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Fagopyrum tataricum (L.) Gaertn.: A Review on its Traditional Uses, Phytochemical and Pharmacology
Lijuan LvYuan XiaDezhi ZouHuarui HanYingli WangHuiyong Fang Minhui Li
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2017 Volume 23 Issue 1 Pages 1-7

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Abstract

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.

Introduction

Fagopyrum tataricum (L.) Gaertn., also known as tartary buckwheat, is a member of the Polygonaceae family. The annual herbaceous plant is ecologically adaptable and grows in diverse environments, spanning the mountainous regions of Inner Mongolia (altitude of 500 – 3900 m), Sichuan, Hebei, Shanxi, Gansu, and other provinces in China. It is widely cultivated in Europe and North America, and has been introduced in Kazakhstan, Russia, and other countries because of increasing demand (Li & Zhang 2001; Wu et al. 2003; Xuan & Tsuzuki 2004). Fagopyrum tataricum possesses an abundance of compounds with medicinal properties, such as flavonoids and phenylpropanoids, and a number of essential amino acids and minerals. It has beneficial effects such as antioxidant, anti-aging, anti-tumour, antibacterial, hypoglycaemic, and hypotensive effects, and can be used for combating symptoms such as fatigue (Zhang et al. 2008; Guo et al. 2010; Lee et al. 2013). For these reasons, F. tataricum plays an important role in healthcare as an adjuvant therapy and as a healthy functional food for the prevention of disease (Zhang et al. 2008).

The aim of this article is to review the traditional uses of the F. tataricum, and summarize its ethnobotanical, phytochemical, and pharmacological characteristics. Through this review, the authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of medicinal plants, investigating them systematically so they can be further developed.

History of ethnomedicinal uses 

Plants have been used as a source of medicine by humankind since ancient times. Fagopyrum tataricum, called ‘Ku Qiao Mai’ in Chinese folklore, is a medicinal plant with a history spanning more than 2000 years. The roots and rhizomes are widely used in traditional Chinese medicine for alleviating pain (including stomach pain and lumbocrural pain), invigorating the spleen, and treating indigestion and traumatic injury. It has been documented in many well-known works, such as Shennong Bencao Jing (Pre-Qin, Eastern Han Dynasty), Qimin Yaoshu (the last year of the Northern Wei Dynasty, A.D. 533–544), Beiji Qianjin Yaofang (Tang Dynasty, A.D. 652), Yinshan Zhengyao (Song Dynasty), Compendium of Materia Medica (Ming Dynasty, A.D. 1590) and Qun Fang Pu·Gupu (Ming Dynasty). Fagopyrum tataricum ‘is bitter in taste,’ according to Shennong Bencao Jing. It improves listening and speaking abilities, as well as promoting immunity and digestive function, per the Compendium of Materia Medica (Tian & Ren 2007). In Korea, F. tataricum is known as the ‘food of the gods.’ In Japan, it is ‘panacea.’

Fagopyrum tataricum not only has medicinal effects, it also possesses rich nutritional value. The plant can be eaten on a long-term basis: its leaves and seeds used as a key ingredient in wine, soy sauce, buckwheat vinegar, bitter-buckwheat tea, and buckwheat ice cream, etc. (Zhao et al. 2002); its seeds processed into nutritional powder and made into biscuits, packaged noodles, macaroni and tofu (Wang et al., 2011). In essence, F. tataricum is an excellent plant resource that concomitantly functions as both medicine and foodstuff.

Phytochemical compounds

Many compounds have been isolated from Fagopyrum tataricum, primarily from its seeds and roots. They include flavonoids, phenylpropanoids, phenolic acids and their derivatives, sterols, terpenoids, and quinonoids, etc. The structures of primarily active substance are illustrated in the figures (Fig. 1–4).

