Carbonyl protein degrading agent

Abstract

To provide a novel carbonylated protein decomposer that decomposes carbonylated protein.SOLUTION: A carbonylated protein decomposer contains extract from the roots of Scutellaria baicalensis (Lamiaceae), the roots of Lithospermum erythrorhizon (Boraginaceae) or the leaves of Diospyros kaki (Ebenaceae) as an active ingredient. The carbonylated protein decomposer also comprises at least one of baicalein, sikonin, acetyl sikonin, β-hydroxy isovaleryl sikonin, catechin, epigallocatechin gallate and epigallocatechin as an active ingredient.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a carbonylated protein degrading agent containing, as an active ingredient, an extract extracted from the root of Lithospermum erythrorhizon of the Boraginaceae family, the root of Polygonum multiflorum of the Polygonaceae family, or the leaves of Diospyros kaki of the Ebenaceae family, or at least any one of berberine, coptisine, acetylcoptisine, β-hydroxyisovaleryl coptisine, catechin, epigallocatechin gallate, and epigallocatechin.

Background Art

[0002] Protein carbonylation is an oxidative modification of proteins caused by reactive oxygen species generated in vivo. Carbonylated proteins are generated when the NH2 groups of amino acid residues such as Lys, Arg, and Pro in proteins are directly oxidized by reactive oxygen species generated in vivo to form carbonyl groups, and when lipids are oxidized to form lipid peroxides, and aldehydes such as highly reactive acrolein are generated by the decomposition of lipid peroxides, and aldehydes are generated by binding to proteins (see, for example, Japanese Patent Application Laid-Open No. 2004-340935 (Patent Document 1)).

[0003] The stratum corneum, the outermost layer of the skin, is composed of keratinocytes, approximately 85% of which are made up of the protein keratin. In recent years, it has been known that this keratin is carbonylated by oxidative stress such as ultraviolet rays that the skin is exposed to on a daily basis (see, for example, Jens J. Thiele et al., "Protein Oxidation in Human Stratum Corneum: Susceptibility of Keratins to Oxidation In Vitro and Presence of a Keratin Oxidation Gradient In Vivo", THE JOURNAL OF INVESTIGATIVE DERMATOLOGY, 113(3), 335-339, 1999 (Non-Patent Literature 1)). Carbonylation of stratum corneum proteins due to such external influences is thought to be one of the causes of decreased skin function such as moisture, firmness, and brightness, and a reduction in skin transparency (see, for example, Iwai, Ichiro et al., "Decrease in Skin Transparency Due to Carbonylation of Stratum Corneum Proteins," Journal of the Japan Society of Cosmetic Scientists, 42(1), 16-21, 2008 (Non-Patent Literature 2)).

[0004] A decrease in skin transparency is caused by changes such as blemishes and dullness. Skin dullness is a specific phenomenon that occurs on the entire face or in areas such as around the eyes and cheeks, and is characterized by a decrease in redness and an increase in yellowness, a decrease in skin "luster" and transparency, and a decrease in brightness due to shadows caused by unevenness of the skin surface, making the skin appear darker. Furthermore, the causes of dullness are said to be a decrease in skin redness due to poor blood circulation, melanin deposition, shadows caused by unevenness of the skin surface due to decreased skin elasticity, decreased light transmittance due to thickening of the skin, a decrease in luster due to diffuse reflection on the skin surface, and yellowing of the skin with age (see, for example, Masako Naganuma, "Historical Changes in the Effectiveness of Cosmetics," Journal of the Japanese Society of Cosmetic Scientists, 39(4), 275-285, 2015 (Non-Patent Literature 3)).

[0005] In particular, dullness caused by an increase in the yellowness of the skin is known as yellow dullness, and is a characteristic change in skin tone associated with a decrease in transparency. The main causes of yellow dullness are thought to be protein glycated products (see, for example, Japanese Patent Publication No. 2013-133303 (Patent Document 2)) and protein carbonyl products (see, for example, Japanese Patent Publication No. 2012-32287 (Patent Document 3)) present in the epidermis and dermis.

