JP2014034525A - Depressant of cell proliferation inhibition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a companion drug for depressing cell proliferation inhibition by resveratrol.SOLUTION: Resveratrol and reduced pyrroloquinoline quinone or pyrroloquinoline quinone are brought into contact with cells in combination. That is, toxicity of resveratrol was found to be reduced by using pyrroloquinoline quinones.

Description

The present invention relates to a composition for reducing the cell growth inhibitory action of resveratrol using pyrroloquinoline quinones.

Resveratrol (also called 5-parahydroxystyryl resorcinol or 3,4 ', 5-stilbenetriol) is a polyphenolic flavonoid found in red wine and its grape skin and seeds, as well as in mulberry, peanut, and yellow It is.

The sirtuin gene has been identified as the mechanisms of aging and lifespan control have been clarified in recent molecular biological studies. This sirtuin gene has attracted attention as a longevity gene that delays aging. Resveratrol is known to have the effect of controlling the activity of sirtuin gene SRIT1 and the like to make cells anti-life (Non-patent Document 1).

In addition to this, resveratrol has many known functions such as female hormone-like action, radical scavenging ability, tyrosinase activity inhibitory action, hyaluronidase activity inhibitory action, antibacterial action, neuroprotective action, and improvement of lipid metabolism. Many studies have been conducted at the cellular level. In addition, it is important in cosmetics, and its application has been proposed (Patent Document 1).

Furthermore, it has been reported that resveratrol is effective in suppressing the reaction with respect to the Maillard reaction that has been known as a browning reaction for foods for a long time (Patent Document 2).
The Maillard reaction is a reaction in which amino groups such as amino acids, proteins, and peptides are bonded non-enzymatically to carbonyl groups such as reducing sugars. This reaction degrades the color, aroma, and physical properties of food. By suppressing it, the quality deterioration of food can be prevented.
Maillard reaction also occurs in vivo. In diabetic patients, accumulation of AGE and protein cross-linking formation occurs due to hyperglycemia, which causes diabetic complications such as neuropathy, retinopathy, and atherosclerosis. It is said that the same reaction progresses especially with aging, which is said to cause aging symptoms such as skin firmness and reduced elasticity, and resveratrol prevents aging by inhibiting this reaction I can do it.

While resveratrol has such an effective effect, it is known to have an action of inhibiting cell proliferation, and administration to cells at a high concentration is difficult (Non-patent Document 3). It is not preferable as a research reagent that the use at a high concentration is restricted despite having many effective functions.
Further, it is not preferable for use as food, pharmaceuticals or cosmetics.

For this reason, the synthesis | combination of the substance which suppresses the cell growth inhibition of resveratrol is performed (nonpatent literature 2). The new derivative is most suitable as a method for increasing the effectiveness by design. However, the synthesis of new materials is costly due to the need to perform many organic reactions and enormous amounts of time. Moreover, since the derivative may lose the function that the original resveratrol had, the function evaluation is also required, and a lot of costs are required. Therefore, it takes a lot of time to become a cheap and easily obtainable substance.

JP 2001-510777 A JP 2002-293736 A

Cell, 127, p1109,2005 Nature reviews Drug Discovery Vol7, p841, 2008 Chemistry central Journal, vol5, p88,2011,

This inventor made it the subject to provide the composition which suppresses the cell growth inhibitory effect of a resveratrol cheaply and easily, and its manufacturing method.

［２］ピロロキノリンキノン類がレスベラトロールに対して重量比で０．０１から１００含むことを特徴とする、［１］記載の細胞増殖阻害抑制剤。
［３］ピロロキノリンキノン類が式２に示す酸化型ピロロキノリンキノン、式３に示す還元型ピロロキノリンキノン又はこれらの塩である、［１］又は［２］記載の細胞増殖阻害抑制剤。

［４］［１］〜［３］いずれか記載の細胞増殖阻害抑制剤を添加した食品。
［５］［１］〜［３］いずれか記載の細胞増殖阻害抑制剤を添加した化粧品。
［６］［１］〜［３］いずれか記載の細胞増殖阻害抑制剤を含む試薬。
［７］［１］〜［３］いずれか記載の細胞増殖阻害抑制剤を溶液又は懸濁液の状態で細胞に接触させる、レスベラトロールの細胞増殖阻害の抑制方法。 As a result of intensive studies on a method for suppressing the cell growth inhibitory effect, the present inventors have reached the present invention. The invention has the following contents.
[1] A cell growth inhibition inhibitor comprising resveratrol represented by Formula 1 and pyrroloquinoline quinones.

