Anti-aging composition capable of regulating and controlling signal channel and promoting generation of skin structure protein, application of anti-aging composition and cosmetic

Abstract

The invention discloses an anti-aging composition capable of regulating and controlling a signal channel to promote generation of skin structural protein, application of the anti-aging composition and cosmetics. The anti-aging composition comprises a first component and a second component, wherein the first component is used for enhancing the stability of collagen mRNA (messenger Ribonucleic Acid) by regulating and controlling HuR protein, and the second component is used for up-regulating collagen gene transcription through a TGF-beta / Smad signal channel. Through the synergistic effect of the two, the transcription of collagen genes and the stability of mRNA (messenger Ribonucleic Acid) are remarkably improved, the expression of I-type collagen, III-type collagen, IV-type collagen, VII-type collagen, XVII-type collagen and the like is remarkably increased, and meanwhile, the synthesis of elastin and fibronectin is also improved. In addition, the composition can also significantly inhibit the generation of inflammatory factors and reactive oxygen species (ROS). According to the anti-aging composition capable of regulating and controlling the signal channel and promoting the generation of the skin structural protein, the application of the anti-aging composition and the cosmetics, the problem of skin aging can be comprehensively improved, the elasticity and compactness of the skin are remarkably improved, and an excellent anti-aging effect is shown.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics, and relates to an anti-aging composition, and in particular to an anti-aging composition capable of regulating signal pathways to promote the production of skin structural proteins, and an application thereof, as well as cosmetics. Background Art

[0002] Skin aging is a complex biological process involving the dynamic changes and regulation of multiple key structural proteins in the extracellular matrix (ECM), which manifests as loss of elasticity, reduced collagen content, and impaired barrier function. It is also affected by a variety of internal and external factors, such as collagen degradation, oxidative stress, and inflammatory response. Collagen, elastin, and fibronectin are the main components of ECM and play an important role in maintaining skin elasticity and firmness. With age, the skin gradually enters a state of chronic low-grade inflammation, namely inflammatory aging, which accelerates skin aging. Proinflammatory factors (such as IL-6, IL-1β, TNF-α, etc.) secreted by senescent cells not only have a negative impact on skin cells, but also stimulate the overexpression of matrix metalloproteinases (MMPs), thereby accelerating the degradation of collagen and elastin, resulting in loss of skin elasticity and firmness. Inflammatory aging is closely related to oxidative stress, and oxidative damage further exacerbates the inflammatory response, forming a vicious cycle.

[0003] In anti-aging research, the TGF-β / Smad signaling pathway has attracted widespread attention as a key pathway for collagen synthesis. This pathway promotes the transcription of collagen genes by activating Smad proteins, thereby increasing collagen synthesis. It is worth noting that the production of collagen is not only regulated at the transcriptional level, but also affected by the complex post-transcriptional regulatory mechanisms.

[0004] The IL-17 signaling pathway plays a key role in the skin aging process. Its activation can induce the overexpression of MMPs and chemokines (CXCL), which destroy skin structural proteins and accelerate the aging process. Therefore, inhibiting the IL-17 signaling pathway has become an important target for anti-aging research. In addition, HuR protein, as an RNA-binding protein, increases the stability of mRNA by binding to the 3'UTR of mRNA, prolongs its half-life, and thus promotes the efficient synthesis of skin structural proteins. HuR protein plays an important role in regulating ECM gene expression, maintaining skin structural homeostasis, promoting repair and anti-aging.

[0005] Most anti-aging ingredients and cosmetics on the market currently focus on improving a specific aspect of skin aging, such as simply increasing a certain type of collagen or improving antioxidant capacity. However, such products usually lack a comprehensive and in-depth molecular regulation strategy, making it difficult to cope with the multiple biological pathways and complex mechanisms involved in the skin aging process. Therefore, a single-dimensional improvement strategy cannot fully cover all aspects of aging, resulting in limited anti-aging effects. Summary of the invention

[0006] In view of the deficiencies in the prior art, the present invention provides an anti-aging composition and its application as well as cosmetics that can regulate signal pathways to promote the production of skin structural proteins, which can comprehensively improve skin aging problems, significantly enhance the elasticity and firmness of the skin, and exhibit excellent anti-aging effects.

