 41, 451-464. that the toxicity and adverse effects of the leaves, roots, and shells Li YF and Guo CJ. (2003). Progress in the study of anti-atherogenic effect 6 L. Lv et al.

of flavonoids.Chin. J. Dis. Control Prev, 7, 239-242. Tian XH and Ren T. (2007). Nutritive healthy Functions and the Lin RF, Shan F, Song JC, et al. (2004). Study on antihypertensive peptides exploitation and utilization of Fagopyrum tataricum. Food Nutr. in from tartary buckwheat bran protein by enzymatic hydrolysis. Food Sci, China, 169-170. 25, 207-209. Tian XH, Liu XF, Yan F, et al. (2008). The Medical Value of the Bitter Lin B, Hu CL, Huang F, et al. (2011). Research progress on chemical Buckwheat and Dietotherapy Recipes. Acad. Period. Farm Prod. Proc, constituents and pharmacological effect of Fagopyrum tataricum. Drugs 31-33. Clin, 26, 29-32. Touil YS, Fellous A, Scherman D, et al. (2009). Flavonoid-induced Liu CL, Chen YS, Yang JH, et al. (2007). Antioxidant activity of tartary morphological modifications of endothelial cells through microtubule (Fagopyrum tataricum (L.) Gaertn.) and common (Fagopyrum stabilization. Nutr. Cancer, 61, 310-321. esculentum moench) buckwheat sprouts. J. Agric. Food Chem, 56, 173- Tsai H, Deng H, Tsai S, et al. (2012). Bioactivity comparison of extracts 178. from various parts of common and tartary buckwheats: evaluation of the Liu SC, Li WX, Liu F, et al. (2007). Identificaiton and evaluation of total antioxidant-and angiotensin-converting enzyme inhibitory activities. flavones and protein content in tartary buckwheat germplasm. J. Plant Chem. Cent. J, 6, 78 Genet. Resour, 8, 317-320. Wang JQ, Wang ZX, Huang J, et al. (2009). Chemical constituents from the Ma Y, Liu B, Yang L, et al. (2011). Characterization and Anti-proliferative seeds of Fagopyrum tataricum (L.) Gaertn. J. Shenyang Pharm. Univ, Activity of Ethanol Extract of Tartary Buckwheat. Int. J. Eng. 26, 270-273. Manufacturing, 1, 7-12. Wang AH, Xiong M, Geng XZ, et al. (2003). The study on nutritional Marone M, D’andrilli G, Das N, et al. (2011). Quercetin abrogates taxol- content analysis and curative effect of Tartary Buckwheat. Food Nutr. in mediated signaling by inhibiting multiple kinases. Exp. Cell Res, 270, China, 47-48. 1-12. Wang LJ, Yang XS, Qin PY, et al. (2013). Flavonoid composition, Pashikanti S, De Alba DR, Boissonneault GA, et al. (2010). Rutin antibacterial and antioxidant properties of tartary buckwheat bran extract. metabolites: novel inhibitors of nonoxidative advanced glycation end Ind. Crops Prod, 49, 312-317. products. Free Radic. Biol. Med, 48, 656-663. Wang M, Wei YM, and Gao JM. (2006). Effects of total flavonoids ectract Peng LX, Wang S, Hu YB, et al. (2012). Determination of β-sitosterol in of Tartary buckwheat germ on serum lipidsin hyperlipidemia rats blood tartary buckwheat by HPLC. J. Southwest Natl. Univ. (Nat. Sci. Edn.), lipid and antioxidation. Acta Nutrimenta Sin, 28, 502-509. 38, 247-251. Wang M, Wei YM, and Gao JM. (2006). Study on antioxidant and Red Prestamo G, Pedrazuela A, Penas E, et al. (2003). Role of buckwheat diet blood cell protecting properties of tartary buckwheat flavonoids. Food on rats as prebiotic and healthy food. Nutr. Res, 23, 803-814. Sci. Technol, 6, 278-283. Quan JS, Li YB, and Tang MD. (2005). Effect of flavone and vitamin E Wang HY and Li Y. (2004). Research Status and Applied Prospect of against injury of cell membrane. Chin. J. Clin. Rehabil, 9, 82-84. Buckewheat. Food Sci, 25, 388-391. Ren Q, Wu CS, and Zhang JL. (2013). Use of on-line stop-flow heart- Wang XF, Dong XN, Fu WJ, et al. (2011). Fagopyrum tataricum (L.) cutting two-dimensional high performance liquid chromatography for chemical composition analysis and the research progress of simultaneous determination of 12 major constituents in tartary buckwheat pharmacological effects. Anim. Sci. Abroad (Pigs and Poultry), 31, 81- (Fagopyrum tataricum Gaertn.). J. Chromatogr. A, 257-262. 