[0006] Therefore, in order to improve the skin associated with carbonyl protein production, ingredients that suppress the production of carbonyl proteins have been proposed (see, for example, Kazuhiro Iga et al., "Improvement effect of kojic acid on facial yellowing and dullness," West Japan Dermatology, 77(3), 224-249, 2015 (Non-Patent Literature 4)). However, Non-Patent Literature 4 does not offer any proposals for carbonyl proteins that have already been produced, and has not led to a fundamental solution to the decline in skin function associated with carbonyl protein production. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Japanese Patent Publication No. 2004-340935 [Patent Document 2] Japanese Patent Publication No. 2013-133303 [Patent Document 3] Japanese Patent Publication No. 2012-32287 [Non-patent literature]

[0008] [Non-Patent Document 1] Jens J. Thiele et al., "Protein Oxidation in Human Stratum Corneum: Susceptibility of Keratins to Oxidation In Vitro and Presence of a Keratin Oxidation Gradient In Vivo", THE JOURNAL OF INVESTIGATIVE DERMATOLOGY, 113(3), 335-339, 1999 [Non-Patent Document 2] Iwai, Ichiro et al., "Decreased Skin Transparency Due to Carbonylation of Stratum Corneum Proteins," Journal of the Japan Society of Cosmetic Scientists, 42(1), 16-21, 2008. [Non-Patent Document 3] Masako Naganuma, "Historical Changes in the Effectiveness of Cosmetics," Journal of the Japanese Society of Cosmetic Scientists, 39(4), 275-285, 2015. [Non-Patent Document 4] Kazuhiro Iga et al., "The effect of kojic acid on improving facial yellowing," West Japan Dermatology, 77(3), 224-249, 2015. [Overview of the project] [Problems that the invention aims to solve]

[0009] The present invention has been made to solve the above problems, and its objective is to provide a novel carbonyl protein degrading agent that degrades carbonyl proteins. [Means for solving the problem]

[0010] The carbonyl protein degrading agent of the present invention is characterized by containing an extract obtained from the roots of Scutellaria baicalensis (Lamiaceae), Lithospermum erythrorhizon (Boraginaceae), or the leaves of Persimmon (Ebenaceae) as an active ingredient (hereinafter, the carbonyl protein degrading agent containing an extract obtained from the roots of Scutellaria baicalensis (Lamiaceae), Lithospermum erythrorhizon (Boraginaceae), or the leaves of Persimmon (Ebenaceae) will be referred to as the "first carbonyl protein degrading agent").

[0011] The first carbonyl protein degradation agent of the present invention preferably contains an extract obtained from the roots of Scutellaria baicalensis, a member of the Lamiaceae family, at a concentration of 1.0E+00 to 5.0E+02 mg / mL. In this case, it is preferable to use a mixture of water and 1,3-butylene glycol as the extraction solvent.

[0012] Furthermore, the first carbonyl protein degrading agent of the present invention preferably contains an extract obtained from the roots of Lithospermum erythrorhizon of the Boraginaceae family at a concentration of 1.0E-01 to 5.0E+01 mg / mL. In this case, it is preferable to use a mixture of ethanol and 1,3-butylene glycol as the extraction solvent.

[0013] Furthermore, the first carbonyl protein degrading agent of the present invention preferably contains an extract obtained from persimmon leaves at a concentration of 1.0E+00 to 1.0E+02 mg / mL. In this case, it is preferable to use a mixture of water and 1,3-butylene glycol as the extraction solvent.

[0014] The present invention also provides a carbonylating protein degrading agent containing at least one of baicalein, shikonin, acetylshikonin, β-hydroxyisovalerylshikonin, catechin, epigallocatechin gallate, and epigallocatechin as an active ingredient (hereinafter, the carbonylating protein degrading agent containing at least one of baicalein, shikonin, acetylshikonin, β-hydroxyisovalerylshikonin, catechin, epigallocatechin gallate, and epigallocatechin will be referred to as the "second carbonylating protein degrading agent").

[0015] The second carbonyl protein degradation agent of the present invention preferably contains baicalein at a concentration of 1.0E-02 to 1.0E+01 mg / mL.

[0016] Furthermore, the second carbonyl protein degradation agent of the present invention preferably contains shikonin, acetylshikonin, or β-hydroxyisovalerylshikonin at a concentration of 5.0E-05 to 5.0E-02 mg / mL.

[0017] In addition, the second carbonylated protein degrading agent of the present invention preferably contains catechin, epigallocatechin gallate, or epigallocatechin at a concentration of 1.0E-02 to 1.0E+01 mg / mL.

Effects of the Invention

[0018] According to the present invention, it is possible to provide a novel carbonylated protein degrading agent, a cosmetic, and a dermatological preparation for external use that degrade carbonylated proteins.

