Animal and Human Studies of Tartary Buckwheat

Statements about the health benefits of consuming Tartary buckwheat often rely on a combination of demonstrations: 1) that a certain chemical compound occurs within the plant; 2) that that compound affects others found within the human body (or the bodies of other animals); and 3) that such effects reduce the likelihood of disease and/or improve the prognosis for ill individuals. There are few observational studies or experiments that directly compare the physiological or health status of individuals (animal or human) who consume buckwheat with the status of those who don’t. Nevertheless, the studies below demonstrate a variety of healthful effects achieved by adding Tartary buckwheat to the diet.



It might seem unnecessary to say that consuming a putative “health food” doesn’t harm people; however, a substance that is healthful at one dosage for one person might be harmful at a different dosage or for a different subject (different age, sex, genetic background, or health history). Therefore, a survey of animal studies on the healthful effects of Tartary buckwheat appropriately begins with a study of its possible toxic effects. Lin et al. (2001) investigated the toxicological safety of a powdered extract of Tartary buckwheat. Those authors subjected mice and Wistar rats to a 30-day feeding trial that compared low, medium, and high dosages of the extract with a control diet. Neither males nor females of either species exhibited a significant difference in feed use efficiency or final body weight due to the dietary treatments. In the experimental mice, the types and frequencies of deformations in sperm cells were unaffected by Tartary buckwheat extract in the diet. Nor did the extract affect the frequency of polychromatic erythrocytic micronuclei in the bone marrow of the mice. Blood levels of hemoglobin and the numbers of erythrocytes and leucocytes in male and female rats were similarly unaffected by Tartary buckwheat extract in the diet. The authors also reported blood levels of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), albumin, total protein, sugar, urea nitrogen, HDL, triglyceride, and cholesterol in the blood of male and female rats. None of these substances was significantly affected by the feeding treatments. The authors reported that the extract had an LD50 greater than 10g/kg, a level considered non-toxic.

As described below in the section Buckwheat Extract Reduces Hyperglycemia and Type II Diabetes, Yao et al (2008) tested the oral toxicity in mice of an extract of Tartary buckwheat bran, and found no ill-effects.


Yang et al. (2014) reported five clinical cases of polyneuropathy with dyskinesia among Chinese males who had treated diabetes with an herbal medication containing Tartary buckwheat. The patients, between 40 and 66 years old, exhibited an onset of toxic peripheral neuropathy after taking six composite tablets (Tartary buckwheat and black tea) orally three or four times per day for between 1.5 and four months. They were admitted for treatment with symptoms that included weakness or numbness of limbs, hoarseness or difficulty swallowing, facial paralysis, shortness of breath, and bladder dysfunction. Symptoms ceased after the patients stopped taking the herbal tablets. Conduction velocity was measured in 30 motor nerves and 20 sensory nerves, with 87 percent of the former and 50 percent of the latter deemed abnormal. There was no evidence of lesions within the central nervous systems of these patients. The authors reported that all of the herbal tablets consumed by these patients had come from a single batch; therefore, rather than Tartary buckwheat, some contaminant might have caused the reported symptoms.


As described in “TARTARY BUCKWHEAT FUNCTIONAL FOODS,” Wang et al. (2013) investigated antioxidative properties of an extract of the bran that was a by-product of the production Tartary buckwheat tea. Those authors also explored the antibacterial properties of that extract, specifically against Staphylococcus aureus, S. epidermidis, and two strains of Proprionibacterium acnes, pathogens associated with acne. Bacterial cell suspensions were plated on nutrient agar, on which were placed 6mm disks impregnated either with 500μg of one of the tested agents, or with 6.4μg of erythromycin. Inhibition was measured as the diameter of the zone surrounding a disk in which bacteria did not grow. The bran extract (“TBBE”) inhibited the growth of all four bacterial strains to a slightly greater degree than isoquercetin, and to a slightly smaller degree than quercetin. At the tested concentrations, rutin exhibited no antibacterial activity. Erythromycin exhibited greater antibacterial activity than TBBE, quercetin, or isoquercetin. Using a micro-broth dilution procedure, the investigators estimated both a minimum inhibition concentration (MIC) and a minimum bactericidal concentration (MBC) for TBBE, isoquercetin, quercetin, and rutin. For all four bacterial strains, quercetin had lower MIC and MBC values than TBBE, which had lower MIC and MBC values than isoquercetin. Rutin had no determinable MIC or MBC at concentrations below 5000 μg/mL, except for the MIC for S. epidermidis of 1024 μg/mL. The authors attributed the greater antibacterial capacity of quercetin, when compared to isoquercetin and rutin, to the greater lipid solubility of the former compound. The cell walls of Gram-positive bacteria are relatively lipid-rich, and thus quercetin might pass more readily through the bacterial cell membrane. Once inside those cells, quercetin might inhibit the synthesis of DNA and RNA.


Foods that are high in dietary fiber or resistant starch can create a feeling of satiety without elevating serum glucose level or the body’s insulin response.  Berti et al. (2005) examined how consumption of a first course of pasta affects caloric intake during the balance of a meal (ham, cream cheese, crackers, chips, strawberry yoghurt, apricot jam tart, apple, banana, and water).  The pasta dishes examined were regular spaghetti (i.e., wheat flour); spaghetti containing 40% oat flour; regular lasagne (wheat flour, 20% egg); buckwheat lasagne (60% common buckwheat flour, 40% precooked rice flour, 30% egg); and carboxymethyl cellulose/buckwheat lasagne (above recipe augmented with 0.5% CMC).  Fourteen healthy male volunteers (average age of 24.0 years) were assigned in random order a course of 200g of each pasta (dressed with 50g of tomato sauce) and pasta courses of twice those quantities.  Additionally, subjects were fed the same meal with no preceding pasta course.  Quantities of items subsequently consumed ad libitum were weighed, and caloric intakes were calculated.

The authors reported that the small pasta servings contained between 1181 and 1323kJ, and the large servings twice those energy values.  The mean intake of the test meal with no pasta course contained 4547kJ.  When a large serving of regular lasagne, regular spaghetti, or oat spaghetti was added as the opening course, the total caloric intake was increased.  However, when the meal started with a small course of any of these pasta items, the total caloric intake was lower than with no pasta course.  When the meal started with a course of buckwheat lasagne or CMC/buckwheat lasagne—large portion or small—the total caloric intake was lower than with no pasta course.  The authors concluded that the substitution of common buckwheat flour for wheat flour in the preparation of lasagne increased the satiating power of the resultant dish.  The mean palatability score of regular lasagne (6.7) was the highest of all these pasta dishes; whereas the mean palatability score of the buckwheat lasagne (4.1) was the lowest.  As discussed in the section on TARTARY BUCKWHEAT AND NUTRITION, Tartary buckwheat contains dietary fiber and resistant starch at levels equivalent to common buckwheat.  Therefore, pasta containing Tartary buckwheat flour would likely have similar effects as the experimental lasagnes that contained common buckwheat flour (both with and without carboxymethyl cellulose).


Jin and Wei (2011) administered (daily, by gavage) three levels of an ethanol extract of Tartary buckwheat seeds for 28 days to randomized groups of 3-month-old mice. Mice that had received the extract were able to swim significantly longer than control mice that had received none. The duration of swimming was positively related to the amount of extract administered (60, 120, or 240mg per kg body weight). Mice receiving those same treatments were euthanized after 90 minutes of swimming, and levels of lactic acid and urea nitrogen were measured in their blood. The blood from mice receiving the buckwheat extract contained significantly lower levels of both metabolic by-products than the blood of control mice. Moreover, the mice receiving the extract contained significantly higher concentrations of glycogen in both liver and muscle tissue. Those mice also had significantly greater concentrations of glutathione peroxidase and superoxide dismutase in skeletal muscle, with levels of those antioxidant enzymes correlated with the level of buckwheat extract received. According to the authors, the putative mechanism by which Tartary buckwheat delays fatigue is that it slows the rise in blood lactic acid, increases tissue glycogen reserve after exercise, and thereby increases the capacity for aerobic and anaerobic exercise. In addition, Tartary buckwheat is rich in flavonoids; together with endogenous antioxidants these compounds can suppress the reactive oxygen species that contribute strongly to muscle fatigue.


Wieslander et al. (2012) conducted a double-blind experiment on the effect of buckwheat consumption on general and mucosal symptoms in 62 healthy female day-care workers in Sweden. The workers were randomly assigned to two groups fed cookies containing either Tartary or common buckwheat flour. The former represented a daily dosage of 156.6 mg of rutin and 197.8 mg of quercetin; the latter represented a daily dosage of 16.3 mg of rutin and undetectable quercetin. After two weeks the groups were switched to the alternative treatment, which was then administered for two additional weeks. At the experiment’s commencement and after weeks 2 and 4, the subjects were questioned about current ocular, nasal, and throat symptoms, as well as headache, fatigue, and nausea symptoms.
Compared to their baseline scores, the combined experimental groups showed significant improvement in nasal irritation, headache (to week 2), and fatigue (to week 4). These changes might have been due to any of the constituent compounds common to both buckwheat species. During the first treatment period, improvement in ocular irritation was significantly better in the group consuming common buckwheat, whereas the improvement in fatigue was significantly better in the group consuming Tartary buckwheat. The greater concentration of rutin in the Tartary buckwheat cookies was likely responsible for the different changes in fatigue scores in the experimental groups.


Kim and co-authors (2005) studied the mechanisms by which flavonoid compounds could protect against inflammatory bowel disease (IBD). IBD is a chronic inflammatory condition that involves the up-regulation of pro-inflammatory factors (such as nuclear factor kappa B [NF𝜿B] and cytokines TNF-⍺ and IL-1β). Inhibition of NF𝜿B is a presumed route by which glucocorticoids and 5-amino-salicylic acid (5-ASA) effectively ameliorate chronic intestinal inflammation. In order to deliver such drugs to the colon orally, they must resist absorption while passing through the stomach and small intestine. Linking a hydrophilic sugar molecule to the therapeutic drug (I.e., creating a glycosolated “prodrug”) could limit the gastrointestinal absorption of the latter. Hydrolyzing (or “deglycosylating”) enzymes produced by microbes would then release the drug within the colon—its site of action.

