JP6267410B2 - Vascular endothelial function improver - Google Patents

Description

  The present invention relates to an agent for improving vascular endothelial function, comprising an onion or an onion processed product.

Vascular endothelial cells, nitric oxide (Nitric Oxide, NO), endothelium-derived hyperpolarizing factor (endothelial derived hyperporlaring factor, EDHF) , vascular smooth muscle tone by releasing various vasoactive substances such prostaglandin I ₂ In addition to regulating cell adhesion, it suppresses cell adhesion and platelet adhesion aggregation (Non-patent Document 1). These abnormalities of vascular endothelial function related to vascular protection are observed in lifestyle-related diseases such as hypertension, hyperlipidemia and diabetes, smoking, menopause, etc., and are considered to be the beginning of arteriosclerotic lesions.

  As a non-invasive and repeatable method for measuring vascular endothelial function, FMD (Flow-Mediated Dilation) measurement is frequently used clinically (Non-Patent Document 2). So far, it has been reported that FMD levels are increased by single or continuous intake of foods and vitamins rich in polyphenols such as tea, cocoa and grapes (Non-Patent Documents 3, 4, 5, 6) .

  Onions are said to have a so-called “blood smoothness” effect, but little is actually known about the effects and mechanisms. On the other hand, it is known that onions contain a large amount of quercetin, a kind of polyphenol.

  Non-patent documents 7-9 can be cited as an example of prior art documents relating to the relationship between quercetin and vascular endothelial function.

  Non-patent document 7 shows that the ingestion of pure quercetin 200 mg by humans increases the nitric oxide degradation products in plasma or urine. However, since the production of nitric oxide by inflammatory reaction is much higher than the production amount of nitric oxide by vascular endothelium, the increase of nitric oxide degradation products does not necessarily reflect the improvement of vascular endothelial function (non-patented) Reference 10). Furthermore, Non-Patent Document 7 merely observes an acute change when quercetin is ingested, and it is unclear from this result whether the endothelial function improves when quercetin is ingested continuously.

  In Non-Patent Document 8, a flavonoid such as quercetin was administered 10 mg / kg once a day for 6 weeks to a spontaneously hypertensive rat (SHR) aged 6-7 weeks. It has been disclosed that endothelium-dependent vasodilation has been significantly increased. However, in this experimental system, the dose of quercetin is very large and is not a clinically applicable dose.

  Non-Patent Document 9 discloses that when a rat continuously ingested an extract extracted from onion skin, which is generally rich in quercetin, a blood pressure lowering action was confirmed. However, Non-Patent Document 9 clearly shows that this effect is not caused by the improvement of the vascular endothelial function but caused by the calcium antagonistic inhibitory action. That is, it has been confirmed that onion-derived quercetin does not have an effect of improving vascular endothelial function. Also, it has not been clarified whether there is a similar effect on healthy people with normal blood pressure.

  It is known that the FMD value decreases due to a temporary increase in blood sugar (sugar load) after meals (Non-Patent Documents 11, 12, and 13). This is generally considered to be caused by an increase in oxidative stress due to an increase in blood glucose and a decrease in vascular endothelial function due to an inflammatory reaction. In recent years, epidemiological studies have shown that postprandial hyperglycemia is a risk of cardiovascular events (Non-Patent Document 14). Improvement of vascular endothelial function under postprandial hyperglycemia conditions leads to prevention of arteriosclerotic lesions and the like, and is also demanded in healthy individuals who do not tend to have diabetes or obesity.

Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr, Feb 2006; 83: 456S-460S T Inoue, H et al Flow-mediated vasodilation as a diagnostic modality for vascular failure.Hypertens Res, 2008; 31 (12): 2105-2113 Grassi D. et al Black tea consumption dose-dependently improves flow-mediated dilation in healthy males.J Hypertens. 2009 Apr; 27 (4): 774-81. Schroeter H. et al (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans.Proc Natl Acad Sci U S A. 2006 Jan 24; 103 (4): 1024-9. Lekakis J. et al Polyphenolic compounds from red grapes acutely improve endothelial function in patients with coronary heart disease.Eur J Cardiovasc Prev Rehabil. 2005 Dec; 12 (6): 596-600. Neunteufl T. et al Effects of vitamin E on chronic and acute endothelial dysfunction in smokers.J Am Coll Cardiol. 2000 Feb; 35 (2): 277-83. Loke W. M. et al, “Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men” Am. J. Clin. Nutr. 88 (4): 1018-25 (2008). Machha A. et al, “Chronic treatment with flavonoids prevents endothelial dysfunction in spontaneously hypertensive rat aorta” J. Cardiovasc. Pharmacol., 46 (1): 36-40 (2005) Naseri M. K. G. et al, “Vasorelaxant and hypotensive effects of Allium cepa peel hydroalcoholic extract in rat”, Pak. J. Biol. Sci., 11 (12): 1569-1575 (2008) Yukihito Higashi, Angiology, Vol. 49: 385-390 (2009) Title L. M. et al Oral glucose loading acutely attenuates endothelium-dependent vasodilation in healthy adults without diabetes: an effect prevented by vitamins C and E. J Am Coll Cardiol. 2000 Dec; 36 (7): 2185-91. Kawano H. et al Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999 Jul; 34 (1): 146-54. Lavi T. et al The acute effect of various glycemic index dietary carbohydrates on endothelial function in nondiabetic overweight and obese subjects.J Am Coll Cardiol. 2009 Jun 16; 53 (24): 2283-7. O'Keefe J.H. and Bell D.S. “Postprandial hyperglycemia / hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor.” Am. J. Cardiol. 2007 Sep 1; 100 (5): 899-904 Weiss E.P. et al Endothelial function after high-sugar-food ingestion improves with endurance exercise performed on the previous day. Am J Clin Nutr. 2008 Jul; 88 (1): 51-7

  There is a demand for an agent for improving vascular endothelial function, which contains a natural ingredient that can be ingested continuously as an active ingredient. In particular, there is a need for a vascular endothelial function improving agent that can improve vascular endothelial function under conditions of temporary blood sugar increase (sugar load) after meals.

  The inventor has surprisingly found that by continuously ingesting the onion bulb extract, the vascular endothelial function is improved, in particular, the vascular endothelial function under a glucose load condition is significantly improved, The present invention has been completed.

The present invention includes the following inventions.
(1) A vascular endothelial function improving agent containing onion or an onion processed product as an active ingredient.
(2) The vascular endothelial function improving agent according to (1), which is a vascular endothelial function improving agent for improving vascular endothelial function after a meal.
(3) The onion or onion-treated product is used so that it can be continuously ingested for 7 days or more in an amount of 10 mg / kg body weight or more in terms of dry matter per day for humans or non-human animals. (1) or (2) the vascular endothelial function-improving agent.

  According to the present invention, there is provided a vascular endothelial function improving agent comprising a naturally-derived component that can be continuously ingested as an active ingredient, particularly a vascular endothelial function improving agent effective for improving the vascular endothelial function under a glucose load condition. The The vascular endothelial function improving agent of the present invention is also effective for healthy people who do not have a tendency to diabetes or obesity.

FIG. 1 shows changes in the fasting FMD value and the FMD value after glucose loading of a subject before and after continuous intake of an onion extract prepared from an onion containing an outer skin, which was measured in Test 1. FIG. 2 shows the changes in fasting FMD of subjects before and after continuous intake of onion extract prepared from onion without skin, as measured in Study 2.

<Active ingredient>
The agent for improving vascular endothelial function of the present invention comprises onion or an onion-treated product as an active ingredient.
Onion refers to plants classified under the scientific name Allium cepa . The variety of onion used in the present invention is not limited.

  The onion used for this invention should just contain the part (bulb part) of the bulb | ball normally eaten, and it does not ask | require whether it contains the crust of the bulb part. Furthermore, it does not matter whether other parts (leaves, roots) of the onion are included. The onion used in the present invention is typically an onion bulb portion having an outer skin or an onion bulb portion from which the outer skin has been removed. It is known that the outer skin of the onion bulb part contains a lot of quercetin, but the results of Test 2 described later suggest that the vascular endothelial function improving action of the onion is not caused by quercetin, and the onion bulb part The hull is not essential.