[2] The cell growth inhibition inhibitor according to [1], wherein pyrroloquinoline quinones are contained in a weight ratio of 0.01 to 100 with respect to resveratrol.
[3] The cell growth inhibition inhibitor according to [1] or [2], wherein the pyrroloquinoline quinone is an oxidized pyrroloquinoline quinone represented by Formula 2, a reduced pyrroloquinoline quinone represented by Formula 3, or a salt thereof.

[4] A food to which the cell growth inhibition inhibitor according to any one of [1] to [3] is added.
[5] A cosmetic to which the cell growth inhibition inhibitor according to any one of [1] to [3] is added.
[6] A reagent comprising the cell growth inhibition inhibitor according to any one of [1] to [3].
[7] A method for inhibiting cell growth inhibition of resveratrol, comprising bringing the cell growth inhibition inhibitor according to any one of [1] to [3] into contact with cells in a solution or suspension state.

According to the present invention, it has become possible to provide a composition that can easily and inexpensively suppress the cell growth inhibitory action of resveratrol.

レスベラトロールは、有機合成法、抽出法のどちらの方法で得られるものでもよい。また純品として単離されたものでなくともよい。混合物としてはブドウ由来の成分として濃縮されたものが手に入れやすい。具体的にはオリザ油化株式会社のレスベラトロールＰ５（レスベラトロール５％含有）やレスベラトロールＷＳＰＣ０．５等を使用できる。 The present invention is a cell growth inhibition inhibitor comprising resveratrol having the structure represented by formula (1) and pyrroloquinoline quinones.

Resveratrol may be obtained by either an organic synthesis method or an extraction method. Moreover, it may not be isolated as a pure product. As a mixture, it is easy to obtain what is concentrated as a grape-derived component. Specifically, Resveratrol P5 (containing 5% resveratrol), resveratrol WSPC0.5, etc. from Oriza Oil Chemical Co., Ltd. can be used.

還元型ピロロキノリンキノンとピロロキノリンキノンは混在しても問題ない。
式２，３に記載した物質はトリカルボン酸化合物である。これらの化合物を使用する場合はこれらの塩でも構わなく、具体的にはアルカリ金属塩、アルカリ土類金属塩、アンモニウム塩として使用することができる。アルカリ金属はトリカルボン酸に対して、モノ、ジ、トリの置換数どれでもよい。また、アルカリ金属との比は０．５、１、１．５のどれでもよい。より好ましくはフリー体、ナトリウム塩、カリウム塩が入手しやすく、使用しやすい。式２、３の化合物は単独、もしくは混合して使用することができる。 In the present invention, pyrroloquinoline quinones refer to pyrroloquinoline quinone (hereinafter sometimes abbreviated as PQQ), reduced pyrroloquinoline quinone or a salt thereof. The pyrroloquinoline quinone has a structure represented by the formula (3), and the reduced pyrroloquinoline quinone has a structure represented by the formula (2).

There is no problem even if reduced pyrroloquinoline quinone and pyrroloquinoline quinone are mixed.
The substances described in Formulas 2 and 3 are tricarboxylic acid compounds. When these compounds are used, these salts may be used, and specifically, they can be used as alkali metal salts, alkaline earth metal salts, and ammonium salts. The alkali metal may have any number of mono, di, and tri substitutions for the tricarboxylic acid. The ratio to the alkali metal may be 0.5, 1, or 1.5. More preferably, free forms, sodium salts, and potassium salts are easily available and easy to use. The compounds of Formulas 2 and 3 can be used alone or in combination.

The reduced pyrroloquinoline quinone of formula (2) can be obtained by reducing the pyrroloquinoline quinone of formula (3). Pyrroloquinoline quinone is a compound that can be obtained by culture or organic synthesis. In the present invention, there is no problem in any method for producing pyrroloquinoline quinone.

