Application of novel peptide UPCP in preparation of medicine for treating and / or preventing psoriasis

Abstract

The invention discloses an application of a novel peptide UPCP in preparation of a medicine for treating and / or preventing psoriasis. Belongs to the technical field of biological medicine. The application discloses the treatment effect of the novel peptide UPCP on psoriasis for the first time, and researches find that the novel peptide UPCP can effectively relieve symptoms of a psoriasis model induced by LSP, TNF alpha and M2 in an in-vitro cell experiment, significantly down-regulate the expression level of psoriasis cell markers, significantly reduce the transcriptional level of psoriasis-related inflammatory factors, and improve the psoriasis treatment effect. The condition of excessive proliferation of HaCaT cells is effectively reduced. In in-vivo experiments, psoriasis symptoms such as skin desquamation, hyperplasia, erythema, thickening and splenomegaly of an imiquimod-induced psoriasis mouse model can be effectively relieved, the effect of treating psoriasis is achieved, and a new theoretical basis and intervention means are provided for clinical treatment of psoriasis.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and more specifically to the application of a novel peptide UPCP in the preparation of drugs for the treatment and / or prevention of psoriasis. Background Technology

[0002] psoriasis( Psoriasis Chronic inflammatory skin disease (CISD) is a common autoimmune chronic inflammatory skin disease with a global prevalence of approximately 2%-3%. The World Health Organization (WHO) has listed it as an important non-communicable disease. This disease causes red patches on the skin covered with silvery-white scales, often accompanied by itching and burning sensations. It can also lead to nail damage and joint destruction, significantly increasing the risk of comorbidities such as cardiovascular disease, metabolic syndrome, and depression. It severely impacts patients' quality of life and mental and physical health, and has become a major global public health burden.

[0003] The pathogenesis of psoriasis is complex, involving the interaction of genetic, environmental, and immune factors. At its core lies the abnormal activation of the innate and adaptive immune systems, and the excessive proliferation and dysdifferentiation of epidermal keratinocytes. Current research elucidates a key pathway that begins with external stimuli triggering the release of the antimicrobial peptide LL37 from keratinocytes. This peptide, combined with the keratinocyte's own nucleic acid, forms a complex that can be recognized by plasmacytoid dendritic cells (pDCs), initiating a type I interferon response. Subsequently, activated myeloid dendritic cells (mDCs) migrate to lymph nodes, secreting cytokines such as IL-23 and TNF-α. IL-23 is crucial for maintaining Th17 cell function, prompting them to continuously produce effector factors such as IL-17A and IL-22. IL-17A can directly drive abnormal proliferation and recruit more inflammatory cells by activating signaling pathways such as NF-κB and JAK-STAT within keratinocytes, forming a positive feedback loop of the IL-23 / IL-17 inflammatory axis. IL-22, on the other hand, inhibits terminal differentiation of keratinocytes, leading to epidermal barrier dysfunction. This complex network of immune-epidermal interactions forms the cornerstone of the pathological manifestations of psoriasis.

[0004] Based on the above mechanisms, current clinical treatments mainly revolve around regulating key immune targets or directly inhibiting excessive epidermal proliferation, including: (1) immune-targeting biological agents (such as antibodies against TNF-α and the IL-23 / IL-17 axis), which are effective but expensive and pose potential infection risks; (2) traditional chemotherapy drugs (such as topical corticosteroids, vitamin D analogs, and systemic drugs such as methotrexate and retinoic acid), which may cause side effects such as liver and kidney damage, skin atrophy, and osteoporosis with long-term use; and (3) physical therapy (such as UVB phototherapy and PUVA), which may increase the risk of skin cancer with long-term use and is not convenient. Therefore, there is an urgent need to develop new, efficient, and safer treatment strategies in clinical practice.