As explained in the section on FLAVONOIDS AND ANTIOXIDANT PROPERTIES in TARTARY BUCKWHEAT AND NUTRITION, rutin is a glycoside of quercetin. Rutin is formed when a molecule of rutinose, a disaccharide, forms a 3-O linkage with a molecule of the isoflavonoid. In Tartary buckwheat, rutin is the most prevalent glycoside of quercetin. If that 3-O bond in the rutin molecule resists hydrolysis by enzymes produced by the host organism (man or rat), then ingested rutin could pass intact into the colon. Enzymes (“rutin glucosidases”) produced by microbes living within the host’s colon there might liberate quercetin from rutin. To establish that rutin could deliver quercetin into the colon of rats, Kim and co-workers had to demonstrate first that rutin was biochemically stable in the small intestine, and then that rutin could be metabolized to quercetin within the large intestine. Moreover, the researchers sought to show that the latter compound had an actual therapeutic effect on colitis. Finally, the authors sought to establish that guercetin ameliorated colonic inflammation by suppressing TNF-⍺-dependent activation of NF𝜿B signaling.

Kim et al. (2005) measured the partitioning of rutin or quercetin betweem a hydrophilic solvent (PBS) and a hydrophobic solvent (chloroform) at pH 6.8. Their apparent partition coefficients—0.02 and 0.68, respectively—illustrate the greater hydrophilicity of rutin compared to quercetin. When rutin (20μM) was incubated at 37°C in hydrochloric acid (pH 1.2) or in a phosphate buffer (pH 6.8), it did not degrade for at least 10 hours. These observations imply that the compound is chemically stable in the upper gastrointestinal tract. The researchers collected the contents of the small intestine and cecum of a dissected 8-week-old male Sprague-Dawley rat. Incubated for 24 hours in the small intestinal contents (diluted to 20 percent in pH6.8 PBS), four-fifths of the rutin remained intact. Incubated in the cecal contents (diluted to 1 percent, 5 percent, or 10 percent), most of the rutin was deglycosolated to quercetin in a concentration-dependent manner. The researchers also incubated quercetin in rat cecal contents at the same dilutions as applied to rutin. Within six hours, virtually all the quercetin had been destroyed in the 5% and 10% cecal dilutions. Therefore, when rutin had been incubated in the cecal contents, the observed rise in the concentration of quercetin integrated both its release from metabolized rutin and also the metabolization of quercetin itself. Incubating rutin in autoclaved cecal contents (10% dilution), the researchers also demonstrated that the deglycosolation of rutin was effected by enzymes; these were degraded by heat. In contrast, when quercetin was incubated in cecal contents that had been autoclaved, the concentration of quercetin declined, although not as rapidly as when the cecal contents had not been autoclaved.

Kim et al. (2005) induced colitis in 8-week-old male Sprague-Dawley rats by injecting 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the colon (at the splenic flexure) through a rubber cannula inserted through the anus. The researchers collected cecal contents from rats six days after the induction of colitis. Rutin was incubated in cecal contents at the same dilutions as described above. Colonic inflamation did not significantly affect the deglycosolation of rutin or accumulation of quercetin when incubated in the cecal contents.

Kim and co-workers also examined the fate of rutin when administered orally to rats with TNBS-induced colitis. Concentrations of both rutin and quercetin were measured in the small intestine (both proximal and distal), the cecum, and the colon at 3-, 5-, and 7-hour intervals after oral administration at 10mg rutin per kg live weight. Rutin reached its greatest concentration in the proximal and distal small intestine three hours after oral administration. Detectable amounts were found in the cecum and colon only after five hours. Quercetin was not detected in the small intestine at any of the sampling times, but was measured in all samples from the cecum and colon (with concentrations reaching 200 μM after 5 hours).

These investigators administered six daily oral doses of rutin (10mg/kg) or of sulfasalazine (30mg/kg) to rats with TNBS-induced colitis. Dissected colons from these rats, from colitis-induced rats receiving neither therapy, and from normal rats were scored for damage. They found that the administration of rutin not only healed the inflammatory damage induced by TNBS, but did so as effectively as sulfasalazine—the most widely used therapy for IBD. Moreover, the treatment with rutin was found to reduce MPO activity in the distal colon of colitis-induced rats by about 45% compared to those receiving no rutin.

In further experiments with rats with TNBS-induced colitis, Kim and co-workers (2015) showed that the therapeutic effect of intra-colonic administration of quercetin was due to that compound itself, and not due to its metabolites: 3-hydroxyphenylacetic acid or 3,4-dihydroxyphenyl-acetic acid. This treatment with 25μM quercetin was as effective as 20mM 5-ASA.

Finally, these researchers used a NF𝜿B-dependent luciferase (NFDL) plasmid to transfect three human colon epithelial cell lines. This enabled them to monitor NF𝜿B activity within the cells from light emissions controlled by the luciferase enzyme. Cells were subsequently cultured in TNF-⍺ and various concentrations of quercetin. In all three lines, NF𝜿B activity was reduced in a dose-dependent manner by exposure to quercetin. The researchers reported that IL-8 activity was similarly reduced in a dose-dependent manner by exposure to quercetin. like NF𝜿B, this cytokine is up-regulated by TNF-⍺. Therefore, quercetin likely ameliorates inflammation in colon cells by suppressing pro-inflammatory signaling that is activated by TNF-⍺.


Hyperglycemia is the term for elevated levels of glucose circulating in the blood. Insulin, synthesized by specialized cells within the pancreas, plays a critical role in the transport of glucose from the bloodstream into mammalian cells. Hyperglycemia can result either from the failure of the pancreas to produce insulin (Type 1 diabetes mellitus) or from the failure of the body’s cells to respond to insulin (Type 2 diabetes mellitus). “Glucose tolerance” is a measure of the body’s ability to respond to a rise in serum glucose, and to transport that glucose into cells. If glucose tolerance is impaired, hyperglycemia persists. Over time this can cause serious secondary symptoms, such as the deterioration of peripheral blood vessels, which in turn can lead to blindness, limb amputations, or even death.

As mentioned in the section on SOLUBLE CARBOHYDRATES in NUTRITIONAL ASPECTS OF TARTARY BUCKWHEAT, buckwheat is one of the best plant sources of D-chiro-inositol (D-CI). D-chiro-inositol can be a component of yet larger molecules that are involved in the cellular uptake of serum glucose. Those compounds act effectively as insulin mimics or substitutes. Streptozotocin (STZ) is a toxin to the insulin-producing cells of the pancreas. A single large dose of STZ can be used in an animal model to induce hyperglycemia. In multiple lower doses, STZ can be used to simulate either Type 1 or Type 2 diabetes. Therefore, streptozotocin-treated rats have been used to evaluate the effectiveness of D-chiro-inositol as a replacement for or supplement to the body’s insulin production.

An intragastric dose of D-chiro-inositol to STZ-treated rats has been shown to diminish the rise in the level of serum glucose that follows an intraperitoneal administration of glucose. Kawa et al. (2003) noted that buckwheat seeds offer a natural dietary source of D-CI that could potentially counteract hyperglycemia. Those authors evaluated the effect of an acute dose of a buckwheat extract concentrate on glucose tolerance in normal rats, and also its effect on elevated serum glucose in fed STZ-treated rats.

An ethanol extract was prepared from the combined “shorts” and “bran” fractions from milled, dehulled groats of ‘Koto’ common buckwheat. The concentrate comprised 0.2% D-CI , 0.1% myo-inositol, 5.7% fagopyritols, and 6.0% sucrose. Following 7 days of acclimation, normal male rats (150-180 g) were given a dose of buckwheat concentrate corresponding to 10 mg of D-CI per kg body weight. A sucrose solution was administered to control rats. After a two-hour fast, glucose (4 g/kg body weight) was administered to those rats intraperitoneally. At subsequent 30 minute intervals, venous blood was drawn and sampled for glucose. For rats receiving either the dose of buckwheat concentrate or the control solution, serum glucose peaked at 30 minutes, at which time the former was significantly lower (-17%) than the latter. The buckwheat extract had improved the glucose tolerance of normal rats.

Kawa et al. (2003) also administered the buckwheat concentrate (10 or 20 mg of D-CI per kg body weight) to rats in which diabetes had been induced by prior intraperitoneal injections of STZ. In the diabetic rats that received the lower dose of buckwheat concentrate, subsequent serum glucose levels declined (significantly so at 60 minutes and subsequently). In the diabetic rats that received the higher concentration of buckwheat extract, after 90 minutes the serum glucose had declined from its initial level. In contrast, in control diabetic rats the concentration of serum glucose did not drop significantly over the two hours following administration of the sucrose placebo. The observed effects of the buckwheat extract were similar in magnitude to those reported when chemically-synthesized D-CI had been administered to rats in which diabetes had been induced with STZ.

Additionally, Kawa et al. (2003) performed an Oral Glucose Tolerance Test to fasting rats in which diabetes had been induced with STZ. The investigators administered buckwheat extract concentrate intragastrically to STZ rats following a 4-hour fast. One hour later, blood was sampled intravenously, and the rats then received 1 g glucose per kg body weigh (in 70% solution, intragastrically). Intravenous blood samples at subsequent 30-minute intervals revealed a rise in serum glucose at 30 minutes and then a decline over the following 90 minutes. Glucose levels were consistently lower in the rats receiving the buckwheat concentrate (at either dosage) than in the corresponding controls; however, these differences were not statistically significant.

While the authors speculated that the observed effects of buckwheat were caused by its constituent D-chiro-inositol, the means by which serum glucose levels were reduced remain unknown. The anti-hyperglycemic effect of D-CI may result from inhibition of hepatic glucose output or by stimulation of glycogen synthesis; by enhanced glucose transport; or by increased glucose utilization or disposal.