The cell growth inhibition inhibitor of the present invention can be easily prepared by mixing resveratrol and pyrroloquinoline quinones. The mixing ratio may be 0.01 to 100 pyrroloquinoline quinones with respect to resveratrol 1 as a weight ratio. Preferably it is 0.05 to 20, more preferably 0.1 to 10.
Mixing can be performed in powder, solution, or suspension. Also, it may be mixed at the time of use. When mixing is performed with powder, the powders can be mixed with each other, or can be mixed using a dispersion medium such as water, alcohol, or fat. In the case of using a dispersion medium, resveratrol is difficult to dissolve in water, so that it can be uniformly mixed by dissolving it in an organic solvent that can be dissolved, specifically, dimethylsulfoxide and adding it to a solution of pyrroloquinoline quinones. In the case of suspension, this can be achieved by adding each powder to water, alcohol, and fat.

In the cell growth inhibition inhibitor of the present invention, resveratrol and pyrroloquinoline quinones, which are the inhibitor composition, may be separately added to the object. In this case, it is preferable that the amount of pyrroloquinoline quinones be 0.01 to 100 with respect to resveratrol 1 by weight. Preferably it is 0.05 to 20, more preferably 0.1 to 10. More preferably, it is 0.1 to 10. When the amount of pyrroloquinoline quinones is less than this range, there is no effect. When the amount is more than this range, the effect of resveratrol is low because there are too many pyrroloquinoline quinones. Moreover, it is preferable to perform addition timing within the range of 0 to 4 hours.

The cell growth inhibition inhibitor of the present invention can be used directly as a reagent for research of cell biology or biochemistry that acts on cells. Moreover, it can be used as a pharmaceutical, a quasi-drug, or a food, a functional food, a feed, or the like added and blended with resveratrol as an active ingredient. The functional food here means food that is ingested for the purpose of maintaining nutrition or supplementing nutrition, such as health food, nutritional supplement, functional nutrition food, and nutritional health food. It can also be used as a cosmetic. Reducing cell growth inhibition is effective as a reduction in toxicity when used at high concentrations. In addition, the formulation reduces the risk of side effects from resveratrol.

Specific examples include capsules, tablets, chewables, tablets, fine granules, granules, powders, drinks, caplets, oral-dissolving tablets, injections, liquids for internal use, etc. Is not to be done. A tablet or capsule is preferable.

In order to commercialize the liquid preparation according to the present invention, various commonly used additives can be blended. Examples of additives include stabilizers, surfactants, solubilizers, buffers, sweeteners, flavoring agents, suspending agents, antioxidants, cooling agents, flavoring agents / fragrances, emulsifiers, pH adjustments. Agents, dispersants, fragrances, preservatives, preservatives and the like.

Examples of the stabilizer include adipic acid, ascorbic acid, sodium L-ascorbate, L-aspartic acid, sodium L-aspartate, sodium sulfite, L-arginine, sodium benzoate, inositol, sodium edetate, erythorbic acid, Sodium erythorbate, sodium citrate, glycine, glycerin, glycerin fatty acid ester, light anhydrous silicic acid, tocopherol acetate, gelatin, polyoxyethylene polyoxypropylene glycol, anhydrous sodium citrate, glyceryl monostearate, sodium hydrogen phosphate, etc. Can be mentioned.

Surfactants include cholesterol, sucrose fatty acid ester, stearyl alcohol, sorbitan sesquioleate, cetanol, sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polysorbate, macrogol, monooleic acid Examples include sorbitan, glyceryl monostearate, sorbitan monolaurate, sodium lauryl sulfate, lauromacrogol and the like.

As solubilizers, L-aspartic acid, L-arginine, sodium benzoate, ethanol, sodium chloride sorbitan fatty acid ester, sodium hydrogen carbonate, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, polysorbate, polyvinyl alcohol , D-mannitol, absolute ethanol and the like.

Buffering agents include ascorbic acid, magnesium L-aspartate, aminoethylsulfonic acid, L-arginine, benzoic acid, sodium benzoate, citric acid, calcium citrate, sodium citrate, disodium citrate, glycine, hydrogen carbonate Use sodium, lactic acid, glucose, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium hydrogen phosphate, sodium metaphosphate, sodium hydrogen phosphate, dipotassium phosphate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, etc. can do.