[0005] In recent years, peptide drugs have shown great potential in the treatment of autoimmune diseases due to their advantages such as small molecular weight, strong targeting, low immunogenicity, and relatively low toxicity. For example, the oral IL-23 receptor antagonist peptide JNJ-2113 showed significant efficacy and durability in a phase II clinical trial for the treatment of moderate to severe plaque psoriasis, demonstrating the feasibility of using peptides to intervene in key pathogenic pathways. However, peptide drugs for the treatment of psoriasis remain scarce globally, with the vast majority still in the preclinical or clinical research stage, and only a handful already on the market.

[0006] Therefore, designing and developing novel peptide drugs to more precisely and safely regulate the immune-epidermal interaction network in response to the complex pathogenesis of psoriasis has significant clinical implications and application prospects. Summary of the Invention

[0007] In view of this, the present invention provides an application of a novel peptide UPCP in the preparation of drugs for the treatment and / or prevention of psoriasis, in order to solve the problems of large side effects, high price and limited efficacy of existing psoriasis treatments, and to provide a new and effective means for the clinical treatment of psoriasis.

[0008] To achieve the above objectives, the present invention adopts the following technical solution:

[0009] The primary objective of this application is to provide the use of a novel peptide UPCP in the preparation of medicaments for the treatment and / or prevention of psoriasis.

[0010] As a preferred technical solution, the novel peptide UPCP is composed of 47 L-type amino acids, including the transmembrane peptide HIV-TAT, and its amino acid sequence is as follows: Novel peptide UPCP: YGRKKRRQRRRYNLRSRTVLCGTCGQPADKASASGSGAQS PQNCSIM, SEQ IDNO.1.

[0011] Another object of this application is to provide a medicine for treating and / or preventing psoriasis, comprising the novel peptide UPCP or a novel peptide UPCP with a labeling group.

[0012] As a preferred technical solution, the medicament for treating and / or preventing psoriasis also includes other pharmaceutical excipients and / or other functional active ingredients.

[0013] As a preferred technical solution, the drug exerts its therapeutic effect by downregulating the transcriptional levels of psoriasis-related inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2.

[0014] As a preferred technical solution, the drug exerts its therapeutic effect by reducing the excessive proliferation of keratinocytes.

[0015] As a preferred technical solution, the drug exerts its therapeutic effect by reducing the cell migration rate of keratinocytes.

[0016] As a preferred technical solution, the drug exerts its therapeutic effect by improving skin desquamation, erythema, epidermal hyperplasia, and splenomegaly.

[0017] As a preferred technical solution, the drug is a topical preparation.

[0018] As a preferred technical solution, the topical preparation includes ointment, cream, gel, lotion, solution, spray or patch.

[0019] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects: This application discloses for the first time the therapeutic effect of a novel peptide UPCP: YGRKKRRQRRRYNLRSRTVLCGTCGQPADKASASGSGAQSPQNCSIM, SEQ ID NO.1, on psoriasis. Studies have shown that this novel peptide UPCP can effectively alleviate symptoms in an in vitro cell model of psoriasis induced by LSP, TNFα, and M2, significantly downregulate the expression levels of psoriasis cell markers KRT6, KRT16, and KRT17, significantly reduce the transcription levels of psoriasis-related inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2, effectively reduce excessive proliferation of HaCaT cells, and inhibit the migration ability of HaCaT cells mediated by LSP, TNFα, and M2. In in vivo experiments, it can effectively alleviate psoriasis symptoms such as desquamation, hyperplasia, erythema, thickening, and splenomegaly in an imiquimod-induced psoriasis mouse model, demonstrating a therapeutic effect on psoriasis and providing a new theoretical basis and intervention method for the clinical treatment of psoriasis. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0021] Figure 1The study aimed to analyze the effect of UPCP on HaCaT cell viability. Specifically, A: the CCK8 assay was used to detect the effect of different concentrations of UPCP on HaCaT cell growth; B: the effect of different concentrations of UPCP on HaCaT cell viability.