[0007] To solve the above technical problem, according to one aspect of the present invention, the following technical solution is adopted:

[0008] An anti-aging composition capable of regulating signal pathways to promote the production of skin structural proteins, the anti-aging composition comprises a first component for enhancing the stability of collagen mRNA by regulating HuR protein and a second component for upregulating collagen gene transcription via TGF-β / Smad signal pathway.

[0009] As an embodiment of the present invention, the first component includes at least one of rice fermentation broth, bifid yeast fermentation product filtrate, resveratrol, vitamin C and / or its derivatives; the second component includes at least one of sialic acid, asiatica glycoside, hydrolyzed proanthocyanidins, and tripeptide-29.

[0010] As an embodiment of the present invention, the method for preparing rice fermentation liquid comprises:

[0011] Put rice into a container, add water into the container, and alpha-ize the rice at 90-110° C.; add amylolytic enzyme after cooling to 45-65° C., and perform enzymolysis for 36-50 hours, wherein the amount of enzyme added is 0.002%-1% of the mass of rice slurry, to obtain rice slurry enzymolysis liquid;

[0012] Inoculating yeast saccharomyces veronae into rice milk enzymatic hydrolysate, the fermentation conditions are: fermentation temperature 30-38°C, fermentation time 20-40 hours, pH value of the fermentation process is between 4.5 and 6.0; after the fermentation is completed, a crude rice fermentation liquid is obtained;

[0013] The fermented rice fermentation liquid is concentrated by vacuum concentration technology and then heated for sterilization, finally obtaining rice fermentation liquid rich in active ingredients.

[0014] As an embodiment of the present invention, the vitamin C and / or its derivatives are used to up-regulate the expression of collagen-related genes and achieve the effect by stabilizing their mRNA;

[0015] As a potent antioxidant, resveratrol can indirectly regulate the stability of collagen-related genes by inhibiting oxidative stress, activating HuR or extending the half-life of mRNA;

[0016] The filtrate of the bifid yeast fermentation product can enhance the stability of collagen mRNA by regulating HuR protein;

[0017] The asiaticoside promotes collagen secretion by fibroblasts by activating TGF-β1 expression and Smad signaling pathway;

[0018] The hydrolyzed proanthocyanidins promote the synthesis of collagen in fibroblasts through the TGF-β1 / Smad signaling pathway and maintain the stability of the extracellular matrix structure;

[0019] The tripeptide-29 promotes the activity and proliferation of fibroblasts by activating the TGF-β pathway, thereby increasing the synthesis of collagen and other extracellular matrix components.

[0020] As an embodiment of the present invention, the mass fraction of the first component in the anti-aging composition is 0.05-8, and the mass fraction of the second component is 0.05-0.8.

[0021] As an embodiment of the present invention, the mass fraction of the first component in the anti-aging composition is 0.25-6, and the mass fraction of the second component is 0.2-0.5.

[0022] As an embodiment of the present invention, the skin structural protein includes at least one of type I, type III, type IV, type VII and type XVII collagen;

[0023] The downstream genes include at least one of chemokines CXCL1, CXCL5, CXCL7, CXCL8, CXCL17 and matrix metalloproteinases;

[0024] The anti-aging composition can regulate genes involved in the IL-17 signaling pathway, thereby increasing the transcription level of collagen genes and the stability of their mRNA;

[0025] The anti-aging composition can promote the production of elastin, fibronectin and other extracellular matrices; the anti-aging composition can inhibit the expression of downstream genes of the IL-17 signaling pathway;

[0026] The anti-aging composition can also significantly inhibit the generation of inflammatory factors and reactive oxygen species, wherein the inflammatory factors are one or more of IL-1β, IL-6, IL-8, PGE2 and NO.

[0027] According to another aspect of the present invention, the following technical solution is adopted: an application of the above anti-aging composition in the preparation of cosmetics.

[0028] As an embodiment of the present invention, the cosmetic is at least one of a facial cream, a lotion, a serum or a cream.

[0029] According to another aspect of the present invention, the following technical solution is adopted: a cosmetic comprising the above-mentioned anti-aging composition.

[0030] The beneficial effect of the present invention is that the composition of the present invention significantly promotes the synthesis of extracellular matrix components through the synergistic effect of multiple anti-aging mechanisms, thereby being able to effectively improve skin aging problems.

