Composition for improving blood pressure or arterial function

Abstract

To provide a composition for improving blood pressure or arterial function.SOLUTION: A composition for improving blood pressure or arterial function contains esparcette honey as an active ingredient.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a composition for improving blood pressure or arterial function. Specifically, the present invention relates to a composition for improving blood pressure or arterial function, which contains espalthe honey as an active ingredient.

Background Art

[0002] Cardiovascular and cerebrovascular diseases are the first and second leading causes of death worldwide and account for approximately one-third of the causes of death in Japan. Since the incidence of these atherosclerotic diseases increases with aging and poor lifestyle habits (such as lack of physical activity, smoking, etc.), it is extremely important to prevent and improve vascular protection and atherosclerotic diseases more simply and effectively by means with fewer side effects and adverse effects. Elevated blood pressure, impaired vascular endothelial function (such as abnormal vasodilation regulation), and increased arterial stiffness (increased arterial wall sclerosis) are strong risk factors for vascular damage, atherosclerotic diseases, and cardiovascular diseases. That is, deterioration of blood pressure and deterioration of arterial functions such as vascular endothelial function and arterial stiffness strongly affect the future onset and prognosis of vascular damage, atherosclerotic diseases, and cardiovascular diseases. Therefore, it is recommended to maintain blood pressure and arterial functions (such as vascular endothelial function, arterial stiffness, etc.) in a favorable state. It is known that blood pressure and arterial functions (such as vascular endothelial function, arterial stiffness, etc.) can be transiently and continuously improved by exercise (physical activity), intake of drugs or foods.

[0003] In recent years, various studies have been conducted on food components for improving blood pressure and arterial function (vascular endothelial function, arterial stiffness, etc.) with the aim of easier intake and reduction of side effects and adverse effects. For example, conventional methods include using cocoa polyphenols to improve arterial stiffness (Patent Document 1), using isomaltulose to suppress the increase in arterial stiffness due to dietary intake (Patent Document 2), using procyanidin B1 and procyanidin B3 derived from pine bark to improve vascular endothelial function (Patent Document 3), using isoxanthoflumol to improve vascular endothelial function (Patent Document 4), using sacha inchi oil to improve vascular endothelial function (Patent Document 5), and using a combination of citrulline and glutathione to prevent or improve the decline in vascular endothelial function (Patent Document 6).

[0004] However, while isomaltulose has been reported to suppress the increase in arterial stiffness after meal intake, it does not have the effect of continuously reducing arterial stiffness. Furthermore, regarding cocoa polyphenols, procyanidin B1 and procyanidin B3, isoxanthoflumol, sacha inchi oil, citrulline, and glutathione, problems include the high calorie intake of the food being provided, the time and effort required for extraction and processing, the difficulty in obtaining effects in the short term, and the fact that the taste is not suitable for continuous intake.

[0005] On the other hand, Yahashi honey has been proposed for use in eradicating Helicobacter pylori, a causative agent of peptic ulcers, and Porphyromonas gingivalis, a causative agent of periodontal disease (Patent Documents 7 and 8). In addition, honey vinegar (brewed vinegar made primarily from honey) has been proposed for use in improving blood flow and sleep induction (Patent Document 9). Honey has also been reported to be useful in alleviating atherosclerosis (Non-Patent Documents 1 and 2).

[0006] However, no compositions for improving blood pressure or arterial function that use a specific type of honey itself as an active ingredient have been reported to date. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] International Publication No. 2017 / 026471 [Patent Document 2] Japanese Patent Publication No. 2021-1139 [Patent Document 3] Japanese Patent Publication No. 2022-33803 [Patent Document 4] International Publication No. 2020 / 116381 [Patent Document 5] Japanese Patent Publication No. 2018-203695 [Patent Document 6] International Publication No. 2013 / 122188 [Patent Document 7] International Publication No. 2008 / 133098 [Patent Document 8] International Publication No. 2013 / 118759 [Patent Document 9] Japanese Patent Publication No. 2020-40901 [Non-patent literature]

[0008] [Non-Patent Document 1] Nutrients,2019,Vol.11,Iss.1,167 [Non-Patent Document 2] Frontiers in Pharmacology,2017,Vol.8,Article 412 [Overview of the project] [Problems that the invention aims to solve]

[0009] As mentioned above, numerous studies have been conducted on various approaches, including exercise, medication, and food, to improve age-related increases in blood pressure and decreased arterial function (such as decreased endothelial function and increased arterial stiffness) associated with aging and poor lifestyle habits. However, with regard to exercise, individuals with low physical fitness or underlying medical conditions may not be able to exercise sufficiently or may find it difficult to continue. Furthermore, the administration of medications can cause significant side effects and adverse effects, making them unsuitable for long-term, daily preventative measures.

[0010] Against this backdrop, there is a need for compositions that can be easily consumed on a daily basis as foods or supplements, and that are expected to have a certain effect, such as temporary or continuous improvement, on blood pressure and arterial function (vascular endothelial function, arterial stiffness, etc.).

[0011] This invention has been made in view of the above circumstances, and the problem it aims to solve is to provide a composition for improving blood pressure or arterial function. [Means for solving the problem]

[0012] The inventors diligently investigated the above-mentioned problems and, as a result, first discovered in in vitro tests that certain types of honey (multifloral honey collected from esparcet flowers and various herb flowers) can activate vascular endothelial cells and enhance resistance to oxidative stress. Next, the inventors focused on esparcet flowers from among the honey sources used in the in vitro tests and conducted clinical trials using monofloral esparcet honey. As a result, they found that a single dose of this honey transiently reduced arterial stiffness and softened arteries, and that continuous consumption of this honey led to a decrease in blood pressure, a reduction in arterial stiffness, and an improvement in vascular endothelial function. Furthermore, the inventors conducted a metabolome analysis of esparcet honey and discovered that esparcet honey has a unique component composition different from commercially available ordinary honey and honey known for its high health benefits (manuka honey). This result also confirmed that esparcet honey possesses advantages that cannot be substituted by other honeys. Based on these findings, the inventors conducted further research and ultimately completed the present invention. In other words, the present invention is as follows:

[0013] [1] A composition for improving blood pressure or arterial function, containing esparcet honey as an active ingredient. [2] The composition according to [1], wherein the arterial function is vascular endothelial function or arterial stiffness. [3] The composition according to [1] or [2] above, which is used for the prevention or improvement of symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function. [4] An oral composition, the composition according to any one of [1] to [3] above. [5] A food composition, the composition according to any one of [1] to [4] above. [Effects of the Invention]

[0014] According to the present invention, a composition useful for improving blood pressure or arterial function can be provided. This composition is also useful for preventing or improving symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function. Esparse honey, which is the active ingredient of the composition of the present invention, is highly safe and has excellent taste. Therefore, the composition of the present invention can be continuously ingested or administered. In addition, the composition of the present invention can obtain excellent improvement effects on blood pressure or arterial function in a short period. For example, desired effects can be obtained even by single ingestion or administration. Esparse honey, which is the active ingredient of the composition of the present invention, is relatively easy to extract and process.

Brief Description of Drawings

[0015] [Figure 1] It is a graph showing the experimental results of Experiment 1-1. Specifically, it is a graph showing the measurement results of the number of viable cells of human umbilical vein endothelial cells (HUVEC) when honey A (in the figure, "ALAY HONEY"), honey K (in the figure, "Kara-Kulja Raw Honey") or honey N (in the figure, "Normal Honey") is added, or when no honey is added (in the figure, "Control"). [Figure 2] It is a graph showing the experimental results of Experiment 1-2. Specifically, it is a graph showing the measurement results of the number of viable cells of human umbilical vein endothelial cells (HUVEC) when, in addition to hydrogen peroxide, honey A (ALAY HONEY), honey K (Kara-Kulja Raw Honey) or honey N (Normal Honey) is added (in the figure, "H2O2+A", "H2O2+K" or "H2O2+N"), when hydrogen peroxide is added and no honey is added (in the figure, "H2O2"), and when neither hydrogen peroxide nor honey is added (in the figure, "C"). [Figure 3] It is one of the graphs showing the experimental results of Experiment 2. Specifically, it is a graph showing the measurement results of haPWV before ingestion of the experimental diet (in the figure, "Base") and 15 minutes, 30 minutes and 60 minutes after ingestion. [Figure 4] It is one of the graphs showing the experimental results of Experiment 2. Specifically, it is a graph showing the measurement results of CAVI before ingestion of the experimental diet (in the figure, "Base") and 15 minutes, 30 minutes and 60 minutes after ingestion. [Figure 5]This is one of the graphs showing the experimental results from Experiment 2. Specifically, it is a graph showing the percentage change from baseline (before intake) of CAVI, which was measured 30 minutes after ingestion of the experimental food. [Figure 6] This is one of the graphs showing the experimental results of Experiment 3. More specifically, it is a graph showing the percentage change in systolic blood pressure before and after the intervention period. [Figure 7] (a) and (b) are graphs showing the experimental results of Experiment 3, respectively. Specifically, (a) is a graph showing %FMD before ("pre" in the figure) and after ("post" in the figure), and (b) is a graph showing the change in %FMD before and after the intervention period. [Figure 8] This is one of the graphs showing the experimental results of Experiment 4. Specifically, it shows the results of hierarchical cluster analysis of detected substances in regular honey, Manuka honey, and Esparceto honey. In the figure, A represents commercially available honey, B represents Manuka honey, and C represents Esparceto honey. [Figure 9] This is one of the graphs showing the experimental results of Experiment 4. Specifically, it is a graph showing the relative area values ​​of adenosine contained in regular honey (Control A), Manuka honey (Control B), and Esparcet honey (Target). [Figure 10] This is one of the graphs showing the experimental results of Experiment 4. Specifically, it is a graph showing the relative area values ​​of lysine contained in regular honey (Control A), Manuka honey (Control B), and Esparcet honey (Target). [Figure 11] This is one of the graphs showing the experimental results of Experiment 4. Specifically, it is a graph showing the relative area values ​​of histidine contained in regular honey (Control A), Manuka honey (Control B), and Esparcet honey (Target). [Figure 12]This is one of the graphs showing the experimental results of Experiment 4. Specifically, it is a graph showing the relative area values ​​of acetylcholine contained in regular honey (Control A), Manuka honey (Control B), and Esparcet honey (Target). [Figure 13] This is one of the graphs showing the experimental results of Experiment 4. Specifically, it is a graph showing the relative area values ​​of GABA contained in regular honey (Control A), Manuka honey (Control B), and Esparcet honey (Target). [Figure 14] This is one of the graphs showing the experimental results of Experiment 4. Specifically, it is a graph showing the relative area values ​​of ornithine contained in regular honey (Control A), Manuka honey (Control B), and Esparcet honey (Target). [Figure 15] This is one of the graphs showing the experimental results of Experiment 4. Specifically, it is a graph showing the relative area values ​​of ADMA contained in regular honey (Control A), Manuka honey (Control B), and Esparcet honey (Target). [Modes for carrying out the invention]

[0016] The composition for improving blood pressure or arterial function of the present invention (which may be simply referred to as "the composition of the present invention" in this specification) is characterized in that it contains esparcet honey as an active ingredient.

[0017] In this specification, "esparcet honey" (which may be referred to as "esparcet honey" in this specification) refers to honey whose main source of nectar is the flowers of the esparcet plant (scientific name: Onobrychis viciifolia, Japanese name: Iga-mame).