As detailed in the section on TARTARY BUCKWHEAT FUNCTIONAL FOODS, Yao et al. (2008) produced an extract of Tartary buckwheat bran that was enriched in free D-chiro-inositol (D-CI). Bran (containing tissue of both the seed coat and the embryo) contains relatively high levels of both D-CI and fagopyritols. Bran was extracted with 60 percent ethanol, and concentrated under reduced pressure. Steaming of this bran extract under pressure apparently hydrolyzed the constituent fagopyritols. Subsequent column chromatography with activated charcoal and ion exchange resins increased the free D-CI concentration to 22 percent.

Yao et al. (2008) tested the oral toxicity of this purified Tartary buckwheat bran extract, administering 20g of extract daily per kg body weight of ICR mice. After 14 days, none of the 20 treated mice had died, all were generally healthy, and body weights were not significantly different from those of control mice.

KK-Ay mice carry a homozygous mutation that causes metabolic abnormalities such as hyperglycemia and glucose intolerance—phenotypically similar to human type 2 diabetes. Yao et al. (2008) fed KK-Ay mice a ration that included 0 (control), 45, 91, or 182 mg of Tartary buckwheat bran extract per kg. After five weeks, these mice were tested for oral glucose tolerance. After fasting overnight, mice receiving all three experimental treatments had lower serum glucose levels than control (diabetic) mice. Dose-dependent differences in the glucose level were also observed 30, 60, and 120 minutes after these mice had received a dose of glucose equivalent to 2 g per kg body weight. Compared to the control diabetic mice, those receiving rations containing bran extract exhibited generally lower plasma levels of C-peptide, glucagon, BUN, triglycerides, and total cholesterol. At the highest treatment level (equivalent to 40 mg D-CI per kg) the decreases in all but the last were statistically significant.

D-chiro-inositol is not the only constituent of Tartary buckwheat that might protect against diabetes. Li et al. (2016) studied the hypoglycemic and hypolipidemic effects in rats of a flavonoid-rich extract from Tartary buckwheat seeds. The ethanol-water (60:40) extract from powdered seeds was subjected to microwaves (600W) at 70°C for 20 minutes, then centrifuged, filtered, and the filtrate evaporated. In the solid product the total flavonoids constituted 27.97mg/g.

To fasting male rats that had been fed a high-fat (45% fat) diet for four weeks, the researchers administered intraperitoneally STZ at a dose of 60mg/kg body weight. Seventy-two hours later, venous blood was drawn and rats were divided into a diabetic control group; low-, middle-, or high-dose Tartary buckwheat treatments (100, 200, and 400mg/kg, respectively); and a group treated with a glibenclamide solution (4mg/kg). Besides those groups, all of which were fed a high-fat diet for 28 days, there was a normal control group maintained on a diet containing 12% fat. Following an overnight fast, venous blood was drawn from the rats in all groups once a week.

Li and co-workers reported that compared to the normal control group, fasting blood glucose levels were initially elevated in all the (diabetic) treatment groups. However, at 14 days glucose levels were significantly lower in all three Tartary buckwheat treatments and the glibenclamide treatment, compared to the diabetic control group. Despite a progressive and dose-dependent response, after 28 days mean glucose levels in all the treatment groups remained significantly higher than in the normal control rats. Similarly, the serum insulin levels were significantly lower in the Tartary buckwheat and glibenclamide groups than in the diabetic control group, as were serum lipid levels (TC, TG, and LDL-C). Conversely, HDL-C levels were significantly higher in those groups than in the diabetic controls.

The investigators conducted an oral glucose tolerance test on the 28th day, with serum glucose measured at 0, 30, 60, and 90 minutes after glucose was administered. For all the treatment groups, serum glucose levels were intermediate between those in the normal control rats and the diabetic control rats, with glucose levels peaking at 30 minutes in all groups.

These results indicate that consumption of a Tartary buckwheat extract containing almost 3 percent total flavonoids can reduce STZ-induced hyperglycemia in rats. An oral glucose tolerance test demonstrated that the extract can improve blood glucose homeostasis, and control the hyperinsulinemia by which the body compensates for high serum levels of glucose. Moreover, the extract countered the abnormal concentration of serum lipids that in diabetics can result from the mobilization of fats from adipose tissue.

Lee et al. (2012) conducted an extensive investigation into the ways that constituents of Tartary buckwheat affect cellular functions related to the uptake of glucose. Those researchers extracted powdered Tartary buckwheat seeds with 75 percent ethanol, and used high-performance liquid chromatography (HPLC) to identify the following flavonoids in that extract: caffeic acid, rutin, quercetin, kaempferol, and quercetin-3-glucoside. Concentrations of rutin and quercetin were estimated at 228.8mg/g and 58.6mg/g, respectively. The researchers then cultured mouse liver cells (line FL83B) under six different treatments: 1) normal F12-K medium; 2) high-glucose (33mM) medium; 3) high-glucose plus buckwheat extract (100 μg/mL); 4) high-glucose plus rutin (23 μg/mL); 5) high-glucose plus quercetin (6 μg/mL); and 6) high-glucose plus rutin plus quercetin. The concentrations of rutin and/or quercetin in the last three of those treatments were the same as in the treatment with buckwheat extract.
After 48 hours these media were replaced with buffer containing insulin (500nM) and the fluorescent glucose analog, 2-NBDG. After incubation for 20 minutes at 37°C, the cells were washed, and the retained 2-NBDG was measured by flow cytometry. The amount of 2-NBDG that was retained in the cells was an indicator of the insulin sensitivity of cells. The uptake of the glucose analog was significantly lower in the high-glucose treatment than in the cells incubated in normal medium. Compared to the treatment containing only elevated glucose, uptake was significantly greater in all the treatments that contained rutin, quercetin, or buckwheat extract. The high-glucose treatment containing buckwheat extract and the treatment containing rutin plus quercetin were not significantly different from the control containing normal medium.

Lee et al. (2012) also investigated the effects of rutin, quercetin, and Tartary buckwheat extract on levels of Protein kinase B (Akt), a serine/threonine-specific protein kinase, in mouse liver cells cultured under high glucose levels. This enzyme is involved in multiple signaling pathways within cells, thus affecting glucose metabolism. The authors extracted the contents of lysed cells from the treatments described above, subjected the lysates to SDS-PAGE, and probed subsequent Western blots with antibodies to Akt and to phosphorylated Akt (p-Akt). The relative amounts of Akt and p-Akt were estimated from the intensity of protein spots detected by chemiluminescence. The authors concluded that the exposure to high concentrations of glucose induced a condition akin to insulin resistance, including inhibition of the Akt pathway. Treatments with buckwheat extract, rutin, quercetin, or rutin + quercetin all activated the Akt pathway, thus increasing the uptake of glucose by the mouse liver cells.
Western blots described above were also probed with antibodies to Glucose transporter 2 (GLUT2), a membrane-bound protein that can facilitate the transport of glucose molecules between liver cells and blood. Whereas the cells in the high-glucose treatment had less expression of GLUT2 than cells incubated in the normal medium, all the high-glucose treatments that also included buckwheat extract, rutin, quercetin, or rutin + quercetin exhibited greater expression of GLUT2 than the normal control (significantly greater in those treatments that included either the buckwheat extract or rutin). The authors concluded that by increasing Akt phosphorylation these treatments had promoted GLUT2 translocation into the plasma membrane of these liver cells, thereby increasing glucose uptake and alleviating the insulin resistance that resulted from elevated glucose in the medium. No synergistic effect of rutin and quercetin was detected in any of these processes.

Lee et al. (2012) also studied the effects of this Tartary buckwheat extract on the glucose tolerance of mice in which hyperglycemia was induced by a high-fructose diet. Four-week-old mice were subjected to six dietary treatments: 1) a standard (control) diet; 2) high-fructose diet (60%); 3) high-fructose plus buckwheat extract (50mg/kg Body Weight); 4) high-fructose plus rutin (11.5mg/kg BW); 5) high-fructose plus quercetin (3mg/kg BW); and 6) high-fructose plus rutin plus quercetin. After week 4 and again after week 8, food was withheld for 12 hours before glucose (2g/kg BW) was administered orally. Venous blood was withdrawn at times 0, 30, 60, 90, and 120 minutes following the glucose administration, and immediately analyzed for glucose content. After eight weeks of treatment, the blood concentrations of both glucose and insulin were significantly elevated in all high-fructose treatment groups compared to the control mice. The mice receiving buckwheat extract or rutin had significantly lower blood levels of glucose and insulin than mice receiving only the high-fructose diet or those receiving high-fructose + quercetin.

At each sampling time after glucose administration, mice that had received the high-fructose diet had the highest blood glucose levels. Mice receiving either rutin or quercetin in addition to high fructose also had elevated glucose levels. Mice receiving the high-fructose diet augmented either with the Tartary buckwheat extract or with rutin + quercetin had blood glucose levels similar to those of the control mice. From these results the researchers concluded that both rutin and the Tartary buckwheat extract increased the cellular uptake of glucose, counteracting to a significant degree the insulin tolerance that is induced by a high-fructose diet.

High levels of fructose in the diet can promote hepatic steatosis, the abnormal accumulation of lipids in liver cells. Those lipids can lead to an accumulation of reactive oxygen species (ROS); the resultant oxidation stress has been implicated in the development of insulin resistance. To examine the ability of liver cells to resist oxidative stress, Lee and co-workers measured the concentration or activity of four antioxidant enzymes in the eight groups of mice after week 8. They found that the groups with buckwheat extract, quercetin and/or rutin in their diet had significantly higher concentrations of the enzyme superoxide dismutase (SOD) than the mice receiving only the high-fructose diet. Similarly, those groups of mice exhibited significantly greater anti-oxidative activity of catalase (CAT) than those on the high-fructose diet. The groups with diets augmented either with rutin or with buckwheat extract had significantly greater levels of activity of glutathione reductase (GR) than those on the high-fructose diet. The groups with diets augmented either with rutin + quercetin or with buckwheat extract had significantly higher activity of glutathione peroxidase (GPx), compared with the group on the high-fructose diet. From these results in a model organism, it appears that the antioxidants in Tartary buckwheat play a role in countering hyperglycemia.

