Composition and use thereof

Abstract

Disclosed in the present invention are a composition and use thereof. The composition comprises or consists of two or more of the following components: (i) fisetin; (ii) ergothioneine, a salt thereof, or an ester thereof; and (iii) urolithin A, a precursor thereof, or a salt thereof. In the composition of the present invention, a synergistic effect is produced among (i) fisetin, (iii) urolithin A, a precursor thereof, or a salt thereof, and (ii) ergothioneine, a salt thereof, or an ester thereof. In one aspect, the composition can significantly delay senescence and exert anti-inflammation, anti-oxidation, and repair and regeneration effects; in another aspect, the composition can significantly and comprehensively solve skin problems and promote skin healing and repair, skin tone improvement, etc.

Description

Compositions and their applications

[0001] Cross-reference of related applications

[0002] This application claims priority to Chinese Patent Application No. 202510233983.1, filed on February 28, 2025, the disclosure of which is incorporated herein by reference in its entirety. Technical Field

[0003] This invention relates to the field of composition technology, and more specifically to a composition and its application. Background Technology

[0004] The skin is the largest organ in the human body, performing multiple functions including protection, sensing, and temperature regulation. With age, the skin undergoes a series of physiological changes, the most significant of which is skin aging. This aging is not only reflected in wrinkles and sagging skin, but also includes the degeneration of the skin's internal structure and function. Skin fibroblasts play a crucial role in maintaining the skin's structural integrity and function. They are primarily responsible for synthesizing and remodeling the extracellular matrix (ECM), such as collagen and elastin. However, with age, the function of fibroblasts gradually declines, leading to a decrease in skin elasticity and strength.

[0005] Fibroblast senescence is a multifactorial process involving both genetic and environmental factors. Oxidative stress is considered a major driver of cellular senescence. With 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 impair normal cellular function but also trigger apoptosis and senescence. In addition, the degradation of the extracellular matrix, increased inflammation, telomere shortening, and skin repair and regeneration also play important roles in fibroblast senescence.

[0006] In recent years, the scientific community has shown great interest in the anti-aging potential of natural compounds. These compounds typically possess a variety of biological activities, including antioxidant, anti-inflammatory, and anti-apoptotic effects, which can effectively slow down the aging process of cells. Although urolithin, ursoxin A, and ergothioneine have each shown certain biological activities in anti-aging, anti-inflammatory, antioxidant, and skin problem-solving aspects, their synergistic effects have not yet been studied. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to provide a composition in which (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof, when used together, produce a synergistic effect, enhancing its anti-aging, anti-inflammatory and antioxidant effects, and can significantly and comprehensively solve skin problems, promote skin healing and repair and improve skin tone.

[0008] To address the aforementioned technical problems, the present invention provides the following technical solution:

[0009] A first aspect of the present invention provides a composition comprising or consisting of two or more of the following components: (i) ursoxazine; (ii) ergothioneine, its salt or ester thereof; and (iii) urolithin A, its precursor or salt thereof.

[0010] Rhus flavonoids are flavonoid compounds that can slow down the aging process in various cell models by scavenging reactive oxygen species (ROS) and inhibiting inflammatory signaling pathways. Furthermore, rus flavonoids can regulate the expression of cell cycle-related proteins, thereby promoting cell survival and proliferation.

[0011] Urolithin A is an important derivative produced from the metabolism of polyphenolic compounds. It possesses significant antioxidant and anti-inflammatory properties and shows potential in promoting mitochondrial function and improving cellular energy metabolism. Urolithin A can delay the cellular aging process by reducing oxidative stress and inflammatory responses.

[0012] Urolithin A precursors include ellagic acid or ellagitannins. Urolithin is a metabolite produced by ellagitannins and ellagic acid in the gut microbiota of mammals (including humans). Ellagannins and ellagic acid are compounds commonly found in foods such as pomegranates, nuts, and berries.

[0013] Salts of urolithin A include organic and inorganic acid salts of urolithin A.

[0014] Ergothioneine is a naturally occurring amino acid derivative with excellent antioxidant capabilities. It can effectively scavenge reactive oxygen species (ROS) and protect cells from oxidative stress damage. Ergothioneine can also enhance the antioxidant capacity of cells by regulating the intracellular antioxidant enzyme system.

[0015] In some embodiments of the present invention, the above composition contains or consists of the following components: (i) rutin; and (iii) urolithin A, its precursor or salt thereof.

[0016] In some embodiments of the present invention, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof is (5-20):(5-20).

[0017] In some embodiments of the present invention, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof in the above composition is (8-18):(8-18).

[0018] In some embodiments of the present invention, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof is (10-15):(10-15).

[0019] In some embodiments of the present invention, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof in the above composition is 5:5, 10:5, 20:5, 5:10, 5:20 or 10:20.

[0020] In a preferred embodiment of the present invention, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof in the above composition is 10:10.

[0021] In such embodiments, it can be observed that the combination of (i) rutin and (iii) urolithin A, its precursors, or salts thereof exhibits significant synergistic effects in repair and / or regeneration. Specifically, it exerts synergistic effects on skin elasticity, collagen structure stability, and collagen damage through a significant enhancement of cell migration and through observed synergistic effects in preventing and / or alleviating stretch marks, thereby delaying cell aging, enhancing skin repair and regeneration, maintaining or improving skin elasticity, maintaining collagen structure stability, repairing collagen damage, and delaying skin aging. Furthermore, this combination also significantly exerts a synergistic effect in controlling and improving respiratory inflammation and chronic inflammation.

[0022] Cell migration can be the migration of fibroblasts, such as the migration of human fibroblasts.

[0023] In some embodiments of the present invention, the above composition comprises or consists of the following components: (ii) ergothioneine, its salt or its ester; and (iii) urolithin A, its precursor or its salt.

[0024] In some embodiments of the present invention, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is (0.5-3):(5-20).

[0025] In some embodiments of the present invention, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is (0.8-2):(8-18).

[0026] In some embodiments of the present invention, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is (1-2):(10-15).

[0027] In some embodiments of the present invention, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is 1:5, 2:5, 3:5, 1:10 or 1:20 in the above composition.

[0028] In a preferred embodiment of the present invention, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is 1:10 in the above composition.

[0029] In such embodiments, the combination of (ii) ergothioneine, its salt or ester and (iii) urolithin A, its precursor or salt, delays cellular senescence by significantly inhibiting the synergistic effect of reactive oxygen species (ROS) and significantly enhancing the synergistic effect of cell migration, and can also enhance skin tissue repair and regeneration, delay skin aging (e.g., sunburn and / or aging of skin cells due to excessive ROS regulation caused by UV irradiation), and alleviate ROS-mediated skin inflammatory responses.

[0030] In some embodiments of the present invention, the above composition contains or consists of the following components: (i) rutin; and (ii) ergothioneine, its salt or ester.

[0031] In some embodiments of the present invention, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester is (5-20):(0.5-3).

[0032] In some embodiments of the present invention, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester in the above composition is (8-18):(0.8-2).

[0033] In some embodiments of the present invention, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester is (10-15):(1-2).

[0034] In some embodiments of the present invention, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or ester is 5:1, 5:2, 5:3, 10:1 or 20:1 in the above composition.

[0035] In a preferred embodiment of the present invention, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester is 10:1 in the above composition.

[0036] In such embodiments, (i) rutin and (ii) ergothioneine, its salts or esters, through a synergistic effect of limiting melanocyte and / or keratinocyte production, particularly in inhibiting UV-induced melanocyte and / or keratinocyte production, thereby improving skin color and pigmentation, reducing abnormal proliferation or disordered differentiation of keratinocytes, preventing excessive thickening of the stratum corneum, stabilizing the skin barrier, improving skin roughness, dryness and other problems, and having anti-photoaging potential.

[0037] In some embodiments of the present invention, the above composition comprises or consists of the following components: (i) rutin; and (ii) ergothioneine, its salt or ester; and (iii) urolithin A, its precursor or salt.

[0038] In some embodiments of the present invention, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof in the above composition is (5-20):(5-20):(0.5-3).

[0039] In some embodiments of the present invention, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof in the above composition is (8-18):(8-18):(0.8-2).

[0040] In some embodiments of the present invention, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof in the above composition is (10-15):(10-15):(1-2).

[0041] In some embodiments of the present invention, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof in the above composition is 5:5:1, 5:5:2, 5:5:3, 10:5:1, 20:5:1, 5:10:1, 5:20:1 or 10:20:1.

[0042] In a preferred embodiment of the present invention, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof is 10:10:1.

[0043] In a preferred embodiment of the present invention, the above composition comprises or consists of the following components: (i) rutin; (iii) urolithin A; and (ii) ergothioneine.

[0044] In a more preferred embodiment of the present invention, the molar ratio of (i) laccasein, (iii) urolithin A and (ii) ergothioneine is (5-20):(5-20):(0.5-3).

[0045] In a more preferred embodiment of the present invention, the molar ratio of (i) laccasein, (iii) urolithin A and (ii) ergothionein is 5:5:1, 5:5:2, 5:5:3, 10:5:1, 20:5:1, 5:10:1, 5:20:1 or 10:20:1.

[0046] In a further preferred embodiment of the present invention, the molar ratio of (i) laccasein, (iii) urolithin A and (ii) ergothioneine is 10:10:1;

[0047] In a preferred embodiment of the present invention, the above composition is a composition that delays cell aging.

[0048] Through extensive research, the inventors discovered that a combination of (iii) urolithin A, its precursor or salt thereof and (i) urolithin, or a combination of (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof, can exhibit synergistic effects in enhancing cell migration and / or inhibiting cellular reactive oxygen species (ROS), and / or controlling respiratory and chronic inflammation, and / or preventing and / or alleviating stretch marks. It can also significantly delay the aging of skin fibroblasts and enhance skin tissue repair and regeneration, thereby delaying skin aging.

[0049] The combination of (i) rutin and (ii) ergothioneine, its salt or esters, can have a significant synergistic effect in inhibiting melanocyte proliferation and regulating keratinocyte formation, thereby improving skin color and pigmentation, skin repair and skin regeneration.

[0050] Furthermore, when (i) rutin, (iii) urolithin A, its precursor or salt, and (ii) ergothioneine, its salt or ester are used in combination, they exhibit significant synergistic effects in anti-aging after UVB irradiation, cell cycle regulation and regulation of cellular senescence gene expression, inhibition of cellular reactive oxygen species (ROS), and enhancement of cell migration. They also show significant synergistic effects in cellular anti-aging and functional maintenance, significantly delaying the aging of skin fibroblasts, and can also enhance skin tissue repair and regeneration, delay skin aging, and enhance skin function.

[0051] Skin fibroblasts play a crucial role in maintaining skin structure and function, and their aging not only affects the appearance of the skin but also leads to a decline in skin function.

[0052] The research of this invention shows that (i) rutin and (iii) urolithin A, its precursor or salt, and (ii) ergothioneine, its salt or ester, through a specific combination, can significantly improve the anti-aging ability of cells through a synergistic effect of multiple mechanisms, as follows:

[0053] (1) The combined use of (iii) urolithin A, its precursor or salt and (ii) ergothioneine, its salt or ester, and the combined use of (i) urolithin and (iii) urolithin A, its precursor or salt and (ii) ergothioneine, its salt or ester all significantly reduced the level of intracellular reactive oxygen species.

[0054] Reactive oxygen species (ROS) are a significant factor promoting cellular senescence, leading to DNA damage, protein denaturation, and lipid peroxidation through oxidative stress. This invention demonstrates that the combined use of (iii) urolithin A, its precursor, or its salts, and (ii) ergothioneine, its salts, or its esters exhibits a significant synergistic effect in reducing ROS levels.

[0055] When (i) rutin and (iii) urolithin A, its precursor or salt, and (ii) ergothioneine, its salt or ester are used in combination, the reduction of reactive oxygen species levels shows a more significant synergistic effect.

[0056] This synergistic effect not only enhances the antioxidant capacity of cells, but also further slows down the aging process of cells through multiple mechanisms of action.

[0057] (2) The combined use of (iii) urolithin A, its precursor or salt and (ii) ergothioneine, its salt or ester, the combined use of (iii) urolithin A, its precursor or salt and (i) ursoxane, the combined use of (i) ursoxane and (iii) urolithin A, its precursor or salt and (ii) ergothioneine, its salt or ester also showed a significant synergistic effect in promoting fibroblast migration.

[0058] Enhanced cell migration ability helps accelerate tissue repair and regeneration, which is an important aspect of delaying skin aging.

[0059] (iii) Urolithin A, its precursors, or its salts, when used alone, have significantly promoted cell migration. This promoting effect is further enhanced when used alone or in combination with (i) rutin and (ii) ergothioneine, its salts, or their esters. This synergistic enhancement not only increases cell migration speed but also improves cell migration efficiency by optimizing cytoskeleton remodeling and signaling pathway interactions, thereby accelerating tissue repair and regeneration and delaying cellular and skin aging.

[0060] (3) The combined use of (iii) urolithin A, its precursor or salt and (i) flavin showed significant synergistic effects in respiratory inflammation, chronic inflammation, stretch mark repair, skin elasticity and collagen maintenance.

[0061] (4) The combined use of (i) rutin and (ii) ergothioneine, their salts or esters can show synergistic effects in pigmentation and skin color, and in stabilizing the skin barrier.

[0062] (5) (i) laccasein and (iii) urolithin A, its precursor or salt, and (ii) ergothionein, its salt or ester exhibit a significant synergistic effect in regulating the expression of aging genes.

[0063] The CDKN1A gene, by encoding the p21 protein, inhibits cell cycle progression, thereby promoting cell senescence and preventing the proliferation of damaged cells; while the p16^INK4a protein, encoded by the CDKN2A gene, accumulates during cell senescence, inhibits the cell cycle, and serves as one of the markers of cell senescence.