[0018] In the present invention, the esparcet honey used is preferably monofloral honey. In this specification, "monofloral honey" refers to honey that is collected entirely or mostly from a single type of flower. That is, monofloral esparcet honey is honey that is collected entirely or mostly from esparcet flowers. From the viewpoint of obtaining excellent effects, the dominance of esparcet pollen (the proportion of esparcet pollen in the total pollen composition of the honey) is preferably 50% or more, more preferably 60% or more, and particularly preferably 70% or more. Here, the dominance of esparcet pollen in esparcet honey is determined by microscopic observation of the esparcet honey.

[0019] The esparcet honey used in the present invention is not particularly limited in its components as long as it is primarily derived from esparcet flowers, but it is preferable that it contains, for example, adenosine, lysine, histidine, acetylcholine, gamma-aminobutyric acid (GABA), ornithine, etc.

[0020] In the present invention, if the esparcet honey used contains adenosine as one embodiment, the concentration of adenosine in the esparcet honey is preferably 10 to 40 nmol / g, and more preferably 20 to 30 nmol / g.

[0021] In the present invention, if the esparcet honey used contains lysine as one embodiment, the concentration of lysine in the esparcet honey is preferably 130 to 170 nmol / g, and more preferably 140 to 160 nmol / g.

[0022] In the present invention, if the esparcet honey used contains histidine as one embodiment, the concentration of histidine in the esparcet honey is preferably 40 to 80 nmol / g, and more preferably 50 to 70 nmol / g.

[0023] In the present invention, if the esparcet honey used contains GABA as one embodiment, the concentration of GABA in the esparcet honey is preferably 35 to 75 nmol / g, and more preferably 45 to 65 nmol / g.

[0024] In the present invention, if the esparcet honey used contains ornithine as one embodiment, the concentration of ornithine in the esparcet honey is preferably 3 to 9 nmol / g, and more preferably 4 to 8 nmol / g.

[0025] In the present invention, the components contained in esparcet honey (e.g., adenosine, lysine, histidine, acetylcholine, GABA, ornithine, etc.) and their concentrations can be confirmed and measured using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) and liquid chromatography-time-of-flight mass spectrometry (LC-TOFMS), as shown in the examples described below.

[0026] The method for producing esparcet honey used in the present invention is not particularly limited, and honey produced by known methods or similar methods may be used. The esparcet honey used in the present invention may be subjected to appropriate treatments such as removal of foreign matter (e.g., fragments of beehives, beeswax, bee larvae, etc.) (e.g., purification treatment such as filtration), sterilization, drying, heat treatment, concentration treatment, etc. The present invention may also use commercially available esparcet honey (i.e., commercially available esparcet honey), and it is particularly preferable that the quality is guaranteed to be suitable for human consumption. When using commercially available esparcet honey, its country of origin (honey harvesting country) is not particularly limited, but examples include the Kyrgyz Republic (Osh Oblast, Kyrgyz Republic, etc.). Examples of commercially available esparcet honey include, but are not limited to, "Osh White Honey Esparcet Honey (RAW Honey)" (product name) manufactured by DOSKE COMPANY.

[0027] In this specification, "improvement" of blood pressure means lowering blood pressure (especially systolic blood pressure), suppressing (maintaining) blood pressure increases, or mitigating (delaying) blood pressure increases.

[0028] The basic structure of an artery is that the vascular wall (arterial wall) is composed of three layers: the intima, media, and adventitia. In this specification, "arterial function" refers to the respective functions of the intima (vascular endothelial cells, etc.), media (smooth muscle cells, etc.), and adventitia (fibroblasts, etc.), as well as the function of the arterial wall composed of these three layers.

[0029] In this specification, "improvement" of arterial function means enhancing arterial function, suppressing the decline of arterial function (maintaining arterial function), or mitigating (delaying) the decline of arterial function.

[0030] Specific examples of arterial function that can be improved by the present invention include vascular endothelial function, arterial stiffness, and arterial compliance, with vascular endothelial function and arterial stiffness being preferred.

[0031] In this specification, "vascular endothelial function" refers to the function of vascular endothelial cells, and specific examples include the regulation of vasodilation or constriction through the release of vasoactive substances (such as nitric oxide).

[0032] In this specification, "improvement" of vascular endothelial function refers to enhancing vascular endothelial function, suppressing the decline of vascular endothelial function (maintaining vascular endothelial function), and mitigating (delaying) the decline of vascular endothelial function. The degree of improvement in vascular endothelial function can be evaluated using indicators such as flow-mediated dilatation (%FMD). %FMD increases as vascular endothelial function improves.

[0033] In this specification, "arterial stiffness" refers to the hardness (flexibility, suppleness) of the arterial wall.

[0034] In this specification, "improvement" of arterial stiffness refers to improving the flexibility and suppleness of the arterial wall, suppressing the hardening of the arterial wall (increase in arterial wall hardening) (maintaining arterial wall flexibility and suppleness), and mitigating (delaying) the hardening of the arterial wall. The degree of improvement in arterial stiffness can be evaluated using indicators such as the Cardio Ankle Vascular Index (CAVI) and heart ankle Pulse Wave Velocity (haPWV). CAVI and haPWV become lower as arterial stiffness decreases.

[0035] In this specification, "composition for improving blood pressure or arterial function" is a concept that encompasses agents for improving blood pressure or arterial function.

[0036] The composition of the present invention may consist solely of esparcet honey, or it may optionally contain, in addition to esparcet honey, materials, additives, carriers, etc., that can be used in ordinary food compositions and pharmaceutical compositions. The materials, additives, and carriers are not particularly limited as long as they do not impair the purpose of the present invention, but examples include excipients, binders, lubricants, disintegrants, solvents, solubilizers, suspending agents, emulsifiers, surfactants, coating substrates, isotonic agents, buffers, thickeners, preservatives, antioxidants, colorants, sweeteners, flavorings, vitamins, minerals, amino acids, proteins, carbohydrates, dietary fiber, oils and fats, etc.

