Composition containing turmeric oil for vascular protection, and food, beverage, and fragrance containing such composition

Abstract

To provide a composition containing turmeric oil for vascular protection inhibiting vascular injury or vascular protection including repair of the vascular injury, and food and beverage and perfume containing such the composition.SOLUTION: The composition according to the present invention, and the food and beverage and the perfume containing such the composition contain turmerones which are one or more compounds selected from the group consisting of AR-turmerone, α-turmerone and β-turmerone to inhibit vascular injury such as fibril damage of blood vessel wall, abdominal aortic aneurysms or breast aortic aneurysms, or repair such vascular injuries, and the food and beverage and the perfume containing such the composition.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a composition containing turmeric oil for vascular protection, and to a food, beverage, and flavor containing such a composition. More specifically, the present invention relates to a composition containing turmerones, which are one or more compounds selected from the group consisting of AR-turmerone, α-turmerone, and β-turmerone, for inhibiting vascular damage such as fibrosis of vascular walls, abdominal aortic aneurysm, or thoracic aortic aneurysm, or for repairing such vascular damage, and to a food, beverage, and flavor containing such a composition. [Background technology]

[0002] Abdominal aortic aneurysm (AAA) is an aneurysm that occurs in the abdominal aorta, located below the diaphragm, and is the most common type of aortic aneurysm. It is believed that weakening of the aortic wall is a major factor in the development of abdominal aortic aneurysms, and that they are caused by structural abnormalities or destruction of the wall due to inflammatory diseases, congenital connective tissue disorders, atherosclerosis, etc.

[0003] In general, it is said that many aortic aneurysms are caused by arteriosclerosis. Arteriosclerosis is a condition in which the walls of the arteries become thicker and harder, and their flexibility and elasticity decrease. Risk factors for arteriosclerosis include high blood pressure, dyslipidemia, and smoking. As preventive measures against these risk factors, doctors may recommend blood pressure management, reducing cholesterol intake in the diet, and quitting smoking. However, little is currently known about food ingredients that are effective in actively preventing aortic aneurysms and the arteriosclerosis that causes them.

[0004] In addition, based on the relationship between smoking and arteriosclerosis, recent research on abdominal aortic aneurysms suggests that nicotine, the main component of cigarette smoke, is closely related to the occurrence and rupture of abdominal aortic aneurysms (see Non-Patent Document 1). Nicotine increases oxidative stress and matrix metalloproteinase (MMP)-2 expression, and induces weakening of the vascular wall by breaking down elastin present in the media of the vascular wall. Nicotine is thought to promote the occurrence of abdominal aortic aneurysms through the above mechanism.

[0005] Under these circumstances, attempts have been made to create a disease model of abdominal aortic aneurysm using nicotine (Non-Patent Documents 2 and 3). Although this disease model uses nicotine, it has been suggested that it may also be used for screening drugs to prevent other common abdominal aortic aneurysms that are not directly caused by nicotine. This is because the process leading to abdominal aortic aneurysm is thought to be common regardless of whether it is mediated by nicotine or not.

[0006] The present inventors have already discovered a health food or pharmaceutical composition for preventing vascular deterioration, which contains sesamin and / or sesamolin as an active ingredient, using a disease model of abdominal aortic aneurysm using nicotine (Patent Document 1). However, there is a need to screen various compounds with other excellent effects and synthesize new compounds to help prevent abdominal aortic aneurysm. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication WO2020 / 003363 [Non-patent literature]

[0008] [Non-Patent Document 1] Kugo H, Zaima N, Tanaka H, ​​Urano T, Unno N, Moriyama T (2017) The effects of nicotine administration on the pathophysiology of rat aortic wall.Biotech Histochem.92(2):141-148.

[0009] [Non-Patent Document 2] Markus U Wagenhaeuser et al. (2018) Chronic Nicotine Exposure Induces Murine Aortic Remodeling and Stiffness Segmentation-Implications for Abdominal Aortic Aneurysm Susceptibility. Front Physiol. 2018 Oct 31;9:1459. doi: 10.3389 / fphys.2018.01459. Summary of the Invention [Problem to be solved by the invention]

[0010] As described above, from the viewpoint of preventing the occurrence of abdominal aortic aneurysm, a method for preventing blood vessel deterioration is required. However, little is known about a method for preventing blood vessel deterioration that leads to the occurrence of abdominal aortic aneurysm, and in particular, about food ingredients that are useful in such a prevention method.