  The onion may be appropriately processed into a desired shape. Onions that have been subjected to physical treatment such as crushing with a mixer or the like are included in the onions of the present invention.

  The onion-treated product is not particularly limited as long as it is a composition obtained by treating the onion, but preferably, the juice obtained by separating the liquid fraction of the onion crushed material, the onion or the juice from the extraction medium The extract obtained by extracting by the above, the juice or extract, or the concentrate or dry product obtained by concentrating or drying the mixture of both. In the present specification, a concentrate or dried product obtained by concentrating or drying the juice or extract or a mixture of both is particularly referred to as “onion extract”. The juice, the extract, or the onion extract (the concentrate or the dried product) may be further provided as a diluted product diluted with a solvent such as water or ethanol. A mixture of two or more of the juice, the extract, and the onion extract may be used as an active ingredient.

  The onion juice can be produced by a method including a squeezing step of separating the liquid fraction in the crushed onion and the solid fraction such as the cell wall and obtaining the liquid fraction. The crushed onion can be prepared by crushing the onion by crushing, pressing, or the like using a mixer, a comitrol, a micromeister, a press, or the like. Separation of the liquid fraction and the solid fraction can be performed by ordinary solid-liquid separation means such as centrifugation and filtration (for example, diatomaceous earth filtration). The squeezing step can be performed simultaneously with crushing, for example, by pressing. The onion before crushing is kept in its original form or cut into an appropriate size and shape, and heated by microwave heating, boiling, steam heating, etc. to deactivate enzyme activities such as glucosidase in the onion in advance. Also good. Further, the squeezing step may be performed after heating the crushed onion to promote the elution of the water-soluble component in the pulverized product into the liquid fraction. When heating the crushed onion, the heating temperature and the heating time are not particularly limited, and for example, the onion can be heated at 60 to 125 ° C. for 5 to 120 minutes. As an onion for squeezing, the onion residue produced when preparing an extract from an onion by the following procedure can also be used.

  The onion extract can be produced by extracting the onion or the juice from the extraction medium. Examples of the extraction medium include organic solvents, solvents such as water, and supercritical fluids such as supercritical carbon dioxide, and solvents are particularly preferable. As the solvent, water, alcohols such as ethanol, organic solvents such as hexane and acetone can be used, and water or ethanol or a mixed solvent of water and ethanol is particularly preferable. When producing an onion extract by solvent extraction, immerse the onion or the juice in an appropriate amount of solvent (for example, 0.5 to 20 times the weight of the onion or the juice (wet weight) on a weight basis), The solvent-soluble component is eluted in the solvent by stirring or standing as appropriate. Although extraction time is not specifically limited, It can be 5 to 120 minutes or more, and it is preferable that it is 15 to 30 minutes. Although extraction temperature is not specifically limited, It can be 0-125 degreeC, and it is preferable that it is 60-125 degreeC. After extraction, a solvent fraction containing a solvent-soluble component and a solid fraction such as a cell wall are separated by the above-mentioned solid-liquid separation means, and the solvent fraction is obtained as an extract. The shape of the onion used for extraction can be the original shape, a state cut into an appropriate size or shape, or the shape of the above pulverized product. The onion used for extraction may be an appropriately dried onion. The onion used for extraction may be obtained by heating the onion in advance and deactivating enzyme activities such as glucosidase in the same manner as described above before pulverization or the like. When the onion residue after extraction can be further squeezed (for example, when the onion is used as it is in its original form or cut into an appropriate size or shape, the squeezed onion after extraction) The residue after extraction may be used for the preparation of the above-mentioned onion juice.

  The onion extract can be produced by concentrating or drying the juice or extract or a mixture thereof. Concentration here refers to reducing the liquid (water and / or extraction solvent) in the juice or extract or a mixture thereof to a final sugar concentration of 50% or more. The sugar concentration can be measured with a commercially available saccharimeter. Drying refers to substantially removing the liquid in the juice or extract or a mixture thereof.