Sweeteners include aspartame, achacha, licorice, fructose, fructose dextrose, dextrose fructose dextrose, reduced maltose syrup, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, high fructose syrup, dextrose, water candy, lactose, sucrose And purified sucrose, honey, saccharin, sodium saccharin, stevia, sucralose, erythritol, xylitol, D-sorbitol, maltitol, maltose, D-mannitol, simple syrup and the like.

As a corrigent, ascorbic acid, L-aspartic acid, DL-alanine, disodium 5'-inosinate, fennel, sodium chloride, orange oil, cacao powder, camphor, glycine, glycerin, L-glutamic acid, saffron, tartaric acid, For example, ginger, D-sorbitol, mint, adipic acid, fumaric acid, peppermint, borneol, menthol, agate, green tea powder, apple juice, apple vinegar, lemon oil, rose oil, royal jelly, and the like can be used.

Examples of the suspending agent include gum arabic, carrageenan, carboxyvinyl polymer, agar, xanthan gum, glycerin fatty acid ester, titanium oxide, sucrose fatty acid ester, stearic alcohol, aluminum stearate, cetanol, purified gelatin, sorbitan fatty acid ester, Examples include soybean lecithin, propylene glycol fatty acid ester, pectin, propylene glycol, polyoxyethylene hydrogenated castor oil, polyethylene glycol, methyl cellulose, glyceryl monostearate, liquid paraffin, and the like.

Examples of antioxidants include ascorbic acid, L-ascorbic acid stearate, sodium hydrogen sulfite, sodium sulfite, erythorbic acid, cysteine hydrochloride, tocopherol acetate, soybean lecithin, butylhydroxyanisole, propyl gallate and the like. .

Examples of the refreshing agent include geraniol, mint water, mint oil, borneol, menthol, mint and the like.

Flavoring agents and fragrances include fennel, ethyl vanillin, ethyl maltol, orange, camphor, keihi, sugar flavor, cinnamaldehyde, cherry flavor, spruce tincture, mint, vanilla flavor, vanillin, bitter essence, fruit flavor, flavor GI, vermouth Examples include flavor, mixed flavor, mint flavor, menthol, eucalyptus oil, agate, lemon powder, lemon oil, rosin, and rose oil.

As an emulsifier, carrageenan, carboxyvinyl polymer, carmellose sodium, guar gum, glycerin fatty acid ester, polyethylene glycol distearate, sucrose fatty acid ester, stearyl alcohol, stearic acid, cetanol, gelatin, sorbitan fatty acid ester, soybean lecithin, hydroxypropyl cellulose , Propylene glycol, propylene glycol fatty acid ester, polyoxyethylene polyoxypropylene glycol, polysorbate, myristyl alcohol, glyceryl monostearate, sorbitan monolaurate, sodium lauryl sulfate and the like.

Examples of pH adjusters include dilute hydrochloric acid, sodium citrate, glycine, succinic acid, acetic acid, tartaric acid, sodium hydroxide, sodium bicarbonate, sodium carbonate, monosodium fumarate, phosphoric acid, trisodium phosphate, sodium hydrogen phosphate, Examples include dipotassium phosphate and sodium dihydrogen phosphate.

Dispersants include aminoalkyl methacrylate polymer RS, gum arabic, oleic acid, carboxyvinyl polymer, carmellose sodium, glycerin, crystalline cellulose, choline phosphate, lecithin, sorbitan sesquioleate, dextrin, corn starch, sorbitan trioleate Hydroxyethyl cellulose, hydroxypropyl cellulose, methyl cellulose, glyceryl monostearate, sodium lauryl sulfate, liquid paraffin and the like can be used.

Examples of the fragrances include fennel, ethyl vanillin, orange oil, camphor, cinnamon, ginger, ginkgo, clove, mint, vanilla, vanillin, borneol, maltol, menthol, eucalyptus, rhubarb, lemon and rose water. .

Examples of the preservative include aminoethyl sulfonic acid, benzoic acid, sodium benzoate, ethanol, sodium edetate, agar, sodium citrate, sodium salicylate, sorbic acid, isopropyl paraoxybenzoate, ethyl paraoxybenzoate, menthol, and the like. .

Preservatives include sodium benzoate, ethanol, sodium edetate, glycerin, salicylic acid, sodium salicylate, D-sorbitol, sorbic acid, isobutyl paraoxybenzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, methyl paraoxybenzoate, propylene A glycol etc. can be mentioned.