[0022] Figure 2 The study focused on the construction of an in vitro cell model of psoriasis. A: Western blot analysis of the effects of different concentrations of LPS on the expression of HaCaT cell keratin markers KRT6, KRT16, and KRT17; B: Western blot analysis of the effects of different concentrations of TNFα on the expression of HaCaT cell keratin markers KRT6, KRT16, and KRT17; C: Western blot analysis of the effects of M2 on the expression of HaCaT cell keratin markers KRT6, KRT16, and KRT17; D: Real-time PCR analysis of the effects of LPS addition on the expression of HaCaT cell keratin markers KRT6, KRT16, and KRT17; E: Real-time PCR analysis of the effects of TNFα addition on the expression of HaCaT cell keratin markers KRT6, KRT16, and KRT17; F: Real-time PCR analysis. The effects of LPS addition on the expression of inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2 in HaCaT cells were detected; G: Real-time PCR was used to detect the effects of TNFα addition on the expression of inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2 in HaCaT cells.

[0023] Figure 3 The effects of LPS, TNF-α, and M2 on the migration ability of HaCaT cells are as follows: A: Representative images of the effects of LPS, TNF-α, and M2 on HaCaT cell migration detected by scratch assay, scale bars=250 μm; B: Quantitative statistical analysis of cell migration rate in A.

[0024] Figure 4The study aimed to improve the phenotype of LPS, TNF-α, and M2-induced HaCaT psoriasis in vitro cell models. Specifically: A: Western blot analysis of the effect of different concentrations of UPCP on the expression of keratin markers KRT6, KRT16, and KRT17 in HaCaT cell models; B: Real-time PCR analysis of the effect of UPCP addition on the expression of inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2 in LPS-induced HaCaT cell models; C: Real-time PCR analysis of the effect of UPCP addition on the expression of inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2 in TNF-α-induced HaCaT cell models; D: Real-time PCR analysis. The effects of UPCP addition on the expression of inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2 in the M2-induced HaCaT cell model were examined. E: CCK8 assay to detect the effect of UPCP on LPS-induced HaCaT cell viability; F: CCK8 assay to detect the effect of UPCP on TNF-α-induced HaCaT cell viability; G: CCK8 assay to detect the effect of UPCP on M2-induced HaCaT cell viability; H: Representative images of the effect of UPCP on the migration ability of LPS, TNF-α, and M2-induced HaCaT cell models, scale bars=250 μm, detected by scratch assay; I-K: Quantitative statistical analysis of cell migration rate in H.

[0025] Figure 5 The following are the effects of different administration methods on mouse skin: A: Schematic diagram of different administration methods of UPCP; B: Representative images of the morphological effects of different administration methods on mouse skin epidermis; C: Representative images of the effects of different administration methods of UPCP on mouse skin tissue detected by HE staining, e represents the epidermis, d represents the dermis, scale bars=200μm; D: Statistical analysis of the effects of different administration methods of UPCP on immune infiltration in mouse skin tissue; E: Statistical analysis of the effects of different administration methods of UPCP on epidermal thickness in mouse skin tissue.

[0026] Figure 6 The following data are presented: FITC-UPCP uptake in mouse skin tissue; A: Schematic diagram of FITC-UPCP application at different time points; B: Detection of FITC-UPCP uptake in mouse skin at different time points using a small animal imaging system; C: Detection of FITC-UPCP uptake in mouse skin at different time points using an immunofluorescence assay.

[0027] Figure 7The objectives are as follows: UPCP improves the imiquimod (IMQ)-induced psoriasis phenotype in mice; A: Schematic diagram of constructing an imiquimod-induced mouse psoriasis model; B: Schematic diagram of indicator detection after intervention in the psoriasis mouse model; C: Representative images of the morphological effects of UPCP on mouse skin epidermis; D: PASI scores of mice in the control group, model group, model treatment group, and positive control group for 7 consecutive days; E: Statistical analysis of PASI scores of mouse skin tissue in different treatment groups; F: HE staining and immunohistochemical experiments to detect skin genomic characteristics and Ki67 expression in different treatment groups; G: Statistical analysis of immune infiltration in mouse skin tissue in untreated groups; H: Statistical analysis of epidermal thickness in mouse skin tissue in untreated groups; I: Statistical analysis of Ki67 expression in mouse skin tissue in different treatment groups.

