Composition for delaying cell senescence and application thereof

Abstract

The invention discloses a composition for delaying cell senescence, and the composition for delaying cell senescence comprises fisetin, urolithin A and ergothioneine, or consists of fisetin, urolithin A and ergothioneine. The invention also discloses an application of the composition for delaying cell aging in preparation of a product for delaying skin fibroblast aging, and an anti-aging preparation containing the composition. According to the composition for delaying cell aging, fisetin, urolithin A and ergothioneine contained in the composition can generate a synergistic effect, aging of skin fibroblasts can be remarkably delayed, and healing and repairing of skin are promoted.

Description

Technical Field

[0001] The present invention relates to the technical field of compositions, and particularly relates to a composition for delaying cell aging and its application. Background Art

[0002] The skin is the largest organ of the human body, undertaking multiple functions such as protection, perception, and body temperature regulation. With the increase of age, the skin will experience a series of physiological changes, and the most significant one is skin aging. This aging is not only reflected in the appearance of wrinkles and relaxation, but also includes the degradation of the internal structure and function of the skin. Skin fibroblasts play a crucial role in maintaining the structural integrity and function of the skin. They are mainly responsible for synthesizing and remodeling the extracellular matrix (ECM), such as collagen and elastin. However, with the increase of age, the function of fibroblasts will gradually decline, resulting in the decrease of skin elasticity and strength.

[0003] The aging of fibroblasts is a multi-factor-driven process, involving genetic and environmental factors. Oxidative stress is considered to be a major driving factor for cell aging. With the increase of age, the level of intracellular reactive oxygen species (ROS) increases significantly, leading to a series of harmful reactions such as DNA damage, protein oxidation, and lipid peroxidation. These reactions not only damage the normal function of cells, but also trigger apoptosis and senescence. In addition, the degradation of the extracellular matrix, the increase of inflammatory reactions, and the shortening of telomeres also play important roles in the aging process of fibroblasts.

[0004] In recent years, the scientific community has shown great interest in the potential of natural compounds in anti-aging. These compounds usually have various biological activities such as antioxidant, anti-inflammatory, and anti-apoptotic, and can effectively slow down the aging process of cells. Fisetin is a natural flavonoid compound extracted from sumac, with strong antioxidant and anti-inflammatory properties. Research shows that fisetin can protect cells from oxidative damage by scavenging excessive ROS. In addition, it can also inhibit inflammatory reactions and delay cell aging by regulating multiple signaling pathways. Urolithin A is an important derivative metabolized from polyphenolic compounds. It is famous for its significant antioxidant and anti-inflammatory properties, and shows potential in promoting mitochondrial function and improving cell energy metabolism. Urolithin A can delay the aging process of cells by reducing oxidative stress and inflammatory reactions. Ergothioneine is a naturally occurring amino acid derivative with excellent antioxidant ability. It can effectively scavenge ROS and protect cells from oxidative stress damage. Ergothioneine can also enhance the antioxidant ability of cells by regulating the intracellular antioxidant enzyme system.

[0005] Although fisetin, urolithin A, and ergothioneine each show good biological activities in anti-aging, their synergistic anti-aging effects in skin fibroblasts have not been fully studied. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a composition for delaying cell aging. When luteolin, urolithin A, and ergothioneine in this composition are used in combination, a synergistic effect will be produced, enhancing its anti-aging effect, and being able to significantly delay the aging of skin fibroblasts and promote the healing and repair of the skin.

[0007] To solve the above technical problem, the present invention provides the following technical solutions:

[0008] In the first aspect of the present invention, there is provided a composition for delaying cell aging, which comprises the following components or consists of them:

[0009] (i) Luteolin;

[0010] (ii) Urolithin A; and

[0011] (iii) Ergothioneine.

[0012] In some embodiments of the present invention, in the composition for delaying cell aging, the molar ratio of luteolin, urolithin A, and ergothioneine is (5 - 20):(5 - 20):(0.5 - 3), for example, it can be 5:5:1, 5:5:2, 5:5:3, 10:5:1, 20:5:1, 5:10:1, 5:20:1, 10:20:1, etc. Preferably, the molar ratio of luteolin, urolithin A, and ergothioneine is 10:10:1.