[0037] The amount of esparcet honey in the composition of the present invention is not particularly limited as long as it is an amount that yields the desired effects and benefits of the present invention, and can be appropriately set depending on the form of the composition of the present invention, the method of intake, etc. However, the lower limit of the content is usually 0.01% by weight or more, preferably 0.1% by weight or more, more preferably 1% by weight or more, even more preferably 3% by weight or more, and particularly preferably 5% by weight or more, relative to the composition of the present invention, and the upper limit of the content is usually 100% by weight or less, preferably 99% by weight or less, more preferably 90% by weight or less, even more preferably 50% by weight or less, and particularly preferably 10% by weight or less, relative to the composition of the present invention.

[0038] The composition of the present invention is not particularly limited in shape and may be in any form, such as solid (including powder), liquid, or paste.

[0039] The method for producing the composition of the present invention is not particularly limited and can be produced by methods known or similar methods.

[0040] The route of intake or administration of the composition of the present invention is not particularly limited, and the composition of the present invention may be taken orally or administered parenterally. Preferably, the composition of the present invention is taken orally, that is, the composition of the present invention is preferably an oral composition. Here, "oral composition" means a composition that is taken orally (e.g., a food composition, an oral pharmaceutical composition, etc.). In this specification, "intake" is a concept that encompasses all of the following: ingestion, eating, drinking, taking, drinking, etc.

[0041] In one embodiment, the composition of the present invention may be provided as a food composition. In this specification, "food composition" also includes beverages (beverage compositions).

[0042] When the composition of the present invention is a food composition, the type of food composition is not particularly limited as long as it does not impair the purpose of the present invention, but examples include confectionery (e.g., candy, drops, gum, gummy candy, fondant, etc.), desserts, frozen desserts, bread, beverages (e.g., soft drinks, tea beverages, alcoholic beverages, jelly drinks, powdered beverages, etc.), seasonings, processed foods (e.g., processed meat products, processed vegetable products, processed seafood products, etc.), prepared foods, soups, dairy products, etc.

[0043] When the composition of the present invention is a food composition, it may be provided as, for example, a health food, a functional food, a health functional food, a food for specified health uses, a nutrient functional food, a food with functional claims, a food for special dietary uses (e.g., food for sick people), a supplement, etc. Here, "supplement" means not only nutritional supplements and nutrient functional foods that supplement nutrients, etc., but also health supplements and health functional foods that have functions that are useful for maintaining, restoring, and promoting health, etc.

[0044] When the composition of the present invention is a food composition, the form of the food composition is not particularly limited, but the composition of the present invention can be prepared, for example, as tablets, pills, capsules (including hard capsules, soft capsules, and microcapsules), powders, granules, fine granules, lozenges, tablets, liquids (including drinks, syrups, emulsions, and suspensions).

[0045] In one embodiment, the composition of the present invention may be provided as a pharmaceutical composition. In this specification, "pharmaceutical composition" includes pharmaceuticals and quasi-drugs.

[0046] When the composition of the present invention is a pharmaceutical composition, the route of administration of the pharmaceutical composition is not particularly limited as long as it does not impair the purpose of the present invention, and may be either oral or parenteral (e.g., intravenous administration), but oral administration is preferred.

[0047] When the composition of the present invention is a pharmaceutical composition, the form of the pharmaceutical composition is not particularly limited, but the composition of the present invention can be prepared, for example, as tablets, pills, capsules (including hard capsules, soft capsules, and microcapsules), powders, granules, fine granules, lozenges, tablets, liquids (including drinks, syrups, emulsions, and suspensions).

[0048] If the composition of the present invention is a pharmaceutical composition, it may contain other pharmacoactive ingredients (drugs) in addition to esparcet honey. The pharmacoactive ingredients are not particularly limited as long as they do not impair the purpose of the present invention, but those that exhibit effects such as improving blood pressure or arterial function (e.g., vascular endothelial function, arterial stiffness, arterial compliance, etc.), or preventing or improving symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function are preferred.

[0049] The composition of the present invention can be suitably used to improve blood pressure. Furthermore, the composition of the present invention can be suitably used to improve arterial function, and in particular, it can be suitably used to improve vascular endothelial function and arterial stiffness. Therefore, in one embodiment, the composition of the present invention may be a composition (improving agent) for improving vascular endothelial function or arterial stiffness.

[0050] As described above, the degree of improvement in vascular endothelial function is evaluated using indicators such as flow-dependent vasodilation (%FMD), and the composition of the present invention can improve %FMD. Therefore, in one embodiment, the composition of the present invention may be a composition for improving (enhancing) flow-dependent vasodilation.

[0051] The compositions of the present invention can be used to prevent or improve symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function. Specific examples of symptoms and diseases that can be prevented or improved by improving blood pressure or arterial function include hypertension, arteriosclerosis, ischemic heart disease (angina pectoris, myocardial infarction), stroke (cerebral infarction, cerebral hemorrhage), renal failure, decreased blood flow, stiff shoulders, cold extremities, edema, decreased physical strength, and decreased endurance exercise capacity. Here, "prevention" of symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function means preventing or delaying the onset (including recurrence) of the symptoms or disease. Furthermore, "improvement" of symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function is a concept that encompasses treatment, meaning curing the symptoms or disease, or suppressing or delaying the progression of the symptoms or disease.

[0052] Arteries have the function of storing blood ejected from the heart by stretching the arterial wall during systole and sending the stored blood to the periphery by returning the stretched arterial wall to its original state during diastole. Through this function, they can suppress the rise in blood pressure during systole, reduce afterload (afterload reduction effect), and flatten fluctuations in blood pressure and blood flow (pulsatile buffering effect). Arteries also have the function of being conduits that transport blood ejected from the heart (conduit function). These functions and effects are impaired by increased arterial stiffness, and it is expected that these functions and effects can be maintained or improved by improving arterial stiffness with the composition of the present invention. Therefore, in one embodiment, the composition of the present invention can be used to improve the afterload reduction effect, pulsatile buffering effect, and conduit function of arteries.