Flavonoids    Flavonoids are the main chemical constituents of F. tataricum in previous phytochemical investigations in which the content of flavonoids is greater than 4% as determined by ultraviolet-visible spectroscopy (Shi et al., 2012). To date, twenty-six flavonoids have been isolated and categorized from F. tataricum (Fig. 1), including flavonols, flavanones, flavone C-glycosides, and O-glycosides. Three flavonols, kaempferol (1), isokaempferol (2), and quercetin (3), have been isolated from an alcohol extraction of F. tataricum (Bao et al. 2003a; Bao et al. 2003b). One flavanone, (-)-liquiritigenin (4), has been isolated from the roots of F. tataricum (Hu et al., 2012). One flavanol, (-)-epicatechin (5), has been found in F. tataricum seeds (Zhang et al., 2011). Twenty-one types of flavone glycosides from F. tataricum have been isolated or identified, including flavone O-glycosides and flavone C-glycosides. Most of them are flavone O-glycosides isolated from seeds, including quercetin-3-Orutinoside-7-O-galactoside (6) and quercetin-3-O-rutinoside-3′-O-glucoside (7) (Saxena & Samaiya 1987; Li & Ding 2001), 5,7,3′,4′-tetramethylquercetin-3-O-rutinoside (8), kaempferol-3-O-rutinoside (9), and quercetin-3-O-rutinoside (10) (Saxena & Samaiya 1987; Bao et al. 2003a), and quercetin-3-O-rutinoside is concentrated in the leaves (>33.41 mg/g) (Xu et al., 2002; Ren et al., 2013). Quercetin-3-rhamnoside (11) and 3′,4′,5,7-4-O-methyl quercetin-3-O-α-L-pyran rhamnose-(1–6)-O-β-D-pyranglucoside (12) has been isolated from whole plants and leaves of F. tataricum (Saxena & Samaiya 1987; Ren et al. 2013). Quercetin-3-O-β-D-glucoside (13), quercetin-3-O-β-D-galactoside (14) and quercetin-3-O-α-L-rhamnoside (15) are found in whole plants (Ren et al., 2013). Quercetin-3-O-β-D-xylosyl-(1→2)-α-L-rhamnoside (16) is also found in F. tataricum at high levels (0.44 – 0.85 mg/g) relative to other flavonoids in various parts of the plant (Ren et al., 2013). Kaempferol-3-O-β-D-galactoside (17) and kaempferol-3-O-β-Dglucoside (18) are present in whole plants (Ren et al. 2013). Quercetin-3-dirhamnoside (19), quercetin-3-rhamnodiglucoside (20), quercitin-3-rutinoglucoside (21), and quercetin-3-rutinodiglucoside (22) have been detected by high performance liquid chromatography-mass spectrometry (HPLC-MS) (Sato et al., 1980). Only four flavone C-glycosides-vitexin (23), orientin (24), isoorientin (25), and isovitexin (26) have been isolated from the sprouts of F. tataricum (Kim et al., 2007).

Phenylpropanoids    Sixteen phenylpropanoids have been found in F. tataricum (Fig. 2). 3′,5′-Dimethoxy-4′-O-β-D-glucopyranosylcinnamic acid (27) has been isolated from the seeds of F. tataricum (Wang et al., 2009). cis-2,4-Dihydroxycinnamic acid (28), 3-(3,4-dihydroxycinnamoyl) quinic acid (29), and 7-hydroxycoumarin (30) have been obtained from the seeds of F. tataricum (Xu et al. 2002; Sun et al. 2008; Zheng et al. 2012). Coumarin (31) has been obtained from the roots of F. tataricum (Hu et al. 2012). Four phenlypropanoid glycosides, 1,3,6-tri-p-coumaroyl-6′-feruloyl sucrose (32), 3,6-di-p-coumaroyl-1,6′-diferuloyl sucrose (33), 1,6,6′-tri-feruloyl-3-p-coumaroyl sucrose (34), and 1,3,6,6′-tetra-feruloyl sucrose (35) have been isolated from whole plants of F. tataricum (Ren et al. 2013). Seven phenylpropanoid glycosides, (3,6-O-di-p-coumaroyl-1-O-acetyl)-β-D-fructofuranosyl-(2→1)-(2′,6′-O-diacetyl)-α-D-glucopyranoside (36), (3,6-O-di-p-coumaroyl-1-O-acetyl)-β-D-fructofuranosyl-(2→1)-(2′-O-acetyl-6′-O-feruloyl)-α-D-glucopyranosi-de (37), (3,6-O-di-p-coumaroyl-1-O-acetyl)-β-D-fructofuranosyl-(2→1)-(2′,4′-O-diacetyl-6′-O-feruloyl)-α-D-glucopyranoside (38), (3-O-p-coumaroyl-6-O-feruloyl)-β-D-fructofuranosyl-(2→1)-(2′-O-acetyl-6′-O-p-coumaroyl)-α-D-glucopyranoside (39), (3,6-O-di-p-coumaroyl-1-O-acetyl)-β-D-fructofuranosyl-(2→1)-(2′-O-acetyl)-α-D-glucopyranoside (40), (1-O-p-coumaroyl-3,6-O-diferuloyl)-β-D-fructofuranosyl-(2→1)-(6′-O-p-coumaroyl)-α-D-glucopyranoside (41), and (1,6-O-di-p-coumaroyl-3-O-feruloyl)-β-D-fructofuranosyl-(2→1)-α-D-glucopyranoside (42) have been isolated from the roots of F. tataricum (Zheng et al. 2012). The phenylpropanoid glycoside content varies among different parts of the same plant (roots > stems > leaves) (Zheng et al. 2012).

