Composition for promoting nitric oxide production

Abstract

To provide a composition for promoting nitric oxide production.SOLUTION: A composition for promoting nitric oxide production is provided, the composition comprising Polygonatum falcatum and / or Foeniculum vulgare.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a composition for promoting the production of nitric oxide comprising naruko lily and / or wikyo.

Background Art

[0002] Vascular endothelial cells are cells that constitute the inner surface of blood vessels and are known to have a function of producing bioactive substances such as nitric oxide (NO). Nitric oxide is one of the vasorelaxing factors derived from vascular endothelium and is produced as a by-product of the conversion reaction of L-arginine to L-citrulline by NO synthase (NOS) in vivo. Nitric oxide is a molecule that contributes to vascular function such as improving vascular elasticity and resistance to arteriosclerosis. Therefore, promoting the production of nitric oxide in vascular endothelial cells is effective in relaxing and dilating blood vessels and suppressing arteriosclerosis.

[0003] As methods for increasing nitric oxide, drugs such as statins and angiotensin II receptor antagonists (ARBs) are known, but daily intake as food can effectively prevent arteriosclerosis and the like on a daily basis. Although it has been known that isoxanthohumol derived from hops (Patent Document 1) and the like have a function of promoting the production of nitric oxide, it can be said that there is a need for nitric oxide-producing components derived from other foods as well.

[0004] On the other hand, the use of naruko lily and wikyo as a composition for stabilizing blood vessels or strengthening the barrier function of blood vessels has been described (Patent Document 2).

[0005] However, no reports have been made on the relationship between naruko lily and wikyo and the action of promoting nitric oxide production or improving vascular endothelial function.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

[0007] The present invention provides a composition for promoting the production of nitric oxide.

[0008] The present inventors have found that naruko and / or wikyo are useful for promoting the production of nitric oxide in vascular endothelial cells. The present invention is based on this finding.

[0009] According to the present invention, the following inventions are provided. (1) A composition for promoting the production of nitric oxide, comprising naruko and / or wikyo. (2) The composition according to (1), wherein the promotion of nitric oxide production is carried out in vascular endothelial cells. (3) A composition for improving vascular endothelial function, comprising naruko and / or wikyo. (4) The composition according to any one of (1) to (3), wherein naruko and / or wikyo contain at least one part selected from the group consisting of fruits, rhizomes, flowers, seeds, buds, leaves, stems, and roots. (5) The composition according to any one of (1) to (4), which is for oral use. (6) The composition according to any one of (1) to (5), wherein the composition is a food or drink or a food additive. (7) The composition according to any one of (1) to (6), wherein the composition is a food with health claims. (8) The composition according to any one of (1) to (7), wherein the composition is at least one selected from the group consisting of foods for specified health uses, foods with nutrient function claims, and foods with functional claims. (9) Use of naruko and / or wikyo in the production of a composition for promoting the production of nitric oxide. (10) Use of naruko and / or wikyo in the production of a composition for improving vascular endothelial function. (11) A method for promoting the production of nitric oxide, comprising administering or causing to be ingested an effective amount of Polygonatum odoratum and / or Glehnia littoralis to a subject in need thereof. (12) A method for improving the function of vascular endothelium, comprising administering or causing to be ingested an effective amount of Polygonatum odoratum and / or Glehnia littoralis to a subject in need thereof. (13) Polygonatum odoratum and / or Glehnia littoralis for promoting the production of nitric oxide. (14) Polygonatum odoratum and / or Glehnia littoralis for improving the function of vascular endothelium.

[0010] According to the present invention, a composition for promoting the production of nitric oxide is provided. Further, according to the present invention, it is also possible to provide a composition for improving the function of vascular endothelium. BRIEF DESCRIPTION OF THE DRAWINGS

[0011]

Figure 1

[0012] According to one aspect of the present invention, a composition for promoting the production of nitric oxide is provided, and the composition for promoting the production of nitric oxide comprises Polygonatum odoratum and / or Glehnia littoralis. In the present specification, "Polygonatum odoratum and / or Glehnia littoralis" means Polygonatum odoratum, Glehnia littoralis, or a combination of Polygonatum odoratum and Glehnia littoralis.