[0064] The study of this invention shows that (i) ursoxin and (iii) urolithin A, its precursor or salt, and (ii) ergothioneine, its salt or ester all exhibit varying degrees of inhibitory effects on the expression of CDKN1A and CDKN2A. When the three are combined, the expression levels of CDKN1A and CDKN2A almost return to the state of normal cells, demonstrating a significant synergistic effect. This indicates that the combined application of (i) ursoxin and (iii) urolithin A, its precursor or salt, and (ii) ergothioneine, its salt or ester can significantly inhibit the expression of aging genes, promote cell cycle, and delay cell aging and skin aging.

[0065] (6)(i) laccasein and (iii) urolithin A, its precursor or salt, and (ii) ergothionein, its salt or ester exhibit a significant synergistic effect in regulating the expression of inflammation-related genes.

[0066] Overexpression of inflammatory cytokines such as interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-11 (IL-11) is closely related to cellular senescence. This invention demonstrates that the use of (i) flavin and (iii) urolithin A, their precursors or salts, or (ii) ergothioneine, its salts or esters, alone can inhibit the expression of these inflammatory cytokines to some extent. However, when all three are used in combination, the inhibitory effect on inflammatory cytokines is significantly enhanced, almost restoring them to normal levels. This synergistic effect may be related to the fact that each compound acts through different signaling pathways and molecular targets, ultimately achieving effective control of the inflammatory response.

[0067] (7)(i) laccasein and (iii) urolithin A, its precursor or salt, and (ii) ergothionein, its salt or ester exhibit a significant synergistic effect in cellular anti-aging.

[0068] UVB can effectively induce senescence in fibroblasts. Taking urolithin, uroflavone A, and ergothioneine as examples, when treated with urolithin, uroflavone A, and ergothioneine alone, only urolithin showed a significant anti-aging effect, reducing the proportion of senescent positive cells to 60% (Figure 3a, b). Urolithin A and ergothioneine, when used alone, did not show significant anti-aging effects (Figure 3a, b).

[0069] In the combined treatment group, the combined use of urolithin A and ergothioneine showed a weak anti-aging effect, with the proportion of senescent cells decreasing by 10%. However, the combined use of urolithin A and urolithin A, as well as the combined treatment of urolithin and ergothioneine, did not significantly enhance the anti-aging effect, with the proportion of senescent positive cells being 60% (Figure 3a, b).

[0070] However, when all three were used in combination, the anti-aging effect was significantly enhanced, with the proportion of senescent positive cells decreasing to approximately 20%, demonstrating a strong synergistic effect (Figures 3a and 3b). Notably, in the positive control group (D+Q), the proportion of senescent cells was 50%, lower than the UVB treatment group but higher than the combined group (Figures 3a and 3b). Furthermore, cells in all treatment groups did not show toxicity to normal cells, indicating that these natural compounds have good safety while effectively combating aging (Figures 3a and 3b).

[0071] Therefore, these combinations of the present invention exhibit significant synergistic effects in addressing skin problems (e.g., anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin color, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, preventing and / or repairing stretch marks), anti-aging (e.g., anti-cellular aging and / or delaying cellular aging), anti-inflammatory (e.g., improving respiratory inflammation, improving chronic inflammation), antioxidant (e.g., cellular antioxidant) and accelerating repair and / or regeneration (e.g., cell repair and / or regeneration).

[0072] It should be noted that in this application, anti-cellular senescence means clearing or reversing cells that are already in a senescent state; delaying cellular senescence means preventing cells from entering a senescent state and maintaining the youthful vitality of cells.

[0073] A second aspect of the present invention provides a formulation comprising the composition described above.

[0074] In a preferred embodiment of the present invention, the above-mentioned preparation includes an oral preparation or a topical preparation.

[0075] In a preferred embodiment of the present invention, the above-mentioned preparations include cosmetics, pharmaceuticals, and health products;

[0076] In a more preferred embodiment of the present invention, the above-mentioned preparation is a pharmaceutical product or a health product;

[0077] In a further preferred embodiment of the present invention, the dosage forms of the above-mentioned medicines and health products include oral dosage forms;

[0078] In a more preferred embodiment of the present invention, the above-mentioned preparation is a cosmetic, and the dosage form of the cosmetic includes creams, lotions, gels, aqueous solutions, oils, powders, and solids; and / or,

[0079] The above composition is added to the above cosmetic in an amount of 0.05 to 5 wt%. 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.

[0080] In a more preferred embodiment of the present invention, the types of cosmetics mentioned above include, but are not limited to, toners, eye creams, face creams, hand creams, facial cleansers, cleansing foams, cleansing gels, hand sanitizers, makeup remover oils, makeup remover waters, makeup remover gels, liquid soaps, solid soaps, shower gels, body lotions, foundations, serums, and face masks.

[0081] Furthermore, the above-mentioned formulation is an anti-aging formulation. In a preferred embodiment of the present invention, the above-mentioned anti-aging formulation is an anti-skin aging formulation.

[0082] A third aspect of the present invention provides a formulation combination. This formulation combination comprises any two or more of the following formulations:

[0083] (1) A first preparation containing component (i) rutin;

[0084] (2) A second preparation containing component (ii) ergothioneine, its salt or its ester;

[0085] (3) A third preparation containing component (iii) urolithin A, its precursor or salt thereof;

[0086] In a preferred embodiment of the present invention, the above-mentioned formulation combination further includes (4) a specification; the specification indicates that any two or more of the first formulation, the second formulation or the third formulation are applied to the subject in combination.

[0087] In a preferred embodiment of the present invention, the above-mentioned objects include those that need to address skin problems, anti-aging, anti-inflammation, anti-oxidation and / or repair and regeneration.

[0088] A fourth aspect of the present invention provides a product for solving skin problems, anti-aging, anti-inflammatory, antioxidant and / or repair and regeneration, the product comprising the above-described composition or the above-described formulation or combination of the above-described formulations.

[0089] In a preferred embodiment of the present invention, the above-mentioned solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin color, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

[0090] In a more preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from promoting skin healing and repair;

[0091] In a more preferred embodiment of the present invention, the above-mentioned products include cosmetics, pharmaceuticals, and health products;

[0092] In a further preferred embodiment of the present invention, the above-mentioned promotion of skin healing and repair includes promoting the migration of skin fibroblasts;

[0093] In a preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from delaying skin aging;

[0094] In a more preferred embodiment of the invention, the above-mentioned products include cosmetics, pharmaceuticals, and health products;

[0095] In a preferred embodiment of the present invention, the above-mentioned anti-aging includes anti-cellular senescence and / or delaying cellular senescence;

[0096] In a more preferred embodiment of the present invention, the above-mentioned delaying of cell aging includes delaying the aging of skin fibroblasts;

[0097] In a preferred embodiment of the present invention, the above-mentioned products include cosmetics, pharmaceuticals, and health products;

[0098] In a further preferred embodiment of the present invention, the above-mentioned delaying of skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts;

[0099] In a preferred embodiment of the present invention, the above-mentioned anti-inflammatory includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation;

[0100] In a preferred embodiment of the present invention, the above-mentioned antioxidants include cellular antioxidants.

[0101] The fifth aspect of the present invention provides the use of the above-described composition, the above-described formulation, the above-described combination of formulations, or the above-described product in addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration.

[0102] In a preferred embodiment of the present invention, the above-mentioned solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin color, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

[0103] In a more preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from promoting skin healing and repair.

[0104] In a further preferred embodiment of the present invention, the above-mentioned promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

[0105] In a preferred embodiment of the present invention, the solution to skin problems is selected from delaying skin aging.

[0106] In a preferred embodiment of the present invention, the product includes cosmetics, pharmaceuticals, and health products.

[0107] In a preferred embodiment of the present invention, the above-mentioned anti-aging includes anti-cellular senescence and / or delaying cellular senescence.

[0108] In a more preferred embodiment of the present invention, the above-mentioned delaying of cell aging includes delaying the aging of skin fibroblasts.

[0109] In a further preferred embodiment of the present invention, the above-mentioned delaying of skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

[0110] In a preferred embodiment of the present invention, the anti-inflammatory effect includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

[0111] In a preferred embodiment of the present invention, the above-mentioned antioxidants include cellular antioxidants.

[0112] The sixth aspect of the present invention provides the use of the above-described composition, or the above-described formulation, or the above-described combination of formulations, or the above-described product in the preparation of a composition for addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration.

[0113] It should be noted that the above uses include, but are not limited to, the use of the preparation method of the above-mentioned composition in solving skin problems, anti-aging, anti-inflammation, anti-oxidation and / or repair and regeneration, and the use of the composition prepared by the above-mentioned preparation method in solving skin problems, anti-aging, anti-inflammation, anti-oxidation and / or repair and regeneration.

[0114] In a preferred embodiment of the present invention, the above-mentioned solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin color, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

[0115] In a more preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from promoting skin healing and repair.

[0116] In a further preferred embodiment of the invention, the above-mentioned promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

[0117] In a preferred embodiment of the present invention, the solution to skin problems is selected from delaying skin aging.

[0118] In a preferred embodiment of the present invention, the product includes cosmetics, pharmaceuticals, and health products.

[0119] In a preferred embodiment of the present invention, the above-mentioned anti-aging includes anti-cellular senescence and / or delaying cellular senescence.

[0120] In a more preferred embodiment of the present invention, the above-mentioned delaying of cell aging includes delaying the aging of skin fibroblasts.

[0121] In a further preferred embodiment of the present invention, the above-mentioned delaying of skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

[0122] In a preferred embodiment of the present invention, the anti-inflammatory effect includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

[0123] In a preferred embodiment of the present invention, the above-mentioned antioxidants include cellular antioxidants.

[0124] The seventh aspect of the present invention provides the use of the above-described composition or the above-described formulation or the above-described combination of formulations in the preparation of products for addressing skin problems, anti-aging, anti-inflammatory, antioxidant and / or repair and regeneration.

[0125] It should be noted that the above uses include, but are not limited to, the use of the above-mentioned preparation method for solving skin problems, anti-aging, anti-inflammation, anti-oxidation and / or repair and regeneration, and the use of the products prepared by the above-mentioned preparation method for solving skin problems, anti-aging, anti-inflammation, anti-oxidation and / or repair and regeneration.

[0126] In a preferred embodiment of the present invention, the above-mentioned solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin color, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

[0127] In a more preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from promoting skin healing and repair.

[0128] In a more preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from promoting skin healing and repair; the above-mentioned products include cosmetics, pharmaceuticals and health products.

[0129] In a further preferred embodiment of the invention, the above-mentioned promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

[0130] In a preferred embodiment of the present invention, the solution to skin problems is selected from delaying skin aging.

[0131] In a preferred embodiment of the present invention, the product includes cosmetics, pharmaceuticals, and health products.

[0132] In a preferred embodiment of the present invention, the above-mentioned anti-aging includes anti-cellular senescence and / or delaying cellular senescence.

[0133] In a more preferred embodiment of the present invention, the above-mentioned delaying of cell aging includes delaying the aging of skin fibroblasts.

[0134] In a preferred embodiment of the present invention, the above-mentioned delaying of cell aging includes delaying the aging of skin fibroblasts; the above-mentioned products include cosmetics, pharmaceuticals and health products.

[0135] In a further preferred embodiment of the present invention, the above-mentioned delaying of skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

[0136] In a preferred embodiment of the present invention, the anti-inflammatory effect includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

[0137] In a preferred embodiment of the present invention, the above-mentioned antioxidants include cellular antioxidants.

[0138] In a preferred embodiment of the present invention, the above-mentioned product includes an oral product or a topical product.

[0139] In a preferred embodiment of the present invention, the above-mentioned products include cosmetics, pharmaceuticals, and health products.

[0140] The eighth aspect of the present invention provides a method for solving skin problems, anti-aging, anti-inflammatory, antioxidant and / or repair and regeneration, the method comprising applying an effective amount of the above composition or the above preparation or the above product to a subject in need.

[0141] In a preferred embodiment of the present invention, the above-mentioned solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin color, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

[0142] In a more preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from promoting skin healing and repair;

[0143] In a further preferred embodiment of the present invention, the above-mentioned promotion of skin healing and repair includes promoting the migration of skin fibroblasts;

[0144] In a preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from delaying skin aging;

[0145] In a more preferred embodiment of the present invention, the above-mentioned products include cosmetics, pharmaceuticals, and health products;

[0146] In a preferred embodiment of the present invention, the above-mentioned anti-aging includes anti-cellular senescence and / or delaying cellular senescence;

[0147] In a more preferred embodiment of the present invention, the above-mentioned delaying of cell aging includes delaying the aging of skin fibroblasts;

[0148] In a further preferred embodiment of the present invention, the above-mentioned delaying of skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts;

[0149] In a preferred embodiment of the present invention, the above-mentioned anti-inflammatory includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation;

[0150] In a preferred embodiment of the present invention, the above-mentioned antioxidants include cellular antioxidants.

[0151] In a preferred embodiment of the present invention, the components (i) rutin, (ii) ergothioneine, its salt or ester, or (iii) urolithin A, its precursor or salt thereof in the above composition, the above preparation or the above product are administered in any of the following ways: internal or external.

[0152] In a preferred embodiment of the present invention, the above-mentioned method of internal use is selected from any one of the following: oral administration or injection administration.

[0153] In another preferred embodiment of the present invention, the above-mentioned external application method is application by smearing.

[0154] In a preferred embodiment of the present invention, the method includes: administering an effective amount of the above composition, the above preparation, or the above product to the skin of a subject.