Phenolic acids and their derivatives    Thirteen phenolic acids and their derivatives have been obtained from F. tataricum (Fig. 3). p-Hydroxybenzoic acid (43), vanillic acid (44), gallic acid (45), syringic acid (46), ferulic acid (47), caffeic acid (48), 2,4-dihyroxycinnamic acid (49), p-coumaric acid (50), O-coumaric acid (51), and protocatechuic acid (52) have been identified from the seeds of F. tataricum (Xu et al., 2002; Sun et al., 2008). p-Hydroxybenzaldehyde (53) and vanillin (54) have been obtained from the roots (Hu et al., 2012), and chlorogenic acid (55) has been isolated from the sprouts of F. tataricum (Kim et al., 2007). In addition, p-hydroxybenzoic acid, vanillic acid, gallic acid, syringic acid, ferulic acid, caffeic acid, p-coumaric acid, O-coumaric acid, and protocatechuic acid have been detected in F. tataricum using reverse-phase high-performance liquid chromatography (RP-HPLC), with ferulic acid present at the highest concentration (1014.36 mg/kg).

Sterols and Terpenoids    Currently, six sterols have been isolated from F. tataricum (Fig. 4). β-Sitosterol (56) and ergosterol peroxide (57) have been obtained from the seeds and hulls. β-Sitosterol has been detected in the different parts of 34 tartary buckwheat varieties using high-performance liquid chromatography (HPLC). It is present in the range of 4.1 mg/100 g – 65.3 mg/100 g (Peng et al., 2012). Daucosterol (58), β-sitosterol palmitate (59) stigmast-4-ene-3, 6-dione (60), and 6-hydroxy stigmasta-4,22-dien-3-one (61) have been isolated from the seeds and roots of F. tataricum (Bao et al. 2003a; Bao et al. 2003b; Hu et al. 2012). Three terpenoids have been reported in F. tataricum (Fig. 4). Ursolic acid (62) has been detected in the seeds (Sun et al. 2008). α-Thujene (63) and α-terpineol (64) have been detected from the leaves of F. tataricum (Samiya & Saxena 1986). Two quinines were isolated from F. tataricum (Fig. 4). Emodin (65) has been obtained from the seeds of F. tataricum (Bao et al., 2003a). 2,5-Dimethoxy benzoquinone (66) has been obtained from the roots of F. tataricum (Hu et al. 2012).

Amino acids and proteins    Sixteen amino acids have been identified from the seeds: glutamic acid (67), arginine (68), lysine (69), threonine (70), valine (71), methionine (72), phenylalanine (73), leucine (74), isoleucine (75), aspartic acid (76), serine (77), proline (78), glycine (79), cystine (80), histidine (81), and tyrosine (82) (Zhang et al., 1998). Moreover, three proteins have also been identified from the seeds: albumin (83), prolamin (84), and glutelin (85) (Guo & Yao 2006). The protein content of tartary buckwheat seed is 14.3%, which is higher than that in rice corn, wheat flour and corn (Liu et al. 2007). The protein content of tartary buckwheat leaves is 18.94% (Wang et al. 2003).

