Oligopeptides and their use in the preparation of anti-aging products

Abstract

This invention relates to the field of cosmetics, and more particularly to oligopeptides and their application in the preparation of anti-aging products. This invention provides an oligopeptide with anti-aging activity, the amino acid sequence of which is shown in any of SEQ ID NO:1 to SEQ ID NO:3. This invention rationally designs and optimizes three α-Klotho-derived oligopeptides (RBA-1, RBA-1d, and RBA-1e) with a clear structural basis and optimized physicochemical properties through high-resolution crystal structure information of the FGF23-FGFR1c-αKlotho ternary complex, systematic truncation screening of the receptor binding arm (RBA), and conformation prediction, for use in skin anti-aging.

Description

Technical Field

[0001] This invention relates to the field of cosmetics, and more particularly to oligopeptides and their application in the preparation of anti-aging products. Background Technology

[0002] There are no reports in the current technology of directly using α-Klotho protein or its active fragments to prepare topical anti-aging skin preparations or related products, nor are there any specific pathways and application methods for α-Klotho to achieve local anti-aging effects by regulating skin cell aging-related phenotypes (such as oxidative damage, cell cycle arrest, collagen degradation, matrix metalloproteinase activity, etc.).

[0003] Therefore, developing a novel application using α-Klotho or its derivatives as active ingredients for skin anti-aging, especially for the protection and repair of UV-induced and naturally aging skin, has significant scientific value and promising prospects for industrial transformation. Summary of the Invention

[0004] In view of this, the present invention provides oligopeptides and their application in the preparation of anti-aging products. The present invention rationally designs and selects three α-Klotho-derived oligopeptides (RBA-1, RBA-1d, and RBA-1e) with clear structural basis and optimized physicochemical properties by combining high-resolution crystal structure information of the FGF23-FGFR1c-αKlotho ternary complex, systematic truncation screening of the receptor binding arm (RBA), and conformation prediction, for use in skin anti-aging.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution: This invention provides an oligopeptide with anti-aging activity, the general formula of which is shown in Formula 1: YLWDVHHSK-X1-X2-X3-X4-X5 (Formula 1) where: X1 is selected from deletion or R; X2 is selected from deletion or L; X3 is selected from deletion or I; X4 is selected from deletion or K; X5 is selected from deletion or V.

[0006] This invention provides an oligopeptide with anti-aging activity, the amino acid sequence of which is any one of SEQ ID NO:1 to SEQ ID NO:3.

[0007] The present invention also provides a method for preparing the above-mentioned oligopeptide, comprising: preparing the oligopeptide by chemical synthesis or biosynthesis.

[0008] This invention also provides the application of the above-described oligopeptides and / or oligopeptides obtained by the above preparation methods in the preparation of anti-aging products.

[0009] In some embodiments of the present invention, the products described in the above applications include: personal care products.

[0010] In some embodiments of the present invention, the oligopeptides described above enhance the expression of type I procollagen C-terminal peptide.

[0011] In some embodiments of the present invention, the oligopeptide described above inhibits the expression of the MMP1 gene.

[0012] In some embodiments of the present invention, the oligopeptide described above enhances the expression of the FGFR1 gene.

[0013] In some embodiments of the present invention, the oligopeptide described above enhances the expression of the Nrf2 gene.

[0014] The present invention also provides a product with anti-aging activity, comprising: the above-mentioned oligopeptide and / or the oligopeptide obtained by the above preparation method.

[0015] In some embodiments of the present invention, the above-mentioned products include: personal care products.

[0016] In some embodiments of the present invention, the personal care products include: basic care products and / or makeup products.

[0017] In some embodiments of the present invention, the cosmetic products include, but are not limited to: (1) Base makeup: Foundation / cream: Used to even out skin tone and cover blemishes; BB cream / CC cream: A lightweight base makeup product that combines skincare and makeup application; Concealer / pen: Used to cover up specific areas such as pimples and dark circles; Loose powder / setting powder: Sets makeup and reduces facial shine.

[0018] (2) Eye makeup: Eyeshadow: Adds color and dimension to the eyes; Eyeliner pencil / liquid / gel: Used to draw lines on the eyes, making them look more vibrant; Mascara: Lengthens and thickens eyelashes, enhancing the depth of the eyes; Eyebrow pencil / powder / gel: Fill in gaps in eyebrows and create the ideal eyebrow shape.