[0028] Figure 8 The objectives are: the effects of UPCP on mouse body weight and spleen; A: changes in body weight of mice in different treatment groups over time; B: quantitative analysis of body weight of mice in different treatment groups; C: representative images of the effects of different treatment groups on the spleen of mice; D: statistical analysis of spleen index of mice in different treatment groups. Detailed Implementation

[0029] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0030] Example 1 The application of a novel peptide UPCP in the preparation of drugs for the treatment and / or prevention of psoriasis; the novel peptide UPCP is composed of 47 L-amino acids, including the transmembrane peptide HIV-TAT (this polypeptide sequence is derived from the C-terminal 36 amino acids of progerin, a pathogenic protein of progerin in children (abbreviated as progerin-C36). To increase the transmembrane properties of the polypeptide, a transmembrane peptide sequence consisting of 11 classical amino acids is added to the N-terminus of the progerin-C36 amino acid sequence, together forming the unique progerin C-terminal peptide (UPCP), the amino acid sequence of which is as follows: Novel peptide UPCP: YGRKKRRQRRRYNLRSRTVLCGTCGQPADKASASGSGAQSPQNCSIM, SEQ IDNO.1.

[0031] Example 2 Cellular safety analysis of the novel peptide UPCP Cell viability assay: The effect of the novel peptide UPCP, a synthetically produced polypeptide, on the proliferation of immortalized human keratinocytes (HaCaT, STCC11801P) remains unclear. To investigate whether UPCP affects HaCaT cell viability, three different concentration gradients were established for the peptide, as detailed below: Experimental group 1: HaCaT cells were cultured in DMEM complete medium with a final concentration of 3 μM UPCP; Experimental group 2: HaCaT cells were cultured in DMEM complete medium with a final concentration of 6 μM UPCP; Experimental group 3: HaCaT cells were cultured in DMEM complete medium with a final concentration of 12 μM UPCP; Control group: DMEM complete culture medium (Vehicle); HaCaT cells were cultured in the four culture media mentioned above, and their viability was detected at 24h, 48h, and 72h using the Cell Counting Kit-8 (CCK-8) (APExBIO k1018) assay. Cell growth curves were then plotted. Figure 1 A), and calculated the cell viability of HaCaT cells after 72 hours of culture based on monitoring data. Figure 1 B).

[0032] Results analysis: such as Figure 1 As shown, the selected doses of UPCP did not have a significant effect on HaCaT cell growth, and preliminary assessments indicated that low concentrations of UPCP had no significant cytotoxicity.

[0033] Example 3 An Investigation into the Effects of Novel Peptide UPCP on Improving the Effects of Different Factors-Induced HaCaT Psoriasis In Vitro Cell Model (1) Establishment of HaCaT in vitro cell model of psoriasis Healthy HaCaT cells were cultured, and when the cell confluence reached 50%-60%, HaCaT cells were cultured in DMEM complete medium containing different inducing factors to establish LPS, TNFα, and M2 (TNFα+IL17A) induced HaCaT psoriasis in vitro cell models, as detailed below: 1) LPS-induced model: HaCaT cells were cultured for 24 h in complete medium containing LPS at final concentrations of 2.5 μg / mL, 5 μg / mL, and 10 μg / mL, respectively.

[0034] 2) TNFα-induced model: HaCaT cells were cultured for 24 h in complete culture medium containing final concentrations of 5 ng / ml TNF-α, 10 ng / ml TNF-α and 20 ng / ml TNF-α, respectively.

[0035] 3) M2 induction model: HaCaT cells were cultured for 24 h in complete medium containing IL17A and TNFα (M2) at a final concentration of 50 ng / mL.

[0036] 4) Control group (Vehicle): HaCaT cells were cultured for 24 h in a complete medium containing an equal volume of solvent (commercial dimethyl sulfoxide, i.e. DMSO).

[0037] Proteins were extracted from the three cell models after culturing for 24 h, and Western blot was used to detect the expression of psoriasis cell markers KRT6, KRT16, and KRT17 proteins.