Several enzymes play a role in balancing the redox (reduction-oxidation) status of tissues by eliminating reactive oxygen species (ROS). An apparent effect of hyperglycemia is a decline in the levels of such in vivo antioxidants, and a concomitant increase in oxidative stress. Transcription of the genes encoding these antioxidant enzymes is initiated by a transcription factor—nuclear related factor 2 (Nrf2). Two major mitogen-activated protein kinase (MAPK) signaling pathways (ERK1/2 and p38) regulate Nrf2, and a third JNK might as well. These signal pathways in turn appear to be regulated by insulin resistance and oxidative stress. If dietary flavonoids can affect these signaling pathways and thus Nrf2, they might also up-regulate such antioxidant enzymes as GR, GPx, CAT, GST, and GSH.

Hu et al. (2016) investigated the protective effects of an extract of Tartary buckwheat seeds against oxidative stress in human liver cells in which insulin resistance had been induced by a high levels of glucose. The investigators sought to determine the underlying mechanisms by evaluating markers of oxidative damage, stress-related signaling pathways, and antioxidant defenses. The extract they used was the same as that used by Hu et al. (2015) (see TARTARY BUCKWHEAT EXTRACT PROTECTS MICE AGAINST VASCULAR AND LIVER DISEASES INDUCED BY A DIET HIGH IN TMAO below). In this extract, concentrations of rutin and quercetin were 536.2 mg/g and 371.6 mg/g, respectively.

Hu et al. (2016) subjected cultured HepG2 cells to a dosage of D-glucose sufficient to induce oxidative stress and insulin resistance. Four treatment groups were first subjected for 24 hours to media that contained the Tartary buckwheat extract at respective concentrations of 0, 25, 50, or 100 μg per mL. Those media were discarded, and then the cells were subjected to a medium containing 30 mM D-glucose for an additional 24 hours. After that exposure to glucose, the cells were exposed to 100nM insulin for 10 minutes. Two additional groups of cells were cultured without exposure to the 30 mM D-glucose challenge or the insulin chase: one of these groups served as a control, and the second received only the 24-hour culture with the buckwheat extract at 100 μg per mL. Cells were then harvested from all six treatments and tested for ROS production, GSH and carbonyl content, and activity levels fo GPx, GR, CAT, and GST.

The authors noted that at these treatment levels, Tartary buckwheat extract showed no effect on either the viability or the proliferation of the human liver cells. They found that compared to control group, the 24-hour high-glucose exposure significantly (p<0.05) increased both ROS generation and protein carbonyl content (which is an indicator of oxidation). The pretreatment with Tartary buckwheat extract countered the glucose-induced oxidative stress (both ROS and carbonyl) in a dose-dependent manner. In fact, in cells that were not challenged with high levels of glucose, exposure to buckwheat extract at 100 μg per mL significantly reduced the level of ROS below the level observed in the control cells. The pattern observed for the level of GSH was opposite to that of ROS: compared to the control, exposure to a high concentration of glucose significantly depressed levels, but that depression was counteracted in a dose-dependent manner by pretreatment with buckwheat extract. Compared to the control, cells exposed to the highest concentration of buckwheat extract (but not to the glucose challenge) contained significantly greater concentrations of GSH.

Compared to the control liver cells, those challenged with elevated glucose exhibited significantly increased activity of the enzymes GPx and GR, but not activity of CAT or GST. While enzyme activity in cells pretreated with buckwheat extract at 25 μg per mL was equivalent of that in the control cells, activity levels of GPx and GR were slightly elevated by the 50 and 100 μg/mL concentrations of buckwheat extract. Compared to the control, cells exposed to the highest concentration of buckwheat extract (but not to the glucose challenge) contained significantly greater concentrations of GPx and GR.

The total cellular level of the transcription factor Nrf2, as well as its level within the nucleus, were compared among 1) the control cells; 2) those that were exposed only to the elevated glucose and the insulin (i.e., buckwheat extract at 0 μg per mL); 3) those that exposed to buckwheat extract at 100 μg per mL, then to glucose, and then to insulin; and 4) those that were exposed to that level of buckwheat extract, but with no subsequent glucose and insulin exposure. Compared to the control treatment, the cells in other three groups exhibited significantly elevated levels of Nrf2—both total and nuclear. In cells exposed to buckwheat extract at 100 μg per mL, but with no subsequent glucose and insulin exposure, the level of Nrf2 in the nucleus was significantly greater than in any other group.

In those four groups of cells, Hu et al. (2016) measured both the phosphorylated and unphosphorylated levels of ERK, JNK and p38. For all three of these MAPKs, phosphorylated levels (e.g., p-ERK, p-JNK, and p-p38) increased significantly in cells subjected to the high-glucose challenge. Exposure to the buckwheat extract alone (without subsequent glucose or insulin) did not modify p-ERK and p-JNK levels; however, the p-p38 level was lower than that found in the control cells. Pre-treatment with buckwheat extract at 100 μg per mL significantly diminished the elevated levels of phosphorylation that the high-glucose challenge had elicited in all three MAPKs. The level of total (i.e., phosphorylated and unphosphorylated) ERK, JNK or p38 was not modified by any treatment. These results suggest that Tartary buckwheat extract can effectively modulate the high-glucose-induced up-regulation of MAPKs and consequently of Nrf2. This up-regulation could effect an increase in transcription of genes for GSH, GPx, and GR. Thus, these regulatory pathways could explain the observed increases in the concentration or activity of antioxidant enzymes, as well as the reduction in oxidative stress in those glucose-challenged liver cells with prior exposure to Tartary buckwheat extract.


Hypertension (persistently elevated blood pressure in the arteries) is a risk factor for several diseases, including atherosclerosis, peripheral vascular disease, heart failure, stroke, and dementia. Arterial blood pressure is determined by cardiac output, total peripheral resistance to blood flow, and arterial stiffness. Total peripheral resistance is increased when arteries are constricted. The degree of constriction is controlled by the balance between a group of chemicals that stimulate the muscles in the walls of arteries to contract (“vasoconstrictors”) and another group that cause those muscles to relax (“vasodilators”). An imbalance that leaves arteries too constricted can lead to atherosclerosis; moreover, by forcing the heart to work harder to maintain blood flow; hypertension can lead to hypertrophy of the heart’s own muscles, and ultimately to heart failure. Among the most potent of known vasoconstrictors are a group of compounds called endothelins. Endothelin-1 (ET-1) is synthesized in the endothelium, the innermost layer of cells in arterial walls. Released into the bloodstream, it can be detected by receptors (ETA) located primarily on smooth muscle cells in arteries, which are thus stimulated to contract. ET-1 is also detected by receptors (ETB) on cells of the endothelium itself. These receptors respond by initiating synthesis of nitric oxide (NO) by the enzyme endothelial nitric oxide synthase (eNOS). Among several physiological functions, nitric oxide stimulates the relaxation of smooth muscle in arteries. Moreover, NO inhibits the release of ET-1, providing a negative feedback on this vasoconstrictive pathway. (It’s thought that NO also has anti-proliferative and anti-inflammatory effects on arterial walls. )

Trimethylamine-N-oxide (TMAO) is an oxidation product of trimethylamine (TMA). TMA is released in the gut by microbial breakdown of several compounds (e.g., choline, betaine, L-carnitine, and lecithin). Elevated levels of TMAO in the blood are strongly associated with arteriosclerosis, although mechanisms are not fully understood. Hu et al. (2015) fed mice a diet rich in TMAO, to observe its effects on several enzymes and other compounds in the blood and liver. The researchers also fed other groups of mice the same TMAO diet augmented with three different levels of an extract of Tartary buckwheat.

Flour from whole seeds was extracted three times with a 75% aqueous solution of methanol refluxed for two hours. Combined crude extracts were centrifuged and evaporated under vacuum. The buckwheat flavonoids were purified by adsorption on an AB-8 resin column, washed with water, desorbed with 60% ethanol solution, and dried. The flavonoid fraction comprised 53.62 percent rutin, 37.16 percent quercetin, and minor quantities of chlorogenic acid, caffeic acid, hypericin, and phloretin. The yield of this extract was 1.8% (w/w) of the Tartary buckwheat flour.

Fifty male mice were divided into five groups, all given free access to a standard rodent chow. A normal (control) group had free access to tap water; the other groups had free access instead to a 1.5% solution of TMAO. Three of those groups receiving TMAO solution also received Tartary buckwheat extract administered intragastrically at daily rates of 200, 400, or 800 mg per kg body weight. Over the 8-week experiment, food and water intake was measured daily and body weights weekly. After eight weeks, blood was drawn, and livers were weighed and sampled. Plasma was analyzed for levels of NO and eNOS; serum was analyzed for levels of ET-1, PGI2, TX-A2, and lipid profiles. Liver tissue was analyzed for levels of NEFA, malondialdehyde (MDA), T-SOD, and GSH-Px.

Compared to mice on the control diet, those receiving TMAO had significantly higher serum levels of ET-1, and significantly lower plasma levels of eNOS and NO. Persistent elevated levels of ET-1 apparently damaged endothelial cells. When the high-TMAO diet was augmented with the buckwheat extract, plasma levels of the enzyme, eNOS, and its product, NO, increased in a dose-dependent manner. Apparently, the buckwheat extract mitigated the damage to arterial endothelium induced by TMAO, and thereby sustained the production of NO within endothelial cells.

Serum concentrations of TX-A2showed a similar trend: increasing significantly with the addition of TMAO to the diet, with that rise countered by the inclusion of the buckwheat extract—significantly so at the higher two treatment levels. In contrast, serum concentrations of PGI2 dropped with the addition of TMAO to the diet, but buckwheat extract countered that reduction. PGI2, a vasodilator, works in opposition to TX-A2, a vasoconstrictor; imbalance between the two can contribute to hypertension.

