A composition for regulating the biomechanical homeostasis of the skin basement membrane and its use

Abstract

The application discloses a kind of compositions for adjusting skin basement membrane biomechanics homeostasis and application thereof, the composition includes andrographolide and Gly-Met-Hyp tripeptide;The mass concentration ratio of andrographolide and Gly-Met-Hyp tripeptide is 1:5~1:20.The andrographolide and Gly-Met-Hyp tripeptide complex composition provided by the application can target Piezo mechanical sensitive channel, block abnormal biomechanics signal transduction, restore basement membrane biomechanics homeostasis, cut off mechanics-inflammation vicious cycle, and improve sensitive skin.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and more particularly to a composition for regulating the biomechanical homeostasis of the skin's basement membrane and its application. Background Technology

[0002] Sensitive skin is a common sub-healthy skin condition characterized by high reactivity. Its core pathological features include impaired skin barrier function, accompanied by increased transepidermal water loss, elevated nerve sensitivity, and chronic low-grade inflammation. Clinical manifestations include discomfort such as stinging, burning, redness, and itching, and it is characterized by frequent recurrence and difficulty in complete cure. Recent studies suggest that the development of sensitive skin is not only related to skin barrier damage and inflammatory responses, but also involves a complex pathological process involving multiple factors such as changes in the epidermal-dermal junction structure, abnormal nerve signals, and the perception of mechanical stimulation.

[0003] The basement membrane, a key supporting structure between the epidermis and dermis, is composed of core components such as type IV collagen, laminin, and type XVII collagen. In addition to its structural support role, the basement membrane also possesses certain biomechanical properties and participates in various physiological processes, including mechanical stress transmission, cell adhesion, and signal transduction, playing a vital role in maintaining skin tissue homeostasis.

[0004] In sensitive skin conditions, the expression of skin basement membrane-related structural proteins is abnormal. Piezo1, a mechanosensitive ion channel expressed in skin cells, can sense changes in extracellular matrix tension, stiffness, and mechanical stimulation, and convert these mechanical signals into intracellular calcium. 2+ Signal response. When an abnormal mechanical signal persists, Piezo1-mediated Ca... 2+ Abnormally enhanced influx may further affect TRPV1-related neurosensitization processes and the activity of the YAP mechano-response signaling pathway. Abnormal activation of YAP signaling can participate in the regulation of inflammation-related gene expression and affect the maintenance of skin structural homeostasis, thereby promoting the formation of sensitive skin-related states such as abnormal skin barrier function, neuroreactivity, and inflammatory responses.

[0005] Current active ingredients in sensitive skin repair cosmetics are mainly designed around moisturizing, soothing, anti-inflammatory, and barrier repair. Existing technologies only focus on lipid replenishment, nerve calming, and inflammation suppression. Research on the biomechanical homeostasis of the basement membrane and mechanosensitive signaling pathways is limited, especially on the Piezo-mediated mechanotransduction pathway. Currently, there is a lack of cosmetic compositions that can simultaneously repair the basement membrane structure and regulate mechanosensitive signals. Aberrant Piezo activation is a key intermediate mediator in skin damage induced by basement membrane biomechanical disturbances. Targeting Piezo to regulate mechanotransduction and restore basement membrane biomechanical homeostasis is a novel core strategy for sensitive skin repair.

[0006] Based on the above description, current sensitive skin care techniques still have the following shortcomings:

[0007] 1. Existing sensitive skin repair technologies have relatively singular targets, focusing mainly on conventional approaches such as moisturizing, anti-inflammation, and nerve soothing. They pay less attention to the regulation of the biomechanical homeostasis and mechanical microenvironment of the skin's basement membrane, making it difficult to fundamentally improve the core problems of loose basement membrane structure and mechanical imbalance.

[0008] 2. Currently, research on the application of Piezo mechanosensitive ion channels in sensitive skin care is relatively limited, and there is a lack of cosmetic technology solutions that can effectively regulate Piezo-mediated mechanotransduction.

[0009] 3. In the currently published literature and patent technology, there are no reports on the application of the andrographolide and Gly-Met-Hyp tripeptide compound system in the repair of sensitive skin, and there are also few disclosures on the technology of this compound system to repair sensitive skin by regulating Piezo channels, stabilizing the mechanical structure of the basement membrane, and blocking the abnormal mechanical signal transmission of the skin.