[0038] Results analysis: As shown in Figures 2A-C, the results indicate that the expression of psoriasis cell markers KRT6, KRT16, and KRT17 was significantly increased in cells after 24 h of treatment with LPS, TNF-α, and M2.

[0039] RNA was extracted from cells in each group, and after reverse transcription, qPCR was performed to detect the transcriptional levels of psoriasis cell markers KRT6, KRT16, KRT17, and psoriasis-related inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2. The experimental results are as follows: Figure 2 As shown in DE, compared with the control group (Vehicle), the transcription levels of psoriasis cell markers KRT6, KRT16, and KRT17 in HacaT cells treated with a final concentration of 5 μg / mL LPS and 10 ng / mL TNFα were significantly upregulated (since both low concentrations of 2.5 μg / mL and high concentrations of 10 μg / mL LPS had a certain degree of promoting or inhibiting effect on the expression of psoriasis cell markers, and although low concentrations of 5 ng / mL and high concentrations of 20 ng / mL TNFα could upregulate the expression of psoriasis cell markers, the effect was not as significant as the final concentration; therefore, the cell model was subsequently selected with a final concentration of 5 μg / mL LPS and 10 ng / mL TNFα). This is consistent with... Figure 2 As shown in FG, final concentrations of 5 μg / mL LPS and 10 ng / mL TNFα significantly upregulated the expression levels of inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2 in HaCaT cells, with β-actin serving as an internal reference gene.

[0040] The gene primer sequences used in this embodiment are shown in Table 1 below.

[0041] Table 1 Primers and their sequences used in this embodiment

[0042] Furthermore, cell scratch assays showed that, compared with control cells, HaCaT cells cultured with 5 μg / ml LPS, 10 ng / ml TNF-α, and M2 (50 ng / mL IL17A + 10 ng / mL TNF-α) significantly promoted cell migration. Figure 3 (A and 3B).

[0043] Based on the above experimental results, LSP, TNFα, and M2 all successfully induced a psoriasis-like phenotype in HaCaT cells. Subsequently, cell models were constructed using 5 μg / ml LPS, 10 ng / ml TNF-α, and 50 ng / mL IL17A + 10 ng / mL TNFα (M2), respectively.

[0044] (2) Novel peptide UPCP improves HaCaT cell psoriasis cell phenotype Experimental group: Healthy HaCaT cells were cultured. When the cell confluence reached 50%-60%, cell models were established using 5 μg / ml LPS, 10 ng / ml TNF-α, and 50 ng / mL IL17A + 10 ng / mL TNF-α (M2), respectively. The control group received an equal volume of dimethyl sulfoxide (DMSO). Simultaneously, two different concentrations (3 μM and 6 μM) of UPCP were added for intervention culture. After 24 h, proteins were extracted, and Western blot was used to detect the expression of psoriasis proliferation markers KRT6, KRT16, and KRT17 proteins.

[0045] Results analysis: As shown in Figure 4A, the experimental results show that, compared with the cell model group, different concentrations of UPCP can significantly downregulate the expression levels of psoriasis cell markers KRT6, KRT16, and KRT17, and the effect of 6 μM UPCP is more significant. The UPCP concentration of 6 μM was selected as the intervention concentration in subsequent experiments.

[0046] RNA was extracted from cells in each group after intervention with the novel peptide UPCP. After reverse transcription, qPCR was performed to detect the transcriptional levels of psoriasis-related inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2. The results showed that in HaCaT cells treated with LSP, TNFα, and M2, the gene expression levels of inflammatory factors were significantly upregulated compared to the control group. However, intervention with the novel peptide UPCP significantly reduced the expression levels of the corresponding inflammatory factors in HaCaT cells. Figure 4 BD).

[0047] The CCK8 assay results were used to detect the effect of the novel peptide UPCP on cell viability. For example... Figure 4 As shown in the EG, compared with the control group, HaCaT cells treated with LSP, TNFα, and M2 showed significantly faster growth and enhanced cell viability, while the novel peptide UPCP effectively reduced the excessive proliferation of HaCaT cells mediated by LSP, TNFα, and M2.