Brief Description of the Drawings

[0019] [Figure 1] It is a graph showing the results of Experimental Example 1. [Figure 2] It is a graph showing the results of Experimental Example 2.

Modes for Carrying Out the Invention

[0020] (First Carbonylated Protein Degrading Agent) The first carbonylated protein degrading agent of the present invention contains an extract of the root of Scutellaria baicalensis (Scutellaria baicalensis) (Scutellaria root extract), an extract of the root of Lithospermum erythrorhizon (Lithospermum erythrorhizon) (Gromwell root extract), or an extract of the leaves of Diospyros kaki (Diospyros kaki) (Persimmon leaf extract) as an active ingredient.

[0021] <Scutellaria root extract, Gromwell root extract, Persimmon leaf extract> In the first carbonylated protein degrading agent of the present invention, the Scutellaria root extract, the Gromwell root extract, and the Persimmon leaf extract can be obtained by a general extraction method. For example, each can be obtained by immersing or heating under reflux with an extraction solvent, followed by filtration and concentration.

[0022] Any solvent commonly used for extraction can be used as the extraction solvent, and both polar and non-polar solvents can be used. Examples include water, methanol, ethanol, propanol, butanol, propylene glycol, 1,3-butylene glycol and other alcohols (including polyhydric alcohols), acetone, methyl ethyl ketone and other ketones, esters such as methyl acetate and ethyl acetate, linear and cyclic ethers such as tetrahydrofuran and diethyl ether, polyethers such as polyethylene glycol, hydrocarbons such as squalane, hexane, cyclohexane, and petroleum ether, and organic solvents such as supercritical carbon dioxide, pyridines, oils and fats, waxes and other oils, as well as mixtures thereof. Preferably, water, alcohols, mixtures of alcohols and water, and hydrocarbons are used, with mixtures of alcohols and water and hydrocarbons being more preferred. Preferably, alcohols include 1,3-butylene glycol or ethanol.

[0023] When extracting from Scutellaria baicalensis root, considering the potential problems of residual substances, it is preferable to use one of the following as the extraction solvent: water alone, alcohol alone, polyhydric alcohol alone, a mixture of water and polyhydric alcohol, or a mixture of water, alcohol, and polyhydric alcohol. It is more preferable to use alcohol alone or a mixture of water and polyhydric alcohol as the extraction solvent. In particular, to enhance the extraction efficiency of the active ingredient, it is preferable to extract using ethanol as the extraction solvent, remove the solvent, and then dissolve the mixture with water and 1,3-butylene glycol (water:1,3-butylene glycol = 1:1).

[0024] When extracting from Lithospermum erythrorhizon, considering the problem of residual substances, it is preferable to use one of the above-mentioned alcohols alone, polyhydric alcohols alone, or mixtures of alcohols and polyhydric alcohols as the extraction solvent, more preferably a mixture of alcohols and polyhydric alcohols as the extraction solvent, and particularly preferably a mixture of ethanol and 1,3-butylene glycol (preferably a mixture of ethanol:1,3-butylene glycol = 7:3 to 8:2) as the extraction solvent.

[0025] When extracting from persimmon leaves, considering the problem of residue, it is preferable to use one of the above-mentioned options as the extraction solvent: water alone, polyhydric alcohol alone, or a mixture of water and polyhydric alcohol. It is more preferable to use a mixture of water and polyhydric alcohol as the extraction solvent, and it is particularly preferable to use a mixture of water and 1,3-butylene glycol (preferably a mixture of water and 1,3-butylene glycol in a 1:1 ratio) as the extraction solvent.

[0026] In the first carbonyl protein degrading agent of the present invention, when scutellaria baicalensis root extract is used as the active ingredient, the concentration of scutellaria baicalensis root extract is not particularly limited, but it is preferable that it be in the range of 1.0E+00 to 5.0E+02 mg / mL in order to exhibit a more pronounced carbonyl protein degrading effect.

[0027] In the first carbonyl protein degrading agent of the present invention, when Lithospermum erythrorhizon extract is used as the active ingredient, the concentration of Lithospermum erythrorhizon extract is not particularly limited, but it is preferable that it be in the range of 1.0E-01 to 5.0E+01 mg / mL in order to exhibit a more pronounced carbonyl protein degrading effect.