[0053] The composition of the present invention may be labeled with indications relating to its use, efficacy, effects, functions, etc. Preferred indications for the composition of the present invention relate to the improvement of blood pressure and arterial function (vascular endothelial function, arterial stiffness, etc.). For example, "improves blood pressure," "improves elevated blood pressure," "lowers elevated blood pressure," "mitigates (gentles) the rise in blood pressure," "helps (supports) maintaining normal blood pressure," "helps (supports) keeping blood pressure healthy," "for those with elevated blood pressure," "for those concerned about blood pressure," "improves arterial function," "improves reduced arterial function," "enhances reduced arterial function," "prevents decline in arterial function," "improves the deterioration of arterial function," "helps (supports) maintaining normal arterial function," "improves vascular endothelial function," "improves reduced vascular endothelial function," "enhances reduced vascular endothelial function," Examples of claims include, but are not limited to, "preventing a decline in vascular endothelial function," "improving the deterioration of vascular endothelial function," "helping (supporting) the maintenance of normal vascular endothelial function," "improving arterial stiffness," "preventing an increase in arterial stiffness," "improving arterial hardening," "preventing arterial hardening," "helping (supporting) the maintenance of arterial flexibility," "helping (supporting) the maintenance of arterial suppleness," "for those with stiffer arteries," "for those concerned about arterial flexibility," "improving vascular hardening," "preventing vascular hardening," "helping (supporting) the maintenance of vascular flexibility," "helping (supporting) the maintenance of vascular suppleness," "for those with stiffer arteries," "for those concerned about vascular flexibility," and "for those concerned about vascular age." Products bearing these claims on their packaging, containers, instructions, accompanying documents, promotional materials (including advertisements and websites) may be included in compositions for improving blood pressure or arterial function. In addition to the above indications, the compositions of the present invention may also be labeled with indications relating to the known uses, efficacy, effects, and functions of esparcet honey (for example, stress reduction, relaxation, improvement of sleep quality, improvement of vision, prevention or improvement of cognitive decline, etc.).

[0054] The target population (target for ingestion, target for administration) of the composition of the present invention is preferably humans, but may also be non-human animals (for example, non-human mammals such as mice, rats, guinea pigs, hamsters, rabbits, cats, dogs, cattle, sheep, and monkeys).

[0055] When the composition of the present invention is intended for use in humans, the target population may be healthy individuals, or, for example, individuals who need or desire improvement in blood pressure or arterial function, or individuals with symptoms or diseases that can be prevented or improved by improvement in blood pressure or arterial function. There are no particular restrictions on the age or sex of the target population. The target population may be, for example, elderly individuals aged 60 or older, 65 or older, or 75 or older.

[0056] The amount of the composition of the present invention ingested or administered may be within the range of an effective amount that can improve blood pressure or arterial function, or an effective amount that can prevent or improve symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function, and may be appropriately set according to the form of the composition of the present invention, method of intake, method of administration, condition of the target, symptoms, age, weight, etc. For example, when the target of the composition of the present invention is a human (adult), the composition of the present invention may be used such that the daily intake or administration amount of esparcet honey is usually 1 to 300 g, preferably 5 to 100 g, more preferably 10 to 50 g. The number of times the composition of the present invention is ingested or administered per day may be once or multiple times (two or more times, preferably two to three times).

[0057] Since the composition of the present invention can produce the desired action or effect with a single ingestion or administration, the ingestion or administration of the composition of the present invention may be a single dose. Alternatively, since esparcet honey, the active ingredient of the composition of the present invention, is highly safe and has excellent taste, the composition of the present invention may be ingested or administered continuously for two days or more. When the composition of the present invention is ingested or administered continuously, the duration of ingestion or administration is not particularly limited, but it is usually about four weeks.

[0058] When the composition of the present invention is used in non-human animals (e.g., non-human mammals, etc.), the composition of the present invention can be prepared as feed (including feed additives). Here, "feed" includes everything that non-human animals ingest orally for nutritional purposes, etc. Examples of feed include pet animal feed (e.g., dog food, cat food, etc.), livestock animal feed, laboratory animal feed, etc. [Examples]

[0059] The present invention will be described in more detail below based on experimental examples, but the present invention is not limited to these experimental examples and may be modified without departing from the scope of the invention. Furthermore, reagents, apparatus, materials, etc. used in the experimental examples are commercially available unless otherwise specified.

[0060] <Experiment 1-1> Human umbilical vein endothelial cells (HUVEC, manufactured by Takara Bio) were placed in a 24-well plate in a 5x10⁶ arrangement. 4 Cells were seeded to a cell / well ratio and incubated for 24 hours in a 37°C, 5% CO2 incubator. Endothelial cell proliferation medium 2 (Takara Bio Inc.) was used as the culture medium. After 24 hours of incubation, honey A, honey K, or honey N was added to a final concentration of 0.5%. Nothing was added to the control group. After standing in a 37°C, 5% CO2 incubator for 24 hours or 48 hours, the number of viable human umbilical vein endothelial cells (HUVECs) was measured.

[0061] ·Honey A Multifloral honey made from the nectar of esparcet flowers and various herb blossoms (manufactured by Doske Company, product name: Osh Honey Natural Herb Mountain Honey (ALAY HONEY)) ·Honey K Multifloral honey made from the nectar of esparcet flowers and various herb blossoms (manufactured by Doske Company, product name: Osh Honey, Valley Mountain Honey (Kara-Kulja Raw Honey)) ·Honey N Regular commercially available honey (Life brand, product name: Pure Honey)

[0062] [Measurement of the number of viable human umbilical vein endothelial cells (HUVECs)] The culture medium was removed from the 24-well plate, washed three times with endothelial cell proliferation medium 2 (Takara Bio Inc.), and then 40 μL / well of viable cell count reagent SF (Nacalai Tesque Inc.) was added. After standing in an incubator for 1 hour to allow color development, the absorbance at 450 nm was measured using a plate reader (Bio-Rad Inc.).