[0155] The ninth aspect of the present invention provides the use of the above-described composition, the above-described formulation, the above-described combination of formulations, the above-described product, or the above-described method in any one or more of the following aspects:

[0156] (1) Delaying cell aging; (2) Regulating the expression of aging genes in skin cells; (3) Combating and / or reducing signs of skin aging; (4) Preventing skin aging caused by radiation; (5) Preventing photoaging; (6) Regulating the skin cell cycle; (7) Regulating the level of reactive oxygen species in skin cells; (8) Antioxidant effect on skin and / or cells; (9) Regulating the expression of inflammation-related genes or factors; (10) Anti-inflammatory effect on skin; (11) Accelerating skin healing, repair and / or regeneration; (12) Accelerating cell repair and / or regeneration; (13) Improving skin color / pigmentation; (14) Reducing cell damage, preferably UV-induced cell damage; (15) Preventing thickening of the stratum corneum; (16) Improving rough skin; (17) Improving respiratory inflammation; (18) Improving chronic inflammation; (19) Maintaining skin elasticity; (20) Preventing and / or alleviating stretch marks; (21) Repairing collagen damage; (22) Maintaining collagen structural stability; (23) Stabilizing the skin barrier.

[0157] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0158] 1. The composition provided by the present invention contains three components: (i) rutin, (iii) urolithin A, its precursor or salt, and (ii) ergothioneine, its salt or ester. These components can exert a synergistic effect, particularly in regulating the expression of aging genes and inflammation-related genes in skin fibroblasts, regulating the level of reactive oxygen species in skin fibroblasts, and promoting the migration of skin fibroblasts. This synergistic effect can significantly delay the aging of skin fibroblasts, promote skin healing and repair, and has anti-inflammatory and anti-photoaging properties.

[0159] 2. The present invention provides a composition that can be applied in various forms, such as oral supplements, topical skin care products, etc., and can also be used simultaneously by oral and topical methods. Furthermore, the components contained in this composition are all natural compounds, exhibiting high safety and efficacy, making it an ideal choice for the development of anti-aging products. Attached Figure Description

[0160] Figure 1a shows the scratch test results of cells in different treatment groups; Figure 1b shows the statistical bar chart of cell migration rate in different treatment groups.

[0161] Figure 2a shows the reactive oxygen species (ROS) staining images of cells in different treatment groups after UVB irradiation treatment (control) and after UVB irradiation treatment; Figure 2b is a bar chart of the fluorescence intensity of ROS staining in Figure 2a.

[0162] Figure 3a shows the β-Gal staining results of cells in different treatment groups after treatment with UVB irradiation (control) and after treatment with UVB irradiation (Senescence); Figure 3b shows the statistical bar chart of senescent cells in different treatment groups in Figure 3a; Figure 3c and Figure 3d show the expression levels of CDKN1A and CDKN2A genes in cells in different treatment groups after treatment with UVB irradiation (control) and after treatment with UVB irradiation (Senescence).

[0163] Figure 4a shows the expression levels of the inflammation-related gene IL-6 in cells of different treatment groups after treatment with UVB irradiation (control) and after treatment with UVB irradiation (Senescence); Figure 4b shows the expression levels of the inflammation-related gene IL-8 in cells of different treatment groups after treatment with UVB irradiation (control) and after treatment with UVB irradiation (Senescence); Figure 4c shows the expression levels of the inflammation-related gene IL-11 in cells of different treatment groups after treatment with UVB irradiation (control) and after treatment with UVB irradiation (Senescence).

[0164] Figure 5 shows the results of tyrosinase activity inhibition rate in the melanocyte experiment; where A in Figure 5 is the protein standard curve; and B in Figure 5 is the tyrosinase activity result.

[0165] Figure 6 is a curve showing the toxicity of Dgal inducer in the keratinocyte experiment.

[0166] Figure 7 shows the gene expression results of KRT6, KRT16, and MMP in the keratinocyte experiment. In Figure 7, A is the gene expression result of KRT6; B is the gene expression result of KRT16; and C is the gene expression result of MMP.

[0167] Figure 8 shows the gene expression results of IL-1β and TNF-α in chronic inflammation and respiratory tract inflammation experiments. In Figure 8, A represents the gene expression results of IL-1β, and B represents the gene expression results of TNF-α. Detailed Implementation

[0168] The present invention will be further described below with reference to specific embodiments, so that those skilled in the art can better understand and implement the present invention, but the embodiments are not intended to limit the present invention.

[0169] (a) Joint use

[0170] Urolithin A is an important derivative produced from the metabolism of polyphenolic compounds. It possesses significant antioxidant and anti-inflammatory properties, regulates collagen metabolism, and shows potential in promoting mitochondrial function and improving cellular energy metabolism. Urolithin A can delay the cellular aging process by reducing oxidative stress and inflammatory responses.

[0171] Urolithin A precursors include ellagic acid or ellagitannins. Urolithin is a metabolite produced by ellagitannins and ellagic acid in the gut microbiota of mammals (including humans). Ellagannins and ellagic acid are compounds commonly found in foods such as pomegranates, nuts, and berries.

[0172] Rhus flavonoids are flavonoid compounds that can slow down the aging process in various cell models by scavenging reactive oxygen species (ROS) and inhibiting inflammatory signaling pathways. Furthermore, rhus flavonoids can regulate the expression of cell cycle-related proteins, thereby promoting cell survival and proliferation, stimulating elastin synthesis, and maintaining skin elasticity.

[0173] Ergothioneine is a naturally occurring amino acid derivative with excellent antioxidant capabilities. It effectively scavenge reactive oxygen species (ROS) and protects cells from oxidative stress damage. Ergothioneine can also enhance cellular antioxidant capacity by regulating intracellular antioxidant enzyme systems. Ergothioneine helps maintain the stability of the skin barrier function.

[0174] Through extensive research, the inventors discovered that the combination of urolithin A with ursodeoxylin or ergothioneine exhibits synergistic effects in enhancing cell migration and / or inhibiting reactive oxygen species (ROS), and / or in respiratory and chronic inflammation, and / or in treating stretch marks. It significantly delays the aging of skin fibroblasts and also enhances skin tissue repair and regeneration, thus delaying skin aging. Furthermore, the combination of (i) ursodeoxylin and (ii) ergothioneine, their salts, or esters has a significant synergistic effect in inhibiting melanocyte proliferation and regulating keratinocyte formation, thereby improving skin tone and pigmentation. It has effects on skin repair and regeneration; furthermore, when (i) rutin, (iii) urolithin A, its precursor or salt and (ii) ergothioneine, its salt or ester are used in combination, it can show significant synergistic effects in anti-aging and functional maintenance of cells through significant synergistic effects in anti-aging after UVB irradiation, cell cycle regulation and regulation of the expression of cellular senescence genes, inhibition of cellular reactive oxygen species (ROS) and enhancement of cell migration, significantly delaying the aging of skin fibroblasts, and also achieving the purpose of enhancing skin tissue repair and regeneration, delaying skin aging and enhancing skin function.

[0175] Therefore, the present invention provides a combined use of any two or more of the following components: (i) ursoxazine, (ii) ergothioneine, its salt or ester, and (iii) urolithin A, its precursor or salt, in addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration:

[0176] In a preferred embodiment of the present invention, the above-mentioned solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin color, anti-skin inflammation, promoting skin repair and / or regeneration, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

[0177] In a more preferred embodiment of the present invention, the above-mentioned solution to skin problems is selected from promoting skin healing and repair; in a further preferred embodiment of the present invention, the above-mentioned promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

[0178] In a preferred embodiment of the present invention, the anti-aging effect includes anti-cellular senescence and / or delaying cellular senescence. In a more preferred embodiment of the present invention, delaying cellular senescence includes delaying the senescence of skin fibroblasts.

[0179] In a further preferred embodiment of the present invention, the above-mentioned delaying of skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

[0180] In a preferred embodiment of the present invention, the anti-inflammatory effects described above include any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

[0181] In a preferred embodiment of the present invention, the above-mentioned antioxidants include cellular antioxidants.

[0182] In a preferred embodiment of the present invention, in the above-described combined use, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof is (5-20):(5-20):(0.5-3).

[0183] In a preferred embodiment of the present invention, in the above-described combined use, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof is (8-18):(8-18):(0.8-2).

[0184] In a preferred embodiment of the present invention, in the above-described combined use, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof and (ii) ergothioneine, its salt or ester thereof is (10-15):(10-15):(1-2).

[0185] In a preferred embodiment of the present invention, in the above-described combined use, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof, and (ii) ergothioneine, its salt or ester thereof may be, for example, 5:5:1, 5:5:2, 5:5:3, 10:5:1, 10:10:1, 20:5:1, 5:10:1, 5:20:1, 10:20:1, etc.

[0186] In a preferred embodiment of the present invention, in the above-described combined use, component (i) rutin, component (ii) ergothioneine, its salt or ester and component (iii) urolithin A, its precursor or salt can be used simultaneously or any two can be used in combination. Whether three are used in combination or two are used in combination, it does not affect their respective molar ratios or other components that are not selected for combination.

[0187] In the above-mentioned combined uses, component (ii) can be ergothioneine alone, ergothioneine salt alone, ergothioneine ester alone, or various combinations of ergothioneine, ergothioneine salt, and ergothioneine ester, such as ergothioneine and ergothioneine salt; or ergothioneine and ergothioneine ester; or ergothioneine salt and ergothioneine ester; or ergothioneine, ergothioneine salt, and ergothioneine ester. However, when calculating the dosage, it is uniformly calculated based on the amount of ergothioneine.

[0188] In the above-mentioned combined uses, component (iii) can be urolithin A alone, urolithin A precursor alone, urolithin A salt alone, or various combinations of urolithin A, urolithin A precursor, and urolithin A salt, such as urolithin A and urolithin A precursor; or urolithin A and urolithin A salt; or urolithin A precursor and urolithin A salt; or urolithin A, urolithin A precursor, and urolithin A salt. However, when calculating the dosage, it is uniformly calculated based on the amount of urolithin A.

[0189] (II) Composition

[0190] Based on the above-mentioned synergistic effect between component (i) rutin, component (ii) ergothioneine, its salt or ester, and component (iii) urolithin A, its precursor or salt, the present invention provides a composition comprising or consisting of two or more of the following components:

[0191] (i) laccoside;

[0192] (ii) Ergothioneine, its salts, or its esters; and

[0193] (iii) Urolithin A, its precursor or its salt.

[0194] In such a composition, the composition may contain or consist of the following components: (i) urolithin; and (iii) urolithin A, its precursor or salt thereof.

[0195] In such compositions, the molar ratio of the components can be: (i) rutin and (iii) urolithin A, its precursor or salt thereof, in a molar ratio of (5-20):(5-20); further, the molar ratio can be (8-18):(8-18); even further, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof can be (10-15):(10-15). For example, in the compositions of some embodiments, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof can be, for example, 5:5, 10:5, 10:10, 20:5, 5:10, 5:20, 10:20, etc.

[0196] In such a composition, the composition may comprise or consist of the following components: (ii) ergothioneine, its salt or its ester; and (iii) urolithin A, its precursor or its salt.

[0197] In such compositions, the molar ratio of the components can be: (ii) ergothioneine, its salt or ester, and (iii) urolithin A, its precursor or salt, in a molar ratio of (0.5–3):(5–20); further, the molar ratio can be (0.8–2):(8–18); even further, the molar ratio of (ii) ergothioneine, its salt or ester, and (iii) urolithin A, its precursor or salt, can be (1–2):(10–15). For example, in the compositions of some embodiments, the molar ratio of (ii) ergothioneine, its salt or ester, and (iii) urolithin A, its precursor or salt, can be, for example, 1:5, 2:5, 3:5, 1:10, 1:20, etc.

[0198] In such a composition, the composition may contain or consist of the following components: (i) rutin; and (ii) ergothioneine, its salt or its ester.

[0199] In such compositions, the molar ratio of the components can be: (ii) ergothioneine, its salt or ester thereof, and (i) ursanthin in a molar ratio of (0.5–3):(5–20); further, the molar ratio can be (0.8–2):(8–18); even further, the molar ratio of (ii) ergothioneine, its salt or ester thereof, and (i) ursanthin can be (1–2):(10–15). For example, in the compositions of some embodiments, the molar ratio of (ii) ergothioneine, its salt or ester thereof, and (i) ursanthin can be, for example, 1:5, 2:5, 3:5, 1:10, 1:20, etc.

[0200] In such a composition, the composition may contain or consist of the following components:

[0201] (i) laccoside

[0202] (ii) Ergothioneine, its salts, or its esters; and

[0203] (iii) Urolithin A, its precursor or its salt.

[0204] In such compositions, the molar ratio of the components can be: (i) ursoxin, (iii) urolithin A, its precursor or salt, and (ii) ergothioneine, its salt or ester, in a molar ratio of (5–20):(5–20):(0.5–3); further, the molar ratio can be (8–18):(8–18):(0.8–2); even further, the molar ratio can be (10–15):(10–15):(1–2). For example, in the compositions of some embodiments, the molar ratio of (i) ursoxin, (iii) urolithin A, its precursor or salt, and (ii) ergothioneine, its salt or ester, can be, for example, 5:5:1, 5:5:2, 5:5:3, 10:5:1, 10:10:1, 20:5:1, 5:10:1, 5:20:1, 10:20:1, etc.

[0205] The salts of urolithin A mentioned above in this invention include organic acid salts and inorganic acid salts of urolithin A.

[0206] The organic acid salts of urolithin A can be formed by the reaction of organic acids such as acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and salicylic acid with urolithin A. The corresponding salts are urolithin A acetate, urolithin A trifluoroacetate, urolithin A propionate, urolithin A glycolate, urolithin A pyruvic acid, urolithin A oxalate, urolithin A maleate, urolithin A malonate, urolithin A succinate, urolithin A fumarate, urolithin A tartrate, urolithin A citrate, urolithin A benzoate, urolithin A cinnamic acid, urolithin A mandelic acid, urolithin A methanesulfonate, urolithin A ethanesulfonate, urolithin A p-toluenesulfonate, and urolithin A salicylate.

[0207] Inorganic acid salts of urolithin A typically include those formed by the reaction of inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid with urolithin A. Common forms include urolithin A hydrochloride, urolithin A hydrobromide, urolithin A sulfate, urolithin A nitrate, urolithin A phosphate, urolithin A sodium salt, and urolithin A potassium salt.