[0013] Luteolin is a flavonoid compound. It can delay the aging process in multiple cell models by scavenging reactive oxygen species (ROS) and inhibiting inflammatory signaling pathways. In addition, luteolin can also regulate the expression of cell cycle-related proteins, thereby promoting cell survival and proliferation. Urolithin A is an important derivative produced by the metabolism of polyphenolic compounds. It has significant antioxidant and anti-inflammatory properties and shows potential in promoting mitochondrial function and improving cellular energy metabolism. Urolithin A can delay the aging process of cells by reducing oxidative stress and inflammatory responses. Ergothioneine is a naturally occurring amino acid derivative with excellent antioxidant capacity. It can effectively scavenge ROS and protect cells from oxidative stress damage. Ergothioneine can also enhance the antioxidant capacity of cells by regulating the intracellular antioxidant enzyme system.

[0014] The inventors have found through a large number of studies that when luteolin, urolithin A, and ergothioneine are used in combination, they can exhibit a significant synergistic effect in the anti-aging and function maintenance of fibroblasts, significantly delaying the aging of skin fibroblasts.

[0015] Skin fibroblasts play a key role in maintaining skin structure and function, and their aging not only affects the appearance of the skin, but also leads to the decline of skin function. The present invention's research shows that fisetin, urolithin A and ergothioneine can significantly improve the anti-aging ability of cells through the synergistic effect of multiple mechanisms, as follows:

[0016] (1) Fisetin, urolithin A and ergothioneine showed significant synergistic effects in regulating the expression of aging genes.

[0017] The CDKN1A gene inhibits the cell cycle by encoding the p21 protein, thereby promoting cell senescence and preventing the proliferation of damaged cells; while the CDKN2A gene encodes the p16 ^ INK4a protein accumulates during cell aging, inhibits the cell cycle and serves as one of the cell aging markers. The present invention's research shows that fisetin, urolithin A and ergothioneine all show varying degrees of inhibitory effects on CDKN1A and CDKN2A expression. In the experiment used in combination, the combination of fisetin and urolithin A or ergothioneine also shows inhibitory effects on CDKN1A and CDKN2A gene expression, but does not show a synergistic effect. However, when the three are combined, the expression levels of CDKN1A and CDKN2A are almost restored to the state of normal cells, showing a significant synergistic effect.

[0018] (2) Fisetin, urolithin A and ergothioneine showed significant synergistic effects in regulating the expression of inflammation-related genes.

[0019] The overexpression of inflammatory factors such as interleukin 6 (IL-6), interleukin 8 (IL-8) and interleukin 11 (IL-11) is closely related to cell aging. The present invention's research shows that the use of fisetin, urolithin A or ergothioneine alone can inhibit the expression of these inflammatory factors to a certain extent. However, when the three are used in combination, the inhibitory effect of inflammatory factors is significantly enhanced, almost returning to normal levels. This synergistic effect may be related to the role played by each compound through different signaling pathways and molecular targets, and ultimately achieves effective control of inflammatory response.

[0020] (3) The combined use of urea pigment, urolithin A and ergothioneine significantly reduced the level of intracellular reactive oxygen species.

[0021] Reactive oxygen is an important factor promoting cell aging, causing DNA damage, protein denaturation and lipid peroxidation by oxidative stress. Research of the present invention shows that although the inhibitory effect of urolithin A and ergothioneine on reactive oxygen is more obvious when used alone, when the three are used in combination, the reduction of reactive oxygen levels is more significant. This synergistic effect not only enhances the antioxidant capacity of cells, but also may further delay the aging process of cells through multiple mechanisms of action.

[0022] (4) Fisetin, urolithin A, and ergothioneine also exhibit significant synergistic effects in promoting fibroblast migration.

[0023] Enhanced cell migration ability contributes to accelerating tissue repair and regeneration, which is an important aspect of delaying skin aging. Urolithin A alone can significantly promote cell migration, and when combined with fisetin and ergothioneine, this promoting effect is further enhanced. The combined use of the three not only increases the migration speed of cells but also may improve the efficiency of cell migration by optimizing the reorganization of the cytoskeleton and the interaction of signaling pathways.