As a concentration method, for example, vacuum evaporation concentration or membrane concentration can be employed.
Vacuum evaporation concentration is generally called vacuum concentration. The degree of vacuum at the time of concentration can be selected as long as the final product can have a sugar content of 50% or more, and is not particularly limited.
Membrane concentration can be performed using a membrane such as a reverse osmosis membrane (RO) or an ultrafiltration membrane (UF). The type of membrane to be used can be selected within a range where the sugar content can be 50% or more, and is not particularly limited.

  Drying can be carried out by drying the juice, the extract, or the concentrate using ordinary means such as freeze drying and drying under reduced pressure.

  At the time of concentration or drying, concentration or drying may be performed by combining the juice, the extract, or the concentrate with other components such as excipients.

<Vascular endothelial function improver>
The vascular endothelial function improving agent of the present invention has an ability to improve vascular endothelial function, particularly the ability to produce nitric oxide (NO) in vascular endothelium. Vascular endothelium NO production ability should be evaluated based on the rate of increase in blood vessel diameter (FMD value (%)) due to blood flow-dependent vasodilation (FMD (Flow-Mediated Dilation)) after hand or foot transfusion. Can do. The FMD value can be measured by a normal FMD inspection apparatus.

  FMD is generally used as a method for measuring vascular endothelial function in humans, but methods other than FMD such as a method using strain gauge plethysmography and a method using fingertip volume pulse wave (Endo-PAT) are also available. You may use. Vascular endothelial function is preferably measured in humans, but may be confirmed by in vivo or ex vivo animal tests or in vitro indicators such as NO production ability using endothelial cells.

  The vascular endothelial function improving agent of the present invention includes arteriosclerosis, chronic kidney disease (CKD), hypertension, dyslipidemia, diabetes, obesity / metabolic syndrome, coronary artery disease, cerebrovascular disease, disseminated intravascular coagulation syndrome (DIC) ), Can be used for the prevention or treatment of diseases such as collagen disease. The vascular endothelial function improving agent of the present invention is effective not only for diabetic patients and subjects who are obese, but also for healthy subjects.

  The vascular endothelial function improving agent of the present invention can improve the vascular endothelial function under post-meal blood glucose elevation (sugar load) conditions. Moreover, since the vascular endothelial function improving agent of the present invention has a naturally-derived component as an active ingredient and has high safety in oral intake, it is suitable for long-term intake. For this reason, the vascular endothelial function improving agent of this invention can suppress continuously the fall of the vascular endothelial function by a daily meal by ingesting continuously.

  The subject of the vascular endothelial function improving agent of the present invention is typically a human, but is not limited to a human and may be other non-human animals, for example, mammals other than humans.

The vascular endothelial function improving agent of the present invention can be used in the form of foods and drinks, pharmaceuticals (including those classified as quasi-drugs, the same applies hereinafter), cosmetics, and the like. Preferably, the composition is orally ingested in the form of food and drink, pharmaceuticals, etc., but is not limited thereto, and other routes such as intravenous administration, intrathecal administration, subcutaneous administration, sublingual The composition may be administered by routes such as administration, rectal administration, vaginal administration, eye drops, nasal administration, inhalation, transdermal administration, and transdermal absorption.

  The vascular endothelial function-improving agent of the present invention preferably contains an amount of onion or an onion-treated product having a desired effect, and may consist entirely of onion or an onion-treated product, It may contain an onion processed product and other components.

The vascular endothelial function improving agent of the present invention may further contain other components. Other components are not particularly limited as long as they are acceptable components in the final form such as foods and drinks, pharmaceuticals, and cosmetics.

  The shape of the vascular endothelial function improving agent of the present invention is not particularly limited and can be liquid, solid or semi-solid.

The aspect of the said food / beverage products is not limited, It can be aspects, such as a health food, a dietary supplement, a nutritional functional food, a food for specified health. The food and drink is onion or onion processed product and other components acceptable as food and drink, for example, fructose glucose liquid sugar, cyclic oligosaccharide, acidulant, thickener, inositol, fragrance, niacin, antioxidant, Vitamins, sweeteners, water and the like can be included.