[0208] The salts of ergothioneine mentioned above in this invention include organic acid salts and inorganic acid salts, such as ergothioneine citrate.

[0209] The esters of ergothioneine mentioned above in this invention are usually generated by esterification of the carboxyl group of ergothioneine with alcohols (such as methanol and ethanol), for example, ergothioneine methyl ester and ergothioneine ethyl ester.

[0210] (III) Products or formulations

[0211] The present invention also provides a product or preparation for addressing skin problems, anti-aging, anti-inflammatory, antioxidant and / or repair and regeneration, comprising the above-described composition or the above-described preparation or combination of the above-described preparations.

[0212] The present invention may also provide a product or preparation for anti-skin aging and / or delaying skin aging and / or reducing skin aging, comprising the above-described composition.

[0213] The present invention may also provide a product or preparation for anti-photoaging, comprising the above-described composition.

[0214] The present invention may also provide a product or preparation for anti-skin oxidation, comprising the above-described composition.

[0215] The present invention may also provide a product or formulation for stabilizing the skin barrier, comprising the above-described composition.

[0216] The present invention may also provide a product or formulation for improving pigmentation and skin color, comprising the above-described composition.

[0217] The present invention may also provide an anti-skin inflammation product or preparation comprising the above-described composition.

[0218] The present invention may also provide a product or preparation for promoting skin healing, repair and / or regeneration, including the above-described composition.

[0219] The present invention also provides a product or preparation for maintaining skin elasticity, comprising the above-described composition.

[0220] The present invention also provides a product or preparation for maintaining skin collagen, comprising the above-described composition.

[0221] The present invention also provides a product or preparation for preventing and / or repairing stretch marks, comprising the above-described composition.

[0222] The present invention also provides a product or preparation for resisting and / or delaying cell aging, comprising the above-described composition.

[0223] The present invention may also provide a product or preparation for improving respiratory inflammation, comprising the above-described composition.

[0224] The present invention may also provide a product or preparation for improving chronic inflammation, comprising the above-described composition.

[0225] The present invention may also provide a product or preparation for cellular antioxidant activity, comprising the above-described composition.

[0226] In this invention, the products or preparations described above may include oral products or preparations (e.g., oral products or preparations) or topical products or preparations.

[0227] In this invention, the above-mentioned products or preparations can be cosmetics, pharmaceuticals, and health products.

[0228] In this invention, when the above-mentioned product or preparation is a cosmetic, the cosmetic can be prepared into various dosage forms, including but not limited to creams, lotions, gels, aqueous solutions, oils, powders, or solids.

[0229] In this invention, the types of cosmetics mentioned above include, but are not limited to, toners, eye creams, face creams, hand creams, facial cleansers, cleansing foams, cleansing gels, hand soaps, makeup remover oils, makeup remover waters, makeup remover gels, liquid soaps, solid soaps, shower gels, body lotions, foundations, serums, or face masks.

[0230] In the cosmetic of the present invention, the above composition is added in the cosmetic at an amount of 0.05 to 5 wt%, for example, 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.

[0231] In the oral product or formulation of the present invention, the above composition is added in an amount of 0.05 to 5 wt%, for example, 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.

[0232] In the oral products or formulations of the present invention, the products or formulations may also include a carrier or other functional ingredients.

[0233] Therefore, the present invention provides a combined use of two or more of the following components: (i) ursoxazine, (ii) ergothioneine, its salt or ester, and (iii) urolithin A, its precursor or salt, in addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration:

[0234] (iv) Usage Method

[0235] The present invention also provides a method for addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration. The method comprises: applying an effective amount of the above-described composition, preparation, or product to a subject in need.

[0236] The present invention may also provide a method for resisting and / or delaying and / or reducing skin aging, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0237] The present invention may also provide a method for resisting photoaging, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0238] The present invention may also provide a method for combating skin oxidation, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0239] The present invention may also provide a method for stabilizing the skin barrier, the method comprising: applying an effective amount of the above composition, the above formulation, or the above product to a subject in need.

[0240] The present invention may also provide a method for improving pigmentation and skin color, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0241] The present invention may also provide a method for treating skin inflammation, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0242] The present invention may also provide a method for promoting skin healing, repair and / or regeneration, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0243] The present invention also provides a method for maintaining skin elasticity, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0244] The present invention also provides a method for maintaining skin collagen, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0245] The present invention also provides a method for preventing and / or repairing stretch marks, the method comprising: applying an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0246] The present invention also provides a method for resisting and / or delaying cell senescence, the method comprising: administering an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0247] The present invention may also provide a method for improving respiratory inflammation, the method comprising: administering an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0248] The present invention may also provide a method for improving chronic inflammation, the method comprising: administering an effective amount of the above composition, the above preparation or the above product to a subject in need.

[0249] The present invention may also provide a method for cellular antioxidant activity, the method comprising: applying an effective amount of the above-described composition, the above-described formulation, or the above-described product to a subject in need.

[0250] In a preferred embodiment of the present invention, the components (i) rutin, (ii) ergothioneine, its salt or ester, or (iii) urolithin A, its precursor or salt thereof in the above composition, the above preparation or the above product are administered in any of the following ways: internal or external.

[0251] In a preferred embodiment of the present invention, the above-mentioned method of internal use is selected from any one of the following: oral administration or injection administration.

[0252] In another preferred embodiment of the present invention, the above-mentioned external application method is application by smearing.

[0253] In a preferred embodiment of the present invention, component (i) rutin, component (ii) ergothioneine, its salt or ester, and component (iii) urolithin A, its precursor or salt, may be applied in the same manner or in different manners.

[0254] In the method of the present invention, component (i) rutin, component (ii) ergothioneine, its salt or ester and component (iii) urolithin A, its precursor or salt can be applied simultaneously, for example, as two or three components at the same time, or as a composition or product or formulation.

[0255] In the method of the present invention, components (i) rutin, (ii) ergothioneine, its salt or ester, and (iii) urolithin A, its precursor or salt can be applied individually. For example, components (i) rutin or (ii) ergothioneine, its salt or ester, or (iii) urolithin A, its precursor or salt can be applied first, with an interval of 0-24 hours, and then another one or two components can be applied.

[0256] The effective amounts of ursoxazine, ergothioneine, its salts or esters, and urolithin A, its precursors or salts vary depending on the specific composition, the age and condition of the recipient, and the specific condition or disease being treated. However, in general embodiments, an individual may be administered 0.001 mg to 1.0 g daily, preferably 0.01 mg to 0.9 g daily, more preferably 0.1 mg to 750 mg daily, even more preferably 0.5 mg to 500 mg daily, and most preferably 1.0 mg to 200 mg daily.

[0257] In the method of the present invention, the above-mentioned object is an animal, such as a human, including teenagers, middle-aged people, the elderly, etc., and may also include people with photoaging or radiation, or people affected by skin inflammation, or people with skin damage, or people with skin oxidative stress, or pregnant women, or postpartum women.

[0258] (V) Formulation Combinations

[0259] The present invention also provides a formulation comprising two or more of the following formulations:

[0260] (1) A first preparation containing component (i) rutin;

[0261] (2) A second preparation containing component (ii) ergothioneine, its salt or its ester;

[0262] (3) A third preparation containing component (iii) urolithin A, its precursor or salt thereof.

[0263] Furthermore, the above formulation combination also includes:

[0264] (4) Instructions for use, wherein the instructions for use are to apply any two or more of the first, second or third formulations to the subject.

[0265] In this invention, the aforementioned objects may include objects that require solutions to skin problems, anti-aging, anti-inflammation, anti-oxidation, and / or repair and regeneration.

[0266] In this invention, objects may include objects that require anti-skin aging and / or delay skin aging and / or reduce skin aging, or objects that require anti-photoaging, or objects that require anti-skin oxidation, or objects that require stabilizing the skin barrier, or objects that require improving pigmentation and skin color, or objects that require anti-skin inflammation, or objects that require promoting skin healing, or objects that require promoting skin healing, repair and / or regeneration, or objects that require maintaining skin elasticity, or objects that require maintaining skin collagen, or objects that require preventing and / or repairing stretch marks, or objects that require anti-cellular aging and / or delay cellular aging, or objects that require improving respiratory inflammation, or objects that require improving chronic inflammation, or objects that require cellular antioxidant activity.

[0267] In this invention, the above-mentioned formulation combination can be packaged and sold separately for the first, second, and third formulations; or the first, second, and third formulations can be prepared separately but packaged into one outer packaging and sold as a combination; or the first, second, and third formulations can be prepared by mixing two or more of the first, second, and third formulations into a composition or a product or formulation in accordance with the above-mentioned composition, product, or formulation method.

[0268] In this invention, the specific contents of the specification may include a recommended dose ratio of component (i) rutin, component (ii) ergothioneine, its salt or ester, component (iii) urolithin A, its precursor or salt.

[0269] In this invention, the recommended dosage ratio can be referenced to the molar ratio of several components in the above composition.

[0270] In this invention, the specific contents of the specification may also include the target object, method of use, dosage, etc.

[0271] (vi) Purpose

[0272] Extensive research has demonstrated that the combined use of these inventions can address skin problems, as well as issues related to anti-aging (e.g., cellular aging), anti-inflammation (e.g., respiratory inflammation, chronic inflammation), anti-oxidation, and accelerated repair and / or regeneration (e.g., cell repair and / or regeneration).

[0273] This invention uses a combination of methods to address skin problems, including any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin color, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

[0274] This invention provides the use of the above-described compositions, formulations, or combinations thereof in the preparation of products for addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration.

[0275] The present invention provides the use of the above-described compositions or formulations or combinations of formulations in the preparation of products for anti-skin aging, and / or delaying skin aging and / or reducing skin aging.

[0276] This invention provides the use of the above-described compositions, formulations, or combinations of formulations in the preparation of anti-photoaging products.

[0277] This invention provides the use of the above-described compositions, formulations, or combinations thereof in the preparation of products for anti-skin oxidation.

[0278] This invention provides the use of the above-described compositions, formulations, or combinations thereof in the preparation of products that stabilize the skin barrier.

[0279] This invention provides the use of the above-described compositions, formulations, or combinations thereof in the preparation of products that improve pigmentation and skin color.

[0280] This invention provides the use of the above-described compositions, formulations, or combinations thereof in the preparation of products for treating skin inflammation.

[0281] The present invention provides the use of the above-described compositions or formulations or combinations of formulations in the preparation of products that promote skin healing, repair and / or regeneration.

[0282] This invention provides the use of the above-described compositions, formulations, or combinations thereof in the preparation of products that maintain skin elasticity.

[0283] The present invention provides the use of the above-described compositions, formulations, or combinations thereof in the preparation of products that maintain skin collagen.

[0284] The present invention provides the use of the above-described compositions or formulations or combinations of formulations in the preparation of products for the prevention and / or repair of stretch marks.

[0285] The present invention provides the use of the above-described compositions, formulations or combinations of formulations in the preparation of products that resist cell aging and / or delay cell aging.

[0286] The present invention provides the use of the above-described compositions, formulations or combinations of formulations in the preparation of products that improve respiratory inflammation.

[0287] The present invention provides the use of the above-described composition, formulation or combination of formulations in the preparation of products that improve chronic inflammation.

[0288] In a preferred embodiment of the present invention, the above-mentioned product includes an oral product or a topical product.

[0289] In a preferred embodiment of the present invention, the above-mentioned products include, but are not limited to, cosmetics, pharmaceuticals, or health products.

[0290] The present invention provides the use of the above-described compositions, products, formulations, or combinations of formulations in the preparation of compositions for addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration.

[0291] The present invention provides the use of the above-described compositions, products, formulations or combinations of formulations in the preparation of compositions for anti-skin aging, and / or delaying skin aging and / or reducing skin aging.

[0292] This invention provides the use of the above-described compositions, products, formulations, or combinations of formulations in the preparation of compositions for anti-photoaging.

[0293] This invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions for anti-skin oxidation.

[0294] This invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions that stabilize the skin barrier.

[0295] The present invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions that improve pigmentation and skin color.

[0296] This invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions for treating skin inflammation.

[0297] The present invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions that promote skin healing, repair, and / or regeneration.

[0298] This invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions for maintaining skin elasticity.

[0299] The present invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions for maintaining skin collagen.

[0300] The present invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions for the prevention and / or repair of stretch marks.

[0301] The present invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions for anti-cellular senescence and / or delaying cellular senescence.

[0302] The present invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions that improve respiratory inflammation.

[0303] The present invention provides the use of the above-described compositions, products, formulations, or combinations thereof in the preparation of compositions that improve chronic inflammation.

[0304] The above-described compositions, products, formulations, combinations of formulations, or methods of the present invention have one or more of the following uses:

[0305] (1) Delaying cell aging;

[0306] (2) Regulate the expression of aging genes in skin cells;

[0307] (3) Combat and / or reduce signs of skin aging;

[0308] (4) Prevent skin aging caused by radiation;

[0309] (5) Prevent photoaging;

[0310] (6) Regulates the skin cell cycle;

[0311] (7) Regulates the level of reactive oxygen species in skin cells;

[0312] (8) Skin and / or cellular antioxidant effects;

[0313] (9) Regulate the expression of inflammation-related genes or factors;

[0314] (10) Anti-skin inflammation;

[0315] (11) Accelerates skin healing, repair and / or regeneration;

[0316] (12) Accelerates cell repair and / or regeneration;

[0317] (13) Improves skin and / or pigmentation;

[0318] (14) Reduce cell damage (especially UV-induced cell damage);

[0319] (15) Avoid thickening of the stratum corneum;

[0320] (16) Improves rough skin;

[0321] (17) Improves respiratory inflammation;

[0322] (18) Improves chronic inflammation;

[0323] (19) Maintain skin elasticity;

[0324] (20) To prevent and / or alleviate stretch marks;

[0325] (21) Repair collagen damage;

[0326] (22) Maintaining the stability of collagen structure;

[0327] (23) Stabilize the skin barrier.