[0013] According to another aspect of the present invention, a composition for improving the function of vascular endothelium is provided, and the composition for improving the function of vascular endothelium comprises Polygonatum odoratum and / or Glehnia littoralis.

[0014] The "Polygonatum odoratum" of the present invention is Polygonatum falcatum, a plant of the genus Polygonatum in the Liliaceae family, also called Narcolan, and native to Japan and East Asia.

[0015] As the parts of Galanthus nivalis used in the present invention, for example, fruits, rhizomes, flowers, seeds, buds, leaves, stems, and roots, etc. are used, and preferably rhizomes are used.

[0016] Galanthus nivalis used in the present invention can be used either raw or dried. According to one embodiment of the present invention, "Galanthus nivalis" is the rhizome of Galanthus nivalis or its dried product, and preferably, it is the rhizome powder obtained by pulverizing the dried rhizome.

[0017] When Galanthus nivalis (including rhizomes, dried powders of rhizomes, extracts, etc.) is commercially available, it may be used as long as it has the objective effects of the present invention.

[0018] The "Foeniculum vulgare" of the present invention is Foeniculum vulgare, a plant of the genus Foeniculum in the Apiaceae family, also called fennel, and native to the Mediterranean coastal areas of Europe.

[0019] As the parts of Foeniculum vulgare used in the present invention, for example, fruits (such as pulp and pericarp), rhizomes, flowers, seeds, buds, leaves, stems, and roots, etc. are used, and preferably fruits are used.

[0020] Foeniculum vulgare used in the present invention can be used either raw or dried. According to one embodiment of the present invention, "Foeniculum vulgare" is the fruit of Foeniculum vulgare or its dried product, and preferably, it is the fruit powder obtained by pulverizing the dried fruit.

[0021] When Foeniculum vulgare (including fruits, dried powders of fruits, extracts, etc.) is commercially available, it may be used as long as it has the objective effects of the present invention.

[0022] Nitric oxide (NO) is synthesized from arginine by nitric oxide synthase (NOS) in vivo. Here, nitric oxide dilates blood vessels by relaxing vascular smooth muscle through information transmission systems such as activation of guanylate cyclase, increase in cyclic guanosine monophosphate (cGMP), release of calcium ions extracellularly, and relaxation of vascular smooth muscle, and exerts an antihypertensive effect, thereby preventing and improving hypertension. In addition, nitric oxide exerts an effect of improving vascular endothelial function by suppressing platelet aggregation by promoting prostaglandin I2 production and suppressing the expression of cell adhesion factors that cause thrombosis, and can prevent and improve arteriosclerosis.

[0023] Vascular endothelial cells are responsible for maintaining the homeostasis of blood vessels, such as the function of maintaining and regulating fluidity and the function of regulating cell migration. Among these functions, the function of maintaining and regulating fluidity is carried out by the function of regulating the relaxation and contraction of blood vessels by vascular endothelial cells, as well as the function of regulating blood coagulation by releasing substances that promote or inhibit blood coagulation. In addition, the regulation of cell migration is carried out by functions such as the regulation of the expression of vascular adhesion factors.

[0024] "Improvement of vascular endothelial function" in the present invention can be non-invasively measured and diagnosed by Flow-Mediated Dilation (FMD) test, plethysmography, etc., and is preferably the promotion of nitric oxide production in vascular endothelial cells.

[0025] According to a preferred embodiment of the present invention, the promotion of nitric oxide production in the present invention is carried out in vascular endothelial cells. The vascular endothelial cells in the present invention include, but are not limited to, for example, cells obtained from a living body, their passaged cells, or established cell lines, etc., and these cells may be differentiated and used as necessary. The vascular endothelial cells in the present invention may be cells derived from any animal, preferably human cells. Specifically, the vascular endothelial cells in the present invention include human renal glomerular endothelial cells (HRGEC), human umbilical vein endothelial cells (HUVEC), human aortic vascular endothelial cells (HAEC), human pulmonary artery vascular endothelial cells (HPAEC), human coronary artery vascular endothelial cells (HCAEC), human iliac artery endothelial cells (HIAEC), human microvascular endothelial cells (HMVEC), etc.