[0019] (3) Cheek makeup: Blush: Adds natural color to the cheeks and improves complexion; Contouring powder / stick: Use shading techniques to make facial contours more three-dimensional; (4) Lip makeup: Lipstick / lip gloss / lip tint: to change or emphasize the color of the lips; Lip liner: Defines the clear outline of the lips and prevents lipstick from bleeding.

[0020] (5) Multifunctional cosmetics: Highlighter sticks / liquids / powders: Highlight high points on the face (such as the bridge of the nose and cheekbones) to create a luminous effect.

[0021] In addition, there are products designed specifically for special occasions, such as waterproof and sweatproof eyeliners and long-lasting, non-fading lipsticks.

[0022] In some embodiments of the present invention, the basic care products include, but are not limited to: Facial cleanser: Gently removes dirt, oil, and makeup residue from the face; Cleansing oil / cleansing water / cleansing balm: specially designed to thoroughly remove makeup, especially waterproof cosmetics; Toner / lotion: Used after cleansing, it can further cleanse the skin's surface of residue, while replenishing the skin's moisture, restoring the skin's pH balance, and laying a good foundation for the absorption of subsequent skin care products; Serum: Contains a high concentration of active ingredients, providing deep nourishment and repair for specific skin problems (such as anti-aging, moisturizing, whitening, etc.); Eye cream: Specially designed for the sensitive area around the eyes, it has the effects of reducing fine lines and dark circles and firming the skin around the eyes. The texture is usually light and easily absorbed. Day / night lotion or cream: It has functions such as protection, repair and nourishment, and promotes cell regeneration. It can provide the skin with the necessary moisture and lock in the replenished moisture. Sunscreen: Used for ultraviolet protection and prevention of photoaging, etc. Face masks: provide extra nourishment and care for the skin, such as hydration, pore cleansing, or brightening of the complexion.

[0023] This invention combines high-resolution crystal structure information of the FGF23-FGFR1c-αKlotho ternary complex, systematic truncation screening, and conformation prediction to rationally design and select three α-Klotho-derived oligopeptides (RBA-1, RBA-1d, and RBA-1e) with clear structural basis and optimized physicochemical properties for skin anti-aging. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0025] Figure 1 Show the standard curve of type I procollagen C-terminal peptide; Figure 2 This indicates the expression level of C-terminal peptide of type I procollagen; Figure 3 This indicates the relative expression level of the MMP1 gene; Figure 4 This indicates the relative expression level of the FGFR1 gene; Figure 5 This indicates the relative expression level of the Nrf2 gene; Figure 6 The attached HPLC chart shows RBA-1; Figure 7 The attached LC-MS diagram of RBA-1 is shown; Figure 8 The attached HPLC chart shows RBA-1d. Figure 9 LC-MS diagram of RBA-1d; Figure 10 The attached HPLC diagram shows RBA-1e. Figure 11 LC-MS diagram of RBA-1e; Wherein: BC: blank control BC; NC: negative control NC; PC: positive control PC; RBA-1: sample group 1; RBA-1d: sample group 2; RBA-1e: sample group 3. Detailed Implementation

[0026] This invention discloses oligopeptides and their application in the preparation of anti-aging products.

[0027] It should be understood that the expression “one or more of…” individually includes each of the objects described after the expression, as well as various different combinations of two or more of the described objects, unless otherwise understood from the context and usage. The expression “and / or” combined with three or more described objects should be understood to have the same meaning, unless otherwise understood from the context.

[0028] The terms “including,” “having,” or “containing,” including the use of their grammatical synonyms, should generally be understood as open-ended and non-restrictive, for example, not excluding other unstated elements or steps, unless otherwise specifically stated or understood from the context.

[0029] It should be understood that the order of the steps or the order in which certain actions are performed is not important as long as the invention remains operational. Furthermore, two or more steps or actions can be performed simultaneously.

[0030] The use of any and all instances or exemplary language such as “e.g.” or “including” in this document is merely intended to better illustrate the invention and is not intended to limit the scope of the invention unless the claims are made. No language in this specification should be construed as indicating that any unclaimed element is essential to the practice of the invention.

[0031] Furthermore, the numerical ranges and parameters used to define the present invention are approximate values, and the relevant values ​​in the specific embodiments have been presented as precisely as possible. However, any value inevitably contains standard deviations due to individual test methods. Therefore, unless explicitly stated otherwise, it should be understood that all ranges, quantities, values, and percentages used in this disclosure are modified with the word "approximately". Here, "approximately" generally means that the actual value is within plus or minus 10%, 5%, 1%, or 0.5% of a specific value or range.