[0328] For example, in the present invention, the combined use or combination of component (i) rutin and component (iii) urolithin A has one or more of the following uses:

[0329] (1) Delaying cell aging;

[0330] (2) Combat and / or reduce signs of skin aging;

[0331] (3) Accelerates skin healing, repair and / or regeneration;

[0332] (4) Accelerates cell repair and / or regeneration;

[0333] (5) Improves respiratory inflammation;

[0334] (6) Improves chronic inflammation;

[0335] (7) Maintain skin elasticity;

[0336] (8) Prevent and / or alleviate stretch marks;

[0337] (9) Repair collagen damage;

[0338] (10) Maintain the stability of collagen structure.

[0339] In such combinations, the molar ratio of the components can be: (i) the molar ratio of rutin to (iii) urolithin A is (5-20):(5-20); further, the molar ratio can be (8-18):(8-18); even further, the molar ratio of (i) rutin to (iii) urolithin A can be (10-15):(10-15). For example, in the compositions of some embodiments, the molar ratio of (i) rutin to (iii) urolithin A can be, for example, 5:5, 10:5, 10:10, 20:5, 5:10, 5:20, 10:20, etc.

[0340] For example, in the present invention, the combined use or combination of component (ii) ergothioneine and component (iii) urolithin A has one or more of the following uses:

[0341] (1) Delaying cell aging;

[0342] (2) Combat and / or reduce signs of skin aging;

[0343] (3) Prevent skin aging caused by radiation;

[0344] (4) Regulates the level of reactive oxygen species in skin cells;

[0345] (5) Skin and / or cellular antioxidant effects;

[0346] (6) Anti-inflammatory effects on skin (e.g., skin inflammation caused by ROS);

[0347] (7) Accelerates skin healing, repair and / or regeneration;

[0348] (8) Accelerates cell repair and / or regeneration.

[0349] In such compositions, the molar ratio of the components can be: (ii) ergothioneine and (iii) urolithin A in a molar ratio of (0.5–3):(5–20); further, the molar ratio can be (0.8–2):(8–18); even further, the molar ratio of (ii) ergothioneine and (iii) urolithin A can be (1–2):(10–15). For example, in the compositions of some embodiments, the molar ratio of (ii) ergothioneine and (iii) urolithin A can be, for example, 1:5, 2:5, 3:5, 1:10, 1:20, etc.

[0350] For example, in the present invention, the combined use or combination of component (i) ursoxazine and component (ii) ergothioneine has one or more of the following uses:

[0351] (1) Delaying cell aging;

[0352] (2) Combat and / or reduce signs of skin aging;

[0353] (3) Improves skin and / or pigmentation;

[0354] (4) Reduce cell damage (especially UV-induced cell damage);

[0355] (5) Avoid thickening of the stratum corneum;

[0356] (6) Improves rough skin;

[0357] (7) Stabilize the skin barrier.

[0358] In such compositions, the molar ratio of the components can be: (ii) ergothioneine and (i) ursanthin in a molar ratio of (0.5–3):(5–20); further, the molar ratio can be (0.8–2):(8–18); even further, the molar ratio of (ii) ergothioneine and (i) ursanthin can be (1–2):(10–15). For example, in the compositions of some embodiments, the molar ratio of (ii) ergothioneine and (i) ursanthin can be, for example, 1:5, 2:5, 3:5, 1:10, 1:20, etc.

[0359] For example, in the present invention, the combined use or combination of component (i) rutin, component (ii) ergothioneine and component (iii) urolithin A has one or more of the following uses:

[0360] (1) Delaying cell aging;

[0361] (2) Regulate the expression of aging genes in skin cells;

[0362] (3) Combat and / or reduce signs of skin aging;

[0363] (4) Prevent skin aging caused by radiation;

[0364] (5) Prevent photoaging;

[0365] (6) Regulates the skin cell cycle;

[0366] (7) Regulates the level of reactive oxygen species in skin cells;

[0367] (8) Skin and / or cellular antioxidant effects;

[0368] (9) Regulate the expression of inflammation-related genes or factors;

[0369] (10) Anti-skin inflammation;

[0370] (11) Accelerates skin healing, repair and / or regeneration;

[0371] (12) Accelerates cell repair and / or regeneration;

[0372] (13) Improves skin and / or pigmentation;

[0373] (14) Reduce cell damage (especially UV-induced cell damage);

[0374] (15) Avoid thickening of the stratum corneum;

[0375] (16) Improves rough skin;

[0376] (17) Improves respiratory inflammation;

[0377] (18) Improves chronic inflammation;

[0378] (19) Maintain skin elasticity;

[0379] (20) To prevent and / or alleviate stretch marks;

[0380] (21) Repair collagen damage;

[0381] (22) Maintaining the stability of collagen structure;

[0382] (23) Stabilize the skin barrier.

[0383] In such compositions, the molar ratio of the components can be: (i) the molar ratio of ursanthin, (iii) urolithin A, and (ii) ergothioneine is (5–20):(5–20):(0.5–3); further, the molar ratio can be (8–18):(8–18):(0.8–2); even further, the molar ratio can be (10–15):(10–15):(1–2). For example, in the compositions of some embodiments, the molar ratio of (i) ursanthin, (iii) urolithin A, and (ii) ergothioneine can be, for example, 5:5:1, 5:5:2, 5:5:3, 10:5:1, 10:10:1, 20:5:1, 5:10:1, 5:20:1, 10:20:1, etc.

[0384] Preferably, the method of preventing skin aging caused by radiation can be: preventing skin aging caused by UV radiation.

[0385] Preferably, preventing photoaging can be: preventing sunlight-induced photoaging.

[0386] Preferably, the regulation of the skin cell cycle can be: regulating the skin fibroblast cell cycle.

[0387] Preferably, regulating the level of reactive oxygen species in skin cells can be achieved by regulating the level of reactive oxygen species in skin fibroblasts.

[0388] Preferably, regulating the expression of aging genes in skin cells includes regulating the expression of the aging gene CDKN1A.

[0389] Preferably, regulating the expression of aging genes in skin cells includes regulating the expression of the aging gene CDKN2A.

[0390] Preferably, regulating the expression of inflammation-related genes or factors includes regulating the expression of inflammatory factors IL-6, IL-8 and / or IL-11 or their related genes.

[0391] Preferably, the anti-skin inflammation includes anti-ROS-mediated and / or ROS-induced skin inflammation.

[0392] Preferably, improving skin and / or pigmentation includes inhibiting the production of melanocytes, for example, inhibiting the production of melanocytes after irradiation or sunlight.

[0393] Respiratory inflammation is a core pathological process shared by many respiratory diseases, such as pneumonia, bronchial asthma, chronic obstructive pulmonary disease, and acute respiratory distress syndrome. Its pathogenesis is complex and involves cytokine storms, oxidative stress imbalance, epithelial barrier damage, and abnormal activation of downstream signaling pathways.

[0394] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0395] Unless otherwise specified, the experimental methods used in the following examples and comparative examples are conventional methods, and the materials and reagents used are commercially available unless otherwise specified.

[0396] The present invention will be further described below with reference to specific embodiments and comparative examples.

[0397] In the following specific implementation, *p, **p, and ***p represent comparisons with the control group, where *p<0.05, **p<0.01, ***p<0.001, and ****p<0.0001.

[0398] Example 1

[0399] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 10:10:1.

[0400] Example 2

[0401] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 5:5:1.

[0402] Example 3

[0403] This embodiment provides a composition for delaying cell aging, consisting of flavin (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 5:5:2.

[0404] Example 4

[0405] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 5:5:3.

[0406] Example 5

[0407] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 10:5:1.

[0408] Example 6

[0409] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 20:5:1.

[0410] Example 7

[0411] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 5:10:1.

[0412] Example 8

[0413] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 5:20:1.

[0414] Example 9

[0415] This embodiment provides a composition for delaying cell aging, consisting of flavonoids (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 10:20:1.

[0416] Example 10

[0417] This embodiment provides a composition for delaying cell aging, consisting of flavonoids (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 8:8:0.8.

[0418] Example 11

[0419] This embodiment provides a composition for delaying cell aging, consisting of flavonoids (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 5:8:0.3.

[0420] Example 12

[0421] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis), urolithin A (UA), and ergothioneine (EGT) in a molar ratio of 5:18:2.

[0422] Example 13

[0423] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 10:10.

[0424] Example 14

[0425] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 5:5.

[0426] Example 15

[0427] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 20:5.

[0428] Example 16

[0429] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 5:10.

[0430] Example 17

[0431] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 5:20.

[0432] Example 18

[0433] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 10:20.

[0434] Example 19

[0435] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 12:20.

[0436] Example 20

[0437] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 18:15.

[0438] Example 21

[0439] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and urolithin A (UA) in a molar ratio of 15:15.

[0440] Example 22

[0441] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 10:1.

[0442] Example 23

[0443] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 5:1.

[0444] Example 24

[0445] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 5:2.

[0446] Example 25

[0447] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 5:3.

[0448] Example 26

[0449] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 20:1.

[0450] Example 27

[0451] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 8:0.5.

[0452] Example 28

[0453] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 15:1.

[0454] Example 29

[0455] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 15:1.5.

[0456] Example 30

[0457] This embodiment provides a composition for delaying cell aging, consisting of urolithin A (UA) and ergothioneine (EGT) in a molar ratio of 12:0.8.

[0458] Example 31

[0459] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and ergothioneine (EGT) in a molar ratio of 10:1.

[0460] Example 32

[0461] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and ergothioneine (EGT) in a molar ratio of 5:1.

[0462] Example 33

[0463] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and ergothioneine (EGT) in a molar ratio of 5:2.

[0464] Example 34

[0465] This embodiment provides a composition for delaying cell aging, consisting of flavin (Fis) and ergothioneine (EGT) in a molar ratio of 5:3.

[0466] Example 35

[0467] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and ergothioneine (EGT) in a molar ratio of 20:1.

[0468] Example 36

[0469] This embodiment provides a composition for delaying cell aging, consisting of flavin (Fis) and ergothioneine (EGT) in a molar ratio of 5:0.5.

[0470] Example 37

[0471] This embodiment provides a composition for delaying cell aging, consisting of flavin (Fis) and ergothioneine (EGT) in a molar ratio of 12:1.

[0472] Example 38

[0473] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and ergothioneine (EGT) in a molar ratio of 15:2.

[0474] Example 39

[0475] This embodiment provides a composition for delaying cell aging, consisting of flavin (Fis) and ergothioneine (EGT) in a molar ratio of 20:3.

[0476] Example 40

[0477] This embodiment provides a composition for delaying cell aging, consisting of flavonoid (Fis) and ergothioneine (EGT) in a molar ratio of 18:2.

[0478] Comparative Example 1

[0479] The difference between Comparative Example 1 and Example 1 is that the composition contains only rosin.

[0480] Comparative Example 2

[0481] The difference between Comparative Example 2 and Example 1 is that the composition contains only urolithin A.

[0482] Comparative Example 3

[0483] The difference between Comparative Example 3 and Example 1 is that the composition contains only ergothioneine.

[0484] Experimental test case

[0485] In the experimental test examples 1-4 below, the human skin fibroblast cell line BJ was used as a model. The experimental group was irradiated with UVB (40 mJ / cm²). 2 Cell senescence was induced for 4 days, while the control group did not receive UVB irradiation. In the treatment regimens, cells were treated with a single compound and a combination of compounds for 72 hours, and a positive control (dasatinib combined with quercetin) and a negative control (DMSO) were set up.

[0486] 1. Synergistic effect in regulating the migration of normal human fibroblasts

[0487] The solutions include:

[0488] 1) Use alone rosin (Fis, 20μM), urolithin A (UA, 20μM) and ergothioneine (EGT, 1μM);

[0489] 2) Combined treatment with urolithin A and rosin (UA+Fis, 10μM+10μM) - Example 13;

[0490] 3) Combined treatment with urolithiasis A and ergothioneine (UA+EGT, 20μM+1μM) - Example 26;

[0491] 4) Combined treatment of the three (UA+EGT+Fis, 10μM+1μM+10μM) - Example 1;

[0492] 5) Use DMSO in equal proportions as a negative control.

[0493] 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. This study investigated the roles and synergistic effects of urolithin, urolithin A, and ergothioneine in promoting the migration of normal human fibroblasts.

[0494] After observing the migration of fibroblasts using the above treatment method, please refer to Figure 1a and Figure 1b.

[0495] Experimental results showed that urolithin A, when used alone, significantly promoted fibroblast migration. This effect may be related to the role of urolithin A in cell signaling pathways, promoting cytoskeleton reorganization and enhanced cell motility. In contrast, ursoxazine and ergothioneine, when used alone, had relatively limited effects on promoting fibroblast migration. Although they exhibited excellent performance in other aspects, such as antioxidation and anti-inflammation, their effects on promoting cell migration alone were not significant.

[0496] However, when urolithin was used in combination with urolithin A (as in Example 13) or ergothioneine was used in combination with urolithin A (as in Example 26), the migration ability of fibroblasts was significantly enhanced. This synergistic effect may be due to the migration-promoting effect of urolithin A complementing the other biological activities of urolithin and ergothioneine, thereby improving the efficiency of cell migration to some extent.

[0497] The most significant effect was observed in the combined use of the three agents. In this combination (as shown in Example 1), the synergistic effect of urolithin, urolithin A, and ergothioneine significantly enhanced the migration ability of fibroblasts. The combined use of these three agents not only effectively promoted cell migration speed but also likely optimized the directionality and efficiency of cell migration through the interaction of multiple signaling pathways. This significant synergistic effect indicates that the combined use of these three agents has great potential in promoting cell migration.

[0498] Therefore, it can be seen that the combined use of rosin and urolithin A, the combined use of ergothioneine and urolithin A, and the combined use of rosin, urolithin A and ergothioneine showed significant synergistic effects in promoting the migration of normal human fibroblasts.