[0026] The composition for promoting nitric oxide production of the present invention and the composition for improving vascular endothelial function may be applied either in vivo or in vitro. When applying the composition for promoting nitric oxide production of the present invention and the composition for improving vascular endothelial function to a subject, the subject to which it is applied includes, but is not limited to, for example, mammals such as humans, primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, horses, sheep, and goats, and rodents such as mice and rats.

[0027] The blending amount of Narcoolepis japonica and / or Wikstroemia sikokiana in the composition for promoting nitric oxide production of the present invention and the composition for improving vascular endothelial function can be appropriately determined according to the use and the intake amount described later. Such a blending amount includes, for example, the dry mass of the rhizome of Narcoolepis japonica or the dry mass of the fruit of Wikstroemia sikokiana relative to the recommended daily intake amount of the composition for promoting nitric oxide production of the present invention and the composition for improving vascular endothelial function, for example, 1 mg to 5000 mg, preferably 1 mg to 1000 mg, and more preferably 1 mg to 500 mg. When the composition of the present invention contains both Narcoolepis japonica and Wikstroemia sikokiana, the above blending amount means their total amount.

[0028] The composition for promoting nitric oxide production and the composition for improving vascular endothelial function of the present invention may be an oral composition or a topical composition. Narukoiri and / or Wikyo in the present invention are preferably absorbed from the digestive tract by oral ingestion, and it is considered that their active ingredients act in the body. Therefore, according to a preferred embodiment of the present invention, the composition for promoting nitric oxide production and the composition for improving vascular endothelial function of the present invention are oral compositions.

[0029] When the composition for promoting nitric oxide production and the composition for improving vascular endothelial function of the present invention are oral compositions, known components (additives) formulated in the oral composition can be further formulated. Such components include, but are not limited to, for example, sweeteners, colorants, preservatives, thickeners, stabilizers, gelling agents, pastes, antioxidants, color developers, bleaching agents, fungicides (mildew preventives), yeast food, gum bases, potassium hydroxide, bitter agents, enzymes, brighteners, fragrances, acidulants, chewing gum softeners, softeners, seasonings, coagulants for tofu, emulsifiers, pH adjusters, swelling agents, nutrient enhancers, others (agents for manufacturing, etc.), food materials, and the like.

[0030] The oral composition in the present invention may be in any of liquid, semi-solid, and solid forms.

[0031] When the composition for promoting nitric oxide production and the composition for improving vascular endothelial function of the present invention are topical compositions, known components (additives) formulated in the topical composition can be further formulated. Such components include, but are not limited to, for example, emulsifiers, hydrating agents, solvents, emollients, stabilizers, thickeners, preservatives, lubricants, chelating agents, fillers, excipients, powders, fragrances, flavors, absorbents, dyes, opacifiers, antioxidants, vitamins, amino acids, and the like.

[0032] The topical composition in the present invention may be in any of liquid, semi-solid, and solid forms.

[0033] The composition for promoting nitric oxide production and the composition for improving vascular endothelial function of the present invention may be any of a pharmaceutical composition, a cosmetic composition, and a food composition (e.g., food and drink, food additives), and is preferably a food composition.

[0034] The composition for promoting nitric oxide production and the composition for improving vascular endothelial function of the present invention may be health functional foods such as foods for specified health use, foods with nutrient function claims, and foods with functional labeling, or may also be manufactured as therapeutic foods (i.e., those for the purpose of treatment, or those prepared based on a menu issued by a doctor and prepared by a dietitian or the like according to it), dietary therapy foods, nursing foods, etc.