83. Samiya GC and Saxena VK. (1986). TLC and GLC studies of the essential Wu ZY, Raven PH, and Hong DY. (2003). Flora of China. Beijing: Science oil from Fagopyrum tataricum leaves. Indian Perfumer, 30, 299-303. Press, PR China, 5, 323. Sato H, Furukawa E, and Sakamura S. (1980). Isolation and identification Xiao H, Verdier-Pinard P, Fernandez-Fuentes N, et al. (2006). Insights into of flavonoids in tartary buckwheat seed (Fagopyrum tatricum Gaertn.). the mechanism of microtubule stabilization by Taxol. Proc. Natl. Acad. Nippon Nogei Kagaku Kaishi, 54, 275-277. Sci, 103, 10166-73. Saxena VK and Samaiya GC. (1987). A new flavonoid from Fagopyrum Xu BC, Xiao G, and Ding XL. (2002). Determination of phenolic acids and tataricum. Fitoterapia, 58, 283. proanthocyanidins in Tartary Buckwheat. Food Fermn. Ind, 28, 32-37. Shi MY, Li JL, Zhang JB, et al. (2012). Determination of the total Xuan TD and Tsuzuki E. (2004). Allelopathic plants: buckwheat flavonoids content in Fagopyrum tartaricum(L.) Gaertn. Pharm. Clin. (Fagopyrum spp.). Allelopathy J, 13, 137-148. Chin. Mat. Med, 3, 23-25. Xue CY, Zhang YH, and Liu YH. (2005). Effective way of tartary Sun BH, Wu YQ, Gao HY, et al. (2008). Chemical constituents of buckwheat flavone reducing the level of blood glucose and blood lipid. Fagopyrum tataricum (L.) Gaertn. J. Shenyang Pharm. Univ, 25, 541- Chin. J. Clin. Rehabil, 9, 111-113. 543. Yan QX and Xu F. (2005). Buckwheat flavone effect on the anoxia brain Takagi T, Takekoshi S, Okabe T, et al. (1998). Quercetin, a flavonol, tissue MDA content in mice. Pharmacol. Clin. Chin. Materia Med, 21, promotes disassembly of microtubules in prostate cancer cells Possible 33. mechanism of its antitumor activity. Acta Histochem. Cytoc, 31, 435- Zhang M. (2004). Study on anti-oxidation activity of tartary buckwheat 445. shell extraction. Food Sci, 25, 312-314. The Traditional Uses, Phytochemical and Pharmacology of Fagopyrum tataricum (L.) Gaertn 7

Zhang Z, Zhou Y, Wang Z, et al. (2001). The anti-oxidized activity of pharmacological effect of Fagopyrum Tataricum’s Chemical flavonoids in tartary buckwheat bran.Pharm. Biotechnol, 8, 217-220. Constituents. J. Inner Mongolia Univ. for Nationalities (Nat. Sci.), 27, Zhang F, Sun WW, Zhang Q, et al. (2011). Chemical constituents of seeds 315-317. of Fagopyrum tataricum (Linn) Gaertn. J. Northwest Sci-Tech. Univ. Zheng CJ, Hu CL, Ma XQ, et al. (2012). Cytotoxic phenylpropanoid Agric. For. (Nat. Sci. Edn.), 39, 199-203. glycosides from Fagopyrum tataricum (L.) Gaertn. Food Chem, 132, Zhang R, Wang YP, and Ren GX. (2008). Research Status of Tartary 433-438. Buckwheat. Spec. Wild Econ. Anim. Plant Res, 1, 74-77. Zhou LX, Lou YN, Fu SL, et al. (2006). Effect of quercetin on proliferation Zhao G, Tang Y, and Wang AH. (2002). Development of Chinese tartary of rat glioma C6 cells. J. Jilin Agric. Univ. (Med. Edn.), 32, 251-253. buckwheat production. Crops, 11-12. Zhao ZQ, Wang RF, Huang FL, et al. (2012). Research progress on