[0024] The second aspect of the present invention provides the application of the composition for delaying cell aging in the preparation of products for delaying the aging of skin fibroblasts. Among them, the products include but are not limited to cosmetics, drugs, and health products.

[0025] Furthermore, the composition for delaying cell aging is used to regulate the expression of aging genes and / or inflammation-related genes in skin fibroblasts.

[0026] Furthermore, the composition for delaying cell aging is used to regulate the reactive oxygen species level in skin fibroblasts.

[0027] The third aspect of the present invention provides the application of the composition for delaying cell aging in the preparation of products for promoting skin healing and repair. Among them, the products include but are not limited to cosmetics, drugs, and health products.

[0028] Furthermore, the composition for delaying cell aging is used to promote the migration of skin fibroblasts.

[0029] The fourth aspect of the present invention provides an anti-aging preparation, which contains the composition for delaying cell aging. Among them, the anti-aging preparation includes but is not limited to cosmetics, drugs, and health products.

[0030] Furthermore, the anti-aging preparation is a drug and a health product, and the dosage forms of the drug and the health product include but are not limited to oral dosage forms.

[0031] Furthermore, the anti-aging preparation is a cosmetic, and the cosmetic can be prepared into various dosage forms, including but not limited to creams, lotions, gels, aqueous solutions, oils, powders, and solids.

[0032] Furthermore, the types of the cosmetics include but are not limited to toners, eye creams, face creams, hand creams, facial cleansers, cleansing foams, cleansing gels, hand sanitizers, makeup removers, makeup remover waters, makeup remover gels, liquid soaps, solid soaps, body washes, body lotions, foundations, serums, and masks.

[0033] Furthermore, the addition amount of the anti-aging composition in the cosmetic is 0.05 - 5 wt%, and for example, it can be 0.05 wt%, 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.8 wt%, 0.9 wt%, 1.0 wt%, 1.5 wt%, 2.0 wt%, 2.5 wt%, 3.0 wt%, 3.5 wt%, 4.0 wt%, 4.5 wt%, 5.0 wt%, etc.

[0034] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0035] 1. The composition for delaying skin aging provided by the present invention, wherein the three components of luteolin, urolithin A and ergothioneine contained therein can produce a synergistic effect in multiple aspects such as regulating the expression of senescence genes and inflammation-related genes in skin fibroblasts, regulating the reactive oxygen species level in skin fibroblasts, and promoting the migration of skin fibroblasts, and can significantly delay the aging of skin fibroblasts and promote the healing and repair of the skin.

[0036] 2. The composition for delaying skin aging provided by the present invention can be applied in various forms, such as oral supplements, topical skin care products, etc. Moreover, the components contained in this composition are all natural compounds, with high safety and effectiveness, which makes it an ideal choice in the development of anti-aging products. Description of the Drawings

[0037] Figure 1 a shows the results of β-Gal staining of cells in different treatment groups after being untreated with UVB irradiation (control) and after being treated with UVB irradiation (Senescence); Figure 1 b is Figure 1 The statistical bar graph of senescent cells in different treatment groups in a; Figure 1 c - d show the expression results of CDKN1A and CDKN2A genes of cells in different treatment groups after being untreated with UVB irradiation (control) and after being treated with UVB irradiation (Senescence);

[0038] Figure 2 show the expression results of inflammation-related genes IL-6, IL-8 and IL-11 of cells in different treatment groups after being untreated with UVB irradiation (control) and after being treated with UVB irradiation (Senescence);

[0039] Figure 3 a shows the photos of reactive oxygen species staining of cells in different treatment groups after being untreated with UVB irradiation (control) and after being treated with UVB irradiation; Figure 3 b is Figure 3Bar chart of fluorescence intensity statistics of reactive oxygen species staining in a

[0040] Figure 4 a shows the results of the scratch test of cells in different treatment groups Figure 4 b is a bar chart of cell migration rate statistics for different treatment groups Detailed implementation mode

[0041] The present invention will be further described below in conjunction with specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the specific embodiments cited are not intended to limit the present invention

