A composition for improving perimenopausal skin aging based on three-hub long-life axle and application thereof

Abstract

The application belongs to the technical field of biological medicine, and relates to a composition for improving perimenopausal skin aging based on a three-hub long-life axis and application thereof. The composition comprises ergothioneine, radix rehmanniae extract, coenzyme Q10, angelica extract, honokiol and ginsenoside. The application starts from the mechanism of perimenopausal estrogen-induced skin aging, combines the advantages of traditional Chinese medicine theory of nourishing yin and moisturizing skin and the AMPK / SIRT1 cell repair regulation of ginsenoside CK, and reestablishes the energy sensing and repair ability of dermal fibroblasts through the synergistic activation of the AMPK-SIRT1-PGC-1a three-hub long-life axis. Ergothioneine, radix rehmanniae extract, coenzyme Q10, angelica extract, honokiol and ginsenoside CK have a synergistic effect on improving perimenopausal skin aging.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology and relates to a composition for improving perimenopausal skin aging based on a three-hub longevity axis and its application, particularly to a composition for improving perimenopausal skin aging based on the synergistic activation of the AMPK-SIRT1-PGC-1α three-hub longevity axis and its application. Background Technology

[0002] Perimenopausal skin changes manifest as dryness, decreased elasticity, deepened wrinkles, melasma / pigmentation, and acne due to relatively increased androgens. The specific pathologies are: ① Estrogen is a key hormone for maintaining dermal collagen synthesis, hyaluronic acid production, and skin hydration; a decline in estrogen leads to approximately 30% collagen loss in the first 5 years after menopause; ② The relative increase in androgens after estrogen decline stimulates excessive sebum secretion and follicular keratosis, causing acne; ③ Increased tyrosinase activity and melanin metabolism disorders exacerbate melasma and pigmentation; ④ Decreased skin antioxidant capacity accelerates photoaging and free radical damage; ⑤ Decreased AMPK / SIRT1 activity in dermal fibroblasts leads to insufficient autophagy and repair capacity, accelerating the skin aging process. The root cause of perimenopausal skin problems is the combined effect of decreased estrogen levels and the decline in cellular energy sensing and repair pathways. General anti-aging skincare products / oral supplements are not designed to address this specific cause.

[0003] The "Tri-Hydrogen Longevity Axis" (AMPK-SIRT1-PGC-1α) is a core network for cellular energy sensing and metabolic regulation. These three components work synergistically through a positive feedback loop to maintain cellular youthfulness. The decline in estrogen during perimenopause may lead to reduced NAD+ levels and decreased SIRT1 activity in dermal fibroblasts, triggering a vicious cycle collapse of the tri-hydrogen longevity axis. This results in insufficient autophagy in fibroblasts, decreased mitochondrial function, and reduced collagen synthesis, accelerating skin aging. Simultaneously, targeting the tri-hydrogen longevity nodes to rebuild the positive feedback loop is a key strategy for improving perimenopausal skin aging.

[0004] Therefore, providing a composition designed for perimenopausal skin aging has become a pressing technical problem to be solved in this field. Summary of the Invention

[0005] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a composition for improving perimenopausal skin aging based on a three-hub longevity axis and its application, particularly relating to a composition for improving perimenopausal skin aging based on the synergistic activation of the AMPK-SIRT1-PGC-1α three-hub longevity axis and its application.

[0006] To achieve this objective, the present invention adopts the following technical solution:

[0007] In a first aspect, the present invention provides a composition for improving perimenopausal skin aging based on a three-hub longevity axis, the composition comprising ergothioneine, Rehmannia glutinosa extract, coenzyme Q10, Angelica sinensis extract, magnolol, and ginsenoside CK.

[0008] Ergothioneine, Rehmannia glutinosa extract, Coenzyme Q10, Angelica sinensis extract, magnolol, and ginsenoside CK target different nodes of the three-axis system.