[0011] As a result of intensive research, the inventors have discovered that turmerones, which are one or more compounds selected from the group consisting of AR-turmerone, α-turmerone, and β-turmerone, have the effect of preventing vascular deterioration induced by nicotine. As a result, the inventors have created a composition for preventing blood vessel deterioration containing turmerones, which are one or more compounds selected from the group consisting of AR-turmerone, α-turmerone, and β-turmerone, as an active ingredient, as well as food, beverages, and fragrances containing such a composition. In other words, the inventors have developed, for the first time, a composition for preventing blood vessel deterioration, which contains as an active ingredient turmerones, which are one or more compounds selected from the group consisting of AR-turmerone, α-turmerone, and β-turmerone, thereby solving the problems of the prior art, as well as food, beverages, and fragrances containing such a composition. [Means for solving the problem]

[0012] The invention of claim 1 relates to a composition for protecting blood vessels, comprising turmeric oil.

[0013] The invention of claim 2 relates to the composition described in claim 1, wherein the active ingredient of turmeric oil is turmerones, and the turmerones are one or more compounds selected from the group consisting of AR-turmerone (chemical formula 1), α-turmerone (chemical formula 2) and β-turmerone (chemical formula 3).

[0014] [ka]

[0015] [ka]

[0016] [ka]

[0017] The invention according to claim 3 relates to the composition according to claim 1 or 2, wherein vascular protection includes inhibiting vascular damage or repairing vascular damage.

[0018] The invention according to claim 4 relates to a composition according to claims 1 to 3, wherein the vascular damage is modeled by fiber destruction of the vascular wall caused by nicotine.

[0019] The invention according to claim 5 relates to the composition according to claims 1 to 4, wherein the vascular injury is abdominal aortic aneurysm or thoracic aortic aneurysm.

[0020] The invention according to claim 6 relates to a composition according to claims 1 to 5, which is administered orally or nasally.

[0021] The invention of claim 7 relates to the composition according to claims 1 to 6, which is used for inclusion in at least one selected from the group consisting of food, beverages, fragrances, aroma oils, scented sachets, incense sticks, tobacco, and electronic cigarettes.

[0022] The invention according to claim 8 relates to a food or drink containing the composition according to claims 1 to 6.

[0023] The invention according to claim 9 relates to a fragrance containing the composition according to claims 1 to 6. Effect of the Invention

[0024] According to the invention of claim 1, since the composition for protecting blood vessels contains turmeric oil, it can easily and efficiently exert protection of blood vessels against vascular deterioration.

[0025] According to the invention of claim 2, the active ingredient of turmeric oil is turmerones, and the turmerones are one or more compounds selected from the group consisting of AR-turmerone, α-turmerone, and β-turmerone, so that vascular protection against vascular deterioration can be easily and efficiently exerted.

[0026] According to the invention of claim 3, vascular protection includes inhibiting vascular damage or repairing vascular damage, so that the invention can be effective in protecting various types of blood vessels.

[0027] According to the invention of claim 4, since the vascular damage is modeled by fiber destruction of the vascular wall caused by nicotine, it is possible to easily and efficiently exert vascular protection against vascular deterioration of the vascular wall caused by nicotine.

[0028] According to the invention of claim 5, since the composition of claims 1 to 4 is one in which the vascular injury is abdominal aortic aneurysm or thoracic aortic aneurysm, it can have an effective preventive effect against abdominal aortic aneurysm or thoracic aortic aneurysm.

[0029] According to the invention of claim 6, the composition is administered orally or nasally, and therefore can be easily administered to a subject.

[0030] According to the invention of claim 7, the composition is used for inclusion in at least one selected from the group consisting of foods, beverages, fragrances, aroma oils, scented sachets, incense sticks, tobacco, and electronic cigarettes, and can be added to various products to exert the effect of protecting blood vessels against blood vessel deterioration.