[0010] 4. Repairing sensitive skin often involves intervention with a single active ingredient. The effect of a single active ingredient on the regulation of the Piezo pathway and the repair of the biomechanical homeostasis of the basement membrane is relatively limited. Further research is needed on the synergistic regulation of the biomechanical homeostasis of the basement membrane and the mechanosensitive signaling pathway among different active components.

[0011] A previously disclosed technology (CN118986771A) discloses a composition containing andrographolide and recombinant human type XVII collagen, and discloses its application in improving skin sensitivity; the composition mainly exerts its skin repair effect by supplementing basement membrane-associated structural proteins.

[0012] However, this regimen uses recombinant human type XVII collagen as the active component, which is a large, fully functional protein. Its mechanism of action is to directly replenish the structural raw materials of the basement membrane exogenously, and it can only exert a static barrier repair effect from the single dimension of "replenishing collagen." There is no record of its role in regulating the expression of key basement membrane components such as type IV collagen and laminin, improving the biomechanical homeostasis of the basement membrane, or the Piezo-mediated mechanosensitive signal transduction process. Furthermore, it does not involve Ca2+. 2+ Regulation of the YAP mechano-signaling pathway in the improvement of sensitive skin.

[0013] Therefore, it is still necessary to develop an active composition that can synergistically regulate the structural homeostasis of the basement membrane and the mechanosensitive signaling pathway to further enhance the effect of improving sensitive skin. Summary of the Invention

[0014] This invention provides a composition for regulating the biomechanical homeostasis of the skin basement membrane and its application. Unlike traditional exogenous supplementation strategies using large-molecule proteins, the GMH tripeptide in this composition is a small-molecule active peptide that does not directly provide collagen structural raw materials. Instead, it actively upregulates the synthesis and expression of two key basement membrane collagen molecules, COL4A1 and COL17A1, by regulating the transcription of endogenous genes in keratinocytes. Simultaneously, this composition can target and regulate the Piezo-mediated Ca2+ flow in the mechanosensitive ion channel. 2+ Overactivation of the influx and downstream YAP pathways can block the vicious cycle of "basement membrane mechanical imbalance - mechanical signal amplification - increased inflammation" from the source of mechanosensory perception.

[0015] The technical solution of the present invention:

[0016] A composition for regulating the biomechanical homeostasis of the skin basement membrane, the composition comprising andrographolide and Gly-Met-Hyp tripeptide; the mass concentration ratio of andrographolide and Gly-Met-Hyp tripeptide is 1:5 to 1:20, and the GMH tripeptide is described in detail in the authorized patent, authorized publication number CN121537474B.

[0017] In the aforementioned composition for regulating the biomechanical homeostasis of the skin basement membrane, the mass concentration ratio of andrographolide to Gly-Met-Hyp tripeptide is 1:15.

[0018] Application of a composition that regulates the biomechanical homeostasis of the skin's basement membrane in the preparation of cosmetics that improve sensitive skin.

[0019] In the application of the aforementioned composition in the preparation of cosmetics for improving sensitive skin, the composition achieves the effect of improving sensitive skin by regulating the biomechanical homeostasis of the skin's basement membrane.

[0020] In the application of the aforementioned composition in the preparation of cosmetics for improving sensitive skin, the regulation of biomechanical homeostasis of the skin basement membrane includes the regulation of Piezo-mediated mechanotransduction.

[0021] In the application of the aforementioned composition in the preparation of cosmetics for improving sensitive skin, the composition regulates Piezo-Ca. 2+ -YAP signal axis achieves the effect of improving sensitive skin.

[0022] In the application of the aforementioned composition in the preparation of cosmetics for improving sensitive skin, the improvement of sensitive skin includes improving one or more of skin redness, stinging, burning, and itching, and increasing the expression of type IV collagen and / or type XVII collagen.

[0023] Compared with the prior art, the beneficial effects of this application are as follows:

[0024] 1) The composition of andrographolide and Gly-Met-Hyp tripeptide provided by the present invention has a significant synergistic effect under a specific ratio; the synergistic index CI calculation results are all less than 1, indicating that the combined use of the two active components can produce a synergistic effect, and its regulatory effect on relevant biological indicators is better than that of each active component used alone.

[0025] 2) The composition can synergistically downregulate TRPV1 gene expression, reduce the neuroreactivity caused by skin mechanical stimulation, and help relieve discomfort symptoms such as stinging and burning in sensitive skin;

[0026] 3) The composition of the present invention can synergistically promote the expression of basement membrane-related structural proteins, increase the expression levels of COL4A1 and COL17A1 genes, and help maintain the structural integrity and biomechanical homeostasis of the basement membrane;

[0027] 4) The composition of this invention can modulate Piezo1-mediated mechanotransduction and reduce the calcium deficiency induced by mechanical stimulation. 2+ Abnormal influx and regulation of YAP signaling pathway activity can reduce mechanical stimulation-induced cellular responses, providing a new intervention approach for improving pathological processes related to sensitive muscle.