[0035] The intake amount of Narcohypnum and / or Wikstroemia per serving or per day in the composition for promoting nitric oxide production and the composition for improving vascular endothelial function of the present invention can be appropriately set according to the age, weight, gender of the subject for promoting nitric oxide production or improving vascular endothelial function, and the index values related to nitric oxide and vascular endothelial function before intake, etc., and also based on non-clinical or clinical test results, etc. The intake period of the composition of the present invention can also be appropriately set, and it is preferably repeated over a long period of time and taken daily. As one embodiment of the present invention, the composition of the present invention has, as the intake amount of the active ingredient contained therein (also referred to as the effective amount of Narcohypnum and / or Wikstroemia), for example, 0.001 to 1000 mg / kg body weight / day, preferably 0.005 to 100 mg / kg body weight / day, more preferably 0.01 to 10 mg / kg body weight / day. Also, such an intake amount is preferably 5 g / day or less, more preferably 2 g / day or less, and even more preferably 1 g / day or less. The number of administrations is, for example, 1 to 5 times a day, preferably 1 to 3 times a day.

[0036] The use of the composition of the present invention for "promoting nitric oxide production" or "improving vascular endothelial function" can be indicated directly or indirectly. Examples of direct indication are descriptions on tangible objects such as the product itself, package, container, label, tag, etc. Examples of indirect indication are advertising and promotional activities through places or means such as websites, storefronts, exhibitions, billboards, bulletin boards, newspapers, magazines, television, radio, mailed items, e-mails, etc. When the composition of the present invention is manufactured as a functional food, etc., for example, "improving vascular endothelial function", "preventing decline of vascular endothelial function", "maintaining vascular health", "maintaining vascular flexibility", or indications or functional indications that can be regarded as the same as these, the functionality based on the action and effect of the components contained as functional components can be indicated.

[0037] According to another aspect of the present invention, there is provided the use of naruko and / or wikyo in the manufacture of a composition for promoting nitric oxide production. According to still another aspect of the present invention, there is provided the use of naruko and / or wikyo in the manufacture of a composition for improving vascular endothelial function.

[0038] According to another aspect of the present invention, there is provided a method for promoting the production of nitric oxide, which comprises administering or causing to be ingested an effective amount of naruko and / or wikyo to a subject in need thereof. According to still another aspect of the present invention, there is provided a method for improving the function of vascular endothelium, which comprises administering or causing to be ingested an effective amount of naruko and / or wikyo to a subject in need thereof. The above method may be a therapeutic method or a non-therapeutic method. When naruko and / or wikyo is administered or caused to be ingested to a subject, the production of nitric oxide in vascular endothelial cells is promoted and the amount of nitric oxide produced increases. Due to such an action, it becomes possible to improve vascular endothelial function.

[0039] Also, according to another aspect of the present invention, naruko yuri and / or wikyou are provided for promoting the production of nitric oxide. Further, according to still another aspect of the present invention, naruko yuri and / or wikyou are provided for improving vascular endothelial function.

[0040] Also, according to another aspect of the present invention, there is provided the use of a composition comprising naruko yuri and / or wikyou for promoting the production of nitric oxide. According to still another aspect of the present invention, there is provided a composition comprising naruko yuri and / or wikyou for improving vascular endothelial function.

[0041] All of the above aspects of use in production, method for promoting the production of nitric oxide, method for improving the function of vascular endothelium, naruko yuri and / or wikyou, and use of a composition comprising naruko yuri and / or wikyou can be carried out in accordance with the description of the composition and method of the present invention.

Examples

[0042] The present invention will be specifically described based on the following examples, but the present invention is not limited to these examples. Unless otherwise specified, the content is expressed in mass%.

[0043] Preparation of buffer etc. The HEPES buffer was prepared as follows. 0.22 g of KCl, 7.7 g of NaCl, 0.14 g of Na2HPO4, 1.8 g of D-glucose, and 7.15 g of HEPES (Dojindo Laboratories) were added to ultrapure water, mixed, adjusted to pH 7.4, and then made up to 1 L with ultrapure water to obtain the HEPES buffer.

[0044] The 2× recording medium was prepared as follows. 0.80 g of KCl, 13.44 g of NaCl, 0.40 g of CaCl2, 0.152 g of MgCl2, 4.98 g of D-glucose, and 9.54 g of HEPES were added to ultrapure water, mixed, adjusted to pH 7.4 (25 °C) using 4 mol / l KOH, and then ultrapure water was added to make the total volume 1 L to obtain the 2× recording medium. Then, after filter sterilization with a 0.2 μm sterilizing filter, it was stored refrigerated (4 °C). At the time of use, it was diluted with ultrapure water to a 1× recording medium and used.