[0031] According to the invention of claim 8, since the food and drink contains the composition according to claims 1 to 6, it is possible to obtain a food and drink having an effect of protecting blood vessels against vascular deterioration.

[0032] According to the invention of claim 9, since the fragrance contains the composition according to claims 1 to 6, a fragrance product having the effect of protecting blood vessels against deterioration can be obtained. [Brief description of the drawings]

[0033] [Figure 1] This is a diagram showing an experimental system for administering turmeric oil intranasally or via the lungs. Absorbent cotton soaked in turmeric oil is attached to the inside of the lid of an Erlenmeyer flask, and the mouse in the flask is exposed to turmeric oil, which is absorbed intranasally or via the lungs. [Diagram 2]This figure shows the effect of turmeric oil exposure on vascular injury in mice by EVG staining. The samples were divided into groups as follows: Group C: 0 min turmeric oil exposure + MF diet + tap water (control without turmeric oil and without nicotine treatment), Group T: 60 min turmeric oil exposure + MF diet + tap water (with turmeric oil and without nicotine treatment), Group CN: 0 min turmeric oil exposure + MF diet + 0.5 mg / mL nicotine solution (without turmeric oil and with nicotine treatment), Group TN: 60 min turmeric oil exposure + MF diet + 0.5 mg / mL nicotine solution (with turmeric oil and with nicotine treatment). The abdominal elastic fibers of mice in each group were stained with Elastica van Gieson (EVG) and observed. The figure is a bar graph showing the elastic plate destruction rate in each group. [Diagram 3] This figure shows the effect of turmeric oil exposure on vascular injury in mice, as observed by the extracellular matrix degrading enzyme MMP-2. The samples were divided into groups as follows: Group C: 0 min exposure to turmeric oil + MF diet + tap water (control without turmeric oil and without nicotine treatment), Group T: 60 min exposure to turmeric oil + MF diet + tap water (with turmeric oil and without nicotine treatment), Group CN: 0 min exposure to turmeric oil + MF diet + 0.5 mg / mL nicotine solution (without turmeric oil and with nicotine treatment), Group TN: 60 min exposure to turmeric oil + MF diet + 0.5 mg / mL nicotine solution (with turmeric oil and with nicotine treatment). MMP-2 was immunostained and observed in the intima, media and adventitia of mice in each group. The figure is a bar graph showing the MMP-positive area (%) in each group. [Figure 4]This figure shows the effect of turmeric oil exposure on vascular injury in mice, as observed by the extracellular matrix degrading enzyme MMP-9. The samples were divided into groups as follows: Group C: 0 min exposure to turmeric oil + MF diet + tap water (control without turmeric oil and without nicotine treatment), Group T: 60 min exposure to turmeric oil + MF diet + tap water (with turmeric oil and without nicotine treatment), Group CN: 0 min exposure to turmeric oil + MF diet + 0.5 mg / mL nicotine solution (without turmeric oil and with nicotine treatment), Group TN: 60 min exposure to turmeric oil + MF diet + 0.5 mg / mL nicotine solution (with turmeric oil and with nicotine treatment). MMP-9 was immunostained and observed in the intima, media and adventitia of mice in each group. The figure is a bar graph showing the MMP-positive area (%) in each group. [Diagram 5] This figure shows the results of measuring the concentration of turmerones (α-turmerone, β-turmerone, AR-turmerone) transferred to the serum of mice exposed to turmeric oil in a flask or orally administered it. The samples were divided into the following groups: C group: 2% CMC + no exposure, ET group: 60 minutes exposure to turmeric oil, LT group: 0.02 mg / g turmeric oil (emulsified with CMC) orally administered, HT group: 0.03 mg / g turmeric oil (emulsified with CMC) orally administered. [Figure 6] This is a diagram showing the measurement results of the concentration of turmerones (α-turmerone, β-turmerone, AR-turmerone) that migrated to the abdominal or thoracic blood vessels when mice were exposed to turmeric oil in a flask or orally administered it. The samples were divided into groups as follows: Group C: 2% CMC + no exposure, Group ET: 60 minutes exposure to turmeric oil, Group LT: 0.02 mg / g turmeric oil (emulsified with CMC) orally administered, Group HT: 0.03 mg / g turmeric oil (emulsified with CMC) orally administered. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] Hereinafter, preferred embodiments of the composition for preventing vascular deterioration according to the present invention will be described.