The present invention will be described more specifically with reference to examples and comparative examples, but the present invention is not limited to these examples.
Resveratrol was manufactured by Wako Pure Chemical. As the pyrroloquinoline quinone disodium trihydrate, Mitsubishi Gas Chemical Co., Ltd. (powder) was used. A free form of reduced pyrroloquinoline quinone (hereinafter sometimes abbreviated as R-PQQ) was produced by the method of International Publication 2011/102387.

レスベラトロールによる細胞増殖阻害がピロロキノリンキノン類を用いることにより回復している。すなわちピロロキノリンキノン類を用いることによってレスベラトロールの毒性は低減されていた。レスベラトロール１に対して０．０１９から１２倍量で有効であった。 Example 1-6, Comparative Example 1
Resveratrol 12.5μg / ML
Resveratrol was dissolved in dimethyl sulfoxide to a concentration of 5 mg / ML. During use, this was dissolved in a medium and used.
Reduced pyrroloquinoline quinone was added to water at 1.5 mg / ML and autoclaved to obtain a suspension. As for pyrroloquinoline quinone, pyrroloquinoline quinone disodium trihydrate was added to water so as to be 1.5 mg / ML, and autoclaved to obtain a solution. These solutions were diluted with a medium at the time of use.
This was performed using Chinese hamster ovary cells (sometimes abbreviated as CHO cells). As a medium, 10% of fetal bovine serum (sometimes abbreviated as FBS, DS Pharma Biomedical Co., Ltd.) was added to α-MEM medium (GIBCO). Culturing was carried out at 37 ° C. under saturated steam with 5% carbon dioxide added.
The CHO cells cultured at 37 ° C. are peeled from the petri dish by trypsin treatment. Remove the detached cells by centrifugation and add medium. Put this in the hemocytometer and count the number of cells.
Using a 96-well plate, place 5000 cells in the well and incubate overnight at 100 μL / well of medium.
The medium was replaced with 200 μl of the medium containing the test substance. Two more days later, the medium was removed, washed twice with the medium, and the number of cells was measured by measuring absorbance at 450 nm with a plate reader using WST (doujinn Cell Counting kit 8). The absorbance at this time is proportional to the number of cells. The same experiment was performed three times, and the average value was taken as the value.
The number of cells in an example in which no pyrroloquinoline quinones were used was calculated as 100.

Inhibition of cell proliferation by resveratrol has been recovered by using pyrroloquinoline quinones. That is, the toxicity of resveratrol was reduced by using pyrroloquinoline quinones. It was effective in an amount of 0.019 to 12 times that of resveratrol 1.

レスベラトロールによる細胞増殖阻害が本発明の添加剤により広い濃度範囲で回復傾向にある。これに対してビタミンであるアスコルビン酸やグルコースにおける細胞の毒性の軽減効果は小さい。 Example 7-12, Comparative Example 2-4
Resveratrol 25μg / ML
Resveratrol was dissolved in dimethyl sulfoxide to a concentration of 5 mg / ML. During use, this was dissolved in a medium and used.
Reduced pyrroloquinoline quinone was added to water at 1.5 mg / ML and autoclaved to obtain a suspension. As for pyrroloquinoline quinone, pyrroloquinoline quinone disodium trihydrate was added to water so as to be 1.5 mg / ML, and autoclaved to obtain a solution. These solutions were diluted with a medium at the time of use.
This was done using Chinese hamster ovary cells. As the medium, 10% of fetal calf serum was added to α-MEM medium. Culturing was carried out at 37 ° C. under saturated steam with 5% carbon dioxide added.
The CHO cells cultured at 37 ° C. are peeled from the petri dish by trypsin treatment. Remove the detached cells by centrifugation and add medium. Put this in the hemocytometer and count the number of cells.
Using a 96-well plate, put 5000 cells in the well and incubate overnight at 100 μL / well of medium.
The medium was replaced with 200 μl of the medium containing the test substance. At this time, resveratrol was tested at 50 μg / ML.
Two more days later, the medium was removed, washed twice with the medium, and the number of cells was measured by measuring absorbance at 450 nm with a plate reader using WST (doujinn Cell Counting kit 8). The absorbance at this time is proportional to the number of cells. Three identical experiments were performed and the average value was taken as the value.
The number of cells in an example not using pyrroloquinoline quinones was calculated as 100. This value corresponds to 70% of the reference example.