Other compounds    One aromatic ester, bis (2-ethylhexyl) benzene-1,2-dicarboxylate (86), is found in the roots (Hu et al. 2012). One miazine, uracil (87), is found in the seeds (Bao et al., 2003a). Nine aldehyde compounds N-trans-feruloyltyramine (88), (E,E)-2,4-decadienal (89), (E)-2-nonenal, 2-phenylethanol (90), (E,E)-2,4-nonadienal (91), hexanal (92), decanal (93), nonanal (94) and 5-hydroxymethyl-2-furfuraldehyde (95) are found in the roots (Samiya & Saxena 1986; Ren et al. 2013).

In addition, minerals such as magnesium, potassium, copper, selenium, and zinc, are also present in F. tataricum (Zhang et al. 2008).

Pharmacological effects

An increasing number of researchers are focusing on the pharmacological activity of F. tataricum. This section describes the primary pharmacological effects studied in recent decades.

Anti-tumour effects    Flavonoids from F. tataricum can decrease the production of intracellular peroxide, remove the intracellular superoxide anions, and significantly inhibit cancer cell growth (Liu et al., 2007). The primary biological flavonoid in tartary buckwheat is quercetin, present at a concentration of about 66.3 ± 1.14 mg/g (Wang et al. 2013). Augmenting quercetin and extending treated time inhibits C6 cell growth and increases the number of cells in G0/Gl phase. It also reduces the number of cells in S and G2/M phases, reduces the expression of Bcl-2 protein (an anti-apoptotic protein), and increases the expression of P53 protein (a tumour suppressor). Up-regulating P53 and down-regulating Bcl-2 induces C6 cell apoptosis (Zhou et al. 2006). In addition, rutin inhibits the proliferation of the human hepatocellular liver carcinoma HepG2 cells in a dose-dependent manner (Ma et al., 2011).

Studies of the mechanism by which flavonoids inhibit proliferation and their potential application against tumours have focused on microtubule stability (Takagi et al. 1998; Gupta & Panda 2002; Jackson & Venema 2006; Touil et al. 2009; Marone et al. 2011). These data demonstrate that some flavonoids, such as quercetin from tartary buckwheat, influence tubulin polymerization and microtubule depolymerization in a manner similar to paclitaxel and colchicine (Gupta & Panda 2002; Xiao et al. 2006). Paclitaxel is a well-established drug for the treatment of different types of cancers, while colchicine binds to soluble tubulin dimers to prevent dimer polymerization into microtubules (Gupta & Panda 2002; Xiao et al. 2006). Quercetin depolymerizes microtubules (Takagi et al. 1998; Gupta & Panda 2002; Jackson & Venema 2006).

By using hormone refractory human prostate cancer cells in culture, Takagi et al. (1998) determined that quercetin causes morphological changes, inhibits cell proliferation, and promotes disassembly of cellular α-microtubules. Immunofluorescence tubulin staining of bovine aortic endothelial cells clearly shows that quercetin upsets normal mitotic and cytoplasmic microtubule polymerization and induces early M-phase cell cycle arrest (Jackson & Venema 2006). Quercetin binds to tubulin at the colchicine site, stimulates the GTPase activity of soluble tubulin, and inhibits microtubule polymerization by inducing conformational changes in tubulin. These findings suggested a novel mechanism of action for natural quercetin: It prevents proliferation by binding tubulin, which disrupts microtubule polymerization (Gupta & Panda 2002). Researchers believe that quercetin has potential clinical use in the treatment of various forms of cancers in combination with known anticancer drugs (Takagi et al. 1998; Gupta & Panda 2002; Jackson & Venema 2006; Xiao et al. 2006; Marone et al. 2011).

Anti-oxidation effects    Fagopyrum tataricum has strong antioxidant activity because it is rich in rutin, quercetin, polyphenols, and many other substances. The shell extract of F. tataricum significantly inhibits spontaneous lipid peroxidation and Fe2+/H2O2 induced hepatic lipid peroxidation in mice livers, with inhibition rates of 38.1% and 24%, respectively (Zhang, 2004). An experiment on the anti-oxidative activities of total flavonoids of tartary buckwheat flour (TFTBF), quercetin, and rutin on rat liver and red blood cell models revealed that quercetin is one of the most important anti-oxidant components in TFTBF, and the inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical of quercetin was 72% higher than TFTBF and rutin (53%, 66%, 69%, 63%) (Wang et al. 2006). The DPPH elimination rate is as high as 70% when the concentration of flavonoid extracted from tartary buckwheat seedlings is 47 µg/mL, significantly higher than seen with vitamin C and vitamin E. These results indicate that the flavonoids of F. tataricum strongly inhibit oxidation and can be used as natural antioxidants (Zhou et al. 2006).