[0035] In this specification, vascular deterioration is used interchangeably with vascular damage, and generally refers to a state in which elastin in the vascular wall is degraded in a blood vessel modeled, but not limited to, by nicotine intake. The degradation of elastin in the vascular wall causes the vascular wall to lose elasticity, promoting the development and rupture of abdominal aortic aneurysms. However, vascular deterioration in this specification also includes cases in which the degradation of elastin in the vascular wall is not necessarily obvious, and includes any type of vascular damage that can be detected, for example, as indicated by molecular markers observed with vascular deterioration or the quantification or detection of specific proteins.

[0036] In this specification, vascular protection includes inhibiting vascular damage, repairing vascular damage, or maintaining a good condition of blood vessels. In addition, this vascular protection broadly includes the general concept of preventing, inhibiting, or blocking deterioration of the vascular wall, such as the degradation of elastin in the vascular wall, and the physiological or chemical mechanism of the protection is not limited to a specific one.

[0037] The composition for preventing deterioration of blood vessels and the food, beverage, and flavor containing such a composition of the present invention contain turmeric oil as an active ingredient. The active ingredient of this turmeric oil is turmerones, and the turmerones are one or more compounds selected from the group consisting of AR-turmerone, α-turmerone, and β-turmerone.

[0038] AR-turmerone has the CAS number 532-65-0 and the structure shown in the following formula (Chemical Formula 4).

[0039] [ka]

[0040] Alpha-turmerone has the CAS number 82508-15-4 and has the structure shown in the following formula (Chemical Formula 5).

[0041] [ka]

[0042] β-Turmerone has the CAS number 82508-14-3 and the structure shown in the following formula (Chemical Formula 6).

[0043] [ka]

[0044] In the present invention, standard products of turmeric oil, AR-turmerone, α-turmerone, and β-turmerone can be used. Also, those obtained from extracts of curry spices and the like can be used, and in particular those obtained from extracts of turmeric can be used.

[0045] Turmeric (English name: Turmeric, scientific name: Curcuma longa) is a monocotyledonous plant of the ginger family. Native to India, it is a perennial plant with a well-developed rhizome, which is used as a raw material for curry powder and as a dye.

[0046] The composition for preventing vascular deterioration of the present invention can contain AR turmerone, α-turmerone, and β-turmerone as active ingredients. AR-turmerone, α-turmerone and β-turmerone are preferably extracted from turmeric rhizomes by steam distillation, hexane extraction or ethyl acetate extraction, because AR-turmerone, α-turmerone and β-turmerone can be extracted in large amounts by extracting turmeric rhizomes by steam distillation, hexane extraction or ethyl acetate extraction.

[0047] The composition of the present invention for inhibiting or repairing vascular damage may contain turmeric oil, AR-turmerone, α-turmerone or β-turmerone as an active ingredient, or an extract containing turmeric oil as an active ingredient, which extract contains turmerones.

[0048] Turmeric oil, AR-turmerone, α-turmerone or β-turmerone is preferably extracted from turmeric rhizome by steam distillation, hexane extraction or ethyl acetate extraction, because by extracting turmeric rhizome by steam distillation, hexane extraction or ethyl acetate extraction, turmeric oil, AR-turmerone, α-turmerone or β-turmerone can be extracted in large amounts.

[0049] Turmeric oil, AR-turmerone, α-turmerone, or β-turmerone can be used alone or in combination of two or more. When turmeric oil, AR-turmerone, α-turmerone, or β-turmerone are used in combination, the mixing ratio is not particularly limited, and they can be mixed in any ratio, for example, between 1:99 and 99:1. As described in detail in the Examples below, turmeric oil, AR-turmerone, α-turmerone, or β-turmerone has the effect of preventing deterioration of blood vessels (e.g., the breakdown of elastin), and therefore the composition of the present invention containing these as active ingredients can be used for various purposes, including medical purposes.