[0048] In addition, the migration of HaCaT cells in a psoriasis model was examined using UPCP. HaCaT cells were seeded into 6-well plates, and streaked when the cell confluence reached 90%. Cells were cultured in serum-free DMEM, serum-free DMEM containing inducing factors (LSP, TNFα, and M2), and serum-free DMEM containing inducing factors and UPCP, respectively. Images were taken at 0h, 12h, and 24h, and cell migration was assessed by statistically analyzing the streak width. Figure 4 As shown in H-4K, treatment of HaCaT cells with LSP, TNFα, and M2 significantly promoted HaCaT cell migration, while the novel peptide UPCP effectively inhibited LSP, TNFα, and M2-mediated cell migration. Figure 4 HK).

[0049] Example 4 An investigation into the improvement of imiquimod-induced psoriasis phenotype by the novel peptide UPCP. (1) UPCP skin administration method and skin safety assessment The novel peptide UPCP is a polypeptide molecule containing a transmembrane peptide sequence. To further explore the safe administration method of UPCP, male wild-type BALB / c mice aged 4-5 weeks were shaved on their backs. UPCP was administered via local application to the dorsal skin and multiple injections into the dorsal skin (100 μL UPCP solution, 4 mg / mL, dissolved in PBS) for one week, and photos were taken periodically. Figure 5A) The safety of UPCP administration and skin safety analysis were evaluated using indicators such as skin tissue observation and dermomics testing. As shown in 5B, compared with the control group, continuous one-week local application of UPCP to the dorsal skin and multi-point injection into the dorsal skin of mice had no significant effect on mouse skin morphology. Immunohistochemical experiments on mouse skin tissue showed that the two different UPCP administration methods had no significant effect on the thickness of the mouse epidermis. Figure 5 C and 5E). However, compared with the control group, subcutaneous multi-point injection increased the number of immune cells in the dermal tissue of mouse skin (C and 5E). Figure 5 (D), therefore, topical application of the medication was subsequently used.

[0050] (2) Analysis of UPCP skin uptake capacity To detect the absorption of the novel peptide UPCP in mouse skin tissue, FITC-UPCP was applied topically to the dorsal skin of mice, and the FITC fluorescence signal of the mouse dorsal skin was detected using a small animal imaging system. Figure 6 A), then mouse skin tissue was collected and frozen sections were prepared, and the fluorescence signal of FITC was collected under a fluorescence microscope.

[0051] The results showed that FITC-UPCP was absorbed by mouse skin tissue 4 hours after dorsal skin application, and FITC fluorescence signal could still be detected 8 hours after dorsal skin application. No obvious fluorescence signal was observed 24 hours after dorsal skin application. Figure 6 B). Frozen section immunofluorescence results showed that FITC-UPCP could be taken up from the epidermis into the dermis within a certain time, and could still be detected in the skin tissue 24 hours after application to the back skin. Figure 6 C).