The flavonoids from F. tataricum also have strong superoxide dismutase (SOD) activity. This promotes antagonistic effects against nonylphenol (which damages cells through lipid peroxidation) and eliminates oxide free radicals from the body (Quan et al., 2005) in a manner similar to SOD activity against active oxygen, except flavonoids from F. tataricum are chemically more stable than SOD (Zhang et al. 2001). At pH 6.0–10.6, especially in alkaline condition, the SOD activity in flavonoids is more stable than SOD activity in human blood erythrocytes. Flavonoid SOD activity is optimally stable at 40. and pH 8.0.

Hypoglycaemic effects    Fagopyrum tataricum is commonly used in traditional medicine as a treatment for diabetes. Its compounds affect blood glucose in experimental diabetic rats and may prevent insulin resistance. At high concentrations (250 mg/L), flavonoids and acarbose have glucosidase inhibition rates of 85% and 62.6%, respectively, with flavonoids stimulating peroxisome proliferator-activated receptor α and γ in a dose-dependent manner (Xue et al. 2005; Berger et al. 2005). Moreover, rutin and its metabolite inhibit advanced glycation end-products (AGEs) (Campbell 2005). In fact, both ethanol extract of buckwheat (EEB) and rutin markedly attenuate the generation of AGEs in vitro. Treatment with EEB and rutin suppresses α-glucosidase and α-amylase activity in a dose-dependent manner, suggesting that F. tataricum can be used as glucosidase and amylase inhibitors (Pashikanti et al. 2010).

Lipid-lowering and cholesterol-lowering effects    Fagopyrum tataricum significantly lowers blood lipids and cholesterol, preventing hyperlipidaemia induced by high-fat diets (Zhang et al. 2006; Lee et al. 2013). Wistar rats fed high-fat diets and gavaged with total flavonoids in F. tataricum bran extracts in three dose groups −1.0 g/kg, (high dose), 0.5 g/kg (medium dose), and 0.2 g/ kg (low dose) - have significantly lower serum triglycerides total cholesterol compared to the high-fat control group, (P < 0.01). A low dose is associated with elevated serum glutathione peroxidase and higher anti-atherogenic index, as well as lower serum malondialdehyde levels and atherogenic index (Wang et al., 2006).

Anti-atherosclerosis effects    Flavonoids from tartary buckwheat inhibit the oxidation of low-density lipoprotein (LDL), preventing atherosclerosis by scavenging free radicals, inhibiting endogenous vitamin E, chelating metal ions, and affecting the activity of related enzymes (Wang et al. 2006). They may also prevent atherosclerosis by inhibiting the secretion of various pro-inflammatory cytokines or by suppressing gene expression (Préstamo et al. 2003). Other possible mechanisms include the inhibition of lipoxygenase, generation of oxidized LDL, regulation of macrophages, and the protective effects of paraoxonase (Préstamo et al. 2003; Li & Guo 2003).

Regulation role of capillary permeability and fragility    The flour and leaves of tartary buckwheat are rich in flavonoids and vitamins, especially rutin (0.8% – 1.5%). Rutin and bioflavonoids have synergistic effects on vitamin C, reducing capillary fragility and permeability. Thus, it can be used as adjuvant therapy agent for the prevention and treatment of hypertension and atherosclerosis (Lan et al. 2005).

Lowing blood pressure effects    Because it is rich in bioflazzvonoids, Fagopyrum tataricum can be used to lower blood pressure. Nitric oxide generation and the abnormal apoptosis of vascular smooth muscle cells have bidirectional regulation effects (Li & Guo 2003). Antihypertensive peptides can be created through enzymatic hydrolysis of proteins in F. tataricum bran (Wang & Li 2004).