[0028] 5) The composition of the present invention can reduce the expression levels of inflammatory factors such as IL-6, IL-8 and COX-2, alleviate mechanical stimulation-induced inflammatory responses, and help improve adverse conditions such as redness in sensitive skin;

[0029] 6) Compared with the existing technical solutions that use exogenous supplementation of type XVII collagen, the present invention uses andrographolide and Gly-Met-Hyp tripeptide to promote the expression of basement membrane-related structural proteins and regulate mechanical signaling pathways, thereby synergistically achieving the repair of basement membrane structural homeostasis and the remodeling of the skin's mechanical microenvironment, providing a brand-new technical solution for sensitive skin care.

[0030] 7) This application innovatively targets and regulates Piezo-Ca 2+ -YAP mechanical signal transduction axis, this regulatory dimension has not yet been addressed by existing sensitive skin repair technologies; this invention regulates Piezo-Ca 2+ -YAP mechano-signaling pathway effectively regulates the biomechanical homeostasis of the basement membrane, making up for the shortcomings of existing technologies that only focus on surface repair and lack targeted regulation of mechano-pathways, and providing a brand-new research and development idea and technical direction for the mechanism-based repair of sensitive skin. Attached Figure Description

[0031] Figure 1 This is a graph showing the effect of different proportions of the composition in Experiment 1 on the relative expression level of COL4A1;

[0032] Figure 2This is a graph showing the effect of Experiment 2 on TRPV1 mRNA expression levels;

[0033] Figure 3 This is a graph showing the effect of Experiment 3 on the expression level of COL4A1 mRNA, a key component of the basement membrane;

[0034] Figure 4 This is a graph showing the effect of Experiment 3 on the expression level of COL17A1 mRNA, a key component of the basement membrane;

[0035] Figure 5 This is a graph showing the effect of Experiment 4 on PIEZO1 mRNA expression levels;

[0036] Figure 6 This is the intracellular calcium ion fluorescence intensity diagram from Experiment 4;

[0037] Figure 7 This is a graph showing the effect of Experiment 4 on YAP mRNA expression levels;

[0038] Figure 8 This is a graph showing the effect of Experiment 5 on the secretion level of the inflammatory factor IL-6;

[0039] Figure 9 This is a graph showing the effect of Experiment 5 on the secretion level of the inflammatory factor IL-8;

[0040] Figure 10 This is a graph showing the effect of Experiment 5 on the secretion level of the inflammatory factor COX-2. Detailed Implementation

[0041] The present invention will be further described below with reference to the accompanying drawings and embodiments, but this should not be construed as limiting the present invention.

[0042] Example

[0043] A composition for regulating the biomechanical homeostasis of the skin basement membrane, the composition comprising andrographolide and Gly-Met-Hyp tripeptide; wherein the mass concentration ratio of andrographolide to Gly-Met-Hyp tripeptide is 1:15.

[0044] The amino acid sequence of the Gly-Met-Hyp tripeptide is: glycine-methionine-hydroxyproline, and its molecular weight is 319.

[0045] The composition also includes one or more cosmetically acceptable excipients.

[0046] The composition can be used to prepare serums, lotions, creams, gels, sprays, masks or freeze-dried formulations.

[0047] Application of a composition that regulates the biomechanical homeostasis of the skin's basement membrane in the preparation of cosmetics that improve sensitive skin.

[0048] The composition improves sensitive skin by regulating the biomechanical homeostasis of the skin's basement membrane.

[0049] Regulating the biomechanical homeostasis of the skin basement membrane includes regulating Piezo-mediated mechanotransduction.

[0050] The composition modulates Piezo-Ca 2+ -YAP signal axis achieves the effect of improving sensitive skin.

[0051] Improving sensitive skin includes reducing one or more of the following symptoms: redness, stinging, burning, and itching, and increasing the expression of type IV and / or type XVII collagen.

[0052] Mechanism Explanation

[0053] It should be noted that the Gly-Met-Hyp tripeptide used in this application is a small molecule tripeptide, whose molecular weight is significantly lower than that of large molecule proteins such as recombinant human type XVII collagen in the prior art;

[0054] Unlike strategies that directly supplement collagen monomers from the outside, Gly-Met-Hyp tripeptide does not serve as a raw material for the basement membrane structure. Instead, it promotes the cell's own synthesis of COL4A1 and COL17A1 by regulating the cell's endogenous transcriptional activity.

