JP2023060053A - Blood vessel aging inhibitory composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel blood vessel aging inhibitory composition.

SOLUTION: A blood vessel aging inhibitory composition contains at least one selected from the group consisting of xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid.

SELECTED DRAWING: None

COPYRIGHT: (C)2023,JPO&INPIT

Description

TECHNICAL FIELD The present disclosure relates to compositions for suppressing vascular aging and the like.

Vascular endothelium exists in the innermost layer of blood vessels and is involved in various functions such as vascular permeability of blood components, vascular contraction and relaxation reactions, regulation of blood coagulation by participating in the coagulation and fibrinolysis system, and control of platelet function. have a function. These functions are deeply related to the production of various physiologically active factors by vascular endothelial cells.

Sirtuins are known to be involved in the suppression of cell senescence by calorie restriction, extension of life span, etc. Sirt1, which is the most studied among the sirtuin family, is cell death suppression, stress resistance, metabolic regulation, anti-inflammatory. , cancer, cell differentiation, cell migration, depression, neurodegenerative diseases, and diabetes.

In vascular endothelial cells, it is known that inhibition of Sirt1 induces cellular senescence, and overexpression of Sirt1 can avoid cellular senescence induction by oxidative stress (Non-Patent Document 1). Sirt1 is also known to directly bind to endothelial nitric oxide-producing enzyme (eNOS) and increase its activity, resulting in increased NO production and vasodilation.

Sirt1 modulates premature senescence-like phenotype in human endothelial cells., J. Mol. Cell Cardiol., 43, 571-579 (2007)

An object of the present invention is to provide a novel composition for suppressing vascular aging.

The present inventors found that a specific component has the effect of enhancing the expression of sirtuin (Sirt1), and made further improvements.

The present disclosure includes subject matter described, for example, in the following sections.
Section 1.
one or more selected from the group consisting of xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid A composition for suppressing vascular aging, comprising:
Section 2.
one or more selected from the group consisting of xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid An anti-oxidative stress or anti-inflammatory composition comprising:
Item 3.
one or more selected from the group consisting of xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid A composition for suppressing active oxygen, comprising:
Section 4.
one or more selected from the group consisting of xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid A composition for activating a sirtuin, comprising:
Item 5.
Item 5. The composition according to any one of Items 1 to 4, which is an oral composition.
Item 6.
Item 6. The composition according to any one of Items 1 to 5, which is a food composition or a pharmaceutical composition.

According to the present disclosure, a composition for inhibiting vascular aging can be obtained. Also according to the present disclosure, in one embodiment, an anti-oxidative stress composition can be obtained. Also according to the present disclosure, in one embodiment, an anti-inflammatory composition can be obtained. Further, according to the present disclosure, in one embodiment, a composition for suppressing active oxygen can be obtained. Also according to the present disclosure, in one embodiment, compositions for activating sirtuins are provided.

1 shows the results of comparing the effects of xanthohumol treatment on the production of active oxygen induced by hydrogen peroxide. Fig. 10 shows the results of comparing the effects of xanthohumol treatment and the presence of xanthohumol on the expression of senescence markers induced by hydrogen peroxide. The effect of the presence or absence of xanthohumol treatment on E. CCL2 expression induced by E. coli LPS. The effect of the presence or absence of xanthohumol treatment on E. E. coli LPS-induced ICAM-1 expression.

Each embodiment included in the present disclosure will be described in further detail below.

The present disclosure provides xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA,
Compositions containing one or more selected from the group consisting of ursolic acid, carnosic acid, and orotic acid are included. Hereinafter, the composition may be referred to as "the composition of the present disclosure". The composition of the present disclosure can be preferably used for vascular aging inhibition, antioxidant stress, anti-inflammatory, active oxygen inhibition, or sirtuin activation.

Xanthohumol may be a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Examples of natural products containing xanthohumol include hops. As xanthohumol, for example, a hop extract or the like can be used as long as it contains xanthohumol.

L-sulforaphane may be either a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Examples of natural products containing L-sulforaphane include broccoli. As L-sulforaphane, for example, broccoli extract can be used as long as it contains L-sulforaphane.

4-Methylumbelliferone may be a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Examples of natural products containing 4-methylumbelliferone include cruciferous plants such as broccoli. As 4-methylumbelliferone, for example, broccoli extract can be used as long as it contains 4-methylumbelliferone.

Magnolol may be a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Natural products containing magnol include, for example, magnolia. As magnol, for example, magnolia extract or the like can be used as long as it contains magnol.