[0050] For example, when the pharmaceutical composition for preventing vascular deterioration is used as a pharmaceutical preparation, it is used as a preventive drug for vascular deterioration in mammals (particularly humans). Furthermore, the pharmaceutical composition for preventing vascular deterioration of the present invention may be contained in a pharmaceutical preparation used in nicotine replacement therapy, and the pharmaceutical composition for preventing vascular deterioration may be used for the purpose of preventing vascular deterioration due to the effects of nicotine intake in nicotine replacement therapy.

[0051] The pharmaceutical composition for preventing deterioration of blood vessels can be formulated into pharmaceutical preparations such as tablets, powders, fine granules, granules, coated tablets, capsules, syrups, troches, inhalants, suppositories, injections, ointments, eye ointments, eye drops, nasal drops, ear drops, pap, lotions, and the like by conventional methods.

[0052] Excipients, binders, lubricants, colorants, flavorings, and, if necessary, stabilizers, emulsifiers, absorption enhancers, surfactants, pH adjusters, preservatives, antioxidants, and the like that are normally used in formulations can be used, and the formulations are prepared by standard methods by appropriately selecting the ingredients and blending amounts that are generally used as raw materials for pharmaceutical preparations.

[0053] When a pharmaceutical preparation containing a pharmaceutical composition for preventing deterioration of blood vessels is administered, the form of administration is not particularly limited, and any commonly used method may be used, and administration may be oral or parenteral. The dosage of the pharmaceutical preparation can be appropriately selected as a pharmaceutical effective amount depending on the severity of symptoms, age, sex, body weight, administration form, specific type of disease, and the like. As an example of the dosage, in the case of oral administration, an appropriate dose for an adult is usually about 3 to 3000 mg / kg of active ingredient, which may be administered once or several times a day.

[0054] Furthermore, from the viewpoint of contributing to general health, the composition of the present invention can be used in various products that are not necessarily for medicinal purposes, such as foods, beverages, flavorings, etc., which are taken orally, nasally, or pulmonary.

[0055] For example, the food for preventing deterioration of blood vessels according to the present invention includes, but is not limited to, various foods or health foods such as soft drinks, dairy products (processed milk, yogurt), confectioneries (jelly, chocolate, biscuits, gum, tablets), and supplements. In this specification, health foods broadly refer to foods sold and used as foods that contribute to maintaining and promoting health, and are a concept that includes functional foods, nutritional functional foods, and foods for specified health uses.

[0056] The amount of turmeric oil, AR-turmerone, α-turmerone or β-turmerone added as an active ingredient in food is not particularly limited and may be appropriately determined depending on the type of food. For example, the content may be added so that the content is within the range of about 0.0005 to 50% by weight as the dry weight of the above-mentioned extract.

[0057] The food for preventing deterioration of blood vessels of the present invention may contain other ingredients such as excipients, flavoring agents, coloring agents, preservatives, thickeners, stabilizers, gelling agents, and antioxidants. Examples of excipients include, but are not limited to, powders such as fine silicon dioxide, sucrose fatty acid esters, crystalline cellulose / sodium carboxymethylcellulose, calcium hydrogen phosphate, starches such as wheat starch, rice starch, corn starch, potato starch, dextrin, and cyclodextrin, crystalline celluloses, sugars such as lactose, glucose, sugar, reduced maltose, starch syrup, fructooligosaccharides, galactooligosaccharides, soybean oligosaccharides, isomaltooligosaccharides, xylooligosaccharides, maltooligosaccharides, and lactofructose, and sugar alcohols such as sorbitol, erythritol, xylitol, lactitol, and mannitol. These excipients can be used alone or in combination of two or more.