Anti-thrombotic effects    Flavonoids from F. tataricum have an inhibitory effect on platelet aggregation and thrombosis induced by adenosine diphosphate, collagen, and thrombin. Hydroxyethyl rutin could prevent thrombosis. However, the antithrombotic mechanism of flavonoids is not clear. Previous studies report that buckwheat flour inhibits angiotensin-I converting enzyme (ACE) activity (Lin et al. 2004). Common hulls extracted using 50% (v/v) ethanol solvent have remarkable inhibitory activity against ACE, with a half maximal inhibitory concentration (IC50) of 30 µg/mL. Based on the ferric reducing antioxidant power assay, the antioxidant activity of common hulls extracted with 50% (v/v) ethanol solvent is superior to the extracts using deionized water solvent or 20% (v/v) ethanol solvent (Tsai et al. 2012).

Protective effects on cerebral ischemia    Canine renal artery occlusion experiments show that tartary buckwheat flavonoids have anti-ischemic effects and can significantly increase serum creatinine in dogs (Lin et al., 2011). In mice with cerebral ischemia, tartary buckwheat flavonoids play a protective role significantly reducing malondialdehyde levels in brain tissue, thereby reducing brain damage (Yan & Xu 2005).

Antibacterial activity    Total flavonoids identified from F. tataricum generally have significant antibacterial effects. A 0.08% flavone solution from F. tataricum can eliminate 83%∼85% of Escherichia coli, Bacillus subtilis, and Staphylococcus aureus at 8 h, and 92% – 93% at 48 h. Researchers believe even stronger antimicrobial activity may be achieved by adding phenolic groups to naturally occurring flavonoids (Wang et al. 2003).

Other activities    An increasing number of pharmacology studies of F. tataricum are being conducted. The hot-plate test was used to observe analgesic effects of tartary buckwheat sprout extracts on mice with dimethybenzene-induced ear edema. Results showed that tartary buckwheat sprout extract has analgesic effects (Hu et al. 2009; Lin et al. 2011). Quercetin has antitussive and anti-asthmatic effects. A study conducted to compare the oestrogen-like activity of flavonoid and daidzin and linseed lignans in tartary buckwheat bran found that these three ingredients, including flavonoid of tartary buckwheat bran, have oestrogen-like effects (Cao et al., 2006; Lin et al., 2011). Lastly, tartary buckwheat is rich in vitamins, especially vitamin B1, which improves digestive function and prevents dermatophytosis (Wang et al. 2011; Zhao et al. 2012).

Toxicity/side-effects    Tartary buckwheat capsule is not mutagenic in rats and mice fed tartary buckwheat extracts continuously. It does not have a negative effect on their growth, development, hamatology, or biochemical and pathological indexes (Wang et al. 2011). However, over-eating the seeds of F. tataricum can affect digestive function (Tian et al. 2008).

Conclusion    With dietary habits gradually focusing more on nutrition, health, and pure and natural products, functional foods are drawing increasingly more attention. Food processed from the seeds, roots, and rhizomes of Fagopyrum tataricum is being used to treat chronic diseases (hypoglycaemia, cardiovascular diseases, and cancer) and to prevent illness through its anti-tumour and antioxidant. Fagopyrum tataricum seeds and roots are added to many health-related products including nutritional powder, health protection tea, and others. In fact, the whole plant of F. tataricum has highly bioactive compounds could be considered appropriate as a functional food. However, it is noteworthy that current studies on the chemical constituents of F. tataricum lack depth.

More studies on the phytochemistry and the mechanism of action of the primary active components should be encouraged for a fuller understanding. Studies on the constituents responsible for its pharmacological activities and the effects of therapy and are needed. An investigation into its potential utilization in the prevention and treatment of chronic diseases (such as type II diabetes) may yield great advances.

In addition, the safety and toxicity of the roots, leaves, and shells of F. tataricum have not been fully explored. Limited data show overeating the seeds can affect digestive function. It follows that the toxicity and adverse effects of the leaves, roots, and shells should be further investigated.

Acknowledgements    This work was financially supported by the “Twelfth Five-year Plan” Program supported by the Ministry of Science and Technology (2012BAI28B02), Specific funds of Traditional Chinese Medicine industry (201407003) and “Supported By Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region” (NJYT13-B18).

References
 
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