[0031] In one use scenario of the present invention, the first component and the second component in the composition of the present invention can synergistically regulate genes related to the IL-17 signaling pathway. Among them, the second component activates the transcription of collagen genes by enhancing the TGF-β / Smad signaling pathway; while the first component enhances the stability of mRNA by promoting the expression of RNA binding protein HuR, thereby significantly improving the transcription level of collagen genes and the stability of mRNA. Therefore, the combination of the two components can significantly increase the content of collagen types I, III, IV, VII and XVII, as well as elastin and fibronectin in the extracellular matrix.

[0032] The combination of the two components can inhibit the expression of downstream genes of the IL-17 signaling pathway, including chemokines CXCL1, CXCL5, CXCL7, CXCL8, CXCL17 and matrix metalloproteinase MMP1; at the same time, it can also significantly inhibit the expression of inflammatory factors IL-1β, IL-6, IL-8, PGE2 and NO, as well as the generation of reactive oxygen species (ROS), indicating that the combination has a significant effect in inhibiting inflammatory responses. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 This is the result diagram of RNA sequencing combined with KEGG pathway enrichment analysis.

[0034] Figure 2 This is a graph showing the results of Western Blot and RIP detection of the effect of the anti-aging composition on HuR protein.

[0035] Figure 3This is a graph showing the effect of the anti-aging composition on the expression of downstream genes and proteins in the IL-17 pathway detected by RT-qPCR and ELISA.

[0036] Figure 4 This is a graph showing the results of the inhibitory effect of the rice fermentation liquid / bird's nest acid composition on inflammatory factors.

[0037] Figure 5 This is a graph showing the results of the inhibitory effect of the rice fermentation broth / bird's nest acid composition on ROS. DETAILED DESCRIPTION

[0038] In order to further understand the present invention, preferred embodiments of the present invention are described below in conjunction with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, rather than limiting the claims of the present invention.

[0039] The description in this section is only for several typical embodiments, and the present invention is not limited to the scope of the embodiments. The same or similar prior art means and some technical features in the embodiments are mutually replaced within the scope of the present invention.

[0040] The present invention discloses an anti-aging composition capable of regulating signal pathways to promote the production of skin structural proteins. The anti-aging composition comprises a first component for enhancing the stability of collagen mRNA by regulating HuR protein and a second component for upregulating collagen gene transcription through TGF-β / Smad signal pathway.

[0041] The first component may include at least one of rice fermentation broth, bifid yeast fermentation product filtrate, resveratrol, vitamin C and / or its derivatives; the second component may include at least one of sialic acid, asiatica glycoside, hydrolyzed proanthocyanidins, and tripeptide-29.

[0042] The mass fraction of the first component in the anti-aging composition can be 0.05-8, and the mass fraction of the second component can be 0.05-0.8. In one embodiment of the present invention, the mass fraction of the first component in the anti-aging composition is 0.25-6, and the mass fraction of the second component is 0.2-0.5.

[0043] The vitamin C and / or its derivatives are used to up-regulate the expression of collagen-related genes and achieve the effect by stabilizing their mRNA;

[0044] As a potent antioxidant, resveratrol can indirectly regulate the stability of collagen-related genes by inhibiting oxidative stress, activating HuR or extending the half-life of mRNA;

[0045] The filtrate of the bifid yeast fermentation product can enhance the stability of collagen mRNA by regulating HuR protein;

[0046] The asiaticoside promotes collagen secretion by fibroblasts by activating TGF-β1 expression and Smad signaling pathway;

[0047] The hydrolyzed proanthocyanidins promote the synthesis of collagen in fibroblasts through the TGF-β1 / Smad signaling pathway and maintain the stability of the extracellular matrix structure;

[0048] The tripeptide-29 promotes the activity and proliferation of fibroblasts by activating the TGF-β pathway, thereby increasing the synthesis of collagen and other extracellular matrix components.