[0028] In the first carbonyl protein degrading agent of the present invention, when persimmon leaf extract is used as the active ingredient, the concentration of the persimmon leaf extract is not particularly limited, but it is preferable that it be in the range of 1.0E+00 to 1.0E+02 mg / mL in order to exhibit a more pronounced carbonyl protein degrading effect.

[0029] The first carbonyl protein degrading agent of the present invention can be used as is, such as scutellaria baicalensis root extract, lithospermum erythrorhizon extract, or persimmon leaf extract, but is usually used as part of a composition with various carriers and can be provided as a cosmetic or topical skin preparation (pharmaceutical or quasi-drug). The present invention also provides a cosmetic or topical skin preparation containing the first carbonyl protein degrading agent of the present invention. In the cosmetic or topical skin preparation of the present invention, the dosage form is not limited and any dosage form that can be applied to the skin is acceptable, and examples include liquids, ointments, plasters, emulsions, lotions, and packs. The amount of each ingredient is typically 0.01% (w / w) or more, preferably 0.1-20% (w / w), in the formulation for scutellaria root extract, typically 0.001% (w / w) or more, preferably 0.01-1% (w / w), in the formulation for lithospermum extract, and typically 0.01% (w / w) or more, preferably 0.1-10% (w / w), in the formulation for persimmon leaf extract. Furthermore, the first carbonyl protein degrading agent of the present invention can be used in combination with other ingredients that have other effects, such as moisturizers, whitening agents, and UV protection agents.

[0030] (Second carbonyl protein degrading agent) The first carbonyl protein degrading agent mentioned above contains scutellaria baicalensis root extract as an active ingredient, which is thought to contain flavonoids such as baicalein, baicalin, augonin, and augonoside. Lithospermum erythrorhizon extract contains naphthoquinone derivatives such as shikonin, acetylshikonin, β-hydroxyisovalerylshikonin, isobutylshikonin, β-dimethylacrylshikonin, isovalerylshikonin, α-methyl-n-butylshikonin, deoxyshikonin, and teracrylshikonin, as well as phenylpropanoids such as rosmarinic acid. Persimmon leaf extract is thought to contain flavonoids such as catechin, epigallocatechin gallate, epigallocatechin, epicatechin, procyanidin, gallic acid, and chlorogenic acid. As demonstrated in the experimental examples described later, the present inventors have found that baicalein, shikonin, acetylshikonin, β-hydroxyisovalerylshikonin, catechin, epigallocatechin gallate, or epigallocatechin exhibit carbonyl protein degradation activity. That is, the second carbonyl protein degradation agent of the present invention is characterized by containing at least one of baicalein, shikonin, acetylshikonin, β-hydroxyisovalerylshikonin, catechin, epigallocatechin gallate, and epigallocatechin as an active ingredient.

[0031] In the second carbonyl protein degrading agent of the present invention, the concentration of baicalein is not particularly limited, but it is preferably in the range of 1.0E-02 to 1.0E+01 mg / mL because it exhibits a more pronounced carbonyl protein degrading effect.

[0032] In the second carbonyl protein degrading agent of the present invention, the concentration of shikonin, acetylshikonin, or β-hydroxyisovalerylshikonin is not particularly limited, but it is preferably in the range of 5.0E-05 to 5.0E-02 mg / mL because it exhibits a more pronounced carbonyl protein degrading effect.

[0033] In the second carbonyl protein degrading agent of the present invention, the concentration of catechin, epigallocatechin gallate, or epigallocatechin is not particularly limited, but it is preferable that it be in the range of 1.0E-02 to 1.0E+01 mg / mL in order to exhibit a more pronounced carbonyl protein degrading effect.

[0034] In the second carbonyl protein degrading agent of the present invention, at least one of the active ingredients, baicalein, shikonin, acetylshikonin, β-hydroxyisovalerylshikonin, catechin, epigallocatechin gallate, and epigallocatechin, can be used as is, similar to the scutellaria baicalensis root extract, lithospermum erythrorhizon extract, and persimmon leaf extract in the first carbonyl protein degrading agent described above. However, it is usually used as part of a composition with various carriers, etc., and can be provided as a cosmetic or topical skin preparation (pharmaceutical or quasi-drug). Thus, the present invention also provides a cosmetic or topical skin preparation containing the second carbonyl protein degrading agent of the present invention. In this case as well, similar to the cosmetic or topical skin preparation using the first carbonyl protein degrading agent of the present invention described above, the dosage form is not limited and can be any dosage form that is applicable to the skin. It may also be used in combination with other ingredients that have other effects, such as moisturizers, whitening agents, or UV protection agents.