Compared to those fed the control diet, mice fed the high-TMAO diet had significantly greater liver and body weights, and a greater ratio between those weights. Compared to the mice on the high-TMAO diets, those also receiving Tartary buckwheat extract at the two higher rates had significantly lower liver and body weights, and a lower ratio between those weights. A similar pattern was observed in the lipid profiles of the experimental groups. Compared to the control mice, those on the high-TMAO diet had significantly higher serum levels of total cholesterol, triglycerides, and LDL-cholesterol. The Tartary buckwheat extract ameliorated those effects, significantly so at the two higher treatment rates (400 and 800 mg/kg body weight). An opposite trend was observed for HDL-cholesterol. Tartary buckwheat extract therefore provided some protection against fatty liver disease that dietary TMAO had induced.

Activity levels of the antioxidant enzymes, T-SOD and GSH-Px, were both lower in the livers of mice that had been fed TMAO, compared to those on the control diet (-31.4% and -29.5%, respectively). However, that enzyme inhibition was significantly counteracted by administration of the Tartary buckwheat extract at the middle and high dosage. Hepatic MDA is a marker for oxidative damage to the lipids in the membranes of liver cells. Dietary TMAO increased the levels of MDA more than two-fold. That TMAO-induced increase was counteracted when the diet also included the buckwheat extract at dosages of 400 or 800 mg/kg body weight. A similar trend was observed in hepatic NEFA contents. These results, as well as histopathological examination of the livers of experimental mice, demonstrated that Tartary buckwheat extract can mitigate liver damage caused by exposure to TMAO. That protective effect might be attributed to the enhanced activity of the liver’s antioxidant enzymes, themselves protected or stimulated by the buckwheat’s flavonoids or other constituents.


The consumption of ethanol (i.e., alcoholic beverages) can cause inflammatory damage to the livers of mammals, including humans. Most of the consumed ethanol is metabolized to acetaldehyde, superoxide ions, and hydrogen peroxide. In the body, acetaldehyde is enzymatically degraded to acetic acid, but nevertheless presents some risk of cancer and DNA damage. Superoxide ions and hydrogen peroxide readily bind to lipids and proteins, potentially resulting in alcoholic fatty liver disease. Similarly, exposure to carbon tetrachloride (CCl4) can lead to the formation of trichloromethyl (CCl3.) and trichloromethylperoxy (CCl3OO.) radicals. Binding of those radicals to lipids, proteins, and nucleic acids can also lead to liver injury, due to lipid peroxidation of cell membranes. Antioxidants in general, and rutin in particular, can protect the liver from some of the injuries caused by reactive oxygen species (ROS). Lee et al. (2013) investigated the effects of an extract from Tartary buckwheat seeds as well as its main isoflavonoid constituents—rutin and quercetin—on the livers of mice exposed to ethanol, and on the livers of rats exposed to CCl4. The investigators extracted powdered whole buckwheat seeds in 75 percent ethanol for two hours. This extract was then concentrated under vacuum, freeze-dried, and stored at -20°C until use.

The mice (5-week-old C57BL/6 males) were divided into six treatment groups, receiving 1) a control liquid diet [47% carbohydrate, 35% fats, and 18% protein]; 2) an ethanol liquid diet [as above, with ethanol substituted for 76.7% of the carbohydrate]; 3) an ethanol diet supplemented with silymarin [200 mg/kg body weight]; 4) an ethanol diet supplemented with Tartary buckwheat extract [50 mg/kg body weight]; 5) an ethanol diet supplemented with rutin [11.5 mg/kg body weight]; and 6) an ethanol diet supplemented with quercetin [3 mg/kg body weight]. These dosages of rutin and quercetin were equivalent to the respective amounts in the diet supplemented with Tartary buckwheat extract. After four weeks on the experimental diets, the mice were sacrificed; blood was collected and assayed for aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total cholesterol (TC), and triglycerides (TG). Tissue from livers was examined for evaluated for morphological abnormalities, and a liver homogenate was assayed for levels of reactive oxygen species (ROS) and products of lipid peroxidation (i.e., 4-hydroxynonenal [HNE] and malondialdehyde [MDA]). Both the blood and the liver homogenate were assayed for levels of three inflammatory factors (TNF-⍺, IL-1β, and IL-6). Liver homogenate was also assayed for activity of several anti-oxidative enzymes: catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST).

Lee et al. (2013) reported that compared to mice on the normal diet, those on the ethanol diet had significantly increased levels of AST, ALT, and ALP. Mice on the ethanol diets augmented with silymarin, Tartary buckwheat extract, rutin, or quercetin all exhibited levels of AST, ALT, or ALP that were significantly lower than those of mice on the ethanol diet (if somewhat higher than those on the control diet). These enzymes are indicators of liver cell death, and thus their lower concentrations in the treatments containing isoflavonoids—either in purified form or in the Tartary buckwheat extract—suggest that these substances protect liver cells from the toxic byproducts of ethanol metabolism. (Silymarin is an extract of the milk thistle that is said to protect the liver from alcohol injury. ) In the histological examination of liver tissue from the experimental mice, treatment with Tartary buckwheat extract, rutin, or quercetin reduced the injury score with regard to inflammation or vacuole formation. Across the experimental diets, these patterns paralleled those of the levels of reactive oxygen species and of the levels of products of lipid per oxidation.

Compared to the control diet, the ethanol diet caused a significant increase in the levels of triglycerides and total cholesterol in both the blood and the liver homogenate, i.e., ethanol-induced hyperlipidemia The authors noted that addition of Tartary buckwheat extract, rutin, or quercetin significantly reduced those levels in both the blood and liver.

Dietary ethanol also significantly increased the liver levels of inflammatory factors. The addition of Tartary buckwheat extract to the ethanol diet significantly reduced those levels, as did rutin for IL-1β and IL-6, and quercetin for TNF-⍺ and IL-1β.

Compared to the the control diet, the ethanol diet caused significant decreases in the activity of several antioxidant enzymes in the liver homogenate: CAT, GPx, GR, GST. Inclusion of Tartary buckwheat extract, rutin, quercetin, or silymarin in diets containing ethanol significantly increased those activities compared to the ethanol diet. The same pattern was observed in the concentration of the antioxidant enzyme, SOD. Moreover, the addition of those substances to the diet protected the liver from the depressive effect of dietary ethanol on the level of glutathione, a tripeptide that protects liver cells against ROS.

The results described above were largely replicated in the experiment that Lee et al. (2013) conducted with CCl4-containing diets fed to rats. Taken together, these results constitute a strong argument that consumption of Tartary buckwheat extract containing high levels of rutin and quercetin might counteract the toxic effects of alcohol on the liver.


Consumption of ethanol can induce not only inflammatory liver disease, but also acute gastric lesions (i.e., hemorrhagic stomach ulcers). Ethanol causes veins in the stomach wall to constrict even as arterioles rapidly dilate—a combination that engorges mucosal capillaries. Such circulatory disturbances lead to the generation of free radicals, which then can damage proteins, nucleic acids, and other essential cellular components. Peroxidation of lipids in cell membranes generates toxic epoxides, aldehydes, and yet more free radicals. Moreover, lipid peroxidation leads to the migration of neutrophils into the gastric mucosa, where these white blood cells generate superoxide radicals, as well as increasing the permeability of fine blood vessels. Thus, ethanol-induced gastric pathology includes not only lesions, but also edema and hemorrhage.

Mitigating these destructive effects are sulphydryl (non-protein SH-containing) compounds, which promote blood flow, and anti-oxidative enzymes (e.g., GSH-Px), which help protect gastric tissue by eliminating H2O2 and lipid hydroperoxides. As mentioned above, flavonoids such as those in Tartary buckwheat are effective scavengers of oxygen free radicals and suppressors of lipid peroxidation. The most prevalent of Tartary buckwheat’s flavonoids, rutin has been shown to protect against gastric ulceration from agents such as reserpine, ethanol, or stress caused by physical restraints.

La Casa et al. (2000) investigated the mechanisms by which rutin protects against ethanol-induced gastric damage in rats. Ethanol (50% v/v) was administered orally to Wistar rats at a rate of 1ml/100g body weight. Rutin was administered orally two hours prior to the alcohol, at a rate of 50, 100, or 200mg/kg BW. (As noted in the section above about rutin and TNBS-induced colitis, the rutin molecule is stable under conditions in the stomachs of rats. ) Rats were sacrificed one hour after the experimental period, lesions were scored macroscopically, and mucosa was collected from the stomach wall. Because lipid peroxidation is accompanied by the production of thiobarbituric acid (TBA), mucosal levels of that compound were compared among treatment groups. Because the infiltration of neutrophils is marked by increased myeloperoxidase activity, the level of MPO was also compared among treatment groups. GSH concentrations and GSH-Px activity were compared among rats receiving the different treatments.

La Casa and co-workers reported that their ulceration index was lower in the rats receiving the rutin treatments compared to those to which only ethanol had been administered. While the index was only significantly reduced at the highest dosage of rutin (p<0.05), each increase in the dosage of rutin showed a corresponding reduction in the ulceration index. Lipid peroxidation, as measured by TBS-reactive substances in the gastric mucosa, was significantly higher in rats to which ethanol was administered, compared to control rats (P<0.001). Treatment with rutin prior to ethanol administration significantly reduced the levels of TBA-reactive compounds, with increasing doses of rutin consistently associated with lower levels of the TBA-reactive compounds. All rats receiving p.o. ethanol had significantly higher levels of MPO activity compared to the control rats. Increasing dosages of rutin were associated with decreasing levels of MPO, although none of those treatments were significantly lower than the rats receiving ethanol but no rutin.

The authors reported that rats receiving only ethanol had significantly depressed level of mucosal GSH-Px compared to control rats; whereas, GSH-Px levels were significantly elevated in all those rats receiving rutin in addition to ethanol (compared either to the ethanol-only or to the control groups). In contrast, at no level did rutin significantly increase the mucosal level of SH-containing compounds compared to levels in either the control rats or those receiving only ethanol. This was true both for non-protein SH compounds (such as the tripeptide, glutathione) and for total SH compounds.