[0052] (3) Novel peptide UPCP improves the phenotype of a mouse model of psoriasis To further investigate the role of the novel peptide UPCP in psoriasis, we constructed an imiquimod (IMQ)-induced mouse psoriasis model and administered UPCP topically for eight consecutive days. Mice were sacrificed on the morning of the ninth day. Skin photographs were taken daily at fixed times during the treatment period to record weight changes. After treatment, dorsal skin sections were fixed, stained with hematoxylin and eosin (HE), and photographed. Figure 7 (A and B). The specific groupings are as follows: Control group: 62.5 mg of petroleum jelly was applied to the bare skin of the back daily, and 100 μL of PBS was applied to the bare skin of the back (approximately 3 cm²) 4 hours later. 2cm); Model group: 62.5 mg of 5% IMQ was applied to bare skin on the back daily, and 100 μL of PBS (approximately 3 cm²) was applied to the bare skin on the back 4 hours later. 2cm); Low-dose intervention group: 62.5 mg of 5% IMQ was applied to the bare skin of the back daily. Four hours later, 100 μL of UPCP solution (2 mg / ml, dissolved in PBS) was applied to the bare skin of the back (approximately 3 cm²) using a moistened cotton swab. 2cm) on top; High-dose intervention group: 62.5 mg of 5% IMQ was applied to the bare skin of the back daily. Four hours later, 100 μL of UPCP solution (4 mg / ml, dissolved in PBS) was applied to the bare skin of the back (approximately 3 cm²) using a moistened cotton swab. 2cm) on top; Positive drug group: 62.5 mg of 5% IMQ was applied to the bare skin of the back daily, followed by 40 mg of commercially available tacrolimus ointment (TAC) 4 hours later; a: Mouse skin phenotype detection To assess the therapeutic effect of UPCP, skin photographs were taken at fixed times daily during the administration period. Figure 7 A and 7B), the results are as follows Figure 7 As shown in CE, compared with the control group, IMQ significantly induced skin lesions in mice, such as obvious desquamation and erythema on the back of the mice, and the PASI score (including three indicators: infiltration, desquamation, and erythema) gradually increased. The positive drug groups TAC and UPCP intervention groups significantly improved the IMQ-induced skin lesion phenotype in mice. Consistently, HE staining showed increased epidermal thickness and immune infiltration in IMQ-model mice, with a significantly increased positive rate of the cell proliferation marker Ki67. The positive drug groups TAC and UPCP intervention groups significantly improved the epidermal thickening, immune infiltration, and Ki67 positivity rate in IMQ-induced psoriatic mouse skin tissue. Figure 7 FI).

[0053] b: Mouse body weight and spleen weight detection Weight was measured at a fixed time every day during the administration period, and the spleen was photographed and weighed after the administration was completed.

[0054] The results are as follows Figure 8 As shown in AD, compared with the control group, the IMQ model group mice showed significant weight loss and splenomegaly. However, the weight change of the mice after UPCP treatment was different from that of the model group, showing an upward trend, and the splenomegaly was relieved.

[0055] Based on the above experimental results, the novel peptide UPCP can effectively improve the psoriatic skin lesion phenotype, as well as the phenotypes of weight loss and splenomegaly in psoriasis model mice.

[0056] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0057] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. The application of a novel peptide UPCP in the preparation of drugs for the treatment and / or prevention of psoriasis.

2. The application according to claim 1, characterized in that, The novel peptide UPCP is composed of 47 L-type amino acids, including the transmembrane peptide HIV-TAT, and its amino acid sequence is as follows: Novel peptide UPCP: YGRKKRRQRRRYNLRSRTVLCGTCGQPADKASASGSGAQS PQNCSIM, SEQ ID NO.

1.

3. A medicine for treating and / or preventing psoriasis, characterized in that, Includes the novel peptide UPCP as described in claim 1 or 2, or a novel peptide UPCP with a labeling group.

4. The medicament for treating and / or preventing psoriasis according to claim 3, characterized in that, It also includes other pharmaceutical excipients and / or other functional active ingredients.

5. The medicament for treating and / or preventing psoriasis according to claim 3 or 4, characterized in that, The drug exerts its therapeutic effect by downregulating the transcriptional levels of psoriasis-associated inflammatory factors IL6, IL1β, IL17, TNF-α, CXCL1, and CXCL2.

6. The medicament for treating and / or preventing psoriasis according to claim 3 or 4, characterized in that, The drug exerts its therapeutic effect by reducing the excessive proliferation of keratinocytes.

7. The medicament for treating and / or preventing psoriasis according to claim 3 or 4, characterized in that, The drug exerts its therapeutic effect by reducing the cell migration rate of keratinocytes.

8. The medicament for treating and / or preventing psoriasis according to claim 3 or 4, characterized in that, The drug exerts its therapeutic effect by improving skin peeling, erythema, epidermal hyperplasia, and splenomegaly.

9. The medicament according to any one of claims 3-8, characterized in that, The drug is a topical preparation.

10. The medicament according to claim 9, characterized in that, The topical preparations include ointments, creams, gels, lotions, solutions, sprays, or patches.

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