[0009] Ergothioneine (EGT): EGT actively accumulates in skin tissue via the OCTN1 transporter on keratinocytes and fibroblasts (unlike the passive distribution of typical oral antioxidants). It activates the Nrf2 / ARE pathway to upregulate endogenous antioxidant enzymes (HO-1, NQO1), scavenges UV-induced ROS to protect dermal collagen fibers, inhibits tyrosinase activity to reduce melanin production, and improves melasma and pigmentation. Additionally, EGT enhances NAD+ through the CSE / H2S / cGPDH pathway. + Levels that activate SIRT1 deacetylase activity.

[0010] Rehmannia glutinosa extract: Rehmannia glutinosa polysaccharides promote the proliferation of dermal fibroblasts and collagen synthesis, improving skin elasticity; catalpol provides antioxidant protection, reducing the degradation of skin collagen by UV and endogenous ROS; verbascoside has potent antioxidant and anti-inflammatory activity, inhibiting MMP expression and reducing collagen degradation. Rehmannia glutinosa, by "nourishing yin and moisturizing dryness," fundamentally improves the skin's moisture content and elasticity during perimenopause (corresponding to the traditional Chinese medicine concept of "yin deficiency leading to malnourishment of the skin"), and regulates immune function to alleviate chronic skin inflammation. Furthermore, catalpol in Rehmannia glutinosa protects the SIRT1 activity of dermal fibroblasts from inflammatory suppression by inhibiting inflammatory pathways such as NF-κB, thereby indirectly maintaining the function of the tri-axis SIRT1 node.

[0011] Coenzyme Q10 provides mitochondrial ATP to support collagen synthesis in dermal fibroblasts (collagen loss accelerates during perimenopause, requiring more energy). As a key cofactor in the mitochondrial electron transport chain, it provides the energy basis for PGC-1α-mediated mitochondrial biogenesis. Studies have confirmed that oral coenzyme Q10 reduces wrinkle depth and improves skin smoothness.

[0012] Angelica sinensis extract: ERβ phytoestrogens partially restore the positive regulation of estrogen on collagen synthesis and hyaluronic acid production. Angelica sinensis "nourishes blood and promotes blood circulation," improving skin microcirculation and nutrient supply. Ferulic acid has antioxidant properties and inhibits melanin synthesis. ERβ activation can partially compensate for the negative impact of decreased estrogen on dermal fibroblast metabolism, providing hormonal signaling support for the downstream collagen synthesis effect of the three-axis.

[0013] Honokiol enhances the endogenous antioxidant capacity of skin cell mitochondria by activating the SIRT3 / SOD2 pathway, reduces skin inflammation (anti-acne) by inhibiting NF-κB, and inhibits androgen-related sebaceous gland overactivation. Honokiol primarily targets the SIRT1 node and SIRT3, a member of the SIRT family. SIRT3, as a deacetylase in mitochondria, enhances mitochondrial antioxidant defense through SOD2, complementing PGC-1α-driven mitochondrial biogenesis; simultaneously, it reduces the inhibition of SIRT1 activity by NF-κB inhibition, indirectly protecting the core execution nodes of the three-hub axis.

[0014] Ginsenoside CK: Ginsenoside CK activates the autophagy process of dermal fibroblasts through the LKB1 / AMPK / SIRT1 pathway, clearing damaged proteins and dysfunctional mitochondria, maintaining cellular youthfulness; it promotes autophagy clearance by activating AMPK and indirectly supports cellular energy metabolism required for collagen synthesis; it alleviates skin "inflammatory aging" by inhibiting NF-κB and protects the collagen network by reducing MMP expression induced by inflammatory factors, thus improving the overall metabolic state of the skin and delaying the accelerated aging process during perimenopause. Ginsenoside CK mainly targets the AMPK node. After AMPK activation, it upregulates NAMPT (NAD... + Increased expression of NAD+ (rate-limiting enzyme in synthesis) + Levels indirectly activate SIRT1, leading to the formation of AMPK-NAD. + The SIRT1-PGC-1α signaling cascade initiates a positive feedback loop in the three-hub longevity axis. In skin fibroblasts, this cascade directly promotes autophagy to clear damaged proteins, mitochondrial biogenesis, and collagen synthesis.