[0042] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the technical field to which the present invention belongs. The terms used in the description of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more of the related listed items

[0043] Unless otherwise specified, the experimental methods used in the following examples and comparative examples are all conventional methods, and the materials, reagents, etc. used, unless otherwise specified, can be obtained from commercial channels

[0044] The present invention will be further described below in conjunction with specific examples and comparative examples

[0045] In the following specific implementation modes, *p, **p, and ***p indicate comparison with the control group, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001

[0046] Example 1

[0047] This example provides a composition for delaying cell aging, which is composed of fisetin (Fis), urolithin A (UA), and ergothioneine (EGT), and their molar ratio is 10:10:1

[0048] Comparative Example 1

[0049] The difference between Comparative Example 1 and Example 1 is that the composition only contains fisetin

[0050] Comparative Example 2

[0051] The difference between Comparative Example 2 and Example 1 is that the composition only contains urolithin A

[0052] Comparative Example 3

[0053] The difference between Comparative Example 3 and Example 1 is that the composition only contains ergothioneine

[0054] Comparative Example 4

[0055] The difference between Comparative Example 4 and Example 1 is that the composition contains fisetin and urolithin A, and their molar ratio is 1:1.

[0056] Comparative Example 5

[0057] The difference between Comparative Example 5 and Example 1 is that the composition contains fisetin and ergothioneine, and their molar ratio is 20:1.

[0058] Comparative Example 6

[0059] The difference between Comparative Example 6 and Example 1 is that the composition contains urolithin A and ergothioneine, and their molar ratio is 20:1.

[0060] Experimental Test

[0061] In this experiment, the human skin fibroblast cell line BJ was used as a model. In the experimental group, cells were irradiated with UVB (40 mJ / cm 2 ) for 4 days to induce cell senescence, and the control group was not irradiated with UVB. In the treatment protocol, cells were treated with single compounds and compound combinations for 72 h, and a positive control (dasatinib combined with quercetin) and a negative control (DMSO) were set. The treatment protocol included:

[0062] 1) Use fisetin (Fis, 20 μM), urolithin A (UA, 20 μM), and ergothioneine (EGT, 1 μM) alone;

[0063] 2) Co - treatment of urolithin A and fisetin (UA + Fis, 10 μM + 10 μM);

[0064] 3) Co - treatment of ergothioneine and fisetin (EGT + Fis, 1 μM + 20 μM);

[0065] 4) Co - treatment of urolithin A and ergothioneine (UA + EGT, 20 μM + 1 μM);

[0066] 5) Triple co - treatment (UA + EGT + Fis, 10 μM + 1 μM + 10 μM);

[0067] In addition, dasatinib and quercetin (D + Q, 1 μM + 20 μM) were used as a positive control, and an equal - proportion DMSO was used as a negative control.

[0068] 1. Synergistic effects of fisetin, urolithin A, and ergothioneine in anti - aging effects and regulation of senescence gene expression

[0069] In the study of skin aging, ultraviolet B (UVB) is one of the most common external factors inducing aging. UVB irradiation promotes the formation of senescent cells through mechanisms such as directly damaging the DNA of skin cells, inducing oxidative stress, and increasing inflammatory responses. Skin fibroblasts, as the main stromal cells of the skin, participate in the synthesis of collagen and elastin, maintaining the structure and function of the skin. Their senescence not only affects the appearance of the skin but may also lead to the weakening of the skin barrier function and skin pathological changes. In recent years, natural plant compounds have attracted attention due to their low side effects and extensive biological activities. This study focused on three natural compounds, fisetin, urolithin A, and ergothioneine, to explore their intervention effects on UVB-irradiation-induced senescence of skin fibroblasts, and whether the combined application of two or three of these compounds could exert a synergistic effect became the core issue of this study.

[0070] β-Galactosidase staining is a classic method for detecting senescence markers, based on the characteristic of a significant increase in the activity of β-galactosidase in senescent cells. By using X-Gal as a substrate, under the catalysis of β-galactosidase, a dark blue product is generated, enabling the visual observation of senescent cells. To evaluate the intervention effects of different treatment groups on senescent cells, the β-galactosidase staining (SA-β-Gal staining) method was used to stain each treatment group, and the results are as Figure 1 shown.