Honokiol may be a natural product or a synthetic product, and may be purified from a natural product or commercially available, and is not particularly limited. Natural products containing honokiol include, for example, magnolia. In addition, as the honokiol, as long as it contains honokiol, for example, a magnolia extract can be used.

Tanshinone I may be a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Examples of natural products containing tanshinone I include Danshen. Moreover, as tanshinone I, as long as it contains tanshinone I, for example, Danshen extract or the like can be used.

Cryptotanshinone may be a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Natural products containing cryptotanshinone include, for example, Danshen. As the cryptotanshinone, for example, Danshen extract or the like can be used as long as it contains cryptotanshinone.

Tanshinone IIA may be a natural product or a synthetic product, and may be purified from a natural product, commercially available, or the like, and is not particularly limited. Examples of natural products containing tanshinone IIA include Danshen. As tanshinone IIA, for example, Danshen extract or the like can be used as long as it contains tanshinone IIA.

Ursolic acid may be a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Natural products containing ursolic acid include, for example, apples, basil, berries, mint, and the like. As ursolic acid, for example, apple extracts, basil extracts, berry extracts, mint extracts and the like can be used as long as they contain ursol.

Carnosic acid may be a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Examples of natural products containing carnosic acid include rosemary and sage. As carnosic acid, for example, rosemary extract, sage extract, etc. can be used as long as they contain carnosic acid.

Orotic acid may be a natural product or a synthetic product, and may be purified from natural products or commercially available, and is not particularly limited. Examples of natural products containing orotic acid include milk and whey. Moreover, as orotic acid, milk, whey, etc. can be used, for example, as long as it contains orotic acid.

The total content of xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid in the composition of the present disclosure is , for example 0.0
01 to 95% by mass is preferred, 0.01 to 90% by mass is more preferred, and 0.1 to 80% by mass is even more preferred.

Compositions of the present disclosure can be utilized as oral compositions. Oral compositions include, for example, pharmaceutical compositions and food compositions (including beverage compositions and food additive compositions).

Compositions of the present disclosure include the components described above and may further include other components. The other components can be appropriately selected depending on the field in which the composition is used. For example, a pharmaceutically or food hygienically acceptable carrier can be used.

When used as a pharmaceutical composition, other ingredients include pharmaceutically acceptable bases, carriers, and/or additives (e.g., solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, , disintegrants, lubricants, etc.). The form of the pharmaceutical composition is also not particularly limited, and examples thereof include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, creams, poultices, and the like. Pharmaceutical compositions in these forms may optionally contain other ingredients such as xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, and ursolic acid. , carnosic acid, or orotic acid can be combined and prepared by a conventional method.

When used as a food composition, examples of other ingredients include bases, carriers, additives, and other ingredients and materials that can be used as foods. In addition, the form of the food composition is not particularly limited. Food (hospital food, sick food, nursing care food, etc.) can be exemplified. These can be prepared by conventional methods. In particular, when preparing a food composition as a health food (dietary supplement, food with nutrient function claims, food for the sick, food for specified health use, product with function claims, etc.) or supplement, continuous intake is easy. For example, it is preferably prepared in the form of granules, capsules, tablets (including chewable tablets, etc.), beverages (beverage powders, drinks, smoothies, etc.), especially capsules, tablets, tablets, beverage powders, drinks. Forms such as medicine, jelly, and gummies are preferred from the viewpoint of ease of ingestion, but are not particularly limited to these. When used as a food additive composition among food compositions, examples thereof include liquid, powder, flake, granule, and paste forms. More specifically, seasonings (soy sauce, sauce, ketchup, dressing, etc.), flakes (furikake), grilled meat sauce, spices, roux paste (curry roux paste, etc.) and the like can be exemplified.

The compositions of the present disclosure contain xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, or orotic acid. can enhance the expression of sirtuins (preferably Sirt1). In one embodiment, the compositions of the present disclosure also contain xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, Alternatively, since it contains orotic acid, oxidative stress can be suppressed. In one embodiment, the compositions of the present disclosure also contain xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, Or because it contains orotic acid, inflammation can be suppressed. In one embodiment, the compositions of the present disclosure also contain xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, Alternatively, since it contains orotic acid, active oxygen can be suppressed. Thus, the compositions of the present disclosure contain xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, or orotic acid. Therefore, vascular aging can be suppressed.