[0015] The composition of this invention targets the specific causes of perimenopausal skin changes (decreased estrogen, relatively increased androgen, and decline in cell repair pathways), forming a six-dimensional skin protection approach: "active targeted anti-oxidation + nourishing and moisturizing + phytoestrogens compensation + collagen synthesis promotion + anti-acne + cell repair regulation." EGT actively accumulates in the skin through OCTN1 (targeting advantage), protecting collagen and inhibiting tyrosinase to lighten pigmentation. Rehmannia glutinosa nourishes yin and moisturizes, fundamentally improving skin hydration. Rehmannia glutinosa polysaccharides promote collagen production, verbascoside has antioxidant and MMP-inhibiting effects, Angelica sinensis ERβ restores the positive regulation of collagen and hyaluronic acid by estrogen, coenzyme Q10 supports collagen synthesis energy, and magnolol has anti-inflammatory and anti-acne properties. Ginsenoside CK activates autophagy through AMPK / SIRT1 to maintain the youthful state of fibroblasts, and protects the collagen network against inflammatory aging. More importantly, ginsenoside CK activates AMPK, upregulates NAMPT, and enhances NAD+. +SIRT1 is activated, and LKB1 is deacetylated to promote AMPK phosphorylation, forming a positive feedback loop. SIRT1 also deacetylates PGC-1α, increasing mitochondrial biogenesis, which in turn boosts AMP / ATP and NAD. + Ergothioneine provides an alternative NAD+ independent of NMN / NR via the CSE / H2S / cGPDH pathway. + This formula, containing magnolol and ginsenoside CK, enhances mitochondrial antioxidant defense through SIRT3 / SOD2, while rehmannia glutinosa protects SIRT1 activity from inflammatory suppression by inhibiting NF-κB. Multiple ingredients synergistically activate the AMPK-SIRT1-PGC-1α positive feedback network, rebuilding the energy sensing, autophagy repair, and collagen synthesis capabilities of dermal fibroblasts. Unlike typical oral beauty products, this regimen addresses the root cause of estrogen decline during perimenopause, combining the advantages of traditional Chinese medicine's "yin-nourishing and skin-moisturizing" theory with the AMPK / SIRT1 cell repair regulation of ginsenoside CK.

[0016] Preferably, the composition comprises, by weight parts, 5-100 parts ergothioneine, 10-100 parts Rehmannia glutinosa extract, 5-200 parts coenzyme Q10, 10-100 parts Angelica sinensis extract, 20-300 parts magnolol, and 1-30 parts ginsenosides.

[0017] The mass fractions of ergothioneine can be selected from 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 parts, etc. The mass fractions of Rehmannia glutinosa extract can be selected from 10, 20, 30, 40, 50, 60, 70, 80, 90, and 100 parts, etc. The mass fractions of coenzyme Q10 can be selected from 5, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, and 200 parts, etc. The mass fractions of Angelica sinensis extract can be selected from 10, 20, 30, 40, 50, and 60 parts, etc. The mass fractions of magnolol can be selected from 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, etc. The mass fractions of ginsenosides can be selected from 1, 2, 5, 8, 10, 12, 15, 18, 20, 22, 25, 28, 30, etc. Other specific values ​​within the above ranges can also be selected, which will not be elaborated here.

[0018] Preferably, the coenzyme Q10 includes reduced coenzyme Q10 and / or oxidized coenzyme Q10.

[0019] Preferably, the ginsenoside is ginsenoside CK.

[0020] Preferably, the composition is prepared by a method comprising the following steps: physically mixing the raw materials to obtain the composition.

[0021] In a second aspect, the present invention provides the use of the composition based on the three-hub longevity axis for improving perimenopausal skin aging according to the first aspect in the preparation of a product having the effect of improving perimenopausal skin aging.

[0022] Preferably, the composition for improving perimenopausal skin aging in the product has a mass percentage content of 5-80%, such as 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, etc. Other specific values ​​within the above range can be selected, and will not be elaborated here.