[0049] In one embodiment of the present invention, the method for preparing rice fermentation liquid comprises:

[0050] (1) putting rice into a container, adding water into the container, and alpha-izing the rice at 90-110° C.; after cooling to 45-65° C., adding amylolytic enzyme, and performing enzymolysis for 36-50 hours, wherein the amount of enzyme added is 0.002%-1% of the mass of rice milk, and obtaining rice milk enzymolysis solution;

[0051] (2) inoculating yeast saccharomyces veronae into rice milk enzymatic hydrolysate, and fermenting under the following conditions: fermentation temperature of 30 to 38° C., fermentation time of 20 to 40 hours, and pH of the fermentation process of 4.5 to 6.0; after the fermentation is completed, a crude rice fermentation liquid is obtained;

[0052] (3) The fermented rice broth is concentrated by vacuum concentration technology, and then heated for sterilization, thereby finally obtaining a rice broth rich in active ingredients.

[0053] The skin structural proteins include at least one of type I, type III, type IV, type VII and type XVII collagen; the downstream genes include at least one of chemokines CXCL1, CXCL5, CXCL7, CXCL8, CXCL17 and matrix metalloproteinases; the anti-aging composition can regulate genes involved in the IL-17 signaling pathway, thereby improving the transcription level of collagen genes and the stability of their mRNA.

[0054] The anti-aging composition can promote the production of elastin, fibronectin and other extracellular matrices; the anti-aging composition can inhibit the expression of downstream genes of the IL-17 signaling pathway; the anti-aging composition can also significantly inhibit the production of inflammatory factors and reactive oxygen species, wherein the inflammatory factors are one or more of IL-1β, IL-6, IL-8, PGE2 and NO.

[0055] The present invention also discloses an application of the anti-aging composition in preparing cosmetics. In one embodiment, the cosmetics are at least one of a facial cream, a lotion, a serum or a cream.

[0056] The present invention further discloses a cosmetic comprising the anti-aging composition.

[0057] Effect experiment of the composition of the present invention

[0058] (1) Experimental methods: This experiment used fibroblasts, which were cultured in high-glucose DMEM medium containing 10% fetal bovine serum. The cell growth conditions were 37°C and 5% CO2 environment. The cells were divided into a blank control group and groups with different concentrations of the composition (grouping is shown in Table 1). After 24 hours of treatment of each group of cells, the cells were collected and total RNA was extracted, followed by reverse transcription to synthesize cDNA. Real-time fluorescence quantitative PCR (qPCR) was used to detect the expression levels of genes related to the main extracellular matrix (ECM) components in the skin, and the internal reference gene GAPDH was used for standardization to calculate the relative expression of each gene. Finally, the gene expression data of each group were statistically analyzed to compare the differences between different treatment groups.

[0059] Table 1 Ratios of components in different groups and their effects on the expression levels of major ECM-related genes

[0060]

[0061]

[0062] (2) Experimental results: The experimental results are as described in Table 1. When the first component (i.e., rice fermentation broth, bifid yeast fermentation product filtrate, resveratrol, vitamin C) and the second component (i.e., hydrolyzed proanthocyanidins, sialic acid, asiaticoside, tripeptide-29) act alone, they can slightly increase the expression levels of ECM-related genes (COL1A1, COL3A1, COL4A1, COL7A1, COL17A1, COL24A1, as well as elastin and fibronectin) in fibroblasts. However, when the two are used in combination, this enhancement effect is significantly enhanced, showing a significant synergistic effect. This is because the first component can regulate HuR protein to enhance the stability of collagen mRNA, while the second component upregulates collagen gene transcription through the TGF-β / Smad signaling pathway, and the two components synergistically significantly increase the production of extracellular matrix components.

[0063] Effect experiment of the composition of the present invention

[0064] More specifically, in this embodiment, the combined effects of rice fermentation broth and sialic acid at different concentrations were tested.

[0065] (1) Experimental methods: This experiment used fibroblasts, which were cultured in high-glucose DMEM medium containing 10% fetal bovine serum. The cell growth conditions were 37°C and 5% CO2 environment. The cells were divided into a blank control group, groups with different concentrations of rice fermentation broth, a sialic acid group, and a sialic acid / rice fermentation broth combination group (grouping is shown in Table 2). After 24 hours of treatment of each group of cells, the cells were collected and total RNA was extracted, followed by reverse transcription to synthesize cDNA. Real-time fluorescence quantitative PCR (qPCR) was used to detect the expression levels of genes related to the main extracellular matrix (ECM) components in the skin, and the internal reference gene GAPDH was used for standardization to calculate the relative expression of each gene. Finally, the gene expression data of each group were statistically analyzed to compare the differences between different treatment groups.