Inhibition of cell growth by resveratrol tends to recover over a wide concentration range with the additive of the present invention. In contrast, ascorbic acid and glucose, which are vitamins, have little effect on reducing cellular toxicity.

レスベラトロールの濃度が非常に高く、細胞障害が非常に高い環境である。しかし、このような過酷な環境に置いてもピロロキノリンキノン類を使用することでレスベラトロールの細胞増殖阻害を緩和させている。レスベラトロール1に対して０．０２４から３倍量で有効であった。 Examples 13-18, Comparative Example 5-7 Resveratrol 50 μg / ML
The same operation as in the previous example was performed. The same experiment was performed three times to increase the concentration of resveratrol and see the effect, and the average value was taken as the value.
The number of cells in an example not using pyrroloquinoline quinones was calculated as 100. The cell concentration at this time was 30% of the cell concentration without adding resveratrol.

It is an environment where the concentration of resveratrol is very high and the cell damage is very high. However, even in such a harsh environment, pyrroloquinoline quinones are used to mitigate cell growth inhibition of resveratrol. It was effective in the amount of 0.024 to 3 times that of resveratrol 1.

Example 19, Comparative Example 8 Cosmetic composition Example 19
Resveratrol 0.8 mg and pyrroloquinolinequinone disodium trihydrate 0.2 mg were dissolved in 10 ml of physiological saline (GIBCO, hereinafter abbreviated as PBS) with phosphate buffer and pH 7.4.
Comparative Example 8
Resveratrol 0.8 mg was dissolved in 10 ml of physiological saline with pH 7.4 containing phosphate buffer.

Example 20 Comparative Example 9 Protein Aging Test Gelatin manufactured by Wako Pure Chemical Industries, Ltd. was dissolved in PBS to a concentration of 0.5 mg / ML. The glucose solution was dissolved in PBS so that the glucose was 0.5 mg / ML.
Example 20
50 μL of the solution of Example 19 was mixed with 100 μL of the gelatin solution and 50 μL of the glucose solution.
Comparative Example 9
50 μL of the solution of Comparative Example 8 was mixed with a mixture of gelatin solution 100 μL and glucose solution 50 μL.
These solutions were placed in a 96-well plate and reacted for 4 days under 37 ° C. saturated steam. Eight of the same solutions were prepared. This was excited at 485 nm using a plate reader, and the fluorescence intensity was measured at 535 nm. The fluorescence intensity of only the phosphate buffer was used as the background.
As a result, the fluorescence intensity with the background subtracted was 2119 for the solution of Example 20 and 2447 for the solution of Comparative Example 9.
Degraded Maillard reaction products are known to emit fluorescence. From the above results, the presence of PQQ reduces the fluorescence intensity and suppresses gelatin (collagen) aging, and PQQ is resveratrol. It did not interfere with the function of and proved effective.

The composition of the present invention can suppress the aging of gelatin, which is a component of the skin, more than when pyrroloquinoline quinones are not used, and is useful as a cosmetic composition. Moreover, since cell growth is not impaired, it is useful as anti-aging.

The present invention is effective in the fields of pharmaceuticals, experimental reagents, foods, cosmetics and the like.

Claims (7)

A cell growth inhibition inhibitor comprising resveratrol represented by Formula 1 and pyrroloquinoline quinones.

The cell growth inhibition inhibitor according to claim 1, wherein pyrroloquinoline quinones are contained in a weight ratio of 0.01 to 100 with respect to resveratrol. The cell growth inhibition inhibitor according to claim 1 or 2, wherein the pyrroloquinoline quinone is an oxidized pyrroloquinoline quinone represented by Formula 2, a reduced pyrroloquinoline quinone represented by Formula 3, or a salt thereof.

The foodstuff which added the cell growth inhibition inhibitor in any one of Claims 1-3. Cosmetics to which the cell growth inhibition inhibitor according to any one of claims 1 to 3 is added. The reagent containing the cell growth inhibition inhibitor in any one of Claims 1-3. A method for inhibiting cell growth inhibition of resveratrol, comprising bringing the cell growth inhibition inhibitor according to any one of claims 1 to 3 into contact with a cell in a solution or suspension state.