[0063] The results are shown in Figure 1. Adding honey A (labeled "ALAY HONEY" in the figure) or honey K (labeled "Kara-Kulja Raw Honey" in the figure) significantly increased the number of viable human umbilical vein endothelial cells (HUVECs) compared to adding honey N (labeled "Normal Honey" in the figure) or the control (labeled "Control" in the figure). These results suggest that multifloral honey, derived from esparcet flowers and various herb flowers, can activate vascular endothelial cells.

[0064] <Experiment 1-2> Human umbilical vein endothelial cells (HUVEC, manufactured by Takara Bio) were placed in a 24-well plate in a 2x10⁶ arrangement. 4Cells were seeded to a density of cells / well and cultured for 2 hours in a 37°C, 5% CO2 incubator. Endothelial cell proliferation medium 2 (Takara Bio Inc.) was used as the culture medium. After culturing, honey A, honey K, or honey N was added to a final concentration of 0.5%. Nothing was added to the control group. After standing in a 37°C, 5% CO2 incubator for 2 hours, hydrogen peroxide was added to a final concentration of 200 μM. After standing in a 37°C, 5% CO2 incubator for 4 hours, the same honey was added again to the wells that had honey added to a final concentration of 0.5%. After standing in a 37°C, 5% CO2 incubator for 4 hours, the number of viable human umbilical vein endothelial cells (HUVECs) was measured. The number of viable human umbilical vein endothelial cells (HUVECs) was measured using the same procedure as in Example 1-1.

[0065] The results are shown in Figure 2. Compared to the control condition (labeled "C" in the figure), the addition of hydrogen peroxide (labeled "H2O2" in the figure) decreased the number of viable human umbilical vein endothelial cells (HUVECs), indicating that oxidative stress reduces the number of viable human umbilical vein endothelial cells (HUVECs). On the other hand, adding honey A or honey K in addition to hydrogen peroxide (labeled "H2O2+A" or "H2O2+K" in the figure) significantly increased the number of viable human umbilical vein endothelial cells (HUVECs), and the decrease in the number of viable human umbilical vein endothelial cells (HUVECs) caused by hydrogen peroxide addition disappeared. However, adding honey N (commercially available regular honey) in addition to hydrogen peroxide (labeled "H2O2+N" in the figure) did not increase the number of viable human umbilical vein endothelial cells (HUVECs). These results suggest that multifloral honey, derived from the nectar of esparcet flowers and various herb blossoms, may enhance the resistance of vascular endothelial cells to oxidative stress.

[0066] <Experiment 2> Fourteen healthy men and women aged 21-26 years were administered the following three types of experimental meals on separate days in a randomized order. Cardio-ankle vascular index (CAVI) and cardiac-ankle pulse wave velocity (haPWV) were measured 15, 30, and 60 minutes after ingestion of the experimental meals using a blood pressure and pulse wave analyzer (Fukuda Denshi Co., Ltd.). CAVI and haPWV were also measured before ingestion of the experimental meals, after 30 minutes of rest in a seated position. Furthermore, the percentage change (%) from baseline (i.e., CAVI before ingestion) of the CAVI measured 30 minutes after ingestion of the experimental meals was calculated using the following formula. [Percentage change from baseline in CAVI 30 minutes after ingestion (%)] = ([CAVI measured 30 minutes after ingestion of experimental food] - [CAVI measured before ingestion of experimental food]) ÷ [CAVI measured before ingestion of experimental food] × 100

[0067] [Experimental food] • Experimental food C: 3.6 mL of purified water per kg of body weight • Experimental food NH: Commercially available regular honey (Life Co., Ltd., product name: Pure Honey) 0.6g / kg body weight + 3mL / kg body weight of purified water • Experimental food KH: Esparcet honey (monoflory honey) (manufactured by Doske Company, product name: "Osh's White Honey Esparcet Honey (RAW Honey), Esparcet pollen dominance: 70% or more") 0.6g / kg body weight + 3mL of purified water / kg body weight

[0068] The results are shown in Figures 3-5. A single dose of esparcet honey's single-flower nectar significantly reduced CAVI and haPWV. These results suggest that a single dose of esparcet honey's single-flower nectar can transiently reduce arterial stiffness and soften arteries.

[0069] <Experiment 3 (Randomized Controlled Trial)> Sixty healthy men and women aged 19-26 were randomly assigned to one of the following three groups. Group C: Group (20 people) that consumed commercially available drinking water (manufactured by KFG Co., Ltd., product name: Natural Mineral Water); intake: 500 mL / day • NH group: A group of 20 people who consumed commercially available regular honey (Life Co., Ltd., product name: Pure Honey); intake: 40g / day • KH group: A group of 20 people who consumed esparcet honey (monofloral honey) (manufactured by Doske Company, product name: "Osh's White Honey Esparcet Honey (RAW Honey)", esparcet pollen dominance: 70% or more); intake: 40g / day In each of the above groups, participants consumed the provided food (i.e., commercially available drinking water, commercially available regular honey, or esparcet honey (monofloral honey)) daily for four weeks. The method of honey consumption in the NH and KH groups was left to the discretion of each participant, and they reported their choices after each consumption period. In the following, the four-week period during which the target food was consumed by the subjects may be referred to as the "intervention period."

[0070] Systolic blood pressure and flow-dependent vasodilation (%FMD) were measured and evaluated for each subject before and after the intervention period. Subjects with no missing data were included in the final analysis (Group C: 17 subjects, Group NH: 18 subjects, Group KH: 18 subjects).

[0071] Furthermore, this study was conducted after review and approval by the Life Science Experimental Ethics Committee of Osaka Institute of Technology.