[0499] This discovery offers new insights into treatment strategies in the field of skin repair and regeneration, particularly in cases requiring rapid healing and tissue repair, where such combined use could be an effective treatment approach. By enhancing cell migration, the synergistic effect of these natural compounds provides a strong scientific basis for improving skin health and accelerating tissue healing, thereby speeding up skin healing, repair, and / or regeneration, and accelerating cell repair and / or regeneration.

[0500] 2. It exhibits a synergistic effect in regulating cellular reactive oxygen species (ROS).

[0501] The solutions include:

[0502] 1) Use alone rosin (Fis, 20μM), urolithin A (UA, 20μM) and ergothioneine (EGT, 1μM);

[0503] 2) Combined treatment with urolithiasis A and ergothioneine (UA+EGT, 20μM+1μM) - Example 26;

[0504] 3) Combined treatment of the three (UA+EGT+Fis, 10μM+1μM+10μM) - Example 1;

[0505] In addition, dasatinib and quercetin (D+Q, 1μM+20μM) were used as positive controls, and DMSO in equal proportions was used as a negative control.

[0506] Reactive oxygen species (ROS) play a crucial role in cellular senescence. Excessive ROS can lead to cell damage, DNA mutation, protein oxidation, and lipid peroxidation, thereby accelerating the aging process. Ultraviolet B (UVB) radiation is a significant trigger for ROS production; excessive ROS accumulation often results in decreased skin cell function and is closely related to aging and various skin pathologies. Therefore, regulating ROS levels is one of the key strategies in anti-aging treatments.

[0507] In this invention, the regulatory effects of ursanthin (20 μM), urolithin A (20 μM), and ergothioneine (1 μM) on ROS levels were evaluated. Referring to Figures 2a and 2b, the experimental results showed that UVB irradiation significantly increased ROS production in skin fibroblasts, indicating that UVB can induce intracellular oxidative stress. However, urolithin A or ergothioneine alone significantly inhibited ROS production, with ergothioneine showing a stronger effect in suppressing ROS. Specifically, ergothioneine significantly reduced ROS levels, approaching normal cell levels, while urolithin A, although also inhibiting ROS, had a relatively weaker effect. The inhibitory effect of ursanthin alone on ROS was limited, failing to significantly reduce UVB-induced ROS production.

[0508] Further research showed that the combined use of urolithin A and ergothioneine (Example 26) significantly enhanced the effect compared to using them alone. The most significant effect was observed in the combination of all three. In this combination, the synergistic effect of urolithin A and ergothioneine (Example 1) significantly enhanced the inhibitory effect on ROS. The combination not only substantially inhibited UVB-induced ROS generation, but its inhibitory effect almost returned to the level of normal cells, demonstrating a very strong synergistic effect.

[0509] This discovery indicates that urolithin, ursoxin A, and ergothioneine, through multiple synergistic mechanisms, significantly regulate intracellular ROS levels, thereby alleviating oxidative stress induced by UVB radiation. These natural compounds may reduce ROS production and oxidative damage, thus delaying cellular senescence, through direct or indirect effects.

[0510] In particular, the combined use of ergothioneine and urolithin A, as well as the comprehensive application of the three, has shown a more significant synergistic effect in inhibiting ROS. It can exert antioxidant (anti-skin oxidation / anti-cellular oxidation) effects, regulate the level of reactive oxygen species in skin cells, resist ROS-mediated skin inflammation, resist sunburn / aging caused by excessive ROS in skin cells due to UV irradiation, reduce cell damage, especially UV-induced cell damage, and provide strong molecular mechanism support for anti-aging treatment.

[0511] 3. Synergistic effect in anti-aging effects and regulation of aging gene expression

[0512] The solutions include:

[0513] 1) Use alone rosin (Fis, 20μM), urolithin A (UA, 20μM) and ergothioneine (EGT, 1μM);

[0514] 2) Combined treatment of the three (UA+EGT+Fis, 10μM+1μM+10μM) - Example 1;

[0515] In addition, DMSO of equal proportion was used as a negative control.

[0516] In exploring the anti-aging mechanisms of urolithin, urolithin A, and ergothionein on skin fibroblasts, this invention focuses specifically on CDKN1A and CDKN2A, two genes closely related to cell cycle regulation and aging. The CDKN1A gene, by encoding the p21 protein, inhibits cell cycle progression, thereby promoting cell senescence and preventing the proliferation of damaged cells. Meanwhile, the p16^INK4a protein encoded by the CDKN2A gene accumulates during cell senescence, inhibiting the cell cycle and serving as a marker of cell senescence.

[0517] Please refer to Figures 3c and 3d. The experimental results show that UVB irradiation significantly induced the expression of CDKN1A and CDKN2A genes, increasing them by approximately 6-fold, reflecting the strong inducing effect of UVB on cellular senescence. In the individually treated experimental groups, ursodeoxylin, urolithin A, and ergothioneine all showed varying degrees of inhibitory effects on the expression of CDKN1A and CDKN2A. Ergothioneine alone significantly reduced the expression levels of these two genes. Urolithin A and ursodeoxylin also showed some inhibitory effects, but not as significantly as ergothioneine.

[0518] The combined effect of the three ingredients from Example 1 was observed. Under this combination, the expression levels of CDKN1A and CDKN2A almost returned to normal cellular levels, and the upregulation of gene expression was significantly suppressed compared to the UVB irradiation group. This finding suggests that uroxin, urolithin A, and ergothioneine may exert their anti-aging effects by regulating the expression of cell cycle inhibitory factors. The combined use of these three ingredients not only effectively combats UVB-induced cellular senescence but also exhibits a significant synergistic effect at the gene expression level, thereby effectively regulating the expression of senescence genes in cells, regulating the cell cycle, and combating and / or reducing signs of skin aging.

[0519] Furthermore, the inventors also observed a similar synergistic effect to that in Example 1 in Example 26 (combination of urolithin A and ergothioneine) (not shown in the figure).

[0520] 4. Synergistic effect in cellular anti-aging

[0521] The solutions include:

[0522] 1) Use alone rosin (Fis, 20μM), urolithin A (UA, 20μM) and ergothioneine (EGT, 1μM);

[0523] 2) Combined treatment of the three (UA+EGT+Fis, 10μM+1μM+10μM) - Example 1;

[0524] In addition, DMSO of equal proportion was used as a negative control.

[0525] In research on skin aging, ultraviolet B (UVB) radiation is one of the most common external factors inducing aging. UVB irradiation promotes the formation of senescent cells through mechanisms such as direct damage to skin cell DNA, 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 aging not only affects the appearance of the skin but may also lead to a weakening of the skin barrier function and pathological changes in the skin. In recent years, natural plant compounds have attracted attention due to their lower side effects and broad bioactivity.

[0526] This study focuses on three natural compounds—rutin, urolithin A, and ergothionein—to explore their intervention effects on UVB-induced senescence of skin fibroblasts. The core question of this study is whether the combined application of two or three of these compounds can exert a synergistic effect.

[0527] β-galactosidase staining is a classic method for detecting aging biomarkers, based on the significantly increased activity of β-galactosidase in senescent cells. Using X-Gal as a substrate, a deep blue product is generated under the catalysis of β-galactosidase, allowing for direct observation of senescent cells. To evaluate the intervention effects of different treatment groups on senescent cells, β-galactosidase staining (SA-β-Gal staining) was used to stain each treatment group, and the results are shown in Figure 1.

[0528] Please refer to Figures 3a and 3b. In cells treated with UVB irradiation alone, approximately 80% of the cells showed senescence-positive results, indicating that UVB can effectively induce fibroblast senescence. In the drug-only treatment group, only flavonoids showed a significant anti-aging effect, reducing the proportion of senescence-positive cells to 60%.

[0529] When the three components were used in combination (the composition of Example 1), the anti-aging effect was significantly enhanced, with the proportion of senescent positive cells decreasing to approximately 20%, indicating a strong synergistic effect of the combination in preventing photoaging and radiation-induced skin aging. Notably, in the positive control group (D+Q), the proportion of senescent cells was 50%, lower than the UVB treatment group but higher than the combination group. Furthermore, cells in all treatment groups did not show toxicity to normal cells, indicating that these natural compounds have good safety while effectively combating aging.

[0530] As the main stromal cells of the skin, dermal fibroblasts participate in the synthesis of collagen and elastin, maintaining the structure and function of the skin. Their aging not only affects the appearance of the skin, but may also lead to a weakening of the skin barrier function and pathological changes in the skin.

[0531] As can be seen from the above four aspects of the effects, the above-mentioned embodiments 1, 13 and 26 of the present invention have shown synergistic effects from different aspects such as fibroblast migration, anti-oxidation, cell cycle regulation and aging gene expression, and UV anti-aging effects. This shows that the combination of the present invention produces a variety of effects such as anti-aging, anti-skin aging, delaying cell aging, counteracting sunburn / aging caused by excessive ROS produced by skin cells due to UV irradiation, and combating and / or reducing skin aging through multiple mechanisms.

[0532] 5. Melanocyte experiment (improves pigmentation and skin color)

[0533] Mouse melanoma cells B16 are a commonly used model for assessing the regulation of melanin synthesis. Excessive melanin synthesis can lead to problems such as uneven skin color and pigmentation. Melanin content and tyrosinase activity are the core indicators reflecting the ability of melanin synthesis. As the key rate-limiting enzyme in melanin synthesis, the activity of tyrosinase directly determines the efficiency of melanin production.

[0534] Using B16 melanocytes as a model, the study verified the effect of reducing melanin production and improving melanin deposition by detecting melanin content and tyrosinase activity.

[0535] B16 cells were cultured in DMEM high glucose medium (containing 10% Fetal bovine serum, 0.2% Plasmocin prophylactic, and 1% Penicillin / Streptomycin) at 37°C (5% CO2).

[0536] Fesedon (purity 98.21%) and urolithin A (purity 99.26%) were both dissolved in anhydrous DMSO and diluted with DMEM medium for cell experiments (DMSO ≤ 0.1%); ergothionein was dissolved in PBS.

[0537] D-galactose (Dgal) was dissolved in DMEM medium; 4-butylresorcinol was dissolved in anhydrous DMSO.

[0538] (1) Establishment and preprocessing of aging model

[0539] Cells were seeded into 96-well plates with Dgal concentrations of 0, 50, 100, 150, 200, 250, 300, 350, and 400 mM, respectively. After 48 h of treatment, the medium was changed and 10% CCK-8 reagent was added. OD450 was measured 2 h later, cell viability was calculated, and a toxicity curve was fitted. The experiment was set up with ≥3 replicates, and the IC20-30 was recorded as the induction concentration.

[0540] (2) Drug treatment

[0541] Take B16 in the logarithmic growth phase, and after reaching 50% confluence, change the solution and perform the following treatment:

[0542] NC group: No special handling;

[0543] Dgal group: Add 250mM Dgal;

[0544] Fis group: 250mM Dgal and 20μM fisetone were added;

[0545] UA group: Added 250mM Dgal and 20μM urolithiasis A;

[0546] EGT group: Added 250mM Dgal and 1μM ergothioneine;

[0547] UA+Fis group: 250mM Dgal, 10μM fisetin, 10μM urolithiasis A added;

[0548] EGT+Fis group: 250mM Dgal, 1μM ergothione, 20μM fisetone added;

[0549] EGT+UA group: Added 250mM Dgal, 1μM ergothioneine, and 20μM urolithiasis A;

[0550] UA+EGT+Fis group: Added 250mM Dgal, 10μM fisetin, 1μM ergothionein, and 10μM urolithiasis A;

[0551] Positive control group: 250 mM Dgal and 10 μM 4-butylresorcinol were added;

[0552] Cells were collected 24 hours after treatment for subsequent experiments.

[0553] (3) Detection

[0554] Tyrosinase activity assay: Tyrosinase activity was detected using a kit (Solepro), and cellular protein content was calibrated using a BCA kit (Solepro).

[0555] Melanin content detection: Add 300 μL melanin lysis buffer (1 mol / L NaOH containing 10% DMSO), incubate at 80°C for 60 min, centrifuge at 4000×g for 10 min, take the supernatant and detect the absorbance at 475 nm; determine the cell protein content for calibration, and calculate the relative melanin content.

[0556] (4) Results

[0557] Core assumptions: Within the 10-20 μM range, the drug regulation rate is linearly positively correlated with concentration (a standard simplified assumption when no concentration gradient data is available); EA: a quantitative measure of enzyme activity (U / mg protein). The inhibitory efficiency of the drug on enzyme activity is calculated, reflecting its ability to inhibit melanin production in cells.

[0558] The obtained protein standard curve is shown in Figure 5A, and the tyrosinase activity results are shown in Figure 5B.

[0559] As shown in Figure 5, both urolithin A and fenestrone treatments significantly inhibited tyrosinase activity, while the inhibitory effect of the combined drugs was better than that of the single drug group (B in Figure 5).

[0560] Further Bliss independence analysis revealed that all these combinations exhibited synergistic effects, as shown in Table 1 below. In Table 1, EA represents the inhibition rate of Fis alone, EB represents the inhibition rate of UA alone, and EC represents the inhibition rate of EGT alone.

[0561] Table 1. Bliss Independence Analysis of Tyrosinase Activity

[0562] The results above show that urolithin A alone has a strong inhibitory effect on tyrosinase and melanin production, while the individual effects of urolithin and ergothioneine are relatively weak. However, when combined in pairs, or in combination of all three, they show synergistic effects, with the highest effect reaching 68.14%.

[0563] The above results indicate that the combination of Fis, UA, and EGT can synergistically inhibit tyrosinase activity, thereby blocking the melanin synthesis pathway at its source, and has the application value of effectively inhibiting melanin production and whitening and fading spots.

[0564] 6. Keratinocyte assay (skin repair and / or regeneration, stabilizing the skin barrier, preventing stratum corneum thickening, and improving rough skin)

[0565] The human immortalized keratinocyte line HaCaT is a classic model for studying the function of skin keratinocytes. As a core component of the skin barrier, abnormal function of keratinocytes can directly lead to skin barrier instability, abnormal stratum corneum metabolism, and exacerbate skin aging and roughness.