[0032] The Klotho protein is composed of several domains: the core structure consists of the KL1 domain, the KL2 domain, the transmembrane region (TM), and the intracellular region (CYT). The extracellular components, consisting of the KL1 and KL2 domains, can be cleaved by membrane proteases, primarily ADAM10 and ADAM17 (α-secretases), forming secreted KL1 and KL2. 3D variable conformation analysis (3DVA) shows that free secreted Klotho (sKL) in solution is not a static, single structure, but rather exhibits continuous, multimodal dynamic conformational changes and significant structural flexibility. The core of this dynamic characteristic lies in the relative movement between the KL1 and KL2 domains, as well as the internal flexibility of KL2 itself. This dynamic property forms the structural basis for its multifunctional, multi-target, and broad-spectrum anti-aging effects.

[0033] This invention provides oligopeptides whose amino acid sequences are shown in Formula 1: YLWDVHHSK-X1-X2-X3-X4-X5 (Formula 1) Where: X1 is selected from missing or R; X2 is selected from missing or L; X3 is selected from missing or I; X4 is selected from missing or K; X5 is selected from either missing or V.

[0034] In some embodiments of the present invention, the amino acid sequence of the above-mentioned oligopeptide is any one of SEQ ID NO:1 to SEQ ID NO:3.

[0035] The oligopeptides provided by this invention can increase the expression of type I procollagen C-terminal peptide, inhibit the expression of MMP1 gene, increase the expression of FGFR1 gene, and increase the expression of Nrf2 gene.

[0036] This invention rationally designs and selects three α-Klotho-derived oligopeptides (RBA-1, RBA-1d, and RBA-1e) with clear structural basis and optimized physicochemical properties by combining high-resolution crystal structure information of the FGF23-FGFR1c-αKlotho ternary complex, systematic truncation screening of the receptor binding arm (RBA), and conformation prediction, for use in skin anti-aging.

[0037] The Chlamydomonas extract (positive control PC) of the present invention comprises 2 wt% Chlamydomonas extract, 80 wt% to 95 wt% isomaltone, 0.1 wt% to 1 wt% lecithin and 5 wt% to 15 wt% glycogen, with a pH of 4-6.

[0038] The ELISA kit was purchased from TAKARA (MK101), a company specializing in the assay of type I procollagen C-terminal peptide (PIP) content.

[0039] In Examples 1-3 and the preparation example of this invention, all raw materials and reagents used are commercially available.

[0040] The present invention will be further illustrated below with reference to the embodiments: Example 1: Screening of Oligopeptides 1. Candidate peptide identification based on ternary complex structure A ternary complex of α-Klotho-FGF23-FGFR1 was constructed using AlphaFold3. Based on confidence scores (pTM / ipTM), a structurally stable and highly confident RBA-like region on α-Klotho was identified. Peptiderive analysis was used to analyze peptides in this region that significantly contribute to the α-Klotho-FGFR1 interface, and Rosetta interface binding energy sequencing was employed to screen for candidate peptides with potential biological activity.

[0041] 2. Prediction of binding sites based on monomer structure

[0042] The meta-PPISP method was used to directly predict binding sites based on the α-Klotho monomer structure information. The binding propensity score for each residue was calculated using three independent methods (neural network, biophysical property prediction model, and empirical energy function), with a score >0.34 as the positive criterion for identifying potential binding peptides.

[0043] 3. Recommendations and mechanisms of action of known derived peptides

[0044] Existing α-Klotho-derived peptides include: KP1 (30 peptides), which works by inhibiting the activation of MAPKs such as ERK1 / 2, JNK, and p38; KP6 (30 peptides), which inhibits the activation of β-catenin and the expression of its downstream target genes; and KP4 (30 peptides), which inhibits the expression of FGFR1 and its downstream pERK1 / 2 protein.

[0045] 4. Basis for the modification of KP1 peptide

[0046] KP1 (sequences 56-87) inhibits TGF-β-induced activation of Smad2 / 3 and MAPK by binding to TGF-β receptor 2 and blocking TGF-β / TβR2 interaction. Based on this mechanism, KP1 can be structurally modified and optimized.

[0047] 5. RBA-1 truncation optimization based on crystal structure

[0048] Based on the 1:1:1 crystal structure of the FGF23-FGFR1c-α-Klotho ternary complex, the RBA-1 peptide was truncated sequentially from the C-terminus by one amino acid increment. AlphaFold3 was used for monomer conformation prediction, and optimized oligopeptides were obtained by considering parameters such as sequence length and positive charge distribution (K / R ratio).