[0072] [%FMD evaluation] %FMD was measured and calculated using an ultrasound imaging device following the procedure below. An ultrasound image analysis program (manufactured by Takei Kiki Kogyo Co., Ltd.) was used for the analysis of vessel diameter. 1) The resting brachial artery diameter of the subject is measured using an ultrasound imaging device (ultrasound echo) (Fujifilm Corporation, FC-1). 2) The subject's upper arm is constricted to induce ischemia. 3) After 5 minutes, remove the tourniquet and measure the diameter of the blood vessel when it is maximally dilated due to reactive hyperemia (maximum dilated vessel diameter). 4) Calculate %FMD using the following formula. [%FMD] = ([Maximum Dilated Vessel Diameter] - [Resting Vessel Diameter]) ÷ [Resting Vessel Diameter] × 100

[0073] The percentage change or amount of change in systolic blood pressure and %FMD before and after the intervention period was calculated using the following formulas. [Percentage change in systolic blood pressure before and after the intervention period (%)] = ([Systolic blood pressure after the intervention period] - [Systolic blood pressure before the intervention period]) ÷ [Systolic blood pressure before the intervention period] × 100 [Change in %FMD before and after the intervention period (%)] = [%FMD after the intervention period] - [%FMD before the intervention period]

[0074] The results are shown in Figures 6 and 7. Comparing the changes before and after the intervention period among the groups, the group that consumed Esparcet honey (KH group) showed a significant downward trend in systolic blood pressure, as well as a significant difference compared to the control group (group that consumed commercially available drinking water, C group) and the group that consumed commercially available regular honey (NH group). In addition, a significant upward trend was observed in %FMD, as well as a significant difference compared to the control group (group that consumed commercially available drinking water, C group) and the group that consumed commercially available regular honey (NH group). These results indicate that continuous consumption of Esparcet honey (Sephardt honey) leads to a decrease in blood pressure and an improvement in vascular endothelial function.

[0075] <Experiment 4 (Metabolome Analysis)> A comprehensive component analysis was conducted using the following three types of honey as samples. This analysis was commissioned to Human Metabolome Technologies, Inc. (HMT).

[0076] • Control A: Regular commercially available honey (Life brand, product name: Pure Honey) Control B: Manuka honey (manufactured by Manuka Health, product name: Manuka Honey MGO263+ (from New Zealand)) • Target: Esparcet Honey (single-flower honey) (Manufactured by Doske Company, product name: Osh's White Honey Esparcet Honey (RAW Honey), Esparcet pollen dominance: 70% or more)

[0077] Each honey sample was analyzed using a combination of capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) and liquid chromatography-time-of-flight mass spectrometry (LC-TOFMS).

[0078] Each sample was pre-treated as described below before being subjected to CE-TOFMS or LC-TOFMS measurement.

[0079] [Pre-treatment for CE-TOFMS measurement] The collected sample was placed in a crushing tube, and 500 μL of methanol solution containing 50 μM internal standard was added. The sample was then crushed using a crusher under cooling conditions (1,500 rpm, 120 seconds x 1 cycle). After crushing, 500 μL of Milli-Q water was added and stirred, and centrifugation was performed (2,300 × g, 4°C, 5 min). After centrifugation, 400 μL of the aqueous layer was transferred to an ultrafiltration tube (Ultrafree MC PLHCC, HMT, centrifugal filter unit 5 kDa). This was centrifuged (9,100 × g, 4°C, 120 min) and ultrafiltration was performed. The filtrate was allowed to dry, and then dissolved again in 50 μL of Milli-Q water for measurement.

[0080] [Pre-treatment for LC-TOFMS measurement] The collected sample was placed in a crushing tube, and 500 μL of 1% formic acid-acetonitrile solution containing 10 μM of internal standard substance was added. The sample was crushed using a crusher under cooling conditions (1,500 rpm, 120 seconds x 2 times). 167 μL of Milli-Q water was added, and the sample was crushed again (1,500 rpm, 120 seconds x 1 time). This was centrifuged (2,300 × g, 4°C, 5 min), and the supernatant was collected. 500 μL of 1% formic acid-acetonitrile and 167 μL of Milli-Q water were added to the precipitate and stirred. After centrifugation, the supernatant was collected and mixed with the previous supernatant. This was transferred to two 300 μL ultrafiltration tubes (NANOSEP 3K OMEGA, PALL), centrifuged (9,100 × g, 4°C, 120 min), and ultrafiltration was performed. Next, phospholipids were removed using solid-phase extraction. The filtrate was allowed to dry, dissolved in 200 μL of 50% isopropanol aqueous solution (v / v), and used for measurement.

[0081] [CE-TOFMS measurement] In this experiment, CE-TOFMS measurements in cation mode and anion mode were performed under the following conditions. Based on the obtained peak intensity and shape, a 1:1 dilution of the sample was used for cation mode measurements, and a 2:2 dilution was used for anion mode measurements.

[0082] • Cationic metabolites (cationic metabolites) 〔Device〕 Agilent CE-TOFMS system (Agilent Technologies) Capillary:Fused silica capillary id50μm×80cm [Measurement conditions] Run buffer:Cation Buffer Solution(p / n:H3301-1001) Rinse buffer:Cation Buffer Solution(p / n:H3301-1001) Sample injection:Pressure injection 50mbar,10sec CE voltage: Positive, 30kV MS ionization: ESI Positive MS capillary voltage: 4,000V MS scan range: m / z 50-1,000 Sheath liquid:HMT Sheath Liquid(p / n:H3301-1020)

[0083] • Anionic metabolites (anion mode) 〔Device〕 Agilent CE-TOFMS system (Agilent Technologies) Capillary: Fused silica capillary id50μm×80cm [Measurement conditions] Run buffer:Anion Buffer Solution(p / n:I3302-1023) Rinse buffer:Anion Buffer Solution(p / n:I3302-1023) Sample injection:Pressure injection 50mbar,22sec CE voltage: Positive, 30kV MS ionization: ESI Negative MS capillary voltage: 3,500V MS scan range: m / z 50-1,000 Sheath liquid:HMT Sheath Liquid(p / n:H3301-1020)

[0084] [LC-TOFMS measurement] In this experiment, LC-TOFMS measurements in positive and negative modes were performed under the following conditions. Based on the obtained peak intensity and shape, a 1:1 dilution of the sample was used for measurements in positive mode, and a 1:1 dilution was used for measurements in negative mode.