[0071] Please refer to Figure 1 Figures a - b. In the cells treated with UVB irradiation alone, approximately 80% of the cells showed positive senescence, indicating that UVB can effectively induce the senescence of fibroblasts. For the drug groups treated alone, only fisetin showed a significant anti-aging effect, and the proportion of senescent positive cells decreased to 60%. When urolithin A and ergothioneine were used alone, they did not show significant anti-aging effects. In the combined treatment groups, the combined use of urolithin A and ergothioneine showed a weak anti-aging effect, with the proportion of senescent cells decreasing by 10%. The combined use of fisetin and urolithin A and the combined treatment of fisetin and ergothioneine did not significantly enhance the anti-aging effect either, and the proportion of senescent positive cells was 60%. However, when the three were used in combination, the anti-aging effect was significantly enhanced, and the proportion of senescent positive cells decreased to approximately 20%, showing a strong synergistic effect. It should be noted that in the positive control group (D + Q), the proportion of senescent cells was 50%, lower than that of the UVB treatment group but higher than that of the triple combination group. In addition, the cells in all treatment groups did not show toxicity to normal cells, indicating that these natural compounds have good safety while effectively anti-aging.

[0072] In the study of the anti-aging mechanism of fisetin, urolithin A and ergothioneine on skin fibroblasts, the present invention pays special attention to CDKN1A and CDKN2A, two genes closely related to cell cycle regulation and aging. CDKN1A gene inhibits cell cycle progression by encoding p21 protein, thereby promoting cell aging and preventing the proliferation of damaged cells; while CDKN2A gene encodes p16 ^ INK4a protein accumulates during cell aging, inhibits the cell cycle and serves as one of the hallmarks of cell aging.

[0073] See also Figure 1 c~d, the experimental results show that UVB irradiation significantly induced the expression of CDKN1A and CDKN2A genes, which increased by about 6 times, reflecting the strong induction effect of UVB on cell senescence. In the experimental groups treated separately, fisetin, urolithin A and ergothioneine all showed different degrees of inhibitory effects on the expression of CDKN1A and CDKN2A. The use of ergothioneine alone significantly reduced the expression levels of these two genes, and urolithin A and fisetin also showed a certain inhibitory effect, but not as significant as ergothioneine.

[0074] In the experiment where the two were used in combination, the combination of fisetin and urolithin A or ergothioneine also showed an inhibitory effect on the expression of CDKN1A and CDKN2A genes, but did not show a synergistic effect. However, it is worth noting the effect of the combined use of the three. Under this combination, the expression levels of CDKN1A and CDKN2A almost returned to the state of normal cells, and the upregulation of gene expression was greatly suppressed compared with the UVB irradiation group. This finding suggests that fisetin, urolithin A and ergothioneine may exert their anti-aging effects by regulating the expression of cell cycle inhibitors. The combined use of the three not only effectively resisted UVB-induced cell senescence, but also showed a significant synergistic effect at the gene expression level.

[0075] 2. Synergistic effects of fisetin, urolithin A and ergothioneine in the regulation of inflammation-related gene expression

[0076] Inflammation is an important contributing factor in the process of skin aging. Ultraviolet B (UVB) irradiation not only directly damages skin cells, but also accelerates the aging process of cells by inducing overexpression of inflammatory factors. Inflammatory factors such as IL-6, IL-8, and IL-11 play a key role in skin inflammatory responses, and their overexpression is closely related to skin aging and various skin pathological conditions. Therefore, regulating the expression of these inflammatory factors is of great significance for delaying skin aging.

[0077] In this invention, we investigated the regulatory effects of fisetin, urolithin A and ergothioneine on the gene expression of inflammatory factors induced by UVB. Figure 2a-c, The experimental results showed that UVB irradiation significantly increased the expression levels of IL-6, IL-8, and IL-11 genes. Among them, the expression of both IL-6 and IL-8 increased by approximately 6-fold, while the expression of IL-11 increased by approximately 12-fold. These results indicate that UVB irradiation triggered a strong inflammatory response in skin fibroblasts.