[0049] RBA-1: YLWDVHHSK RLIKV (KL2) (as shown in SEQ ID NO:1); RBA-1d: YLWDVHHSK R (KL2) (as shown in SEQ ID NO:2); RBA-1e: YLWDVHHSK (KL2) (as shown in SEQ ID NO:3).

[0050] Preparation Example

[0051] The target peptide was prepared using a solid-phase peptide synthesis (SPPS) method based on the Fmoc strategy. This method efficiently constructs specific amino acid sequences by immobilizing the peptide chain on an insoluble resin support, enabling stepwise deprotection and amino acid coupling reactions. First, a suitable solid-phase resin was selected as the support for peptide chain growth. Before synthesis, an appropriate amount of resin was added to the reactor and thoroughly soaked in dichloromethane (DCM) to swell the resin, followed by filtration to remove the solvent. After resin pretreatment, the first Fmoc-protected amino acid at the C-terminus of the target peptide sequence was immobilized onto the resin. Specifically, the Fmoc-protected amino acid was dissolved in DMF, and an appropriate amount of N,N-diisopropylethylamine (DIEA) was added as a basic catalyst. The mixture was reacted with the resin at room temperature for approximately 2 hours, allowing the amino acid to be linked to the resin via ester bonds. After the reaction was complete, to prevent unreacted active sites from generating side reactions in subsequent reactions, an appropriate amount of DIEA and methanol was added to the system, and the reaction continued for approximately 30 minutes to block residual active sites. The solvent was then removed, and the resin was washed multiple times with DMF. By repeating the cyclical steps of "Fmoc deprotection—amino acid coupling—detection" described above, the desired amino acids can be sequentially introduced onto the resin, thereby gradually constructing a complete peptide chain structure. After all amino acid residues are linked, the resin is thoroughly washed and dried for later use. After the peptide chain is constructed, it is cleaved from the resin using a trifluoroacetic acid (TFA) cleavage system, simultaneously removing side-chain protecting groups to obtain the target crude peptide product. After the cleavage reaction, the reaction solution is concentrated, and the crude peptide is precipitated with an appropriate solvent. The obtained crude peptide is dissolved and purified by preparative high-performance liquid chromatography (HPLC). The target peak is collected and the purified peptide product is obtained by freeze-drying. The purity of the final product is determined by HPLC, and the molecular weight is confirmed by liquid chromatography-mass spectrometry (LC-MS) to verify the correctness of the peptide structure and purity level. The peptide product that passes the quality inspection is reviewed by quality control (QC) and quality assurance (QA) and can be used for subsequent research or related applications.

[0052] Example 2: Detection of C-terminal peptides of type I procollagen

[0053] The content level of procollagen type I C-terminal peptide (PIP) in different sample systems was quantitatively detected using enzyme-linked immunosorbent assay (ELISA). Based on the characteristic of PIP as a key marker of collagen synthesis, PIP is generated and released extracellularly during collagen synthesis from the cleavage of type I procollagen, and its content is positively correlated with collagen regeneration capacity.

[0054] 1. Cell inoculation

[0055] Fibroblasts were selected, and after reviving the cells, they were seeded into 12-well plates and incubated overnight in a CO2 incubator (37°C, 5% CO2).

[0056] 2. Test Grouping

[0057] The experiment included a blank control (BC), a negative control (NC), a positive control (PC), and a sample group, with three replicate wells in each group. The grouping is shown in Table 1. In Table 1, the test samples for each group were diluted with DMEM culture medium (Gibco) to achieve the required final concentrations as specified in Table 1.

[0058] Table 1 Test grouping information for Example 2

[0059] 3. LPS stimulation

[0060] According to the test groups, when the cell deposition rate in the 12-well plates reached 50%–70%, the drugs were administered to the groups, with 3 replicates per group. Except for the blank control BC, which was added with 1 mL of untreated DMEM culture medium, each well of the other groups was added with 1 mL of DMEM culture medium containing the corresponding test sample and LPS (5 μg / mL). After drug administration, the wells were placed in an incubator and incubated for 24 h.

[0061] 4. Administration

[0062] Simultaneously with LPS stimulation, drug administration was performed according to the test groups in Table 1, with three replicates per group. 2 mL of DMEM culture medium was added to each well of the blank control (BC) and negative control (NC), 2 mL of DMEM culture medium containing Chlamydomonas extract was added to each well of the positive control (PC), and 2 mL of DMEM culture medium containing the corresponding concentration of the test sample was added to each well of the sample group. After drug administration, the 12-well plate was placed in a CO2 incubator (37℃, 5% CO2) for 24 h. The above stimulation and drug administration steps were repeated three times.