Merendino et al. (2014) studied oxidative status and blood pressure in hypertensive rats fed pasta that contained Tartary buckwheat sprouts. (Production of sprouts and pasta are described in FUNCTIONAL FOODS section. ) The researchers measured several markers of cardiovascular function in spontaneously-hypertensive and normotensive (WKY) 12-week-old male rats fed diets that included either commercial all-durum pasta or pasta enriched with Tartary buckwheat powdered sprouts. Rats were sacrificed after six weeks on the experimental diets, and plasma total antioxidant capacity was determined by DPPH radical scavenging and by oxygen radical absorbance capacity (ORAC). In both the normatensive and spontaneously-hypertensive rats, both assays for antioxidant capacity showed significantly greater capacity in those rats fed the Tartary buckwheat-enriched diets. Those rats also showed significantly improved plasmatic oxidative response—as indicated by lower plasma levels of protein carbonyl and of malondialdehyde (MDA). The hypertensive rats that had been fed the buckwheat-enhanced diet showed significantly higher levels of endogenous vasodilators (bradykinin and NO metabolite) and a lower level of a vasoconstrictor (endothelin-1).

Merendino et al. (2014) noted, “It is important to note that the levels of blood pressure-related biochemical parameters in the normotensive control rats did not change significantly, which indicates that TBSP [Tartary buckwheat sprout powder] does not have any contraindications for a healthy group of animals.”


Cheng et al. (2016) evaluated diets containingTartary buckwheat (‘Liuku No. 3’) or common buckwheat (‘Xinnong No. 1’) on renal injury in high salt-induced hypertension in rats.  Eight-week-old male Sprague Dawley rats were randomly assigned to four treatments (n=12 each):  1) a control receiving a normal diet containing 0.5% salt; 2) those receiving a high-salt diet (8% salt); 3) those receiving a diet containing high salt and 15% w/w freeze-dried Tartary buckwheat.; and 4) those receiving a diet containing high salt and 15% freeze-dried common buckwheat powder.  The two buckwheat powders contained similar percentages of macronutrients; however, the level of polyphenols in the Tartary buckwheat powder was 109mg/g, whereas the level in the common buckwheat powder was 39.4mg/g.

Daily food intake and increase in body weight were similar in all treatment groups.  At the end of seven weeks, the ratio of kidney mass:body mass was elevated in all groups on high salt diets, compared to the control group.  However, this rise was significantly smaller in rats also consuming buckwheat powder.  The researchers measured systolic blood pressure once weekly over the 7 weeks.   From the 4th week onward, blood pressure was lower in rats consuming either buckwheat powder compared to those on the high salt diet (p<0.05).

After 7 weeks, Cheng et al. (2016) measured serum levels of sodium ions (Na+) and malondialdehyde (MDA); compared to the control rats, Na+ was elevated by 15% and MDA by 49%.  Those increases were significantly smaller in rats also consuming either of the buckwheat powders.  The addition of high salt to the rats’ diet significantly depressed the bioavailability of nitric oxide (NO) and the activity of the antioxidant enzyme, superoxide dismutase (SOD).  Those decreases were significantly smaller in the rats that had also consumed either of the buckwheat powders.

Kidneys were removed from euthanized rats, and the cortexes were homogenized and centrifuged.  Activity of the membrane-bound phosphatase, Na+/K+-ATPase, was measured in the supernatant.   Enzymatic activity was significantly lower in rats on the high salt versus the control diet.  Enzymatic activity was significantly higher in rats receiving either buckwheat powder compared to those on the high salt diet.  The researchers isolated total RNA from rat kidney cells, and primers for Na+/K+-ATPase were amplified by PCR.  The level of mRNA for that gene showed the same pattern as the level of Na+/K+-ATPase activity.  Western blots of rat kidney proteins revealed the same relative levels of Na+/K+-ATPase among the four treatments.

Western blots were also used to assay levels of ERK and NF-𝜿B p65.  Kidneys of rats on the high salt diet had higher levels of both of these signaling peptides compared to control rats.  Rats consuming either buckwheat powder had significantly lower levels of both peptides compared to rats on the high salt diet.  In line with these biochemical differences, the rats receiving either of the buckwheat powders showed fewer histological signs of renal pathology compared to the rats on the high salt diet.

Cheng et al. (2016) suggested that the protective effect of buckwheat powder against salt-induced hypertension might result directly from protection of kidney cells from reactive oxygen species (ROS).  However, their observations also suggest that buckwheat’s antioxidant effects on vascular tissue could also play a role.


As noted above in the section TARTARY BUCKWHEAT EXTRACT PROTECTS MICE AGAINST VASCULAR AND LIVER DISEASES INDUCED BY A DIET HIGH IN TMAO, insulin is an important regulator of arterial tone. At normal concentrations, insulin stimulates arterial relaxation by promoting the endothelium to produce nitrous oxide (via the phosphatidylinositol 3-kinase [PI3K]/Akt/ endothelial nitric oxide synthase [eNOS] pathway). However, insulin also stimulates the secretion of the powerful vasoconstrictor, endothelin-1 (ET-1), via the mitogen-activated protein kinase pathway. Insulin resistance can disrupt the function of vascular endothelial tissue—impairing the production of NO and/or stimulating the production of ET-1, and thereby causing hypertension. Oxidative stress—when high levels of reactive oxygen species (ROS) overwhelm the cells’ protective antioxidants—can cause excessive scavenging of NO, and deplete its availability in vascular tissue. Antioxidant compounds in the diet might ameliorate oxidative stress, protect NO, and thereby prevent or mitigate hypertension.

Hou et al. (2017) investigated whether long-term administration of an extract from Tartary buckwheat could lower blood pressure in rats which were genetically “spontaneously hypertensive” (i.e., SHRs). This extract was the same as that developed by Hu et al. (2015) and described above (TARTARY BUCKWHEAT EXTRACT PROTECTS MICE AGAINST VASCULAR AND LIVER DISEASES INDUCED BY A DIET HIGH IN TMAO). Their experiment comprised five treatment groups of eight six-week-old male rats each: 1) Wistar-Kyoto (WKY) rats with normal blood pressure; 2) SHRs; 3) SHRs administered buckwheat extract (daily oral gavage, at 50 mg/kg body weight); 4) SHRs administered buckwheat extract (at 100 mg/kg BW daily); and 5) SHRs administered buckwheat extract (at 200 mg/kg BW daily). Systolic blood pressure was recorded every two weeks. After eight weeks, mesenteric arterioles were harvested and cultured for the measurement of vasodilator response.

After eight weeks, the authors observed no differences among treatment groups in the body weights of the rats. The systolic blood pressure of the SRZs was significantly greater than that of the WKY (control) rats: 221 versus 119 mmHg. Administration of Tartary buckwheat extract had lowered systolic blood pressure of SRZs in a dose-dependent manner: 210, 189, and 185 mmHg at the 50, 100, and 200 mg/kg BW dosages, respectively. Similar trends were observed among the treatment groups in their fasting glucose and fasting insulin levels. The authors reported that the ability of insulin to elicit dose-dependent vasorelaxation was diminished in the segments of arterioles from the SHRs, compared to the WKY rats. Vascular segments from SHRs that had received daily administrations of Tartary buckwheat extract (at 100 mg/kg body weight) exhibited significantly greater relaxation in response to insulin than did segments from SHRs that had not received the buckwheat extract. Arterioles from the buckwheat-treated SHRs produced significantly more NO than did the arterioles from SHRs that had not received the buckwheat treatment.

To demonstrate that the buckwheat extract had actually enhanced insulin signaling within the arterial endothelium of the SHR’s, the researchers compared the relaxation of mesenteric segments from the different treatments in response to different concentrations of sodium nitroprusside (SNP), an endothelium-independent vasodilator. They observed no difference among the treatments in the dosage response curve. Hou et al. (2017) also found that SHRs that had received the Tartary buckwheat extract (at 100mg/kg BW daily) had significantly greater phosphorylation of Akt (at serine 473) and eNOS (at serine 1177) in arteriole tissue than did SHRs that had not received the buckwheat treatment. Together, these results confirmed the direct action of the Tartary buckwheat treatment on insulin-signaling in the arterial endothelium.

Oxidative stress induces the phosphorylation of IRS-1 at serine 307, thereby attenuating the phosphorylation of tyrosine in that molecule. This reduces the effectiveness of insulin in activating the Akt/eNOS pathway. To determine whether the buckwheat extract had improved vascular insulin sensitivity in the hypertensive rats by altering the phosphorylation of IRS-1, the authors measured the relative levels of phosphorylation at serine 307 and tyrosine 1222 in the WKY rats, SHRs without buckwheat treatment, and the SHRs that had received the buckwheat extract (at 100mg/kg BW daily). Compared to the mesenteric arterioles of control rats, levels of IRS-1 phosphorylation were significantly elevated at the serine 307 site, and significantly depressed at the tyrosine 1222 site in the arteriole segments of SHRs. The 8-week administration of buckwheat extract significantly reversed both those trends. The authors concluded that the Tartary buckwheat extract had facilitated insulin signaling in vascular tissue of hypertensive rats by lowering the level of serine phosphorylation in IRS-1. Importantly, further experiments indicated that quercetin was the active ingredient in the Tartary buckwheat extract that was responsible for its vasodilatory effect on the vascular tissue of spontaneously-hypertensive rats.


Because high levels of serum cholesterol (particularly LDL) are associated with the risk of cardiovascular disease, many studies have explored dietary factors that might lower levels of cholesterol in the blood.  As discussed in the section “BUCKWHEAT AND CHOLESTEROL,” protein in buckwheat flour, once digested, can bind with bile salts.  By promoting the excretion of bile salts via the feces, buckwheat protein digests might diminish their recycling via the enterohepatic circulation.  Because buckwheat contains substantial amounts of flavonoids, and because the presence of these compounds has been shown to affect serum lipid levels, these compounds constitute another avenue by which buckwheat could protect against cardiovascular disease.