[0023] Preferably, the dosage form of the product includes tablets, capsules, granules, powders, gummies, oral liquids, or beverages.

[0024] Preferably, the product also includes auxiliary materials.

[0025] Preferably, the excipients include any one or a combination of at least two of solvents, emulsifiers, dispersants, wetting agents, binders, stabilizers, colorants, diluents, flavoring agents, or fillers.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] The composition of this invention targets the specific causes of perimenopausal skin changes (decreased estrogen, relatively increased androgen, and decline in cell repair pathways), forming a six-dimensional skin protection approach: "active targeted anti-oxidation + nourishing and moisturizing + phytoestrogens compensation + collagen synthesis promotion + anti-acne + cell repair regulation." EGT actively accumulates in the skin through OCTN1 (targeting advantage), protecting collagen and inhibiting tyrosinase to lighten pigmentation. Rehmannia glutinosa nourishes yin and moisturizes, fundamentally improving skin hydration. Rehmannia glutinosa polysaccharides promote collagen production, verbascoside has antioxidant and MMP-inhibiting effects, Angelica sinensis ERβ restores the positive regulation of collagen and hyaluronic acid by estrogen, coenzyme Q10 supports collagen synthesis energy, and magnolol has anti-inflammatory and anti-acne properties. Ginsenoside CK activates autophagy through AMPK / SIRT1 to maintain the youthful state of fibroblasts, and protects the collagen network against inflammatory aging. More importantly, ginsenoside CK activates AMPK, upregulates NAMPT, and enhances NAD+.+ SIRT1 is activated, and LKB1 is deacetylated to promote AMPK phosphorylation, forming a positive feedback loop. SIRT1 also deacetylates PGC-1α, increasing mitochondrial biogenesis, which in turn boosts AMP / ATP and NAD. + Ergothioneine provides an alternative NAD+ independent of NMN / NR via the CSE / H2S / cGPDH pathway. + The product contains magnolol, which enhances mitochondrial antioxidant defense through SIRT3 / SOD2, and citronellol from Rehmannia glutinosa, which protects SIRT1 activity from inflammatory suppression by inhibiting NF-κB. These multiple ingredients synergistically activate the AMPK-SIRT1-PGC-1α positive feedback network, overcoming the limitations of existing single-ingredient formulations that cannot simultaneously repair the collapse of multiple nodes across the three-hub axis. This achieves a more comprehensive and systematic anti-skin aging effect than single antioxidants or single hormone supplements.

[0028] Unlike general oral beauty products, this program addresses the root cause of estrogen decline during perimenopause, combining the advantages of traditional Chinese medicine theory of "nourishing yin and moisturizing the skin" with the AMPK / SIRT1 cell repair regulation of ginsenoside CK. Attached Figure Description

[0029] Figure 1 This is the result of a test on the hydroxyproline content in mouse skin.

[0030] Figure 2 These are the results of a mouse skin epidermal thickness test.

[0031] Figure 3 These are the results of a mouse dermal thickness test.

[0032] Figure 4 These are the results of a full-thickness test of mouse skin. Detailed Implementation

[0033] The technical solution of the present invention will be further illustrated below through specific embodiments. Those skilled in the art should understand that the embodiments described are merely illustrative of the present invention and should not be construed as limiting the invention.

[0034] The sources of the active ingredients in the products involved in the following examples and comparative examples are as follows (only the active ingredients are shown; other necessary excipients contained in commercially available raw materials are not described):

[0035] Rehmannia glutinosa extract was purchased from Xi'an Xiaocao Botanical Technology Co., Ltd.

[0036] Angelica extract was purchased from Guangdong Qingyunshan Pharmaceutical Co., Ltd.

[0037] The Coenzyme Q10 is reduced Coenzyme Q10, purchased from Cocrystal Health Industry (Zhejiang) Co., Ltd.

[0038] Example 1

[0039] This embodiment provides a composition for improving perimenopausal skin aging, the composition comprising, by weight parts, 50 parts ergothioneine, 50 parts Rehmannia glutinosa extract, 100 parts coenzyme Q10, 50 parts Angelica sinensis extract, 100 parts magnolol, and 20 parts ginsenoside CK.