[0066] Table 2 Ratios of components in different groups and their effects on the expression levels of major ECM-related genes

[0067]

[0068] (2) Experimental results: The experimental results are shown in Table 2. When sialic acid and rice fermentation broth act alone, they can slightly increase the expression levels of ECM-related genes (COL1A1, COL3A1, COL4A1, COL7A1, COL17A1, COL24A1, as well as elastin and fibronectin) in fibroblasts. However, when the two are used in combination, this enhancement effect is significantly enhanced, showing an obvious synergistic effect. In addition, when the synergistic concentrations of sialic acid and rice fermentation broth are 0.25% respectively, the best effect can be achieved, and further increasing the concentration of the active ingredient has limited effect on the promotion effect of the composition.

[0069] RNA sequencing and KEGG pathway analysis

[0070] In this example, rice fermentation broth and bird's nest acid were used as examples to study the action pathway of the combination of these two components.

[0071] (1) Experimental method: Fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum and maintained at 37°C and 5% CO2. The cells were divided into four groups: a) blank control group, b) 0.5% rice fermentation broth group, c) 0.5% sialic acid group, and d) 0.25% sialic acid and 0.25% rice fermentation broth combination group. After each group of cells was treated for 24 hours, high-throughput RNA sequencing technology and KEGG pathway enrichment analysis were used to identify differentially expressed genes and their related signal pathways.

[0072] (2) Experimental results: Figure 1As shown in the figure, compared with the rice fermentation broth or sialic acid treatment group alone, the rice fermentation broth and sialic acid treatment group significantly increased the RNA transcript expression of multiple collagen-related genes (fold change>1.5, baseMean>1000, q value<0.05). Further KEGG pathway analysis showed that after the combined treatment of rice fermentation broth and sialic acid, a total of 636 differentially expressed genes were significantly enriched in the IL-17 signaling pathway and the ECM receptor interaction pathway (log2FC>0.5, baseMean>1000, q value<0.05). Among them, rice fermentation broth mainly regulates genes related to the IL-17 signaling pathway, while sialic acid mainly regulates genes related to the TGF-β / Smad signaling pathway in the extracellular matrix (ECM) receptor interaction pathway.

[0073] Composition enhancing effect on collagen mRNA stability

[0074] HuR is a key RNA binding protein in the IL-17 signaling pathway, which can bind to the 3'UTR region of gene mRNA, thereby increasing its stability. Therefore, this example aims to explore the effect of sialic acid and rice fermentation broth on the binding of HuR to the 3'UTR region of collagen gene, and further evaluate whether it can enhance the stability of collagen mRNA.

[0075] (1) Experimental method: Fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum and maintained at 37°C and 5% CO2. The cells were divided into four groups: a) blank control group, b) 0.5% rice fermentation broth group, c) 0.5% sialic acid group, and d) 0.25% sialic acid and 0.25% rice fermentation broth combination group. After each group of cells was cultured for 24 hours under the corresponding concentration treatment, the nuclear cytoplasm separation technology and Western Blot analysis were used to detect the level of HuR protein in the cytoplasm and nucleus. The RNA immunoprecipitation (RIP) technology was used to further explore the binding of HuR protein to collagen gene mRNA such as COL1A1. Finally, the cells were treated with the global methylation inhibitor 3-deazaadenosine (3-DAA), and the stability of gene mRNA such as COL1A1 was evaluated in combination with the luciferase reporter gene experiment.

[0076] (2) Experimental results: Figure 2 As shown in A, compared with the control group, sialic acid group or rice fermentation broth group treated alone, the stability of luciferase mRNA in cells treated with sialic acid and rice fermentation broth composition was significantly improved. In addition, the stability of TGFB1, COL1A1 and CXCL8 gene mRNA in the rice fermentation broth group and the composition group was also significantly enhanced. Figure 2The RIP experiment in B further shows that the rice fermentation liquid and the composition can promote the binding of HuR protein to the 3'UTR region of the TGFB1 gene, thereby improving the stability of the TGFB1 gene mRNA and promoting the expression of TGFB1, thereby enhancing the synthesis of collagen; on the other hand, the composition can also directly promote the binding of HuR to the 3'UTR region of the COL1A1 gene, improve the stability of the COL1A1 gene mRNA, and thus promote the expression of COL1A1. The above results show that the composition of guanidine and rice fermentation liquid significantly promotes the binding of HuR to COL1A1-3'UTR, thereby effectively protecting mRNA from degradation, and the rice fermentation liquid plays a leading role in this process. In addition, the composition can significantly improve the stability of the mRNA of collagen genes such as COL1A1, further supporting the key role of HuR protein in the regulation of mRNA stability.