In their study of Swedish day-care workers discussed above, Wieslander et al. (2011) also studied possible effects of buckwheat consumption on lung function, dyspnoea, and markers related to cardiovascular disease. Compared to their baseline scores, the combined experimental groups showed significant reductions in total serum cholesterol and HDL cholesterol (after 4 weeks). Of various measures of lung function, only Forced Vital Capacity showed significant improvement (at 4 weeks). Three markers of inflammation—-levels of serum myeloperoxidase (MPO), serum eosinophilic cationic protein (ECP), and nitrous oxide in exhaled air (NO)-—were not significantly affected by buckwheat consumption. When changes in the high-rutin (Tartary buckwheat cookie) treatment were compared with those in the low-rutin (common buckwheat cookie) treatments, the decline in the serum concentration of myeloperoxide in the former group was significantly greater than in the latter group (at week 4). Moreover, a generalized least-squares model of log-transformed scores for serum MPO showed a substantial negative effect from consumption of Tartary buckwheat. Since MPO is an indicator of neutrophilic inflammation, its reduction implies that rutin has an anti-inflammatory effect.

Lee et al. (2010) investigated the hypolipidemic (cholesterol-lowering) effect of common buckwheat leaves and flowers when added to a high-fat diet.  Leaves and flower parts of common buckwheat grown in Daejon, Korea were air-dried and powdered to pass through a 60-mesh sieve.  For six weeks, groups of male rats (N=10) were fed ad libidum a normal control diet, high-fat diet, or high-fat diet supplemented with buckwheat powder (5% by weight).  Energy content of these diets were 386.2, 498.7, and 501.1 kcal/100g, respectively.  The rats in the high-fat diet had significantly higher energy intake and body weight gain than those in the control group or the group whose high-fat diet was supplemented with buckwheat powder.  The two high-fat groups had identical feed efficiency ratios—significantly higher than that of the control.  In relation to body weight, the liver, heart, and kidney of the rats fed buckwheat powder were significantly smaller than those of the other groups.  The combined weights of adipose tissues (epididymal, perirenal, and interscapular) were lowest in the control group and highest in high-fat diet without buckwheat.

Lee and co-workers (2010) found that the addition of buckwheat powder lowered total plasma cholesterol by 35.9 percent compared to the high-fat diet, and 29.1 percent compared to the control diet.  Total plasma triglycerides were 26.2 percent lower in the buckwheat-augmented diet compared to the high-fat diet, and 34.2 percent lower compared to the control.  Although plasma HDL cholesterol concentration was lowest in the group whose diet included buckwheat powder, the ratio of HDL to total cholesterol was higher in that group than in the group fed a high-fat diet without buckwheat (and equivalent to the control group).  For rats fed a high-fat diet (49.6% of total caloric intake from fats), the addition of buckwheat powder significantly lowered the Atherogenic Index. This index, an estimate of the risk  of cardiovascular disease, was similar to that observed in rats fed a low-fat diet (11.7% of total calories from fat).

Concentrations of triglycerides, cholesterol, and acidic sterol were all higher in feces from the buckwheat-fed rats than from rats on either the control or high-fat diet; the differences in triglyceride and acidic sterol level were significant (p<0.05).

The researchers also isolated hepatic microsomes from rats subjected to the three diets, and assayed these for activity of 3-Hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase and acyl-CoA:cholesterol acyltransferase (ACAT).  The activity of both enzymes was significantly greater in the buckwheat-supplemented diet than in either the control or the high-fat diet.  The authors speculated that the plasma cholesterol reduction effected by the buckwheat powder upregulated HMG-CoA reductase and ACAT as a homeostatic response.


As discussed in “FLAVONOIDS AND ANTIOXIDANT PROPERTIES” oxidative stress within cells causes lipid peroxidation, and the production of dicarbonyls such as isolevuglandins (IsoLGs, 4-oxo-2-nonenal, and malondialdehyde (MDA). These highly-reactive compounds form covalent bonds with proteins, DNA, and phospholipids—inducing inflammation and cytotoxicity. These in turn play an important role in the development of atherosclerosis, which can cause heart attacks and strokes.

While dietary antioxidants might lower intracellular levels of reactive oxygen species (ROS) and thus of lipid peroxidation, trials employing vitamins C or E have shown little effect on atherosclerosis. Elevating the dosages of such non-specific antioxidants might depress the oxidative status of cells enough to interfere with essential cell signaling pathways or anti-bacterial activity. Therefore, an alternative therapy might include compounds that selectively react with lipid dicarbonyl molecules without lowering the levels of ROS generally. Such a compound, 2-hydroxybenzylamine (2-HOBA, also known as 2-aminomethyl phenol), was first detected in seeds of common buckwheat decades ago (Koyama, 1971). Tao et al. (2019) tested the ability of 2-HOBA to suppress atherosclerosis in a hyperlipidemic mouse model. The authors also tested 4-HOBA, an isomer that has been shown to be non-reactive with dicarbonyl species.

Located on the cell surface, the protein Low-Density Lipoprotein Receptor (LDLR) mediates the removal of cholesterol-rich LDL from plasma into cells (primarily within the liver). Mice that are homozygous for a defective mutation in the gene encoding LDLR (i.e., LDLR-/- mice) exhibit elevated levels of LDL in their blood (i.e., hypercholesterolemia). Tao et al. (2019) fed 8-week-old female LDLR-/- mice a western-type diet for 16 weeks. Besides control mice that received only water, treatment groups received water containing either 2-HOBA or its isomer, 4-HOBA (at estimated daily dosage of 200mg/kg body weight). Based on cross-sectional examinations of proximal aortas, mice treated with 2-HOBA exhibited a reduction of at least 31 percent of atherosclerosis compared to either the control mice or the mice treated with 4-HOBA. The extent of aortic atherosclerosis, as estimated from en face examination, was at least 59 percent less in 2-HOBA-treated mice than in control mice or those receiving 4-HOBA. There was no significant difference among treatments in plasma levels of either total cholesterol or triglyceride. In a similar experiment with male LDLR-/- mice, the extent of atherosclerosis in the proximal aorta was reduced by 37 percent, and that in the entire aorta by 45 percent in mice receiving the 2-HOBA treatment. The percentage of necrotic area in the proximal aorta was about one-quarter as great in mice receiving the 2-HOBA treatment compared to those receiving 4-HOBA or the controls receiving water.

The authors stained the proximal aortas and measured MDA adduct by immunofluorescence. The 2-HOBA treatment reduced the amount of adduct by two-thirds compared either to the 4-HOBA treatment or the control. The quantity fo MDA-adducts was 59 percent lower in 2-HOBA-treated mice compared to 4-HOBA-treated mice. The quantity of IsoLG-adducts was 23 percent lower in 2-HOBA-treated mice compared to 4-HOBA-treated mice. Further observations confirmed that these differences were attributable to 2-HOBA scavenging of lipid dicarbonyls. Tao and co-authors concluded, “Taken together, dicarbonyl scavenging using 2-HOBA offers therapeutic potential in reducing atherosclerosis development and the risk of clinical events resulting from formation of vulnerable atherosclerotic plaques.”


Wang et al. (2009) investigated the effects of Tartary buckwheat bran extract (“TBBE”) on the lipid profiles of rats that were fed a high-fat diet. This extract was derived from bran that was itself a by-product of flour production, as described in the section on TARTARY BUCKWHEAT FUNCTIONAL FOODS. Seven-week-old male Wistar rats were randomly assigned to groups (n=10) receiving treatments: 1) a recommended (“control”) diet; 2) a 10-percent-fat (“high-fat control”) diet; 3) a high-fat diet augmented augmented with TBBE at a (low) dosage of 0.2g/kg body weight; 4) a high-fat diet augmented by TBBE at a (medium) dosage of 0.5g/kg BW; or 5) a high-fat diet augmented by TBBE at a (high) dosage of 1.0g/kg BW. After 10 days, rats on the high-fat diet had had serum levels of total triglycerides and total cholesterol that were more than three times those of rats on the control diet. At that time, rats started receiving either distilled water or TBBE solution at 10 mL/kg body weight daily by gavage for six weeks. At the end of that treatment period, blood drawn from carotid arteries was analyzed for total triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), apoA1, apoB, SOD, GSH-Px and MDA. Homogenized liver tissue was analyzed for TG, TC, SOD, GSH-Px, and MDA.

The authors found that the different dietary treatments showed no statistically-significant difference in the increase in body weight. By the second week of treatment, serum TG decreased in the rats in all three TBBE treatments and serum TC decreased in the two treatments with the higher TBBE dosages. After the sixth week of treatment, serum TG and TC levels were significantly lower (P<0.01) in every TBBE treatment compared to rats on the HFC diet. The serum of rats receiving the lowest dosage of TBBE contained a lower concentration of TC than those receiving the normal control diet. Serum levels of HDL-C, LDL-C, apoA1, or apoB did not display consistent patterns across the different treatment groups.

In the liver tissue, the concentrations of TG and TC were significantly lower (P<0.05) in all the TBBE treatment groups compared to the high-fat control group. Activity of SOD was greater in rats receiving TBBE than those in the high-fat control diet (an increase between 4.9 and 17.1 percent), but lower than in those receiving the normal control diet. MDA levels in the liver tissue of rats receiving TBBE treatments was between 35.7 and 29.0 percent lower than the level in rats on the high-fat control diet. The authors concluded that TBBE might mitigate the increases in total triglycerides and total cholesterol in both the blood and livers of hyperlipidemic rats. The mechanism by which TBBE effected these changes was unclear. At the lowest dosage of TBBE, GSH-Px activity was elevated, presumably inhibiting lipid peroxidation and MDA formation, and thus repressing the formation of atheromatous plaque.