[0566] Simulating skin aging and abnormal keratinization, the expression levels of genes related to keratin synthesis were detected by quantitative real-time PCR to verify the efficacy of the combination in skin barrier, keratin metabolism, and other aspects.

[0567] HaCaT cells were cultured in DMEM high glucose medium (containing 10% Fetal bovine serum, 0.2% Plasmocin prophylactic, and 1% Penicillin / Streptomycin) at 37°C and 5% CO2.

[0568] Fesedon (purity 98.21%) and urolithin A (purity 99.26%) were both dissolved in anhydrous DMSO and diluted with DMEM medium for cell experiments (DMSO ≤ 0.1%); ergothionein was dissolved in PBS.

[0569] D-galactose (Dgal) was dissolved in DMEM medium; dasatinib and quercetin were dissolved in anhydrous DMSO.

[0570] (1) Establishment and preprocessing of aging model

[0571] Cells were seeded into 96-well plates with Dgal concentrations of 0, 50, 100, 150, 200, 250, 300, 350, and 400 mM, respectively. After 48 h of treatment, the medium was changed and 10% CCK-8 reagent was added. OD450 was measured 2 h later, cell viability was calculated, and a toxicity curve was fitted. The experiment was set up with ≥3 replicates, and the IC20-30 was recorded as the induction concentration.

[0572] According to the toxicity curve in Figure 6, the concentration of Dgal that induces HaCaT cell senescence is 250 mM.

[0573] (2) Combined drug treatment

[0574] Take HaCaT in the logarithmic growth phase, and after reaching 50% confluence, change the medium and perform the following treatment:

[0575] NC group: No special handling;

[0576] Dgal group: Add 250mM Dgal;

[0577] Fis group: 250mM Dgal and 20μM fisetone were added;

[0578] UA group: Added 250mM Dgal and 20μM urolithiasis A;

[0579] EGT group: Added 250mM Dgal and 1μM ergothioneine;

[0580] UA+Fis group: 250mM Dgal, 10μM fisetin, 10μM urolithiasis A added;

[0581] EGT+Fis group: 250mM Dgal, 1μM ergothione, 20μM fisetone added;

[0582] EGT+UA group: Added 250mM Dgal, 1μM ergothioneine, and 20μM urolithiasis A;

[0583] UA+EGT+Fis group: Added 250mM Dgal, 10μM fisetin, 10μM urolithiasis A, and 1μM ergothioneine;

[0584] Control group: supplemented with 250mM Dgal, 0.1μM dasatinib, and 5μM quercetin;

[0585] After 48 hours of treatment, cells from each group were collected and total RNA was extracted. The expression level of KRT16 in each group was detected by qPCR (β-actin was used as the internal reference). The experiment was set up with ≥3 replicates to evaluate the synergistic effect of the combined drug treatment. Based on this, the expression levels of KRT6 and MMP1 in some combinations were randomly selected for further detection. The results are shown in Figure 7.

[0586] (3) Results:

[0587] Core assumption: Within the 10-20 μM range, the drug regulation rate is linearly positively correlated with concentration (the standard simplified assumption when no concentration gradient data is available); RE: Represents Relative Expression, which is the expression level of the target gene (such as KRT6, KRT16, MMP1) relative to the internal reference gene (β-actin) calculated by qPCR (2^-ΔΔCt method).

[0588] Quantitative analysis of the damage repair efficiency of the experimental group:

[0589] As shown in Figure 7, Dgal treatment significantly upregulated KRT6, KRT16, and MMP1, indicating abnormal keratinocyte function and impaired skin barrier. Fesedon, urolithin A, and ergothione treatment alone all inhibited the overexpression of these genes, and the combined inhibitory effect was superior to that of the single-drug groups.

[0590] Further Bliss independence analysis was used to obtain the inhibition rate and synergistic effect of KRT 16 expression level of these combinations, as shown in Table 2 below. It can be seen that all combinations have a synergistic effect on KRT 16 expression level. In Tables 2 to 4, EA represents the protection rate of Fis alone, EB represents the protection rate of UA alone, and EC represents the protection rate of EGT alone.

[0591] Table 2. Independence Analysis of KRT16 Bliss

[0592] Based on this, the inhibition rates of the combination of fisetin and urolithin A, and the combination of fisetin and ergothionein at the KRT6 expression level were calculated, and the results of the effects were obtained by Bliss independence analysis, as shown in Table 3 below. It can be seen that these combinations have a synergistic effect on the inhibition rate of KRT6 expression level.

[0593] Table 3. KRT6 Bliss Independence Analysis

[0594] Based on this, the inhibition rate of the combination of fisetin and urolithin A on the expression level of MMP1 was calculated and the effect was obtained by Bliss independence analysis, as shown in Table 4 below. It can be seen that the combination has a synergistic effect on the inhibition rate of MMP1 expression level.

[0595] Table 4. Independence Analysis of MMP1 Bliss

[0596] The results above show that the combination of the present invention can synergistically and significantly inhibit the expression of KRT6, KRT16 and MMP1 in keratinocytes, indicating that it has the functions of improving skin barrier function, improving skin roughness, improving barrier damage, preventing stratum corneum thickening, and helping skin repair and / or regeneration.

[0597] 7. Synergistic role in the regulation of inflammatory factor / related gene expression (anti-skin inflammation, anti-inflammatory, chronic inflammation)

[0598] Inflammation is a significant contributing factor to skin aging. Ultraviolet B (UVB) radiation not only directly damages skin cells but also accelerates cellular aging by inducing the overexpression of inflammatory factors. Inflammatory factors such as IL-6, IL-8, and IL-11 play crucial roles in skin inflammation, 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 importance in delaying skin aging.

[0599] In this invention, we investigated the regulatory effects of urolithin, urolithin A, and ergothioneine on the expression of UVB-induced inflammatory cytokine genes. Referring to Figures 4a, 4b, and 4c, the experimental results showed that UVB irradiation significantly increased the expression levels of IL-6, IL-8, and IL-11 genes. Specifically, the expression of IL-6 and IL-8 increased approximately 6-fold, while the expression of IL-11 increased approximately 12-fold. These results indicate that UVB irradiation triggers a strong inflammatory response in skin fibroblasts.

[0600] In treatment groups using ursolic acid, urolithin A, or ergothioneine alone, these compounds all inhibited UVB-induced inflammatory cytokine gene expression to varying degrees. Urolithin showed a more significant effect in inhibiting IL-6, ergothioneine showed a more significant effect in inhibiting IL-8, while urolithin A showed some advantage in inhibiting IL-11 expression.

[0601] When treated with the composition of Example 1, the gene expression levels of IL-6, IL-8, and IL-11 almost returned to the normal state of cells not exposed to UVB irradiation. The combined use of these three components not only effectively counteracted the overexpression of inflammatory factors induced by UVB irradiation but also exhibited a strong synergistic effect.

[0602] This indicates that through synergistic regulation via multiple pathways and targets, urolithin, ursoxin A, and ergothionein can significantly reduce the expression of inflammatory factors, alleviate inflammatory responses, treat or combat chronic inflammation, and fight skin inflammation, thereby delaying cell aging and chronic inflammation.

[0603] 8. Respiratory tract inflammation / chronic inflammation

[0604] Alveolar epithelial cells are an important component of the respiratory mucosal barrier and key effector cells for the occurrence and amplification of inflammatory responses. Under inflammatory stimulation, they can secrete large amounts of pro-inflammatory factors such as IL-1β and TNF-α, mediating inflammatory cascade reactions and aggravating lung tissue damage.

[0605] Human lung adenocarcinoma A549 cells possess the typical biological characteristics of alveolar type II epithelial cells. They are stable in cell traits, easy to culture in vitro, and can accurately simulate the inflammatory response process of respiratory epithelial cells. They are a classic cell model for screening anti-inflammatory drugs in vitro, verifying the efficacy of inflammation regulation, and elucidating molecular mechanisms, providing a reliable experimental vehicle for respiratory inflammation intervention research.

[0606] This experiment used lipopolysaccharide (LPS) to induce A549 cells to establish an inflammation model, simulating the inflammatory response process of respiratory epithelial cells. The expression levels of keratin synthesis-related genes were detected by quantitative real-time PCR to verify the efficacy of the combination in respiratory / chronic inflammation.

[0607] Based on human lung adenocarcinoma (non-small cell lung cancer) A549, this study used quantitative real-time PCR to investigate the regulatory role of the combination of inflammatory genes IL-1β and tumor necrosis factor TNF-α in respiratory tract / chronic inflammation.

[0608] A549 cells were cultured in DMEM high glucose medium (containing 10% Fetal bovine serum, 0.2% Plasmocin prophylactic, and 1% Penicillin / Streptomycin) at 37°C and 5% CO2.

[0609] Fesedon (purity 98.21%) and urolithin A (purity 99.26%) were both dissolved in anhydrous DMSO and diluted with DMEM medium for cell experiments (DMSO ≤ 0.1%); ergothionein was dissolved in PBS.

[0610] Lipopolysaccharide (LPS) is soluble in sterile water.

[0611] (1) Inflammation model establishment and pretreatment

[0612] Cells were seeded into 96-well plates with LPS concentrations of 0, 0.3125, 0.625, 1.25, 2.5, 5, 10, 20, and 40 mg / mL, respectively. After 24 h of treatment, the medium was changed and 10% CCK-8 reagent was added. OD450 was measured after 1 h, cell viability was calculated, and a toxicity curve was fitted. The experiment was set up with ≥3 replicates, and the IC20-30 was recorded as the induction concentration.

[0613] Based on the toxicity curve and relevant induction concentration data, the concentration of LPS that induces inflammation in A549 cells is 10 mg / mL.

[0614] (2) Joint processing

[0615] Take A549 in the logarithmic growth phase, and after reaching 50% confluence, change the solution and perform the following treatment:

[0616] NC group: No special handling;

[0617] LPS group: 10 mg / mL lipopolysaccharide was added;

[0618] Fis group: 10 mg / mL lipopolysaccharide and 20 μM fisetone were added;

[0619] UA group: supplemented with 10 mg / mL lipopolysaccharide and 20 μM urolithiasis A;

[0620] Fis+UA group: 10 mg / mL lipopolysaccharide, 10 μM fisetone, and 10 μM urolithiasis A were added;

[0621] After 24 hours of treatment, cells from each group were collected and total RNA was extracted. The expression levels of IL-1β and TNF-α were detected by qPCR (β-actin was used as the internal control). The experiment was set up with ≥3 replicates to evaluate the synergistic effect of the combined drug treatment. The results are shown in Figure 8.

[0622] (3) Results:

[0623] As shown in Figure 8, LPS treatment significantly upregulated IL-1β and TNF-α, indicating abnormal cell function and successful induction of an inflammatory response. Urolithin A and fisetin had a certain inhibitory effect on the LPS-induced inflammatory response in A549 cells, and the inhibitory effect was significantly enhanced when urolithin A and fisetin A were combined.

[0624] Core assumption: Within the 10-20 μM range, the drug regulation rate is linearly positively correlated with concentration (the standard simplified assumption when no concentration gradient data is available); RE: Represents Relative Expression, which is the expression level of the target gene (such as IL-1β, ITNF-α) relative to the internal reference gene (β-actin) calculated by qPCR (2^-ΔΔCt method).

[0625] Quantitative analysis of the damage repair efficiency of the experimental group:

[0626] Further analysis of the synergistic effect of the combination of IL-1β and TNF-α using Bliss independence analysis is shown in Tables 5 and 6 below. It can be seen that the combination has a synergistic effect in terms of the expression levels of IL-1β and TNF-α.

[0627] Table 5. IL-1β Bliss Independence Analysis

[0628] Table 6. TNF-αBliss Independence Analysis

[0629] The results above show that the inflammatory model of A549 cells induced by lipopolysaccharide (LPS) was successfully established in this experiment, simulating the inflammatory response process of respiratory epithelial cells. By verifying the synergistic inhibitory effect of the combination of fisetin and urolithin A on IL-1β and TNF-α in this model, the synergistic efficacy of this combination in respiratory / chronic inflammation was demonstrated.

[0630] 9. Stretch marks

[0631] Wrinkles are the raised lines that form on the skin's surface, resulting from a decrease in elastin and collagen, leading to rough, loose, and inelastic skin. While aging is a major cause of wrinkles, not all wrinkles are caused by aging; for example, stretch marks from pregnancy can also appear.

[0632] Stretch marks are a special type of stretch mark, appearing as atrophic linear patches. They are a common skin problem after pregnancy. During pregnancy, the expansion of the abdomen causes red, wavy patterns to appear on the skin of the abdomen, which turn into white scar lines after childbirth.

[0633] This invention compares the effects of using Examples 1, 13, 25, and 36 of a commercially available stretch mark cream (composed of pure cocoa butter, vitamin E, elastin, collagen, and shea butter) on stretch mark removal (length, width, and color).

[0634] Target audience: Mothers who have given birth and have new stretch marks, aged 22-45.

[0635] Usage period: 3 months

[0636] Instructions for use: The abdomen was divided into two regions along the midline. One side was randomly selected as the application site for the product, and the other side as the control site. A fresh stretch mark of similar severity was marked on each side for clinical evaluation of the target lesion. The above-described embodiment and commercially available stretch mark cream were distributed to subjects for abdominal massage (10 subjects per product), once a day, at a dosage of 5-10g per application.

[0637] Clinical evaluation criteria: The assessment includes four aspects: overall repair of stretch marks, area of ​​stretch marks, color of stretch marks, and degree of laxity of stretch marks. A 6-point scoring system (0-5 points) is used: 5 points represents a perfect condition and 0 points represents a severe condition.

[0638] Statistical analysis of the evaluation results revealed that the embodiments of the present invention can effectively improve the overall repair of stretch marks, the area of ​​stretch marks, the color of stretch marks, and the laxity of stretch marks. In particular, the effects of Embodiments 1 and 13 are significantly better than those of the control group.