[0078] In the treatment groups using fisetin, urolithin A, or ergothioneine alone, these compounds were able to inhibit the expression of inflammatory factor genes induced by UVB to varying degrees. Fisetin showed a relatively significant effect in inhibiting IL-6, ergothioneine showed a relatively significant effect in inhibiting IL-8, while urolithin A showed certain advantages in inhibiting the expression of IL-11.

[0079] However, when the two were used in combination, the inhibitory effect was not further enhanced. It is worth noting the effect of the three combined. In this combination, the gene expression levels of IL-6, IL-8, and IL-11 almost returned to the normal cell state without UVB irradiation. The combined use of the three not only effectively counteracted the overexpression of inflammatory factors caused by UVB irradiation but also showed a strong synergistic effect. Thus, through the synergistic regulation of multiple pathways and multiple targets, fisetin, urolithin A, and ergothioneine can significantly reduce the expression of inflammatory factors, alleviate the inflammatory response, and thus delay cell aging. This finding indicates that the synergistic effect of fisetin, urolithin A, and ergothioneine in anti-inflammation provides important theoretical support for the development of new anti-aging treatment strategies. By effectively regulating the expression of inflammation-related genes, these natural compounds can not only alleviate UVB-induced skin inflammation but may also play a therapeutic role in a wider range of skin pathological conditions.

[0080] 3. Fisetin, urolithin A, and ergothioneine show a synergistic effect in regulating cellular reactive oxygen species (ROS)

[0081] Reactive Oxygen Species (ROS) play a key role in the process of cell aging. Excessive ROS can cause cell damage, DNA mutation, protein oxidation, and lipid peroxidation, thus accelerating the aging process. Ultraviolet B (UVB) irradiation is an important inducer of ROS production, and excessive ROS accumulation often leads to a decline in skin cell function and is closely related to aging and various skin pathological conditions. Therefore, regulating the ROS level is one of the key strategies in anti-aging treatment.

[0082] In the present invention, the regulatory effects of fisetin (20 μM), urolithin A (20 μM), and ergothioneine (1 μM) on the ROS level were evaluated. Please refer to Figure 3a~b, the experimental results show that ultraviolet B irradiation significantly increased the generation of ROS in skin fibroblasts, indicating that ultraviolet B can induce oxidative stress in cells. However, the use of urolithin A or ergothioneine alone can significantly inhibit the generation of ROS, among which ergothioneine showed a stronger effect in inhibiting ROS. Specifically, ergothioneine can significantly reduce the level of ROS, close to the level of normal cells, and although urolithin A can also inhibit ROS, the effect is relatively weak.

[0083] The inhibitory effect of fisetin alone on ROS is relatively limited, and it fails to significantly reduce the generation of ROS induced by ultraviolet B. Further studies have shown that when urolithin A and ergothioneine are used in combination, although the effect of inhibiting ROS is enhanced compared to their use alone, it is still not optimal. The most significant effect is the combined use of the three. In this combination, the synergistic effect of fisetin, urolithin A and ergothioneine significantly enhances the inhibitory effect of ROS. The combination of the three not only significantly inhibits the generation of ROS induced by ultraviolet B, but also its inhibitory effect is almost restored to the level of normal cells, showing a strong synergistic effect.

[0084] This finding suggests that fisetin, urolithin A, and ergothioneine work synergistically through multiple mechanisms to significantly regulate the level of ROS in cells, thereby reducing the oxidative stress caused by ultraviolet B irradiation. These natural compounds may directly or indirectly reduce the production of ROS, reduce oxidative damage, and thus delay cell aging. In particular, the combined use of ergothioneine and urolithin A, as well as the comprehensive application of the three, showed a more significant synergistic effect in inhibiting ROS, providing strong molecular mechanism support for anti-aging treatment.

[0085] 4. Synergistic effects of fisetin, urolithin A and ergothioneine in regulating the migration of normal human fibroblasts

[0086] Cell migration is a crucial biological process in tissue repair and regeneration. For skin fibroblasts, enhanced migration ability helps accelerate wound healing and tissue regeneration. In this study, the role of fisetin, urolithin A and ergothioneine in promoting the migration of normal human fibroblasts and their synergistic effects were investigated.