[0055] Furthermore, this application is the first to discover Piezo-Ca. 2+ - The YAP signaling axis plays a core mediating role in the mechanotransmission of sensitive muscles. The combination system of andrographolide and Gly-Met-Hyp tripeptide can synergistically inhibit the overactivation of this signaling axis, thereby blocking the occurrence of sensitivity from the upstream of mechanosensory.

[0056] The mechanism of action described above is fundamentally different from existing technologies that improve the epidermal barrier by simply supplementing with type XVII collagen exogenously.

[0057] Verification Experiment

[0058] Experiment 1: Effect of different proportions of the composition on the relative expression level of COL4A1

[0059] 1.1 Sensitive muscle cell model constructed by treating keratinocytes (HaCaT) with 10 μM capsaicin (CAP) for 24 h; blank control group, CAP model group and sample group were set up;

[0060] The compositions in the sample group included three compound systems with andrographolide (AG) and Gly-Met-Hyp tripeptide (GMH) in ratios of 1:10, 1:15 and 1:20; specifically, andrographolide (AG) was 2 ppm, and Gly-Met-Hyp tripeptide (GMH) was 20 ppm, 30 ppm and 40 ppm respectively.

[0061] 1.2 Experimental Results

[0062] The results are as follows Figure 1 As shown in the table (Note: Statistical analysis was performed between groups. Compared with group BC, "*" indicates significance, ***P<0.001, **P<0.01, *P<0.05; compared with group CAP, "#" indicates significance, ###P<0.001, ##P<0.01, #P<0.05; compared with single sample groups, "&" indicates significance, &&&P<0.001, &&P<0.01, &P<0.05), compared with the blank control group, the COL4A1 mRNA expression level in the CAP model group was significantly downregulated, proving that CAP stimulation causes insufficient synthesis of the skin basement membrane structural protein COL4A1, thereby affecting basement membrane homeostasis;

[0063] Compared to the CAP lesion model group, the expression level of COL4A1 was upregulated to varying degrees after CAP was combined with different proportions of the composition. The 1:15 composition group showed a significantly stronger effect on improving COL4A1 expression than the other two composition groups. Therefore, the 1:15 composition group was used in subsequent experiments.

[0064] Experiment 2: Synergistic effect of the composition on the relative expression level of TRPV1

[0065] 2.1 Sensitive muscle cell model constructed by treating keratinocytes (HaCaT) with 10 μM capsaicin (CAP) for 24 h; blank control group, CAP model group and sample group were set up;

[0066] The composition in the sample group included andrographolide (AG) at a dose concentration of 2 ppm and Gly-Met-Hyp tripeptide (GMH) at a dose concentration of 30 ppm.

[0067] The effects of the composition on the regulation of key components and biomechanical homeostasis of the basement membrane were evaluated by detecting changes in Piezo / TRPV1, YAP pathway, calcium ion fluorescence intensity, and key components of the basement membrane using RT-qPCR and fluorescent probe methods.

[0068] Table 1 Experimental group design

[0069]

[0070] Note: Blank control (BC); modeling stimulant (CAP); sample group (AG); tripeptide (Gly-Met-Hyp).

[0071] 2.2 Experimental Test Results

[0072] Table 2. Synergistic effect of the composition on relative TRPV1 expression level

[0073]

[0074] Note: The data in the table are mainly based on the combined effect calculation of the model group; the non-model group is only used as a control. The combined effect of the composition is evaluated based on the Bliss independent model, i.e., the combination index CI = (EA + EB - EA * EB) / EAB. If the synergistic effect value CI < 1, then the combination of A and B has a synergistic effect; otherwise, the combination of A and B has an antagonistic effect.

[0075] The results are as follows Figure 2 As shown in the table (Note: Statistical analysis was performed between the groups. Compared with the BC group, "*" indicates significance, ***P<0.001, **P<0.01, *P<0.05; compared with the CAP group, "#" indicates significance, ###P<0.001, ##P<0.01, #P<0.05; compared with the single sample group, "&" indicates significance, &&&P<0.001, &&P<0.01, &P<0.05), compared with the blank control group, the TRPV1 mRNA expression level in the CAP model group was significantly upregulated, the model was successfully constructed, and it can simulate the hyperresponsive state of skin nerves;

[0076] After treatment with CAP in combination with GMH, AG single components or combinations, the expression level of TRPV1 mRNA was downregulated in each group compared with the CAP model group.