Also, in one preferred embodiment, the compositions of the present disclosure are capable of enhancing expression of heme oxygenase-1 (HO-1). HO-1 is a rate-limiting enzyme for heme metabolism induced by nuclear factor erythroid 2-related factor 2 (Nrf2), and is known to have the effect of improving vascular endothelial function. there is That is, the composition of the present disclosure can enhance vascular endothelial function by enhancing HO-1 expression.

The compositions of the present disclosure can be used to activate sirtuins (enhance sirtuin expression). In particular, the compositions of the present disclosure can be used to activate Sirt1 (enhance Sirt1 expression). Also, in one embodiment, the compositions of the present disclosure can be used to reduce oxidative stress. Also, in one embodiment, the compositions of the present disclosure can be used to reduce inflammation. Also, in one embodiment, the compositions of the present disclosure can be used to suppress active oxygen. Also, in one embodiment, the compositions of the present disclosure can be used to inhibit vascular aging. In addition, in one embodiment, the composition of the present disclosure can enhance the expression of Sirt1, so that it exhibits effects such as anti-aging effects, anti-arteriosclerosis effects, vasodilation effects, and prevention of diabetic complications. can be used, and the composition of the present disclosure can be preferably used for such applications. For example, the composition of the present disclosure can be used for applications such as anti-aging, anti-arteriosclerosis, vasodilation, and prevention of diabetic complications. In addition, since the composition of the present disclosure can suppress oxidative stress, it is possible to prevent diseases caused by increased oxidative stress (e.g., cancer; hypertension; arteriosclerosis; dyslipidemia; elevated hyperlipidemia; thrombosis). disease; ischemic heart disease such as angina pectoris and myocardial infarction; diabetes; diabetic complications; periodontal disease, etc.). In addition, since the composition of the present disclosure can suppress inflammation, diseases caused by vascular inflammation (e.g., hypertension, arteriosclerosis, dyslipidemia, elevated hyperlipidemia, thrombosis, diabetes, diabetic complications, periodontal disease, etc.) can be preferably used for prevention and/or treatment. In addition, since the composition of the present disclosure can suppress active oxygen, diseases caused by an increase in active oxygen (for example, cancer, hypertension, arteriosclerosis, dyslipidemia, elevated hyperlipidemia, thrombosis) disease, ischemic heart disease, diabetes, diabetic complications, periodontal disease, etc.). In addition, since the composition of the present disclosure can suppress vascular aging, diseases caused by vascular aging (e.g., arteriosclerosis; ischemic heart diseases such as angina pectoris and myocardial infarction; cerebral hemorrhage, cerebral infarction) Stroke such as; periodontal disease, etc.) can be preferably used for prevention and/or treatment.

The composition of the present disclosure may be labeled with descriptions of its use, efficacy, effect, function, type of active ingredient, type of functional ingredient, method of ingestion, and the like. “Labeling” refers to pharmaceutical compositions, health foods (dietary supplements, functional food, food for the sick, food for specified health use, products with function claims, etc.), supplements, food for the sick (hospital food, food for the sick). or nursing care food, etc.). In addition, "indication" includes all indications for informing consumers of the use, efficacy, effect, function, etc. of the composition of the present disclosure. This display may be a display that reminds or infers the content of the preceding paragraph, and may include all displays regardless of the purpose of display, the content of display, the object or medium to be displayed, and the like. Examples include display on product packages and containers, display on product advertisements, price lists, and transaction documents, display or distribute these, or provide these by electromagnetic (Internet, etc.) methods. .

When the composition of the present disclosure is a food with functional claims, for example, "helps (supports) keep blood vessels supple", "helps (supports) keep blood vessels soft", "blood vessels Helps maintain flexibility (supports), Helps maintain antioxidant capacity of blood vessels (supports), Helps maintains youthful blood vessels (supports), Strengthens blood vessels "Helps (supports) blood vessels", "Helps (supports) maintain blood vessel strength", "For those who are concerned about suppleness of blood vessels", "For those who are concerned about softness of blood vessels", "For those concerned about flexibility of blood vessels", "For those concerned about antioxidant power of blood vessels", "For those concerned about youthfulness of blood vessels", "For those concerned about strength of blood vessels" , ``For those concerned about age of blood vessels'', ``Preventing aging of blood vessels'', ``Maintaining smooth blood circulation'', ``Helping (supporting) smooth blood circulation'', `` To help (support) smooth blood flow,” “to maintain the original strength of blood vessels,” “to bring out the original strength of blood vessels,” “for rejuvenation of blood vessels,” “improvement of blood vessel function.” Helps maintain (supports), "helps (supports) improve vascular function", "improves intravascular environment", "helps (supports) maintains intravascular environment", "improves intravascular environment" Indications such as "helps (supports) blood vessel tone", "maintains blood vessel tone", "helps (supports) blood vessel tone", etc. can be attached. It should be noted that the terms are not limited to the above examples, and terms that are synonymous with such meanings can be used.