[0077] Therefore, the combined use of bird's nest acid and rice fermentation liquid can significantly increase the expression of collagen genes compared to a single ingredient. Bird's nest acid mainly promotes the expression of mRNA by enhancing the activity of the collagen gene promoter, while rice fermentation liquid inhibits the degradation of collagen mRNA by improving the stability of mRNA.

[0078] Effects of the combination on downstream genes of the IL-17 signaling pathway

[0079] (1) Experimental method: Fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum, maintained at 37°C and 5% CO2, and divided into: a) blank control group, b) 0.5% rice fermentation broth group, c) 0.5% sialic acid group, and d) 0.25% sialic acid and 0.25% rice fermentation broth combination group. After each group of cells was treated with the corresponding concentration for 24 hours, RT-PCR was used to detect the expression of IL-17 signaling pathway downstream genes (chemokines CXCL1, CXCL5, CXCL7, CXCL8, CXCL17 and matrix metalloproteinase MMP1), and ELISA was used to detect the changes in the proteins related to these genes.

[0080] (2) Experimental results: Figure 3 The results showed that the rice fermentation liquid group significantly inhibited the expression of CXCL1, CXCL5, CXCL7, CXCL8, CXCL17 and MMP1 genes and their corresponding proteins, while the inhibitory effect of sialic acid on these downstream genes was relatively mild. In addition, the combination of rice fermentation liquid and sialic acid did not show a stronger inhibitory effect than the rice fermentation liquid alone. This result shows that in the combination, it is mainly the rice fermentation liquid that regulates the expression of genes related to the IL-17 signaling pathway.

[0081] Inhibitory effect of the composition on inflammatory factors

[0082] (1) Experimental method: Fibroblasts were cultured in DMEM medium containing 10% fetal bovine serum, maintained at 37°C and 5% CO2, and irradiated with UVA for 20 min (10 J / cm 2 ). The groups were: a) blank control group, b) 0.5% rice fermentation broth group, c) 0.5% sialic acid group, and d) 0.25% sialic acid and 0.25% rice fermentation broth combination group. After 24 hours of treatment, the mRNA and protein expressions of several common inflammatory factors (IL-1β, IL-6, IL-8, PGE2 and NO) in the cells were detected by RT-PCR and ELISA; at the same time, the generation of intracellular reactive oxygen species (ROS) was detected by flow cytometry.

[0083] (2) Experimental results: Figure 4 The data in the study showed that the use of sialic acid or rice fermentation broth alone can effectively reduce the mRNA and protein expressions of inflammatory factors such as IL-1β, IL-6, IL-8, PGE2 and NO. However, the combined use of sialic acid and rice fermentation broth showed significantly better effects than the individual components. In addition, Figure 5 The results showed that the combination of sialic acid and rice fermentation broth not only effectively reduced the generation of intracellular ROS, but also the effect was significantly better than using sialic acid or rice fermentation broth alone.

[0084] Therefore, the combined use of bird's nest acid and rice fermented liquid exhibits synergistic effects in anti-inflammatory and antioxidant effects. Compared with the use of any one ingredient alone, it can more effectively reduce the expression of multiple inflammatory factors and reduce the generation of intracellular reactive oxygen species, thereby enhancing the overall anti-inflammatory and antioxidant effects.

[0085] Preparation of anti-aging cream

[0086] The composition of the anti-aging cream in this example is shown in Table 3.

[0087] The composition of the anti-aging cream of Example 2 is the same as that of Example 1, but the anti-aging composition is 0.25% of the filtrate of the fermentation product of bifida yeast and 0.25% of asiaticaside.

[0088] The composition of the anti-aging cream of Example 3 is the same as that of Example 1, but the anti-aging composition is 0.25% of Veratrum and 0.2% of hydrolyzed proanthocyanidins.

[0089] The composition of the anti-aging cream of Example 4 is the same as that of Example 1, but the anti-aging composition is 0.25% vitamin C and 0.25% bird's nest acid.