[0045] The loading buffer (final concentration 2.5 μM DAF-FM DA) was prepared as follows. 5 mL of 2× recording medium, 50 μL of 1.25 mM probenecid, 500 μL of 50 μM DAF-FM DA (Diaminofluorescein-FM diacetate) (Goryo Chemical Co., Ltd.), and 4.95 mL of ultrapure water were mixed to obtain the loading buffer.

[0046] Preparation of test substance sample to be applied to endothelial cells As the test substance 1 (positive control), disodium adenosine triphosphate (ATP) (FUJIFILM Wako Pure Chemical Corporation) was used. ATP and HEPES buffer were mixed to obtain the test substance 1 sample (n = 4). Furthermore, as the test substance 2, powder of Wikstroemia fruit (sterilized product) (Nippon Powder Chemical Co., Ltd.) was used. The powder of Wikstroemia fruit and HEPES buffer were mixed to obtain the test substance 2 sample (n = 4). Furthermore, as the test substance 3, powder of Coptis japonica rhizome (sterilized product) (Nippon Powder Chemical Co., Ltd.) was used. The powder of Coptis japonica rhizome and HEPES buffer were mixed to obtain the test substance 3 sample (n = 4).

[0047] Culture of endothelial cells The eighth-generation human coronary artery endothelial cells (Human coronary artery endothelial cells; HCAEC, Kurabo Industries Ltd.) were seeded in 96-well plates and cultured to confluence using HuMedia-EG2 (Kurabo Industries Ltd.). The day before the test, the medium was changed to a medium without serum from HuMedia-EG2 and cultured overnight. After overnight culture, the medium was changed to 100 μL / well of loading buffer and cultured at 37 °C and 5% CO2 for 1 hour. After the culture, the supernatant was removed, 100 μL / well of recording medium was added, and it was used as a measurement sample. Test substance 1 samples to test substance 3 samples were added to the above measurement samples so that the final concentration of test substance 1 was 10 μM and the final concentrations of test substance 2 and 3 were each 50 μg / mL, and cultured at 37 °C. After 50 seconds, the fluorescence intensity was measured. In addition, only HEPES buffer was added to the control group.

[0048] Measurement of fluorescence intensity For the measurement samples to which the above test substance samples were added, the fluorescence intensity (ex. 485 nm, em. 535 nm) was measured using a plate reader (Infinite 200 PRO, TECAN). The obtained results (mean value ± standard deviation) are shown in Figure 1. For the fluorescence intensity of each test substance relative to the fluorescence intensity of the control group, a significant difference test between groups (control group vs test substance 1 (ATP)-added group, control group vs test substance 2 (wikyo)-added group, control group vs test substance 3 (narcissus)-added group) was performed by Tukey's test (significance level: p < 0.05). As a result, a significant difference was observed between the test substance 2 (wikyo)-added group and the test substance 3 (narcissus)-added group and the control group. From the above results, it was shown that narcissus and wikyo have a physiological effect (vascular endothelial function-improving effect) of enhancing nitric oxide (NO) production in vascular endothelial cells.

Claims

Claim 1 A composition for promoting the production of nitric oxide, comprising naruko lily and / or wikyo. Claim 2 The composition according to claim 1, wherein the promotion of nitric oxide production is carried out in vascular endothelial cells. Claim 3 A composition for improving vascular endothelial function, comprising naruko lily and / or wikyo. Claim 4 The composition according to claim 1 or 3, wherein naruko lily and / or wikyo comprises at least one part selected from the group consisting of fruits, rhizomes, flowers, seeds, buds, leaves, stems, and roots. Claim 5 The composition according to claim 1 or 3, which is for oral use. Claim 6 The composition according to claim 1 or 3, wherein the composition is a food or drink or a food additive. Claim 7 The composition according to claim 1 or 3, wherein the composition is a health functional food. Claim 8 The composition according to claim 1 or 3, wherein the composition is at least one selected from the group consisting of foods for specified health uses, foods with nutrient functions, and foods with functional claims.

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