[0040] The preparation method is as follows: the raw materials are physically mixed to obtain the product.

[0041] Example 2

[0042] This embodiment provides a composition for improving perimenopausal skin aging, the composition comprising, by weight parts, 20 parts ergothioneine, 90 parts Rehmannia glutinosa extract, 150 parts coenzyme Q10, 20 parts Angelica sinensis extract, 50 parts magnolol, and 30 parts ginsenoside CK.

[0043] The preparation method is the same as in Example 1.

[0044] Example 3

[0045] This embodiment provides a composition for improving perimenopausal skin aging, the composition comprising, by weight parts, 80 parts ergothioneine, 20 parts Rehmannia glutinosa extract, 40 parts coenzyme Q10, 80 parts Angelica sinensis extract, 260 parts magnolol, and 5 parts ginsenoside CK.

[0046] The preparation method is the same as in Example 1.

[0047] Example 4

[0048] This embodiment provides a composition for improving perimenopausal skin aging. The only difference between this composition and Example 1 is that "ginsenoside CK" is replaced with "ginsenoside Rb1" in equal amounts, while other components and contents remain unchanged.

[0049] The preparation method is the same as in Example 1.

[0050] Example 5

[0051] This embodiment provides a composition for improving perimenopausal skin aging. The only difference between this composition and Example 1 is that "ginsenoside CK" is replaced with "ginsenoside Rb2" in equal amounts, while other components and contents remain unchanged.

[0052] The preparation method is the same as in Example 1.

[0053] Comparative Example 1

[0054] This comparative example provides a composition for improving perimenopausal skin aging, which differs from Example 1 only in that it does not contain ergothioneine, and the reduced mass of ergothioneine is proportionally allocated to the mass of Rehmannia glutinosa extract, coenzyme Q10, Angelica sinensis extract, magnolol and ginsenoside CK, while the other components and contents remain unchanged.

[0055] The preparation method is the same as in Example 1.

[0056] Comparative Example 2

[0057] This comparative example provides a composition for improving perimenopausal skin aging, which differs from Example 1 only in that it does not contain Rehmannia glutinosa extract, and its reduced mass is proportionally allocated to the mass of ergothioneine, coenzyme Q10, Angelica sinensis extract, magnolol and ginsenoside CK, while other components and contents remain unchanged.

[0058] The preparation method is the same as in Example 1.

[0059] Comparative Example 3

[0060] This comparative example provides a composition for improving perimenopausal skin aging, which differs from Example 1 only in that it does not contain coenzyme Q10, and the reduced mass of coenzyme Q10 is proportionally allocated to the mass of ergothioneine, Rehmannia glutinosa extract, Angelica sinensis extract, magnolol and ginsenoside CK, while the other components and contents remain unchanged.

[0061] The preparation method is the same as in Example 1.

[0062] Comparative Example 4

[0063] This comparative example provides a composition for improving perimenopausal skin aging, which differs from Example 1 only in that it does not contain Angelica sinensis extract, and its reduced mass is proportionally allocated to the mass of ergothioneine, Rehmannia glutinosa extract, coenzyme Q10, magnolol and ginsenoside CK, while other components and contents remain unchanged.

[0064] The preparation method is the same as in Example 1.

[0065] Comparative Example 5

[0066] This comparative example provides a composition for improving perimenopausal skin aging, which differs from Example 1 only in that it does not contain magnolol, and the reduced mass of magnolol is proportionally allocated to the mass of ergothioneine, Rehmannia glutinosa extract, coenzyme Q10, Angelica sinensis extract and ginsenoside CK, while the other components and contents remain unchanged.

[0067] The preparation method is the same as in Example 1.

[0068] Comparative Example 6

[0069] This comparative example provides a composition for improving perimenopausal skin aging, which differs from Example 1 only in that it does not contain ginsenoside CK, and its reduced mass is proportionally allocated to the mass of ergothioneine, Rehmannia glutinosa extract, coenzyme Q10, Angelica sinensis extract and magnolol, while the other components and contents remain unchanged.