[0058] Examples of flavoring agents include, but are not limited to, fruit juice extracts such as bontang extract, lychee extract, apple juice, orange juice, yuzu extract, peach flavor, and plum flavor; sweeteners such as acesulfame K, sucralose, erythritol, oligosaccharides, mannose, xylitol, and isomerized sugars; tea components such as green tea, oolong tea, banaba tea, eucommia tea, iron ginseng tea, Job's tears tea, Gynostemma tea, Makomo tea, kelp tea, and yogurt flavor.

[0059] The composition of the present invention may be added to beverages, including, but not limited to, fruit juices such as orange, apple, grape, peach, passion fruit, and plum, teas such as green tea, oolong tea, banaba tea, eucommia tea, iron ginseng tea, pearl barley tea, gynostemma tea, makomo tea, and kelp tea, coffee, cocoa, lactic acid bacteria beverages, milk beverages, and alcoholic beverages such as beer, whiskey, chuhai, and various cocktails.

[0060] Furthermore, the composition of the present invention can be taken by direct inhalation as a fragrance component. The composition of the present invention can be inhaled as a volatile component of turmeric oil as it is, or can be used in combination with other fragrance components (e.g., citrus flavors, etc.). Due to its inhalable feature, it can also be added to at least one selected from the group consisting of fragrances, aroma oils, scented bags, incense sticks, tobacco, and electronic cigarettes. The composition of the present invention is absorbed via the nose or lungs and transferred into the blood. EXAMPLES

[0061] The effects of the present invention will be made clearer by describing examples of the present invention below. However, the present invention is not limited to the following examples.

[0062] <Preparation of steam distillate> 1 kg of turmeric rhizome was crushed and steam at normal pressure was passed through it to recover 20 kg of condensate. This condensate was centrifuged to obtain 25 g of a pale yellow oily liquid.

[0063] <Preparation of hexane extract> 1 kg of turmeric rhizomes was crushed and extracted with 5,000 ml of hexane at 40°C for 1 hour with stirring, and 4,200 ml of the supernatant was filtered through filter paper. The residue was then extracted with 2500 ml of hexane at 40°C for 0.5 hours with stirring, and filtered through filter paper. The solvent contained in the resulting extract was removed using an evaporator (40°C) to obtain a hexane extract of turmeric.

[0064] <Preparation of ethyl acetate extract> The residue after hexane extraction of turmeric was dried, and extracted with 5000 ml of ethyl acetate at 40°C for 1 hour by stirring, and 4800 ml of the supernatant was filtered through filter paper. The solvent contained in the obtained extract was distilled off with an evaporator (40°C) to obtain an ethyl acetate extract of turmeric. The yields of the hexane extract and the ethyl acetate extract are shown in Table 1 below.

[0065] [Table 1]

[0066] The hexane extract was analyzed using GCMS under the following conditions: Column: Intertcap Pure Wax (0.25id x 0.25μm x 60m) ·Injection volume; 1.0μl Heating: Hold at 50℃ for 2 minutes, heat up 2.5℃ / min to 240℃ Vaporization room temperature: 250℃ Carry gas flow rate: Helium 1.2ml / min Split ratio: 1 / 80 From the results of the GCMS analysis, the compounds were estimated to be AR-turmerone, α-turmerone, and β-turmerone using the attached library search (Wiley7n and NIST08). The hexane extract contained 9.9% AR-turmerone, 30.4% α-turmerone, and 11.5% β-turmerone.

[0067] The hexane extract was fractionated under the following HPLC conditions. Column: L-column ODS (20i.d. x 250mm) ·Mobile phase;water:acetonitrile(20:80,v / v) ·Flow rate: 18.9ml / min Column temperature: room temperature Detection: UV 243nm ·Injection volume; 10μl The active ingredients of the hexane extract were obtained as pale yellow oily substances from the fractions with RT of 7.5, 10.5 and 11.0, respectively.

[0068] The above light yellow oily substance was analyzed under the GCMS conditions described in paragraph

[0066] above, and the results were used to confirm that the compounds were AR-turmerone, α-turmerone, and β-turmerone, respectively, using the attached library search (Wiley7n and NIST08) and NMR analysis (confirmed by comparison with the literature values ​​in Hideji Itokawa, Fusayoshi Hirayama, Kazuko Funakoshi and Koichi Takeya Chem.Pharm.Bull.33(8)3488-3492(1985) and Shin-ichi Uehara, Ichiro Yasuda, Koichi Takeya, Hideji Itokawa Yakugaku Zasshi 112(11),817-823).