[0063] 5. ELISA Method

[0064] After 24 hours of incubation, the cell culture medium was collected and transferred to centrifuge tubes, then centrifuged at 12,000 rpm for 10 minutes. 2 μL of the supernatant was taken and diluted with 100 μL of sample diluent. Subsequent analysis was performed according to the ELISA kit instructions. All samples and standards were prepared in triplicate.

[0065] 6. Statistical Analysis of Results

[0066] GraphPad Prism was used for plotting, and a four-parameter logistic regression model was used to fit the standard curve. Other results are expressed as Mean ± SD. Compared with the negative control NC, the significance was [not specified in the original text]. *This means that a p-value < 0.05 indicates that... * A p-value < 0.01 indicates that... ** A p-value < 0.001 indicates that... *** A p-value < 0.0001 indicates that... **** .

[0067] 7. Experimental Results

[0068] Standard curve in PIP testing method: ; Where, Min = -1657; Max = 1.818; EC 50 =1×10 -1789 HillSlope=0.001664.

[0069] Based on the four-parameter curve fitting results, R 2 =0.9949, which is greater than 0.99, so the curve meets statistical requirements. This standard curve can be used to calculate the PIP content. Based on the standard curve, the following can be calculated: Figure 1 As shown.

[0070] Table 2 Standard Curve Test Results

[0071] Table 3 Summary of Type I Procollagen C-terminal Peptide Test Results

[0072] Table 3 corresponds to Figure 2 The data.

[0073] 8. Analysis of Experimental Results

[0074] This test induces oxidative damage in cells through LPS treatment and inhibits collagen synthesis in fibroblasts. Type I procollagen C-terminal peptide (PIP) is a precursor to collagen synthesis, and detecting the synthesis of type I procollagen C-terminal peptide in fibroblasts is one of the indicators of fibroblast aging. Figure 2 As shown, PIP levels decreased significantly by 35.2% after LPS (negative control NC) treatment compared to the blank control BC group. Compared to LPS alone (negative control NC), the positive control PC (Chlamydomonas extract) increased PIP levels by 43.41%. Compared to LPS (negative control NC), treatment with sample group 1 (RBA-1), sample group 2 (RBA-1d), and sample group 3 (RBA-1e) significantly increased PIP expression levels, with increases of 16.13%, 17.09%, and 24.01%, respectively.

[0075] Example 3: Detection of MMP1, FGFR1, and Nrf2

[0076] 1. Cell inoculation

[0077] Fibroblasts were selected, and after reviving the cells, they were seeded into 12-well plates and incubated overnight in a CO2 incubator (37°C, 5% CO2).

[0078] 2. Test Grouping

[0079] The experiment included a blank control (BC), a negative control (NC), a positive control (PC), and a sample group, with three replicate wells in each group. The grouping is shown in Table 4. In Table 4, the test samples for each group were diluted with DMEM culture medium (Gibco) to achieve the required final concentrations as specified in Table 4.

[0080] Table 4 Test grouping information for Example 3

[0081] 3. LPS stimulation

[0082] According to the test groups, when the cell deposition rate in the 12-well plates reached 50%–70%, the drugs were administered to the groups, with 3 replicates per group. Except for the blank control BC, which was added with 1 mL of untreated DMEM culture medium, each well of the other groups was added with 1 mL of DMEM culture medium containing the corresponding test sample and LPS (5 μg / mL). After drug administration, the wells were placed in an incubator and incubated for 24 h.

[0083] 4. Administration

[0084] Simultaneously with LPS stimulation, drug administration was performed according to the test groups in Table 4, with three replicates per group. 2 mL of DMEM culture medium was added to each well of the blank control (BC) and negative control (NC), 2 mL of DMEM culture medium containing Chlamydomonas extract was added to each well of the positive control (PC), and 2 mL of DMEM culture medium containing the corresponding concentration of the test sample was added to each well of the sample group. After drug administration, the 12-well plate was placed in a CO2 incubator (37℃, 5% CO2) for 24 h. The above stimulation and drug administration steps were repeated three times.

[0085] 5. qPCR method

[0086] 1) RNA extraction and qPCR

[0087] RNA extraction: Total RNA was extracted from each group of cells using the Tiangen Total RNA Extraction Kit, following the instructions. The concentration and purity of the RNA were measured using a spectrophotometer to ensure OD... 260 / OD 280 Between 1.8 and 2.0.