[0087] See also Figure 4 a~b, the experimental results show that urolithin A can significantly promote the migration of fibroblasts when used alone. This effect may be related to the role of urolithin A in cell signaling pathways, which promotes the reorganization of the cytoskeleton and the enhancement of cell movement. In contrast, when fisetin and ergothioneine are used alone, the effect of promoting fibroblast migration is relatively limited. Although they perform well in other aspects, such as anti-oxidation and anti-inflammation, their effect in promoting cell migration alone is not significant.

[0088] However, when luteolin or ergothioneine is used in combination with urolithin A, the migratory ability of fibroblasts is significantly enhanced. This synergistic effect may be due to the complementary nature of the migratory promoting effect of urolithin A and the other bioactivities of luteolin and ergothioneine, thereby improving the efficiency of cell migration to a certain extent.

[0089] Most notably, the effect of the triple combination is remarkable. In this combination, the synergistic effect of luteolin, urolithin A, and ergothioneine significantly enhances the migratory ability of fibroblasts. The triple combination not only effectively promotes the migration speed of cells but also may optimize the directionality and efficiency of cell migration through the interaction of multiple signaling pathways. This significant synergistic effect indicates that the triple combination has great potential in promoting cell migration.

[0090] It can be seen from this that the combined use of luteolin, urolithin A, and ergothioneine exhibits a significant synergistic effect in promoting the migration of normal human fibroblasts. This finding provides new ideas for treatment strategies in the field of skin repair and regeneration. Especially in cases where rapid healing and tissue repair are required, the combined use of these three substances may become an effective treatment method. Through enhancing the cell migratory ability, the synergistic effect of these natural compounds provides a strong scientific basis for improving skin health and accelerating tissue healing.

[0091] The above-described embodiments are merely preferred embodiments cited to fully illustrate the present invention, and the protection scope of the present invention is not limited thereto. Equivalent substitutions or transformations made by those skilled in the art on the basis of the present invention are all within the protection scope of the present invention. The protection scope of the present invention shall be subject to the claims.

Claims

1. A composition for delaying cell aging, characterized in that: The composition for delaying cell aging comprises or consists of the following components: (i) Fisetin; (ii) urolithin A; and (iii) Ergothioneine.

2. A composition for delaying cell aging according to claim 1, characterized in that: In the composition for delaying cell aging, the molar ratio of fisetin, urolithin A and ergothioneine is (5-20):(5-20):(0.5-3).

3. A composition for delaying cell aging according to claim 2, characterized in that: In the composition for delaying cell aging, the molar ratio of fisetin, urolithin A and ergothioneine is 10:10:

1.

4. Use of the composition for delaying cell aging according to any one of claims 1 to 3 in the preparation of a product for delaying skin fibroblast aging; wherein: The products include cosmetics, medicines and health products.

5. The use according to claim 4, characterized in that: The composition for delaying cell aging is used to regulate the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or, The composition for delaying cell aging is used for regulating the level of active oxygen in skin fibroblasts.

6. Use of the composition for delaying cell aging according to any one of claims 1 to 3 in the preparation of products that promote skin healing and repair; wherein: The products include cosmetics, medicines and health products.

7. The use according to claim 6, characterized in that: The composition for delaying cell senescence is used for promoting the migration of skin fibroblasts.

8. An anti-aging preparation, characterized in that The anti-aging preparation comprises the composition for delaying cell aging according to any one of claims 1 to 3; wherein the anti-aging preparation comprises cosmetics, medicines and health products.

9. The anti-aging preparation according to claim 8, characterized in that The anti-aging preparation is a medicine and a health product, and the dosage form of the medicine and the health product includes an oral dosage form.

10. The anti-aging preparation according to claim 8, characterized in that The anti-aging preparation is a cosmetic, and the dosage form of the cosmetic includes cream, lotion, gel, water, oil, powder and solid; and / or, The composition for delaying cell aging is added in an amount of 0.05 to 5 wt % in the cosmetic.

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