The composition of the present disclosure can be taken in one or more (preferably 2-3) divided doses. In addition, although humans are preferred as ingestion targets, non-human mammals other than humans may also be used. Subjects for ingestion include, for example, humans with low sirtuin expression levels, humans with low Sirt1 expression levels, humans with a high amount of active oxygen in the blood, people who desire suppression of inflammation in blood vessels, and suppression of oxidative stress in blood vessels. Desired human, diseases caused by increased oxidative stress (e.g., cancer; hypertension; arteriosclerosis; dyslipidemia; elevated hyperlipidemia; thrombosis; diabetes; diabetic complications; periodontal disease, etc.), diseases caused by inflammation of blood vessels (e.g., hypertension, arteriosclerosis, dyslipidemia, elevated hyperlipidemia, thrombosis, People with or suspected of having diabetes, diabetes complications, periodontal disease, etc.), diseases caused by increased active oxygen (e.g., cancer, hypertension, arteriosclerosis, dyslipidemia, elevated hyperlipidemia, thrombosis, ischemic heart disease, diabetes, diabetic complications, periodontal disease, etc.), diseases caused by vascular aging (e.g., arteriosclerosis; angina, myocardial infarction, etc.) hemorrhagic heart disease; stroke such as cerebral hemorrhage and cerebral infarction; periodontal disease, etc.);

In this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present disclosure encompasses all arbitrary combinations of the constituent elements described herein.

Also, the various characteristics (property, structure, function, etc.) described for each of the embodiments of the disclosure described above may be combined in any way to identify subject matter encompassed by the disclosure. That is, the present disclosure encompasses all subject matter consisting of any and all possible combinations of the features described herein.

The contents of the present disclosure will be specifically described using the following examples. However, the present disclosure is by no means limited to these. In the following, experiments are conducted under atmospheric pressure and normal temperature conditions, unless otherwise specified. In addition, "%" means "% by mass" unless otherwise specified.

1. Effect on gene expression Each sample shown in Table 1 was prepared using DMSO as a solvent so that the concentration was 10 mM. Human umbilical vein endothelial cells (HUVECs, manufactured by Sanko Junyaku Co., Ltd.) were cultured in a 12-well plate by mixing 2 μl of the obtained preparation with MCDB131 medium (998 μl) containing 2 vol % FBS and 10 mM L-glutamine. (final concentration 20 μM) and incubated for 6 hours. As a control, DMSO containing no sample shown in Table 1 was used and treated in the same manner.

Next, total RNA was extracted using Total RNA Mini Kit (manufactured by BIO-RAD). Single-stranded cDNA was extracted from 0.5 μg of total RNA using PrimeScript
It was synthesized using RT reagent Kit (manufactured by Takara Bio Inc.). Quantitative analysis of Sirt1 and HO-1 mRNA was performed using a real-time PCR system (manufactured by Applied Biosystems). In addition, Premix Ex Taq (manufactured by Takara Bio Inc.), Assay-on-Demand, and Gene Expression Products (Hs01009005_m1 for Sirt1, Hs01110250_m1 for HO-1, and Hs02387368_g1 for RPS1 8: Applied Biosystems) for quantitative real-time PCR analysis used. Each quantitative data was corrected for the expression level of Ribosomal protein S18 (RPS18). Table 1 shows the expression level (relative value) of each gene when the samples shown in Table 1 are used, assuming that the corrected expression level of each gene in the control is 1, as a gene expression fold.

Xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid were associated with Sirt1 gene It was found to increase the expression level by more than 1.5 fold. Also, xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid were associated with HO -1 was found to increase the gene expression level by more than 2-fold. From these results, xanthohumol, L-sulforaphane, 4-methylumbelliferone, magnolol, honokiol, tanshinone I, cryptotanshinone, tanshinone IIA, ursolic acid, carnosic acid, and orotic acid enhance the expression of Sirt1. By doing so, it is considered that an excellent vascular aging inhibitory effect and the like can be achieved.