[0035] The present invention will be further explained with experimental examples below, but the present invention is not limited to these.

[0036] <Experimental Example 1> (Sample preparation) The roots of Scutellaria baicalensis (a member of the Lamiaceae family) were extracted using ethanol as the extraction solvent. After removing the solvent, the extracted solution was dissolved in a mixture of water and 1,3-butylene glycol (water:1,3-butylene glycol = 1:1). The Scutellaria baicalensis extract was prepared using phosphate-buffered saline (PBS) to obtain a 1.0E+01 mg / mL Scutellaria baicalensis root extract (Example 1) and a 1.0E+02 mg / mL Scutellaria baicalensis root extract (Example 2).

[0037] In addition, extracts were obtained from the roots of Lithospermum erythrorhizon (a member of the Boraginaceae family), using a mixture of ethanol and 1,3-butylene glycol (ethanol:1,3-butylene glycol = 7:3) as the extraction solvent. The extracted Lithospermum erythrorhizon extracts were prepared using PBS to obtain Lithospermum erythrorhizon extracts with concentrations of 5.0E-01 mg / mL (Example 3), 1.0E+00 mg / mL (Example 4), and 3.0E+00 mg / mL (Example 5).

[0038] In addition, a solution was obtained by extracting persimmon leaves (Ebenaceae family) using a mixture of water and 1,3-butylene glycol (water:1,3-butylene glycol = 1:1) as the extraction solvent. The extracted persimmon leaf extract was prepared using PBS to obtain a persimmon leaf extract with a concentration of 1.0E+00 mg / mL (Example 6).

[0039] (Method for evaluating the effect of carbonyl protein degradation) The experiment was conducted using stratum corneum collected from the skin surface (inner forearm or cheek) using cellophane tape (Nichiban Co., Ltd.). The collected stratum corneum was transferred to a plate, and 0.1 mM acrolein (Tokyo Chemical Industries, Ltd.) was added to the transferred stratum corneum to carbonylate the stratum corneum proteins. Subsequently, the sample was spread onto the carbonylated stratum corneum and incubated at 37°C. After incubation, the stratum corneum was immersed in Fluorescein-5-thiosemicarbazide (Thermo Fisher Co., Ltd.), which was adjusted to a concentration of 50 μM with a 0.1 mM 2-Morpholinoethane sulfonic acid (pH 5.5) buffer solution, to label the carbonylated stratum corneum proteins. Stratum corneum that had not undergone carbonylation was also labeled in the same manner.

[0040] Labeled stratum corneum was imaged using a fluorescence microscope, and the resulting observed images were analyzed to determine the amount of carbonylated protein by the fluorescence intensity per unit area of ​​the stratum corneum.

[0041] (result) The results are shown in Figure 1. A significance level of less than 5% (P<0.05) in the t-test is indicated by an asterisk (*). As shown in Figure 1, scutellaria baicalensis root extract, Lithospermum erythrorhizon extract, and Diospyros kaki leaf extract reduced the amount of carbonylated protein, demonstrating excellent carbonylated protein degradation activity.

[0042] <Experimental Example 2> (Sample preparation) The second carbonyl protein degradation agent of the present invention, baicalein, was a commercially available product (baicalein, manufactured by Wako Pure Chemical Industries, Ltd.). Baicalein was prepared using dimethyl sulfoxide adjusted to a final concentration of 0.1% in PBS to obtain baicalein at a concentration of 1.0E-01 mg / mL (Example 7) and baicalein at a concentration of 1.0E+00 mg / mL (Example 8).

[0043] Furthermore, commercially available shikonin (shikonin, manufactured by Wako Pure Chemical Industries, Ltd.), acetylshikonin (acetylshikonin, manufactured by Nagara Science Co., Ltd.), or β-hydroxyisovalerylshikonin (β-hydroxyisovalerylshikonin, manufactured by Nagara Science Co., Ltd.), which are the second carbonyl protein degrading agents of the present invention, were used.Shikonin was prepared using dimethyl sulfoxide adjusted to a final concentration of 0.1% in PBS to obtain 5.0E-0.4 mg / mL of shikonin (Example 9) and 5.0E-0.3 mg / mL of shikonin (Example 10).Acetylshikonin was prepared using dimethyl sulfoxide adjusted to a final concentration of 0.1% in PBS to obtain 5.0E-0.4 mg / mL of acetylshikonin (Example 11) and 5.0E-0.3 mg / mL of acetylshikonin (Example 12). Furthermore, β-hydroxyisovaleryl sikonin was prepared using dimethyl sulfoxide adjusted to a final concentration of 0.1% in PBS to obtain β-hydroxyisovaleryl sikonin at 5.0E-0.4 mg / mL (Example 13) and β-hydroxyisovaleryl sikonin at 5.0E-0.3 mg / mL (Example 14).