[0070] The preparation method is the same as in Example 1.

[0071] Test Example 1

[0072] Modeling method: Six- to eight-week-old female C57BL / 6 mice were naturally fed for 7 days, and their body weight was recorded. They were anesthetized intraperitoneally with sodium pentobarbital (50 mg / kg). A dorsal incision was made, with hair shaved 1 cm below the ribs and 0.5 cm from the spine, followed by routine disinfection. The incision was approximately 3 cm long. The skin was cut, expanded, and dissected. The psoas muscle was cut 1 cm below the ribs from the spine, revealing the adipose tissue surrounding the ovaries and the closely connected uterine horns. Surrounding blood vessels and fallopian tubes were ligated, and the ovaries were removed. The same procedure was performed on the other side. After confirming no bleeding, the muscle layer and skin were sutured together. The incision was disinfected with povidone-iodine, and the incision was checked and cleaned regularly. All mice were kept in a 35-37 ℃ warming table until awake. The surgical diary was recorded as day 0. Carbofuran 5 mg / kg was administered subcutaneously for pain relief once daily for 3 days post-surgery. Vaginal smears were used to observe changes in the estrous cycle starting 7 days post-surgery. The control group underwent sham surgery (exposing the ovaries but not removing them).

[0073] Vaginal smear preparation: 20 µL of physiological saline was pipetted into the mouse vagina and aspirated 2-3 times. The aspirated smear was then transferred to a glass slide. After drying, the slide was stained with Wright's stain and observed under a light microscope. The establishment of the model was considered successful when no changes in the estrous cycle were observed for 5 consecutive days.

[0074] Once the model was successfully established (i.e., 21 days post-surgery), mice were divided into groups of 8. The control and model groups received no medication, while the sample group was administered the composition once daily by gavage for 8 weeks.

[0075] 1. Skin hydroxyproline content

[0076] Skin samples were taken from the midline of the mouse back (fixed position, about 2 cm × 2 cm, to maintain consistency of sampling), subcutaneous fat and fascia were removed, and the samples were cut into small pieces of about 5 mm × 5 mm. After the moisture was absorbed by filter paper, the samples were weighed accurately, each weighing about 100 mg, and stored immediately at -80°C.

[0077] Add 1 mL of 6 mol / L HCl (weight:volume = 1:10) to the precisely weighed skin sample, homogenize thoroughly in an ice bath until no visible tissue clumps remain, then hydrolyze in a 110℃ oven for 24 h. After hydrolysis, neutralize to pH 7 with 6 mol / L NaOH, add deionized water to a final volume of 5 mL, mix well, and centrifuge at 12000 r / min, 4℃ for 20 min. Collect the supernatant for analysis. The hydroxyproline content in mouse skin tissue was determined using the Nanjing Jiancheng Hydroxyproline (HYP) Assay Kit A030-2-1.

[0078] The results are as follows Figure 1 As shown, Figure 1 In the figures, * indicates p < 0.05 compared to the model group, ** indicates p < 0.01 compared to the model group, and *** indicates p < 0.001 compared to the model group; # indicates p < 0.05 compared to Example 1, ## indicates p < 0.01 compared to Example 1, and ### indicates p < 0.001 compared to Example 1. Hydroxyproline is a specific amino acid of collagen, accounting for approximately 13.4% of the total amino acids in collagen, and its content is highly linearly positively correlated with the total amount of collagen. The experimental results show that the content of hydroxyproline in the skin tissue of the model group was significantly reduced, indicating a significant decrease in the content of collagen in the skin. After continuous administration for 8 weeks in groups 1-3, the content of hydroxyproline in the skin tissue was significantly increased. This result indicates that the complete composition of the present invention can effectively promote the synthesis of collagen in the skin. Changing the components of the composition of the present invention or lacking any component will lead to a significant decrease in the effect.