[0069] <Effect of turmeric oil administration on vascular protection> Next, to confirm whether turmeric oil has the effect of preventing vascular deterioration, a test was conducted in which turmeric oil was administered to mice.

[0070] The test procedure is detailed below. First, 4-week-old male Slc / ddY mice (Japan SLC, Inc.) were acclimated for 5 days and then randomly assigned to the following 4 groups. Group C: 0 min of turmeric oil exposure + MF diet + tap water (control without turmeric oil and nicotine treatment) Group T: 60 min of turmeric oil exposure + MF diet + tap water (with turmeric oil, no nicotine treatment) CN group: 0 min turmeric oil exposure + MF meal + 0.5 mg / mL nicotine solution (no turmeric oil, nicotine treatment), TN group: 60 min of turmeric oil exposure + MF diet + 0.5 mg / mL nicotine solution (with turmeric oil and nicotine treatment)

[0071] In the present invention, turmeric oil exposure was performed using an experimental system in which mice were exposed to gaseous turmeric oil and turmeric oil was administered intranasally or intrapulmonary. We investigated whether administration using this system could be used in the same way as oral administration. The experimental system for exposing mice to gaseous turmeric oil is shown in Figure 1. Mice were placed in an Erlenmeyer flask, and absorbent cotton soaked in turmeric oil was attached to the inside of the Erlenmeyer flask's lid. The mice were exposed to turmeric oil for 60 minutes, with three exposure cycles per week. It was confirmed that mice absorbed turmeric oil through the nose and lungs (see below).

[0072] Mice in Group C (control group) and Group T (turmeric oil exposure group) were provided with distilled water for two weeks. In this example, turmeric oil isolated from hexane extract was used. On the other hand, mice in the CN group (control + nicotine group) and the TN group (turmeric oil exposure + nicotine group) were supplied with a nicotine solution containing nicotine (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) at a concentration of 0.5 mg / ml in tap water instead of tap water for two weeks. At the same time, the mice in each group were fed MF diet (solid powder feed for laboratory animals, manufactured by Oriental Yeast Co., Ltd.) for two weeks. Group C (control group) and group CN (control + nicotine group) did not receive the above turmeric oil exposure during the two-week experimental period. The T group (turmeric oil exposure group) and the TN group (turmeric oil exposure + nicotine group) received the above turmeric oil exposure treatment in a 60-minute cycle three times per week.

[0073] After two weeks of turmeric oil exposure and dietary administration, the mice in each group were sacrificed. Blood and the thoracic and abdominal aorta were isolated from sacrificed mice. Serum was isolated from the collected blood, and the isolated thoracic aorta and abdominal aorta were fixed in 4% paraformaldehyde (Nacalai Tesque, Inc.), immersed in a 10% sucrose solution, and then embedded in OCT compound (Sakura Finetech Japan, Inc.) to serve as measurement samples. The measurement samples were stored at -80°C until use.

[0074] Next, cross sections of the thoracic aorta and abdominal aorta with a thickness of 5 μm were prepared using a cryostat (CM1850, manufactured by Leica Biosystems) and mounted on slide glasses.

[0075] From the destruction rate of the elastic laminar wavy structure, the degree of decomposition of the elastic laminar wavy structure containing elastin in the vascular wall can be confirmed. Therefore, by calculating the loss rate of elastic plate-like structures, it is possible to confirm the decomposition of elastin by nicotine, as well as the preventive effect of turmeric oil on the decomposition of elastin caused by nicotine. The rate of loss of the wavy structure of the elastic plate was determined by staining the elastic fibers with EVG staining, identifying areas where the wavy structure was lost due to flattening or fragmentation of the elastic plate, and calculating the ratio of the area of ​​the lost area to the total area of ​​the elastic plate.