  The pharmaceutical dosage form is not particularly limited, and examples thereof include capsules, tablets, granules, injections, suppositories, patches, ointments, fine granules, caplets, powders, liquids, and troches. For pharmaceuticals, onions or processed onions are used as pharmaceutically acceptable other formulation materials such as excipients, disintegrants, lubricants, binders, antioxidants, coloring agents, anti-aggregation agents, absorptions. It can be produced by formulating a combination of an accelerator, a solubilizer, a stabilizer and the like as appropriate.

  The form of the cosmetic is not limited, and may be, for example, a cosmetic cream, a lotion, a milky lotion, a lotion pack, a dispersion, a cleaning agent, or the like. Cosmetics can be prepared by appropriately combining onion or an onion-treated product and other components acceptable as cosmetics, such as excipients and carriers.

  The intake amount of the vascular endothelial function improving agent of the present invention is not particularly limited, and can be appropriately set according to the intake route, the age, weight, symptom, etc. of the subject human or animal. For example, the vascular endothelial function improving agent is preferably an active ingredient onion or onion processed product per day, preferably 10 mg / kg body weight or more (preferably adult human or non-human animal) in terms of dry matter. The same applies hereinafter), more preferably 30 mg / kg body weight or more. Ingestion is preferably oral, but is not limited thereto. Intake of the vascular endothelial function improving agent can be performed once to several times a day.

  The vascular endothelial function improving agent of the present invention is preferably taken continuously. Preferably, the daily dose is taken continuously for 7 days or longer, more preferably 14 days or longer, particularly preferably 30 days or longer.

Test 1
Materials and methods
Subjects and study design
This was a self-control study in which 22 healthy men were used as subjects, and various indicators were compared before and after continuous onion extract intake. The intake period was 4-5 weeks, and during the period, we asked them to take the test meal every day. On the first day of the intake period and the day after the last day, pre- and post-ingestion tests were performed.

  The dinner the day before the test and the test meal were consumed by 21:00 (hereinafter, only water can be consumed). All inspections were conducted in an environmental test room (adjusted to 24 ° C and 50% RH by air conditioning). Visited at 9 or 10 o'clock and started inspection. Body weight was measured at the start of the test, and after resting at the desk for 1 hour, FMD values, systolic blood pressure, diastolic blood pressure, heart rate, resting blood flow, and rate of increase in blood flow were measured. Thereafter, a juice containing 75 g maltose was ingested, and the FMD value and the like were measured again 1 hour after ingestion.

Test meal onion extract powder: Peeled onion (Hokkaido northern maple), cut 1/4, added 100 parts by weight of water, and extracted by heating at 95 ° C for 15 minutes. After sieving, the residue portion was squeezed and added to the liquid portion. The obtained liquid was filtered to remove the fiber component, and then concentrated to Brix 50 with an evaporator. The obtained extract was sterilized at 85 ° C. for 10 minutes. The obtained extract was freeze-dried and then pulverized to obtain about 6 parts by weight of onion extract powder.

  Test meal: To the onion extract powder 2.2g obtained above, add 0.59g of skin-derived quercetin raw material (PA-5 manufactured by Yokohama Yushi Co., Ltd.), 1.5g of lactose (excipient), and 18.5mg of sucralose (sweetener) 4.3 g of powdery test meal was obtained.

  4.3 g of the above test meal was suspended in 120 ml of water once a day. The intake time does not matter. Table 1 shows the nutritional components in 4.3g of the test meal.

FMD value measurement
For the measurement of the FMD value, an FMD measuring apparatus manufactured by UNEXX Corp. was used. The measurement method was performed according to the already reported guidelines for FMD measurement (T Inoue, H et al Flow-mediated vasodilation as a diagnostic modality for vascular failure. Hypertens Res, 2008; 31 (12): 2105- 2113; and Mary C. et al Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J. Am. Coll. Cardiol., 2002; 39 ( 2): 257-265).