[0088] Reverse transcription: Take 1 μg of total RNA and use TOYOBO's ReverTra Ace™ qPCR RT Master Mix for reverse transcription to synthesize cDNA.

[0089] qPCR: Using cDNA as a template, qPCR reactions were performed on a real-time quantitative PCR instrument using SYBR™ Green Realtime PCR Master Mix. The reaction volume was 20 μL, including 10 μL SYBR™ Green Realtime PCR Master Mix, 0.8 μL upstream primer (F-sequence), 0.8 μL downstream primer (R-sequence), 2 μL cDNA template, and 6.4 μL ddH2O. The reaction conditions were: 95℃ pre-denaturation for 30 seconds; 95℃ denaturation for 5 seconds, 60℃ annealing for 30 seconds, for a total of 40 cycles. Using GAPDH as an internal reference gene, the relative expression levels of MMP1, FGFR1, and Nrf2 genes were calculated using the 2^-ΔΔCt method.

[0090] Table 5 Primer sets for each gene

[0091] 6. Statistical Analysis of Results

[0092] GraphPad Prism was used for plotting, and results are expressed as Mean ± SD. One-way ANOVA was used for comparisons between groups. Significance was determined by comparing with the negative control (NC). * This means that a p-value < 0.05 indicates that... * A p-value < 0.01 indicates that... ** A p-value < 0.001 indicates that... *** A p-value < 0.0001 indicates that... **** .

[0093] like Figure 3 As shown, MMP1 promotes collagen degradation, and inhibiting MMP1 can protect collagen and exert anti-aging effects. Test results showed that, compared with the blank control BC, the negative control NC significantly increased the MMP1 gene expression level, up to 8 times. Compared with the negative control NC, the positive control PC, sample group 1 (RBA-1), and sample group 2 (RBA-1d) significantly inhibited the MMP1 gene expression level, with inhibition rates of 51.31%, 33.04%, and 30.66%, respectively.

[0094] Table 6 Summary of MMP1 gene test results

[0095] Table 6 corresponds to Figure 3 The data.

[0096] like Figure 4 As shown, FGFR1 is an important transmembrane receptor. Activation of this receptor can activate downstream signaling pathways. The test results showed that compared with the blank control BC, the negative control NC inhibited the expression level of FGFR1 gene. However, compared with the negative control NC, the positive control PC and sample group 1 (RBA-1), sample group 2 (RBA-1d), and sample group 3 (RBA-1e) significantly increased the expression level of FGFR1 gene, with enhancement rates of 152.44%, 51.11%, 69.33%, and 80%, respectively.

[0097] Table 7 Summary of FGFR1 gene test results

[0098] Table 7 corresponds to Figure 4 The data.

[0099] like Figure 5 As shown, Nrf2 is an important antioxidant factor, and promoting Nrf2 can play an anti-aging role through anti-oxidation. The test results showed that compared with the blank control BC, the negative control NC inhibited the expression level of Nrf2 gene. However, compared with the negative control NC, the positive control PC and sample group 1 (RBA-1), sample group 2 (RBA-1d), and sample group 3 (RBA-1e) could significantly increase the expression level of Nrf2 gene, with enhancement rates of 284.38%, 410%, 216.25%, and 159.38%, respectively.

[0100] Table 8 Summary of Nrf2 gene test results

[0101] Table 8 corresponds to Figure 5 The data.

[0102] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. An oligopeptide with anti-aging activity, characterized in that, Its amino acid sequence is shown in any of SEQ ID NO:1 to SEQ ID NO:

3.

2. The method for preparing oligopeptides according to claim 1, characterized in that, include: The oligopeptides are prepared by chemical synthesis or biosynthesis.

3. The use of the oligopeptide as described in claim 1 in the preparation of anti-aging personal care products.

4. The application as described in claim 3, characterized in that, The oligopeptide enhances the expression of C-terminal peptide of type I procollagen.

5. The application as described in claim 3, characterized in that, The oligopeptide inhibits the expression of the MMP1 gene.

6. The application as described in claim 3, characterized in that, The oligopeptide enhances the expression of the FGFR1 gene.

7. The application as described in claim 3, characterized in that, The oligopeptide enhances the expression of the Nrf2 gene.

8. A personal care product with anti-aging activity, characterized in that, include: The oligopeptide as described in claim 1.

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