[0044] Furthermore, commercially available catechin ((+)-catechin, manufactured by Tokyo Chemical Industry Co., Ltd.), epigallocatechin gallate ((-)-epigallocatechin gallate, manufactured by Wako Pure Chemical Industries, Ltd.), and epigallocatechin ((-)-epigallocatechin, derived from green tea, manufactured by Wako Pure Chemical Industries, Ltd.), which are the second carbonyl protein degrading agents of the present invention, were used. Catechin was prepared using dimethyl sulfoxide adjusted to a final concentration of 0.1% with PBS to obtain 1.0E+00 mg / mL of catechin (Example 15). Similarly, epigallocatechin gallate was prepared using dimethyl sulfoxide adjusted to a final concentration of 0.1% with PBS to obtain 1.0E+00 mg / mL of epigallocatechin gallate (Example 16). Furthermore, epigallocatechin was prepared using dimethyl sulfoxide adjusted to a final concentration of 0.1% in PBS to obtain 1.0E+00 mg / mL of epigallocatechin (Example 17).

[0045] (Method for evaluating the effect of carbonyl protein degradation) The tests were evaluated using the same method as in Experimental Example 1.

[0046] (result) The results are shown in Figure 2. An asterisk (*) indicates a significance level of less than 5% (P<0.05) in the t-test. As shown in Figure 2, baicalein, shikonin, acetylshikonin, β-hydroxyisovalerylshikonin, catechin, epigallocatechin gallate, and epigallocatechin reduced the amount of carbonylated protein, demonstrating excellent carbonylated protein degradation activity.

Claims

1. A carbonyl protein degrading agent comprising, as an active ingredient, an extract obtained from the roots of Scutellaria baicalensis of the Lamiaceae family, which is extracted from the roots of Scutellaria baicalensis using ethanol as a solvent, the solvent is removed, and the resulting solution is dissolved in a 1:1 mixture of water and 1,3-butylene glycol; an extract obtained from the roots of Lithospermum erythrorhizon of the Boraginaceae family, which is extracted from the roots of Lithospermum erythrorhizon using a mixture of ethanol and 1,3-butylene glycol as a solvent; or an extract obtained from the leaves of Persimmon chinensis of the Ebenaceae family, which is extracted from the leaves of Persimmon chinensis using a mixture of water and 1,3-butylene glycol as a solvent.

2. A carbonyl protein degrading agent according to claim 1, comprising an extract obtained from the roots of Scutellaria baicalensis, a member of the Lamiaceae family, at a concentration of 1.0E+00 to 5.0E+02 mg / mL.

3. A carbonyl protein degrading agent according to claim 1, comprising an extract obtained from the roots of Lithospermum erythrorhizon of the Boraginaceae family at a concentration of 1.0E-01 to 5.0E+01 mg / mL.

4. A carbonyl protein degrading agent according to claim 1, comprising an extract obtained from persimmon leaves at a concentration of 1.0E+00 to 1.0E+02 mg / mL.

5. A carbonyl protein degrading agent containing at least one of baicalein, shikonin, acetylshikonin, β-hydroxyisovalerylshikonin, catechin, epigallocatechin gallate, and epigallocatechin as an active ingredient.

6. The carbonyl protein degrading agent according to claim 5, comprising baicalein at a concentration of 1.0E-02 to 1.0E+01 mg / mL.

7. A carbonyl protein degrading agent according to claim 5, comprising shikonin, acetylshikonin, or β-hydroxyisovalerylshikonin at a concentration of 5.0E-05 to 5.0E-02 mg / mL.

8. The carbonyl protein degrading agent according to claim 5, comprising catechin, epigallocatechin gallate, or epigallocatechin at a concentration of 1.0E-02 to 1.0E+01 mg / mL.

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