[0079] 2. Take back skin tissue fixed for 24 h, dehydrate stepwise with ethanol solution; clear twice with xylene, 1 h each time; then immerse in paraffin in a 60℃ oven for 30 min, followed by embedding and sectioning, with a section thickness of 5µm. Perform HE staining on back skin tissue sections. Randomly select 3-5 fields of view from each section and use Image Pro-Plus image analysis software to measure the full-thickness thickness, epidermal thickness, and dermal thickness of the back skin. The vertical distance from the basal layer to the outermost layer of the epidermis is measured as the epidermal thickness, and the distance from the epidermal-dermal junction to the dermal-subcutaneous junction is measured as the dermal thickness. The full-thickness thickness = epidermal thickness + dermal thickness, and take the average value.

[0080] The effects of each test sample on the epidermal thickness, dermal thickness, and full-thickness thickness of mouse skin are as follows: Figure 2-4 As shown, Figure 2-4 In the text, * indicates p < 0.05 compared to the model group, ** indicates p < 0.01 compared to the model group, and *** indicates p < 0.001 compared to the model group; # indicates p < 0.05 compared to Example 1, ## indicates p < 0.01 compared to Example 1, and ### indicates p < 0.001 compared to Example 1.

[0081] Perimenopause causes estrogen deficiency, leading to slowed epidermal renewal, reduced keratinocyte proliferation, and thinning of the epidermis. Furthermore, the dermis accounts for the majority (80-90%) of skin thickness and is rich in collagen fibers. Estrogen withdrawal results in decreased dermal collagen synthesis and increased degradation, leading to significant dermal thinning. Changes in dermal and epidermal thickness are important morphological indicators of skin aging; therefore, perimenopausal skin exhibits obvious signs of aging. Experimental results showed that the epidermal, dermal, and full-thickness thicknesses of the model group were significantly reduced, indicating significant skin aging. After 8 weeks of continuous administration in Examples 1-3, the epidermal, dermal, and full-thickness thicknesses of the skin tissue were significantly increased. These results demonstrate that the complete composition of this invention can effectively improve the epidermal, dermal, and full-thickness thicknesses of skin tissue. Changing the components of the composition or omitting any component will significantly reduce the effectiveness.

[0082] The above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A composition for improving perimenopausal skin aging based on a three-pivot longevity axis, characterized in that, The composition includes ergothioneine, Rehmannia glutinosa extract, coenzyme Q10, Angelica sinensis extract, magnolol, and ginsenosides.

2. The composition for improving perimenopausal skin aging according to claim 1, characterized in that, The composition comprises, by weight parts, 5-100 parts of ergothioneine, 10-100 parts of Rehmannia glutinosa extract, 5-200 parts of coenzyme Q10, 10-100 parts of Angelica sinensis extract, 20-300 parts of magnolol, and 1-30 parts of ginsenosides.

3. The composition for improving perimenopausal skin aging according to claim 1 or 2, characterized in that, The coenzyme Q10 includes reduced coenzyme Q10 and / or oxidized coenzyme Q10.

4. The composition for improving perimenopausal skin aging according to any one of claims 1-3, characterized in that, The ginsenoside mentioned is ginsenoside CK.

5. The composition for improving perimenopausal skin aging according to any one of claims 1-4, characterized in that, The composition is prepared by a method comprising the following steps: physically mixing the raw materials to obtain the composition.

6. The use of the composition based on the three-pivot longevity axis for improving perimenopausal skin aging according to any one of claims 1-5 in the preparation of a product having the effect of improving perimenopausal skin aging.

7. The application according to claim 6, characterized in that, The composition in the product that improves perimenopausal skin aging has a mass percentage of 5-80%.

8. The application according to claim 6 or 7, characterized in that, The dosage forms of the products include tablets, capsules, granules, powders, gummies, oral liquids, or beverages.

9. The application according to any one of claims 6-8, characterized in that, The product also includes auxiliary materials.

10. The application according to claim 9, characterized in that, The excipients include any one or a combination of at least two of the following: solvents, emulsifiers, dispersants, wetting agents, binders, stabilizers, colorants, diluents, flavoring agents, or fillers.

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