[0090] Table 3 Proportions of components in Examples 1-3 and Comparative Examples 1-3

[0091]

[0092]

[0093] The preparation method of the facial cream comprises the following steps:

[0094] a. Obtaining the aqueous phase: Place water in a container with a stirring device and stir, fully wet and mix the humectant and thickener, add them into the water, stir until completely dissolved, and heat to 75-80°C;

[0095] b. Obtain the oil phase; heat the softener, skin conditioner and emulsifier to 75-80°C and stir until completely dissolved;

[0096] c. Emulsification: Add the mixture of step b to the aqueous phase of step a, stir at 300 rpm for 5 minutes and homogenize at 3000 rpm for 5 minutes;

[0097] d. After cooling to 35-38°C, add the anti-aging composition and preservatives, stir at 300 rpm and homogenize at 3000 rpm for 5 minutes to obtain the desired cream.

[0098] Anti-aging cream efficacy verification

[0099] (1) Test samples: the facial creams of Examples 1 to 3 and Comparative Examples 1 to 3 described in Table 3.

[0100] (2) Subjects and research plan: 210 healthy women (age range 22-45 years, average age 37.1 years) were randomly divided into 7 groups, 30 in each group, regardless of gender, and each group used products with the same formula. All subjects signed a written informed consent. Before enrollment, according to the inclusion and exclusion criteria, the subjects were asked about their medical history, health status, etc., and the skin of the test site was evaluated for compliance and skin color test screening, and the relevant data were recorded.

[0101] (3) Test method: Use the sample once in the morning and once in the evening every day for a trial period of 8 weeks. Each subject applies an appropriate amount of the test sample to one side of the facial skin, and does not apply the test sample to the other side.

[0102] (4) Instrument testing: The test environment conditions (temperature 20-22°C, humidity 40-60%) were set according to the test requirements, and the subjects were required to adapt to the test environment for at least 20 minutes. Cutometer (CK, Germany) was used to evaluate skin elasticity (R2 value) and firmness (F4); ultrasonic equipment (Cortex Technology, Denmark) was used to obtain skin ultrasound images and evaluate changes in collagen.

[0103] Wherein, skin elasticity improvement rate (%) = (average skin elasticity of each group after using the example face cream - average skin elasticity of each group before use) / average skin elasticity of each group before use * 100%;

[0104] Skin firmness probability (%) = (average skin firmness of each group after using the example cream - average skin firmness of each group before use) / average skin firmness of each group before use | * 100%;

[0105] Collagen density change rate (%) = (average collagen density of each group of skin after using the example cream - average collagen density of each group of skin before use) / average collagen density of each group of skin before use * 100%

[0106] Table 4 Anti-wrinkle and anti-aging effects of facial creams of Example 1 and Comparative Examples 1 to 3

[0107] sample R2 improvement rate after 8 weeks (%) F4 improvement rate after 8 weeks (%) Collagen density increase rate after 8 weeks (%) Example 1 28.4 14.4 59.8 Example 2 23.2 12.5 50.8 Example 3 25.5 13.1 49.0 Example 4 27.6 13.7 54.1 Comparative Example 1 1.3 1.8 1.9 Comparative Example 2 9.3 5.4 10.3 Comparative Example 3 6.2 4.8 8.4

[0108] (5) Experimental results: From the results in Table 4, it can be seen that after using the cream, the cream with two components showed significant effects in improving skin elasticity, firmness and collagen levels. Among them, in Examples 2 to 4, the anti-aging creams respectively contained the bifid yeast fermentation product filtrate / asiaticoside anti-aging composition, the resveratrol / hydrolyzed proanthocyanidin anti-aging composition and the vitamin C / 0.25% bird's nest acid anti-aging composition, showing excellent anti-aging effects and significantly improving the elasticity, firmness and collagen density of the skin.

[0109] In addition, taking the combination of rice fermentation liquid and bird's nest acid as an example, it can be found that compared with the group without rice fermentation liquid and bird's nest acid (Comparative Example 1) or only containing bird's nest acid (Comparative Example 2) or rice fermentation liquid (Comparative Example 3), the combination of rice fermentation liquid and bird's nest acid (Example 1) showed a more significant effect in improving skin elasticity, firmness and collagen levels. Specifically, the Example 1 group is better than each control group in improving skin elasticity and firmness, and the content of collagen is also significantly increased. These results show that the rice fermentation liquid and bird's nest acid in the cream can more effectively improve the overall quality of the skin and slow down the skin aging process through synergistic action.