2. Observation of Reactive Oxygen (ROS) Human umbilical vein endothelial cells cultured for 24 hours in MCDB131 medium containing 10 μM xanthohumol, 1% by volume FBS, and 2 mM L-glutamine were washed with PBS(−) and treated with 500 μM Stimulation was performed for 1 hour in serum-free medium containing hydrogen peroxide. After stimulation, the cells were washed with PBS(−), CellROX Green (manufactured by Invitrogen) and Hoechst 33342 (manufactured by Invitrogen) were added, and incubated at 37° C. for 30 minutes to fluorescently stain ROS and nuclei. After staining, the cells were fixed with 4% by weight paraformaldehyde, and fluorescence observation was performed with a fluorescence microscope BZ-II (manufactured by Keyence Corporation). Cells not treated with xanthohumol or hydrogen peroxide were used as a control. Figure 1 shows cells not treated with xanthohumol and hydrogen peroxide (upper left), cells treated with hydrogen peroxide alone (lower left), cells treated with xanthohumol alone (upper right), and xanthohumol and hydrogen peroxide. Observations of cells treated with hydrogen oxide (bottom right) are shown.

Xanthohumol was found to suppress the production of ROS induced by hydrogen peroxide. From these results, it was found that xanthohumol exhibits an excellent effect of suppressing active oxygen.

3. Observation of cellular senescence It is known that Senescence β-Galactosidase is overexpressed in senescent cells. Human umbilical vein endothelial cells cultured for 24 hours in MCDB131 medium containing 10 µM xanthohumol, 1 vol% FBS, and 2 mM L-glutamine were washed with PBS (-) and treated with 500 µM hydrogen peroxide, 1 vol%. Stimulation was performed with MCDB131 medium containing FBS and 2 mM L-glutamine for 24 hours. After stimulation, the cells were washed with PBS(-), stained with β-Galactosidase using Senescence β-Galactosidase Staining Kit (manufactured by Cell Signaling), and observed under a microscope. Cells not treated with xanthohumol or hydrogen peroxide were used as a control. Figure 2 shows cells not treated with xanthohumol and hydrogen peroxide (upper left), cells treated with hydrogen peroxide alone (lower left), cells treated with xanthohumol alone (upper right), and xanthohumol and hydrogen peroxide. Observations of cells treated with hydrogen oxide (bottom right) are shown.

Xanthohumol was found to suppress the expression of senescence markers induced by hydrogen peroxide. From these results, it was found that xanthohumol exerts an excellent vascular aging inhibitory effect.

4. Effect on Gene Expression Human umbilical vein endothelial cells cultured for 24 hours in MCDB131 medium containing 10 μM xanthohumol, 1 vol % FBS, and 2 mM L-glutamine were washed with PBS(−) and treated with 100 ng/mL E . The cells were further cultured in MCDB131 medium containing E. coli LPS, 1 vol % FBS, and 2 mM L-glutamine for 6 hours. After washing the cells with PBS(-), total RNA was extracted using RNeasy Mini Kit (manufactured by Qiagen). Single-stranded cDNA was extracted from 0.5 µg of total RNA using PrimeScript RTr.
It was synthesized using reagent Kit (manufactured by Takara Bio Inc.). Quantitative analysis of CCL2 and ICAM-1 mRNA was performed using a real-time PCR system (manufactured by Applied Biosystems). Premix Ex Taq (manufactured by Takara Bio Inc.), Assay-on-Demand, Gene Expression Products (Hs00234140_m1 for CCL2, HS00164932_m1
for ICAM-1: Applied Biosystems) was used for quantitative real-time PCR analysis. Each quantitative data was corrected for the expression level of Ribosomal protein S18 (RPS18). As controls, xanthohumol or E. A similar analysis was performed using cells cultured in medium without E. coli LPS. xanthohumol and E. When the expression level of CCL2 or ICAM-1 is set to 1 relative to the expression level of RPS18 extracted from cells cultured in a medium containing no E. coli LPS, the relative values are shown in FIGS. 3 and 4. FIG.

E. It was confirmed that E. coli LPS induces the expression of CCL2 and ICAM-1, which are inflammatory genes. In contrast, xanthohumol is an E. It was found to remarkably suppress gene expression of CCL2 and ICAM-1 induced by E. coli LPS. From these results, it was found that xanthohumol exhibits excellent anti-inflammatory effects and the like.

Claims (5)

A composition for suppressing vascular aging containing carnosic acid and/or orotic acid. A sirtuin-activating composition containing carnosic acid and/or orotic acid. 3. The composition of claim 2, wherein the sirtuin is Sirtl. The composition according to any one of claims 1 to 3, which is an oral composition. The composition according to any one of claims 1 to 4, which is a food composition or a pharmaceutical composition.

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