[0076] The cross sections of the prepared abdominal aorta were stained with EVG to measure the loss rate of the elastic lamina wavy structure. In groups C and T, a densely stacked elastic lamina wavy structure was observed (elastic lamina destruction rate 14-19%), whereas in group CN, significant destruction of the elastic lamina wavy structure was observed (elastic lamina destruction rate 26%). However, in group TN, significant recovery of the destroyed elastic lamina wavy structure was observed (elastic lamina destruction rate 15%). These results indicate that turmeric oil can prevent damage to the elastic laminar wavy structure, including elastin, in the thoracic aortic vascular wall caused by nicotine intake (Figure 2).

[0077] Next, the effect of turmeric oil exposure on vascular injury in nicotine-treated mice was examined by observing the extracellular matrix degrading enzymes MMP-2 and MMP-9, respectively, which were detected by immunohistochemistry.

[0078] Immunostaining for MMP-2, shown in Figure 3, showed that exposure to turmeric oil increased the MMP-2-positive area in the intima and media in the CN group compared to the C group, and tended to suppress the nicotine-induced increase in the MMP-2-positive area in the TN group compared to the CN group.

[0079] Immunostaining for MMP-9, shown in Figure 4, demonstrated that turmeric oil exposure increased the MMP-9-positive area in the adventitia in the CN group compared with the C group, and inhibited the nicotine-induced increase in the MMP-9-positive area in the TN group compared with the CN group.

[0080] Next, they conducted experiments to examine the transfer of turmeric oil into the bloodstream when exposed to gaseous turmeric oil in a flask and when administered orally. First, 4-week-old male Slc / ddY mice (Japan SLC, Inc.) were acclimated for 5 days and then randomly assigned to the following 4 groups. Group C: 2% CMC + no exposure ET group: 60 minutes exposure to turmeric oil LT group: Turmeric oil 0.02 mg / g (emulsified with CMC) was orally administered. HT group: Turmeric oil 0.03mg / g (emulsified with CMC) was orally administered. Thirty minutes after oral administration or 60 minutes after exposure to turmeric oil, each mouse was sacrificed, blood was collected and dissected to measure the concentrations of turmeric oils (α-turmerone, β-turmerone, and AR-turmerone) in each mouse.

[0081] The results of serum measurements showed that all turmerones were significantly increased in the ET group compared to the C group, and that the amount of AR-turmerone transferred was equivalent in the ET and LT groups (Figure 5). These results showed that turmerones can be transferred into the blood at the same level as oral administration even when exposed in a gaseous state.

[0082] The measurement results of the concentration of turmeric analogs (α-turmerone, β-turmerone, AR-turmerone) that migrated to the abdominal or thoracic blood vessels showed that in the abdominal blood vessels, there was no significant difference in all turmerone analogs in the ET group compared to the C group, and in the thoracic blood vessels, all turmerone analogs were significantly increased in the ET group compared to the C group (Figure 6), indicating that in the experimental system of the present invention, turmerone analogs due to exposure / oral administration were significantly observed in the thoracic blood vessels. [Industrial Applicability]

[0083] The composition according to the present invention, and the food, beverage, and flavoring containing such a composition contain turmeric oil, AR-turmerone, α-turmerone, or β-turmerone as an active ingredient, and therefore can prevent blood vessel deterioration. Therefore, the present invention can be suitably used as a food, beverage, or flavoring for preventing blood vessel deterioration.

Claims

1. A composition for protecting blood vessels, comprising turmeric oil, the active ingredient of which is a turmerone, the turmerone being one or more compounds selected from the group consisting of AR-turmerone, α-turmerone, and β-turmerone, and inhibiting vascular damage.

2. The composition of claim 1 , wherein the vascular injury is modeled by fibrous destruction of the vascular wall caused by nicotine.

3. 3. The composition of claim 1, wherein the vascular injury is an abdominal aortic aneurysm or a thoracic aortic aneurysm.

4. The composition according to any one of claims 1 to 3, which is administered orally or nasally.

5. The composition according to any one of claims 1 to 4, which is used for inclusion in at least one selected from the group consisting of food, beverages, fragrances, aroma oils, scented sachets, incense sticks, tobacco, and electronic cigarettes.

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