Kuwabara et al. (2007) examined the effects of buckwheat sprouts on the plasma cholesterol concentration, fecal steroid excretion, and hepatic mRNA expression related to cholesterol metabolism in rats. Seeds of one variety of common buckwheat (‘Kitawasesoba’) and two of Tartary buckwheat (‘Hokkai T8’ and ‘Hokkai T9’) that had been harvested in Hokkaido, Japan were germinated in the dark and then grown for 5 days in the light at 22ºC. Leaves and stems were harvested at day 9 (common buckwheat) or day 10 (Tartary buckwheat), weighed, and freeze-dried, and ground. The authors randomly assigned 8-week-old male rats to four groups (n=5). Treatments were cholesterol-free diets augmented 5 percent (w/w) with sprout powder from one of the buckwheat varieties, or 5 percent with ⍺-cornstarch (control). Diets augmented with sprout powder from ‘Kitawasesoba,’ ‘Hokkai T8,’ and ‘Hokkai T9’ contained rutin concentrations of 17, 160 and 213 mg/kg body weight/ d, respectively. Fecal excretion was collected for 3 days at the end of the 4-week treatment, and blood was collected from fasting rats. Diets were resumed for 24 hours prior to the rats being sacrificed for the collection of livers, ceca, and blood.

Feed intake, gain in body weight, and final fresh weight of liver and cecum did not vary significantly among the treatments. Compared to the control group, the groups whose feed was supplemented with sprout powder from ‘Kitawasesoba’ common buckwheat or from ‘Hokkai T8’ Tartary buckwheat exhibited significantly higher fecal matter excretion (dry weight basis). Among the four groups there was no significant difference in plasma levels of triglycerides, HDL cholesterol, or non-HDL cholesterol. Plasma levels of total cholesterol were significantly lower in the groups receiving Tartary buckwheat powder compared to the control group (1.87 and 1.93 mmol/L versus 2.30 mmol/L). Moreover, total cholesterol was significantly lower in the group consuming ‘Hokkai T8’ sprout powder compared to the group consuming the common buckwheat powder (2.20 mmol/L).

Kuwabara et al. (2007) found that the level of cholesterol in liver tissue was higher in the rats on the control diet than on those on any of the diets containing buckwheat sprout powder. The level of cholesterol in feces was lower in rats on the control diet, compared to those on the buckwheat diets. A similar pattern was observed in the fecal levels of coprostanol and of total neutral steroids. None of these contrasts was significant at p<0.05. Levels of individual bile acids (cholic acid, deoxycholic acid, chenodeoxycolic acid, and lithocholic acid) and their total concentration were consistently lower in the feces of the control rats than in the feces of rats consuming buckwheat sprout powders. While some of those differences were significant, there was no significant difference between the level of any bile acid in feces from rats consuming common versus Tartary buckwheat sprout powder. A similar pattern was observed for cecal concentrations of short chain fatty acids (acetate, propionate, and n-butyrate), that is, levels were lower in control rats compared to those consuming buckwheat sprout powder. The authors observed that the addition of buckwheat sprout powder promoted cecal fermentation processes in the rats.

Those authors extracted total hepatic mRNA from the experimental rats. Semi-quantitative RT-PCR amplification, and the subsequent hybridization of PCR products with the respective inner oligonucleotides were used to measure the expression of genes for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and cholesterol 7 ⍺-hydroxylase. Significantly higher levels of mRNA for both genes were found in livers from rats fed ‘Hokkai T9’ Tartary buckwheat sprout powder than in livers of control rats. Higher levels of mRNA of both genes were found in rats fed ‘Hokkai T8’ Tartary or ‘Kitawasesoba’ common buckwheat sprout powder than in livers of control rats; however, these differences were significant only for cholesterol 7 ⍺-hydroxylase. The authors suggested that stimulation of hepatic bile acid synthesis from cholesterol might be a mechanism by which buckwheat sprout powders decreased plasma concentrations of cholesterol.


Danihelová et al. (2013) investigated the concentrations of polyphenols in extracts from hulls of nine varieties of common buckwheat and one of Tartary buckwheat. Varieties were grown at Piešťany, Slovak Republic in 2011. Hulls were removed mechanically and extracted with methanol at room temperature for 24 hours. After evaporated extract was dissolved in DMSO, the level of total polyphenols was estimated by Folin-Ciocalteau’s colorimetric assay. Hulls of ‘Madawaska’ Tartary buckwheat contained 635mg Gallic Acid Equivalents per 100g hull dry weight. The hulls of the nine common buckwheat varieties contained between 167 and 406mg GAE per 100g DW. The ability of hull extract to scavenge free radicals generated by DPPH. With activity expressed in equivalents of the antioxidant Trolox, hulls from ‘Madawaska’ exhibited 1039 μM Trolox-equivalents per gram hull dry weight. The common buckwheat varieties exhibited between 19 and 471 μM TE per gram DW. The median activity of those nine varieties was 21.22 μM TE per gram DW.

The antiproliferative effect of buckwheat hull extract on HeLa human cervical cancer cells was measured in vitro with a mitochondrial cytotoxicity test. At 100μg of extract per mL of cell culture, the conversion by viable cells of tetrazolium salt to formazan was measured spectrophotometrically. After a 72-hour exposure at 37°C, the cell counts were reduced by at least 36.5% and by as much as 49.5%, compared to a DMSO control. The antiproliferative effect of the sole Tartary buckwheat variety was less than that of six of the nine common buckwheat varieties.


Kim et al. (2007) investigated the ability of various extracts from hulls of common buckwheat to kill the cells of several different lines of human cancers. A 70 percent ethanol extract from hulls was sequentially fractionated with n-hexane, chloroform, ethyl acetate, ethanol, and water. An in vitro cell proliferation assay of each fraction tested its cytotoxic effect against each of these human cell lines: A549 lung carcinoma, MCF-7 breast cancer, AGS stomach adenocarcinoma, HeLa cervical adenocarcinoma, and Hep3B hepatocellular carcinoma. Each hull extract fraction was also tested against each of 293 lines of adenovirus-transformed primary human embryonic kidney cells—considered to have more normal characteristics than cancer cells.

The proliferation of human breast adenoid carcinoma (MCF-7) cells was inhibited in a dose-dependent manner by all the hull extracts at concentrations between 0.25 and 1.00 mg/mL; at the highest concentration, inhibition was at least 60 percent. Extracts in ethyl acetate, hexane, and chloroform tended to have the greatest effect. The authors reported similar results with A549 lung carcinoma, Hep3B hepatocellular carcinoma, AGS stomach adenocarcinoma, and HeLa cervical adenocarcinoma cell lines. Lower levels of inhibition were observed in the embryonic kidney cell lines—under 40 percent even at the highest concentration.
The authors sought to verify these anti-tumor properties in an animal model.

To initiate the formation of solid tumors in mice, Kim et al. (2007) transplanted seven-day-old sarcoma-180 cells subcutaneously into the groin of the mice at a dose of 1.0X106 cells per mouse. Beginning 24 hours after sarcoma transplantation, the buckwheat hull extract fractions, at doses of 25 or 50 mg/kg body weight, were injected intraperitioneally daily for 20 days. The control mice were injected with a 0.9% NaCl solution. After 26 days, the resultant tumors were dissected and weighed. Compared to the control group, mice receiving all of the fractions of buckwheat hull extract had tumors of significantly-smaller weight. At the lower dosage, tumor weight was reduced between 11.97 percent (aqueous fraction) and 33.34 percent (ethyl acetate fraction). At the higher dosage, tumor weight was reduced between 31.35 percent (aqueous fraction) and 51.99 percent (ethyl acetate fraction). While Kim and co-authors could not attribute the anti-cancer activity of the extracts to particular chemical constituents, they suggested that buckwheat hull, an inexpensive waste product, could be used in functional foods or pharmaceutical mixtures.


Ishii et al. (2008) investigated the effect of an ethanol extract of powdered sprouts of common buckwheat on inflammation caused by lipopolysaccharide (LPS). LPS is a component of the cell walls of gram-negative bacteria, capable of eliciting a massive response from some phagocytes and macrophages of a host’s immune system. The chemokine, Interleukin-8, and the cytokine, Tumor Necrosis Factor alpha (TNF-⍺), are mediators of this potentially-fatal inflammatory response. Antioxidant compounds, such as the flavonoids found in buckwheat, can disrupt the signaling pathway that leads to inflammation, thereby offering some protection against septic shock. These authors tested the effects of the sprout extract and various purified flavonoid compounds on the expression of an interleukin gene (IL-8) in cultured human colon cancer cell lines that had been exposed to LPS. The secretion of IL-8 from the exposed cells was significantly reduced in the presence of the buckwheat extract. Applied individually, none of the purified flavonoids—vitexin, isovitexin, orientin, isoorientin, keracyanin, chlorogenic acid, or rutin—was as effective as the sprout extract in reducing the expression of the IL-8 gene (even at a concentration twice that measured in the sprout extract). The authors passed the buckwheat extract through a column containing a resin to which most flavonoids fail to bind, and they measured the inflamation-inhibiting potential of the fraction that had passed through that column. They then eluted the fraction that had been retained by the resin, and measured the inflamation-inhibiting potential of that fraction. The authors found that the fraction passing through the column had less anti-inflammatory activity than the fraction that was retained by the column. Thus, the inhibition of the IL-8 gene appeared to be caused by some unknown component of the buckwheat sprout other than the flavonoids. Because the most active compound in the sprout extract was unidentified, its concentration—and even its presence—in a corresponding extract from Tartary buckwheat sprouts cannot be inferred.

Ishii et al. (2008) also measured the expression of TNF-⍺ and IL-6 genes in the spleens and livers of LPS-induced mice, to which common buckwheat sprout extract had been administered orally by gavage. In both organs, mRNAs for both genes were significantly reduced (p<0.05) by administration of the buckwheat extract four hours prior to the sacrifice of 8-week-old female mice. Serum levels of these two cytokines were similarly depressed in mice that had received sprout extract, compared to mice that had been exposed to LPS but no extract.

HeLa (human cervical adenocarcinoma) cells can produce high levels of IL-6 and IL-8 without induction by LPS. Therefore, suppression of those genes by buckwheat sprout extract would demonstrate that its anti-inflammatory effect was due to its direct action on those genes, rather than by blocking the binding of LPS to TLR4. The authors found that genes for both IL-6 and IL-8 were suppressed by extract of common buckwheat sprouts.