[0110] This is because rice fermentation broth and bird's nest acid can synergistically regulate genes involved in the IL-17 signaling pathway, in which rice fermentation broth enhances the stability of collagen mRNA by regulating HuR protein, while bird's nest acid upregulates the transcription of collagen genes through the TGF-β / Smad signaling pathway. The synergistic effect of the two significantly improved the transcription of collagen genes and the stability of mRNA, significantly increased the expression of collagen types I, III, IV, VII and XVII, and also increased the synthesis of elastin and fibronectin. In addition, the composition can also significantly inhibit the generation of inflammatory factors and reactive oxygen species (ROS). Therefore, the combination of rice fermentation broth and bird's nest acid can comprehensively improve skin aging problems through the synergistic effect of multiple anti-aging mechanisms.

[0111] In summary, the anti-aging composition and its application as well as the cosmetics proposed in the present invention that can regulate signal pathways to promote the production of skin structural proteins can comprehensively improve skin aging problems, significantly enhance the elasticity and firmness of the skin, and show excellent anti-aging effects.

[0112] It will be easily understood by those skilled in the art that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An anti-aging composition capable of regulating signal pathways to promote the production of skin structural proteins, characterized in that: The anti-aging composition comprises a first component for enhancing the stability of collagen mRNA by regulating HuR protein and a second component for upregulating the transcription of collagen gene by TGF-β / Smad signaling pathway.

2. The anti-aging composition according to claim 1, characterized in that: The first component includes at least one of rice fermentation broth, bifid yeast fermentation product filtrate, resveratrol, vitamin C and / or its derivatives; the second component includes at least one of sialic acid, asiatica glycoside, hydrolyzed proanthocyanidin and tripeptide-29.

3. The anti-aging composition according to claim 1, characterized in that: The rice fermentation liquid preparation method comprises: Put rice into a container, add water into the container, and alpha-ize the rice at 90-110° C.; add amylolytic enzyme after cooling to 45-65° C., and perform enzymolysis for 36-50 hours, wherein the amount of enzyme added is 0.002%-1% of the mass of rice slurry, to obtain rice slurry enzymolysis liquid; Inoculating yeast saccharomyces veronae into rice milk enzymatic hydrolysate, the fermentation conditions are: fermentation temperature 30-38°C, fermentation time 20-40 hours, pH value of the fermentation process is between 4.5 and 6.0; after the fermentation is completed, a crude rice fermentation liquid is obtained; The fermented rice broth is concentrated by vacuum concentration technology and then heated for sterilization to finally obtain rice broth rich in active ingredients.

4. The anti-aging composition according to claim 1, characterized in that: The mass fraction of the first component in the anti-aging composition is 0.05-8, and the mass fraction of the second component is 0.05-0.

8.

5. The anti-aging composition according to claim 1, characterized in that: The mass fraction of the first component in the anti-aging composition is 0.25-6, and the mass fraction of the second component is 0.2-0.

5.

6. The anti-aging composition according to claim 1, characterized in that: The skin structural protein includes at least one of type I, type III, type IV, type VII and type XVII collagen; The downstream genes include at least one of chemokines CXCL1, CXCL5, CXCL7, CXCL8, CXCL17 and matrix metalloproteinases; The anti-aging composition can regulate genes involved in the IL-17 signaling pathway, thereby increasing the transcription level of collagen genes and the stability of their mRNA; The anti-aging composition can promote the production of elastin, fibronectin and other extracellular matrices; the anti-aging composition can inhibit the expression of downstream genes of the IL-17 signaling pathway; The anti-aging composition can also significantly inhibit the generation of inflammatory factors and reactive oxygen species, wherein the inflammatory factors are one or more of IL-1β, IL-6, IL-8, PGE2 and NO.

7. Use of the anti-aging composition according to any one of claims 1 to 6 in the preparation of cosmetics.

8. The use according to claim 7, characterized in that: The cosmetic is at least one of a facial cream, a lotion, a serum or a cream.

9. A cosmetic, characterized in that: The cosmetic comprises the anti-aging composition according to any one of claims 1 to 6.

Images