[0077] The combination intervention group showed the most significant downregulation of TRPV1 mRNA;

[0078] Based on the results of the Bliss model synergistic index calculation, it can be seen that the compound composition has a significantly better effect on inhibiting TRPV1 mRNA expression than the single active components GMH and AG, and there is a synergistic inhibitory effect. This indicates that the composition can synergistically downregulate TRPV1 mRNA expression, thereby alleviating CAP-induced skin nerve hyperresponsiveness.

[0079] Experiment 3: Synergistic effect of the composition on the relative expression levels of COL4A1 and COL17A1

[0080] 3.1 The experimental design is as in Experiment 2.

[0081] 3.2 Experimental Test Results

[0082] Table 3. Synergistic effect of the composition on the relative expression level of COL4A1, a key component of the basement membrane.

[0083]

[0084] Table 4. Synergistic effect of the composition on the relative expression level of COL17A1, a key component of the basement membrane.

[0085]

[0086] Note: The data in the table are mainly based on the combined effect calculation of the model group; the non-model group is only used as a control. The combined effect of the composition is evaluated based on the Bliss independent model, i.e., the combination index CI = (EA + EB - EA * EB) / EAB. If the synergistic effect value CI < 1, then the combination of A and B has a synergistic effect; otherwise, the combination of A and B has an antagonistic effect.

[0087] The results are as follows Figure 3 and Figure 4 As shown, compared with the blank control group, the mRNA expression levels of basement membrane-related genes COL4A1 and COL17A1 in the CAP stimulation group were significantly reduced, suggesting that CAP-induced mechanical stimulation may lead to a decrease in the ability to synthesize basement membrane-related structural proteins and affect the structural homeostasis of the skin basement membrane.

[0088] Compared with the CAP damage model group, the expression levels of COL4A1 and COL17A1 were upregulated to varying degrees after CAP was combined with GMH, AG single components or combination. Among them, the combination group showed a significantly better repair and enhancement effect on the expression of the two basement membrane proteins than the GMH and AG single active ingredients group.

[0089] The results of the Bliss model synergistic index calculation show that, for the two basement membrane indices COL4A1 and COL17A1, the combined system exhibits significantly better repair activity than the single active component, demonstrating a synergistic repair effect.

[0090] The above results indicate that the compound composition can synergistically reverse the decrease in expression of key basement membrane proteins caused by CAP, promote the synthesis of COL4A1 and COL17A1, improve the basement membrane structure, stabilize the underlying support structure of the skin barrier, and improve the sensitive and fragile state of the skin from the basement membrane level.

[0091] Experiment 4: Effect of the composition on Piezo-Ca 2+ - Synergistic effect of relative expression levels of key indicators in the YAP signaling pathway

[0092] 4.1 The experimental design is as in Experiment 2.

[0093] 4.2 Experimental Test Results

[0094] Table 5. Synergistic effect of the composition on the relative expression level of PIEZO1

[0095]

[0096] Table 6. Effects of the composition on Ca 2+ Synergistic effect of relative fluorescence intensity level

[0097]

[0098] Table 7. Synergistic effect of the composition on relative YAP expression levels

[0099]

[0100] Note: The data in the table are mainly based on the combined effect calculation of the model group; the non-model group is only used as a control. The combined effect of the composition is evaluated based on the Bliss independent model, i.e., the combination index CI = (EA + EB - EA * EB) / EAB. If the synergistic effect value CI < 1, then the combination of A and B has a synergistic effect; otherwise, the combination of A and B has an antagonistic effect.

[0101] The results are as follows Figure 5-7 As shown, compared with the blank control group, the expression levels of PIEZO1 mRNA, intracellular calcium ion fluorescence intensity, and YAP mRNA were significantly increased in the CAP model group, indicating that CAP induction successfully activated Piezo-Ca. 2+ -YAP signal path;

[0102] Compared with the CAP model group, the CAP+GMH group, CAP+AG group, and CAP+ combination group all downregulated the mRNA expression of PIEZO1 and YAP to varying degrees and reduced the intracellular calcium ion fluorescence intensity. Among them, the CAP+ combination group showed the best inhibitory effect on the three pathway indicators.

[0103] Based on the synergistic index calculated by the Bliss model, it can be found that the combined system has better regulation than the single active components GMH and AG for the three detection targets PIEZO1, calcium ion signal and YAP, and has synergistic effect.