[0085] • Cationic metabolites (positive mode) 〔Device〕 LC system:Agilent 1200series RRLC system SL(Agilent Technologies) Column: ODS column, 2×50mm, 2μm MS system:Agilent LC / MSD TOF (Agilent Technologies) [Measurement conditions] Column temp.: 40℃ Mobile phase A: H2O / 0.1% HCOOH Mobile phase B:Isopropanol:Acetonitrile:H2O(65:30:5) / 0.1% HCOOH,2mM HCOONH4 Flow rate: 0.3 mL / min Runtime: 20 min Post time: 7.5 min Gradient condition:0-0.5min:B 1%,0.5-13.5min:B 1-100%,13.5-20min:B 100% MS ionization mode:ESI Positive MS Nebulizer pressure: 40 psi MS dry gas flow: 10 L / min MS dry gas temp: 350℃ MS capillary voltage: 4,000V MS scan range: m / z 100-1,700 Sample injection: 1 μL

[0086] • Anionic metabolites (negative mode) 〔Device〕 LC system:Agilent 1200series RRLC system SL(Agilent Technologies) Column: ODS column, 2×50mm, 2μm MS system:Agilent LC / MSD TOF (Agilent Technologies) [Measurement conditions] Column temp.: 40℃ Mobile phase A: H2O / 0.1% HCOOH Mobile phase B:Isopropanol:Acetonitrile:H2O(65:30:5) / 0.1% HCOOH,2mM HCOONH4 Flow rate: 0.3 mL / min Runtime: 20 min Post time: 7.5 min Gradient condition:0-0.5min:B 1%,0.5-13.5min:B 1-100%,13.5-20min:B 100% MS ionization mode:ESI Negative MS Nebulizer pressure: 40 psi MS dry gas flow: 10 L / min MS dry gas temp: 350℃ MS capillary voltage: 3,500V MS scan range: m / z 100-1,700 Sample injection: 1 μL

[0087] For each peak detected by CE-TOFMS and LC-TOFMS, the automated integration software "MasterHands ver.2.18.0.1" (developed by Keio University) was used to automatically extract peaks with a signal-to-noise (S / N) ratio of 3 or higher. The mass-to-charge ratio (m / z), peak area value, migration time (MT) for CE-TOFMS, and retention time (RT) for LC-TOFMS were obtained. Based on the m / z and MT or RT values ​​of the detected peaks, a search and matching were performed against substances (287 compounds) registered in the HMT metabolite library and the Known-Unknown library. The tolerance for the search was set at ±0.5 min for MT, ±0.3 min for RT, and ±10 ppm (CE-TOFMS) and ±25 ppm (LC-TOFMS) for m / z. Analysis of commercially available regular honey (Control A) revealed 199 substances (69.3%), analysis of Manuka honey (Control B) revealed 243 substances (84.7%), and analysis of Esparcet honey (Target) revealed 177 substances (61.7%).

[0088] Hierarchical cluster analysis was performed on the detected substances in regular honey (Control A), Manuka honey (Control B), and Esparcet honey (Target). Hierarchical cluster analysis was performed using the statistical analysis software R.

[0089] The results are shown in Figure 8. The esparcet honey (Target) contained unique clusters that were not present in regular honey (Control A) or manuka honey (Control B).

[0090] For adenosine, lysine, histidine, acetylcholine, γ-aminobutyric acid (GABA), ornithine, and asymmetric dimethylarginine (ADMA), the peak area values ​​of these substances were converted to relative area values ​​using the following formula and compared between the samples. The results are shown in Figures 9-15. [Relative Area] = [Area of ​​Target Peak] ÷ ([Area of ​​Internal Standard] × [Sample Volume]) Furthermore, for adenosine, lysine, histidine, GABA, and ornithine, the peak area corrected with an internal standard was used as the calibration curve, and the concentration was calculated using a 100 μM single calibration dose (200 μM internal standard). The results are shown in Table 1 below.

[0091] [Table 1]

[0092] As shown in Figures 9-14 and Table 1, Esparcet honey contained higher levels of adenosine, lysine, histidine, acetylcholine, GABA, and ornithine compared to regular honey and Manuka honey. Furthermore, as shown in Figure 15, ADMA was not detected in Esparcet honey.

[0093] From these results, it was found that Esparcet honey has a unique component composition that differs from ordinary honey and Manuka honey, and these results further support the idea that Esparcet honey possesses advantages that other honeys cannot replicate. [Industrial applicability]

[0094] According to the present invention, a composition useful for improving blood pressure or arterial function can be provided. This composition is also useful for preventing or improving symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function. Esparcet honey, the active ingredient in the composition of the present invention, is highly safe and has excellent taste, making it possible to continuously ingest or administer the composition of the present invention. Furthermore, the composition of the present invention can produce excellent blood pressure or arterial function improvement effects in a short period of time, and the desired effects can be obtained even with a single ingestion or administration. Esparcet honey, the active ingredient in the composition of the present invention, is relatively easy to extract and process.

Claims

1. A composition for improving blood pressure or arterial function, containing esparcet honey as an active ingredient.

2. The composition according to claim 1, wherein the arterial function is vascular endothelial function or arterial stiffness.

3. The composition according to claim 1 or 2, used for the prevention or improvement of symptoms or diseases that can be prevented or improved by improving blood pressure or arterial function.

4. The composition according to claim 1 or 2, which is an oral composition.

5. A food composition according to claim 1 or 2.

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