[0639] This demonstrates that the above-mentioned combined application of the present invention can prevent and remove stretch marks, maintain skin elasticity, repair collagen damage, maintain collagen structure stability, alleviate skin aging, and stabilize the skin barrier.

[0640] The above-described embodiments are merely preferred embodiments provided to fully illustrate the present invention, and the scope of protection of the present invention is not limited thereto. Equivalent substitutions or modifications made by those skilled in the art based on the present invention are all within the scope of protection of the present invention. The scope of protection of the present invention is defined by the claims.

Claims

1. A composition, characterized in that, The composition comprises or consists of two or more of the following components: (i) ursoxin; (ii) ergothionein, its salt or ester; and (iii) urolithin A, its precursor or salt.

2. The composition according to claim 1, characterized in that, The composition comprises or consists of the following components: (i) ursanthin; and (iii) urolithin A, its precursor or salt thereof.

3. The composition according to claim 2, characterized in that, In the composition, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof is (5-20):(5-20).

4. The composition according to claim 2, characterized in that, In the composition, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof is (8-18):(8-18).

5. The composition according to claim 2, characterized in that, In the composition, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof is (10-15):(10-15).

6. The composition according to claim 2, characterized in that, In the composition, the molar ratio of (i) rutin and (iii) urolithin A, its precursor or salt thereof is 5:5, 10:5, 20:5, 5:10, 5:20 or 10:

20.

7. The composition according to claim 2, characterized in that, In the composition, the molar ratio of (i) laccasein and (iii) urolithin A, its precursor or salt thereof is 10:

10.

8. The composition according to claim 1, characterized in that, The composition comprises or consists of the following components: (ii) ergothioneine, its salt or its ester; and (iii) urolithin A, its precursor or its salt.

9. The composition according to claim 8, characterized in that, In the composition, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is (0.5-3):(5-20).

10. The composition according to claim 8, characterized in that, In the composition, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is (0.8-2):(8-18).

11. The composition according to claim 8, characterized in that, In the composition, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is (1-2):(10-15).

12. The composition according to claim 8, characterized in that, In the composition, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is 1:5, 2:5, 3:5, 1:10 or 1:

20.

13. The composition according to claim 8, characterized in that, In the composition, the molar ratio of (ii) ergothioneine, its salt or its ester and (iii) urolithin A, its precursor or its salt is 1:

10.

14. The composition according to claim 1, characterized in that, The composition comprises or consists of the following components: (i) rutin; and (ii) ergothioneine, its salt or ester.

15. The composition according to claim 14, characterized in that, In the composition, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester is (5-20):(0.5-3).

16. The composition according to claim 14, characterized in that, In the composition, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester is (8-18):(0.8-2).

17. The composition according to claim 14, characterized in that, In the composition, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester is (10-15):(1-2).

18. The composition according to claim 14, characterized in that, In the composition, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester is 5:1, 5:2, 5:3, 10:1 or 20:

1.

19. The composition according to claim 14, characterized in that, In the composition, the molar ratio of (i) rutin and (ii) ergothioneine, its salt or its ester is 10:

1.

20. The composition according to claim 1, characterized in that, The composition comprises or consists of the following components: (i) ursanthin; (ii) ergothioneine, its salt or ester thereof; and (iii) urolithin A, its precursor or salt thereof.

21. The composition according to claim 20, characterized in that, In the composition, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof, and (ii) ergothioneine, its salt or ester thereof is (5-20):(5-20):(0.5-3).

22. The composition according to claim 20, characterized in that, In the composition, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof, and (ii) ergothioneine, its salt or ester thereof is (8-18):(8-18):(0.8-2).

23. The composition according to claim 20, characterized in that, In the composition, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof, and (ii) ergothioneine, its salt or ester thereof is (10-15):(10-15):(1-2).

24. The composition according to claim 20, characterized in that, In the composition, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof, and (ii) ergothioneine, its salt or ester thereof is 5:5:1, 5:5:2, 5:5:3, 10:5:1, 20:5:1, 5:10:1, 5:20:1, or 10:20:

1.

25. The composition according to claim 20, characterized in that, In the composition, the molar ratio of (i) rutin, (iii) urolithin A, its precursor or salt thereof, and (ii) ergothioneine, its salt or ester thereof is 10:10:

1.

26. The composition according to claim 20, characterized in that, The composition comprises or consists of the following components: (i) rutin; (ii) ergothioneine; and (iii) urolithin A.

27. The composition according to claim 26, wherein the molar ratio of (i) rutin, (iii) urolithin A and (ii) ergothioneine is (5-20):(5-20):(0.5-3).

28. The composition according to claim 26, characterized in that, In the composition, the molar ratio of (i) rutin, (iii) urolithin A and (ii) ergothionein is 5:5:1, 5:5:2, 5:5:3, 10:5:1, 20:5:1, 5:10:1, 5:20:1 or 10:20:

1.

29. The composition according to claim 26, characterized in that, In the composition, the molar ratio of (i) rutin, (iii) urolithin A and (ii) ergothioneine is 10:10:

1.

30. The composition according to any one of claims 1 to 29, characterized in that, The composition is a composition that delays cell aging.

31. A formulation, characterized in that, The formulation comprises the composition according to any one of claims 1-30.

32. The formulation according to claim 31, characterized in that, The preparations include oral preparations or topical preparations.

33. The formulation according to claim 31, characterized in that, The preparations include cosmetics, pharmaceuticals, and health products.

34. The formulation according to claim 33, characterized in that, The preparations are pharmaceuticals and health products.

35. The formulation according to claim 34, characterized in that, The dosage forms of the medicines and health products include oral dosage forms.

36. The formulation according to claim 33, characterized in that, The formulation is a cosmetic, and the dosage forms of the cosmetic include creams, lotions, gels, aqueous solutions, oils, powders, and solids; and / or, The composition is added to the cosmetic at an amount of 0.05–5 wt%.

37. The formulation according to any one of claims 31 to 36, characterized in that, The preparation is an anti-aging preparation.

38. The formulation according to claim 37, characterized in that, The anti-aging agent is an anti-skin aging agent.

39. A formulation combination, characterized in that, The formulation combination includes any two or more of the following formulations: (1) A first preparation containing component (i) rutin; (2) A second preparation containing component (ii) ergothioneine, its salt or its ester; (3) A third preparation containing component (iii) urolithin A, its precursor or salt thereof.

40. The formulation combination according to claim 39, characterized in that, The formulation combination also includes (4) instructions; the instructions instructing that any two or more of the first formulation, the second formulation or the third formulation be administered to the subject in combination.

41. A product for addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration, characterized in that, The product comprises the composition of any one of claims 1-30, the formulation of any one of claims 31-38, or the combination of formulations of claims 39 or 40.

42. The product according to claim 41, characterized in that, The solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin tone, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

43. The product according to claim 42, characterized in that, The solutions to skin problems are selected from those that promote skin healing and repair.

44. The product according to claim 43, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

45. The product according to claim 44, characterized in that, The promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

46. ​​The product according to claim 43, characterized in that, The solution to skin problems mentioned is selected from delaying skin aging.

47. The product according to claim 46, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

48. The product according to claim 41, characterized in that, The anti-aging measures include anti-cellular senescence and / or delaying cellular senescence.

49. The product according to claim 48, characterized in that, The delay in cell aging includes delaying the aging of skin fibroblasts.

50. The product according to claim 49, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

51. The product according to claim 50, characterized in that, The method of delaying skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

52. The product according to claim 41, characterized in that, The anti-inflammatory effect includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

53. The product according to claim 41, characterized in that, The antioxidants mentioned include cellular antioxidants.

54. Use of a composition of any one of claims 1-30, an formulation of any one of claims 31-38, a combination of formulations of claims 39 or 40, or a product of any one of claims 41-53 in addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration.

55. The use according to claim 54, characterized in that, The solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin tone, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

56. The use according to claim 55, characterized in that, The solutions to skin problems are selected from those that promote skin healing and repair.

57. The use according to claim 56, characterized in that, The promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

58. The use according to claim 55, characterized in that, The solution to skin problems mentioned is selected from delaying skin aging.

59. The use according to claim 58, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

60. The use according to claim 54, characterized in that, The anti-aging measures include anti-cellular senescence and / or delaying cellular senescence.

61. The use according to claim 60, characterized in that, The delay in cell aging includes delaying the aging of skin fibroblasts.

62. The use according to claim 61, characterized in that, The method of delaying skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

63. The use according to claim 54, characterized in that, The anti-inflammatory effect includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

64. The use according to claim 54, characterized in that, The antioxidants mentioned include cellular antioxidants.

65. Use of a composition of any one of claims 1-30, or an formulation of any one of claims 31-38, or a combination of formulations of claims 39 or 40, or a product of any one of claims 41-53, in the preparation of a composition for addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repair and regeneration.

66. The use according to claim 65, characterized in that, The solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin tone, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

67. The use according to claim 66, characterized in that, The solutions to skin problems are selected from those that promote skin healing and repair.

68. The use according to claim 67, characterized in that, The promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

69. The use according to claim 66, characterized in that, The solution to skin problems mentioned is selected from delaying skin aging.

70. The use according to claim 69, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

71. The use according to claim 65, characterized in that, The anti-aging measures include anti-cellular senescence and / or delaying cellular senescence.

72. The use according to claim 71, characterized in that, The delay in cell aging includes delaying the aging of skin fibroblasts.

73. The use according to claim 72, characterized in that, The method of delaying skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

74. The use according to claim 65, characterized in that, The anti-inflammatory effect includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

75. The use according to claim 65, characterized in that, The antioxidants mentioned include cellular antioxidants.

76. The use of a composition of any one of claims 1-30, or an formulation of any one of claims 31-38, or a combination of formulations of claims 39 or 40, in the preparation of a product for addressing skin problems, anti-aging, anti-inflammatory, antioxidant, and / or repairing and regenerating.

77. The application according to claim 76, characterized in that, The solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin tone, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

78. The application according to claim 77, characterized in that, The solutions to skin problems are selected from those that promote skin healing and repair.

79. The application according to claim 78, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

80. The application according to claim 79, characterized in that, The promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

81. The application according to claim 77, characterized in that, The solution to skin problems mentioned is selected from delaying skin aging.

82. The application according to claim 81, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

83. The application according to claim 76, characterized in that, The anti-aging measures include anti-cellular senescence and / or delaying cellular senescence.

84. The application according to claim 83, characterized in that, The delay in cell aging includes delaying the aging of skin fibroblasts.

85. The application according to claim 84, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

86. The application according to claim 85, characterized in that, The method of delaying skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

87. The application according to claim 76, characterized in that, The anti-inflammatory effect includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

88. The application according to claim 76, characterized in that, The antioxidants mentioned include cellular antioxidants.

89. The application according to any one of claims 76-88, characterized in that, The products include oral or topical products.

90. A method for solving skin problems, anti-aging, anti-inflammatory, antioxidant and / or repair and regeneration, characterized in that, The method comprises administering to a subject in need an effective amount of the composition of any one of claims 1-30, the formulation of any one of claims 31-38, or the product of any one of claims 41-53.

91. The method according to claim 90, characterized in that, The solutions to skin problems include any one or more of the following: anti-skin aging and / or delaying skin aging and / or reducing skin aging, anti-photoaging, anti-skin oxidation, stabilizing the skin barrier, improving pigmentation and skin tone, anti-skin inflammation, promoting skin healing, repairing and / or regenerating, maintaining skin elasticity, maintaining skin collagen, or preventing and / or repairing stretch marks.

92. The method according to claim 91, characterized in that, The solutions to skin problems are selected from those that promote skin healing and repair.

93. The method according to claim 92, characterized in that, The promotion of skin healing and repair includes promoting the migration of skin fibroblasts.

94. The method according to claim 91, characterized in that, The solution to skin problems mentioned is selected from delaying skin aging.

95. The method according to claim 94, characterized in that, The products include cosmetics, pharmaceuticals, and health supplements.

96. The method according to claim 90, characterized in that, The anti-aging measures include anti-cellular senescence and / or delaying cellular senescence.

97. The method according to claim 96, characterized in that, The delay in cell aging includes delaying the aging of skin fibroblasts.

98. The method according to claim 97, characterized in that, The method of delaying skin fibroblast aging includes regulating the expression of aging genes and / or inflammation-related genes in skin fibroblasts; and / or regulating the level of reactive oxygen species in skin fibroblasts.

99. The method according to claim 90, characterized in that, The anti-inflammatory effect includes any one or more of the following: improving respiratory inflammation or improving chronic inflammation.

100. The method according to claim 90, characterized in that, The antioxidants mentioned include cellular antioxidants.

101. The use of a composition of any one of claims 1-30, or an formulation of any one of claims 31-38, or a combination of formulations of claims 39 or 40, or a product of any one of claims 41-53, or a method of any one of claims 90-100, in any one or more of the following aspects: (1) Delaying cell aging; (2) Regulate the expression of aging genes in skin cells; (3) Combat and / or reduce signs of skin aging; (4) Prevent skin aging caused by radiation; (5) Prevent photoaging; (6) Regulates the skin cell cycle; (7) Regulates the level of reactive oxygen species in skin cells; (8) Skin and / or cellular antioxidant effects; (9) Regulate the expression of inflammation-related genes or factors; (10) Anti-skin inflammation; (11) Accelerates skin healing, repair and / or regeneration; (12) Accelerates cell repair and / or regeneration; (13) Improves skin tone / pigmentation; (14) Reduce cell damage; (15) Avoid thickening of the stratum corneum; (16) Improves rough skin; (17) Improves respiratory inflammation; (18) Improves chronic inflammation; (19) Maintain skin elasticity; (20) To prevent and / or alleviate stretch marks; (21) Repair collagen damage; (22) Maintaining the stability of collagen structure; (23) Stabilize the skin barrier.

102. The application according to claim 101, characterized in that, In the reduction of cell damage in (14), the cell damage is UV-induced cell damage.

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