[0104] The above results indicate that the composition can synergistically inhibit abnormal activation of Piezo channels, block the massive influx of extracellular calcium ions, and simultaneously reduce the overactivation of downstream YAP pathways, thereby blocking the sensitive cascade response triggered by mechanical stimulation of sensitive muscles from the upstream of mechanosensory perception.

[0105] Experiment 5: The composition has anti-inflammatory effects.

[0106] 5.1 Sensitive muscle cell model constructed by treating keratinocytes (HaCaT) with 10 μM capsaicin (CAP) for 24 h; blank control group, CAP model group and sample group were set up;

[0107] The composition in the sample group included andrographolide (AG) at a dose concentration of 2 ppm and Gly-Met-Hyp tripeptide (GMH) at a dose concentration of 30 ppm.

[0108] The anti-inflammatory effect of the composition was evaluated by detecting inflammatory factor-related indicators using ELISA.

[0109] Table 8 Experimental Group Design

[0110]

[0111] Note: Blank control (BC); modeling stimulant (CAP); sample group (AG); tripeptide (Gly-Met-Hyp).

[0112] 5.2 Experimental Test Results

[0113] Table 9. Synergistic effect of the composition on the secretion level of the inflammatory cytokine IL-6

[0114]

[0115] Table 10 Synergistic effect of the composition on the secretion level of the inflammatory cytokine IL-8

[0116]

[0117] Table 11 Synergistic effect of the composition on the secretion level of the inflammatory cytokine COX-2

[0118]

[0119] Note: The data in the table are mainly based on the combined effect calculation of the model group; the non-model group is only used as a control. The combined effect of the composition is evaluated based on the Bliss independent model, i.e., the combination index CI = (EA + EB - EA * EB) / EAB. If the synergistic effect value CI < 1, then the combination of A and B has a synergistic effect; otherwise, the combination of A and B has an antagonistic effect.

[0120] The results are as follows Figure 8-10 As shown, compared with the blank control group, the secretion of inflammatory factors IL-6, IL-8 and COX-2 in the cell supernatant of the CAP model group was significantly increased, indicating that CAP stimulation can effectively induce cellular inflammatory response.

[0121] Compared with the CAP model group, after intervention with CAP combined with GMH, AG single active substances or combinations, the release levels of the three inflammatory factors all decreased to varying degrees. Among them, the CAP combined with combination group had the most significant inhibitory effect on the secretion of IL-6, IL-8 and COX-2 among all intervention groups.

[0122] The results of the Bliss model synergistic index analysis show that the inhibitory activity of the combined system against the three inflammatory markers is better than that of GMH and AG as single active components, indicating a synergistic inhibitory effect.

[0123] The above results demonstrate that the compound composition can synergistically weaken the massive release of pro-inflammatory factors induced by CAP, inhibit the excessive secretion of inflammatory mediators, effectively alleviate the cellular inflammatory response induced by CAP stimulation, and reduce the inflammatory stress damage associated with sensitive skin.

Claims

1. A composition for regulating the biomechanical homeostasis of the skin basement membrane, characterized in that: The composition comprises andrographolide and Gly-Met-Hyp tripeptide; the mass concentration ratio of andrographolide and Gly-Met-Hyp tripeptide is 1:5 to 1:

20.

2. The composition for regulating the biomechanical homeostasis of the skin basement membrane according to claim 1, characterized in that: The mass concentration ratio of andrographolide to Gly-Met-Hyp tripeptide is 1:

15.

3. The use of the composition according to any one of claims 1 to 2 in the preparation of cosmetics for improving sensitive skin.

4. The use of the composition according to claim 3 in the preparation of cosmetics for improving sensitive skin, characterized in that: The composition improves sensitive skin by regulating the biomechanical homeostasis of the skin's basement membrane.

5. The use of the composition according to claim 4 in the preparation of cosmetics for improving sensitive skin, characterized in that: The regulation of biomechanical homeostasis of the skin basement membrane includes the regulation of Piezo-mediated mechanotransduction.

6. The use of the composition according to claim 3 in the preparation of cosmetics for improving sensitive skin, characterized in that: Piezo-Ca was regulated by the composition. 2+ -YAP signal axis achieves the effect of improving sensitive skin.

7. The use of the composition according to claim 3 in the preparation of cosmetics for improving sensitive skin, characterized in that: The improvement of sensitive skin includes improving one or more of the following: redness, stinging, burning, and itching, and increasing the expression of type IV collagen and / or type XVII collagen.

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