  After moving to the bed and resting for 20 minutes, the FMD value was measured by a conventional method. In addition, the measurement position was marked with surgical tape at the time of measurement before sugar loading, and the measurement was performed at the same position at the time of measurement after sugar loading. At the time of the inspection before continuous intake, the distance from the elbow to the measurement position was measured, and the measurement position was aligned even in the measurement after continuous intake.

Statistical analysis R language (a programming language for statistical analysis) was used for statistical analysis.
Analysis of FMD value, systolic blood pressure, diastolic blood pressure, heart rate, resting blood vessel diameter, and blood flow increase rate was performed by analysis of variance of two repeated measures (continuous intake of onion extract and glucose load) (significance level) p <0.05). When there was a paired interaction, a paired t-test was performed as a subtest. For analysis of body weight and BMI, a paired t-test was performed (significance level p <0.05).

result
Subject background and intake situation The subject background is shown in Table 2.
All 23 subjects completed the study without discontinuation or dropout. The average intake period was 30 days, and the average intake of the test meal was 29. During the intake period, there were no adverse events that could be attributed to test meal intake. Data was excluded because one of the subjects had a problem with the method of intake. There was no change in body weight or BMI with ingestion.

FMD value change
Changes in FMD values were significant in all of the main effects of glucose load, the main effects of continuous onion extract intake, and the interaction between the two (Table 3).

  When subtests were conducted for interaction, FMD values decreased significantly with glucose load both before and after continuous intake (p <0.01). Fasting FMD increased by 0.8 percentage points with continuous intake, and the increase was significant (p <0.05). The FMD value after glucose load increased by about 1.6 percentage points with continuous onion extract intake, and the increase was significant (FIG. 1).

The change systolic blood pressure and heart rate of various indices were significantly increased by glucose load (Table 3). In addition, no significant changes were observed in the diastolic blood pressure, resting blood vessel diameter, and blood flow increase rate before and after intake and due to glucose load. No significant changes in body weight and BMI were observed before and after ingestion.

Consideration
Changes in FMD values With continued onion extraction, the fasting FMD values tended to increase slightly. Furthermore, FMD values after glucose loading increased significantly after continuous intake. There was no change in blood flow increase rate, blood pressure, pulse, etc. before and after the onion extract intake. Therefore, the improvement of FMD value is considered to be due to the improvement of vascular endothelial function. From these results, it was shown that continuous intake of onion extract prevents a decrease in endothelial function due to glucose load.

  So far, it has been reported that the endurance exercise on the previous day improves the vascular endothelial function after ingesting a high sugar diet in healthy individuals (Non-patent Document 15). In addition, it has been reported that when vitamins C and E are taken simultaneously with glucose, a decrease in FMD value is suppressed (Non-patent Document 11). However, there is no report that the intake of food up to the previous day suppresses the decrease in post-prandial FMD levels in healthy people, and this result gives new knowledge.

  It is unclear what mechanism the intake of onion extract improved the decrease in vascular endothelial function after glucose loading.

  It is clinically significant that even a healthy person who does not tend to have diabetes or obesity can suppress a decrease in vascular endothelial function due to postprandial hyperglycemia by continuous intake of onion extract. According to the present invention, even a healthy person can make the endothelial function more healthy by taking onion extract.

The systolic blood pressure and heart rate increased significantly by changing glucose load of various indices . Although it may be possible due to cold stimulation of the beverage, the amount of change is slight and it does not have a significant effect on the results.

Test 2
Method
A self-control study was conducted in which 4 healthy men were used as subjects and various indicators were compared before and after continuous onion extract intake. The intake period was 4 weeks, and we asked them to take the test meal every day during the period. On the first day of the intake period and the day after the last day, pre- and post-ingestion tests were performed. 4 healthy men once a day for 3 months, 3.1g of powdered extract (powder containing 9mg of quercetin) obtained by heating, squeezing, filtering, concentrating and drying onion without skin Ingested (regardless of ingestion time).

  Onion extract powder: A commercially available onion (north maple) was peeled and cut 1/4 with a knife equally when viewed from above to obtain 100 parts by weight of an onion bulb. This was heated at 120 ° C. for 20 minutes and then crushed with a home-use mixer (MX-X107 National). The liquid crushed material was centrifuged using a centrifuge (himac CR21 manufactured by Hitachi, rotor: RPR9-2) at 4 ° C., 8000 rpm, and 15 min. The supernatant was freeze-dried to obtain about 6 parts by weight of a powdery extract.

  Ingestion method: In Test 2, do not use skin-derived quercetin raw materials or excipients, suspend only 3.1 g of the powdered extract obtained in the above procedure once a day in 120 ml of water. got.

  For the measurement of the FMD value, an FMD measuring apparatus manufactured by UNEXX Corp. was used. The measurement method was performed according to the already reported guidelines for FMD measurement (T Inoue, H et al Flow-mediated vasodilation as a diagnostic modality for vascular failure. Hypertens Res, 2008; 31 (12): 2105- 2113; and Mary C. et al Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: A report of the International Brachial Artery Reactivity Task Force. J. Am. Coll. Cardiol., 2002; 39 ( 2): 257-265).

  After moving to the bed and resting for 20 minutes, the FMD value was measured by a conventional method. In addition, the measurement position was marked with surgical tape at the time of measurement before sugar loading, and the measurement was performed at the same position at the time of measurement after sugar loading. At the time of the inspection before continuous intake, the distance from the elbow to the measurement position was measured, and the measurement position was aligned even in the measurement after continuous intake.

  The dinner the day before the test and the test meal were consumed by 21:00 (hereinafter, only water can be consumed). All inspections were conducted in an environmental test room (adjusted to 24 ° C and 50% RH by air conditioning). Visited at 9 or 10 o'clock and started inspection. Body weight was measured at the start of the examination, and after resting at the desk for 1 hour, FMD values, systolic blood pressure, diastolic blood pressure, heart rate, resting blood vessel diameter, and blood flow increase rate were measured.

The results are shown in Table 5 and FIG. Fasting FMD increased by about 0.6 percentage points (p = 0.05). There was no change in other hemodynamics.

  The onion extract used in Test 2 has a significantly lower quercetin content than the onion extract used in Test 1. However, in Test 2, it was confirmed that the fasting FMD value increased to the same level as in Test 1 by continuous onion extract intake. This clearly shows that the improvement of vascular endothelial function by ingestion of onion extract is not due to quercetin. The quercetin content contained in the onion extract used in the present invention is not particularly limited.

Claims (2)

Onion bulb crushed material having an outer skin, juice 1 that is a liquid fraction of an onion bulb portion crushed, onion bulb portion having an outer skin, or extract 1 that is an extract of the juice 1 above, Juice 2 or onion which contains the concentrate or dried product of juice 1 or extract 1 or a mixture of both as an active ingredient, or is a liquid fraction of onion bulb crushed material, onion bulb crushed material Contains as an active ingredient the extract 2 which is the extract of the bulb part or the juice 2, the concentrate 2 or the dried product of the juice 2 or the extract 2 or a mixture of both , and the quercetin raw material derived from the onion peel In order to improve the vascular endothelial function after eating in healthy people, the vascular endothelial function depends on blood flow-dependent vasodilation (FMD (Flow-Mediated Dilation)) after hand or foot blood transfusion. An agent for improving vascular endothelial function for oral intake , which is a vascular endothelial function evaluated based on the rate of increase in blood vessel diameter (FMD value (%)) . Onion bulb crushed material having an outer skin, juice 1 that is a liquid fraction of an onion bulb portion crushed, onion bulb portion having an outer skin, or extract 1 that is an extract of the juice 1 above, Juice 1 or extract 1 or a mixture of both, or a dried product , a crushed product of an onion bulb part, a squeezed juice 2, an onion bulb part or the squeezed liquid fraction of an onion bulb part Extract 2, which is extract 2 of the above, extract 2 or extract 2 or a mixture or a mixture of both , and quercetin raw material derived from onion peel are dried per day for healthy individuals The vascular endothelial function-improving agent according to claim 1, wherein the vascular endothelial function-improving agent according to claim 1, wherein the vascular endothelial function-improving agent is used so as to be ingested continuously for 7 days or more in an amount of 10 mg / kg body weight or more in terms of physical weight.

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