CN109939117B - Application of cycloastragenol in preparation of medicine for treating psoriasis - Google Patents

Abstract

The invention relates to a new application of cycloastragenol, in particular to an application of cycloastragenol in preparing a medicament for treating psoriasis. Cycloastragenol can effectively improve skin thickening and inflammatory factor infiltration of diseased skin. For psoriasis model mice induced by imiquimod, the cycloastragenol can obviously improve the skin thickening condition of the lesion part and simultaneously reduce the level of inflammatory factors infiltrated in the skin of the lesion part in a dose-dependent manner.

Description

Application of cycloastragenol in preparation of medicine for treating psoriasis

Technical Field

The invention relates to a new application of cycloastragenol, in particular to an application of cycloastragenol in preparing a medicament for treating psoriasis

Background

Since the chemical structure of Cycloastragenol (CAG) has been reported, the research on the compound is very little, and no report is found so far about the pharmacological activity, especially the effect of treating diseases related to psoriasis. The invention mainly discovers that the cycloastragenol has a remarkable improvement effect on psoriasis models.

Cycloastragenol (CAG), which has the following structural formula:

disclosure of Invention

Use of cycloastragenol in preparing medicine for treating psoriasis is provided.

Specifically, the method comprises the following steps:

1. pharmacological experiment of cycloastragenol

Mouse psoriasis model induced by imiquimod^[1]

C57BL/6 female mice are taken, aged 6-8 weeks and 18-22 g, and are bred in an SPF animal room at 21 +/-2 ℃, and the mice are freely drunk by drinking water and are alternately eaten 12 hours day and night. After anesthetizing the mice with 1% sodium pentobarbital, the back hair of the mice was scraped off over an area of approximately 2cm by 2cm to expose the skin of the back. Two days later, mice were randomly divided into 6 groups, a normal group (Sham group), a model group (Imiquimod, IMQ group), a low, medium, and high dose group (12.5mg/kg, 25mg/kg, 50mg/kg) of Cycloastragenol (CAG), and Andrographolide (android group, 10 mg/kg). The normal and model groups were dosed with equal amounts of PBS, and the remaining groups were gavaged once daily at 0.1ml per dose. In each group, except the normal group, an equivalent amount of imiquimod cream was applied evenly to the back skin of the mice each day.

The overall erythema and scaling status is scored according to Clinical Psoriasis Area and Severity Index (PASI) at 0-4: 0 min, none; 1 point, slight; 2 points, medium; grade 3, severe; 4 points, extremely severe.

Thereafter, the body weights of the mice were recorded daily and scored. Mice were sacrificed at day 6, and then the expression level of inflammatory factors in the skin was examined and pathological sections of the skin were observed.

Model references: [1] shao, T.Tan, Y.Tan, Y.Sun, X.Wu, Q.Xu, Andrographide alleviates immiquimod-induced psioriasis in microorganism via indicating autophagic protein analysis of MyD88, Biochemical Pharmacology,115(2016)94-103.

2. Analysis of results of pharmacological experiments on cycloastragenol

1) Effect of Cycloastragenol on Imquimod-induced psoriasis model in mice

As shown in fig. 1, the PASI scores were significantly higher for the normal group (Sham group) compared to the model group (IMQ group); cycloastragenol (CAG)12.5mg/kg, 25mg/kg, 50mg/kg group was able to dose-dependently decrease the PASI score.

As shown in figure 2, compared with the normal group, the skin of the model group is obviously swollen, scales are generated, the administration of the cycloastragenol can obviously eliminate the swelling and reduce the scales, and the HE dyeing result shows that the cycloastragenol can obviously inhibit the thickening of the epidermis.

As shown in FIG. 3, the expression levels of the inflammatory factors IL-1 β, IL-6, IL-17A, IL-22 and IL-23A in the skin of the model group were significantly increased as compared with the normal group; the cycloastragenol can reduce the expression level of inflammatory factors in a dose-dependent manner after administration.

The cycloastragenol can be used for treating diseases related to psoriasis and preparing corresponding medicaments.

Note: cycloastragenol is purchased from Jiangsu Yongjian medicine science and technology limited company, and the purity is more than 98 percent.

Advantageous effects

1. For an imiquimod-induced psoriasis model of a mouse, 12.5mg/kg, 25mg/kg and 50mg/kg of cycloastragenol after intragastric administration can obviously reduce the PASI score, relieve the skin thickening and reduce the expression levels of inflammatory factors IL-1 beta, IL-6, IL-17A, IL-22, IL-23A and the like in the skin, and the effect is dose-dependent.

The results indicate that the cycloastragenol can improve the relevant symptoms of psoriasis, so the cycloastragenol can be applied to the treatment of the psoriasis relevant diseases.

Drawings

Figure 1 experimental results of cycloastragenol on imiquimod-induced psoriasis model in mice. Mice were randomly divided into 6 groups, a normal group (Sham group), a model group (Imiquimod, IMQ group), a low, medium, and high dose group (12.5mg/kg, 25mg/kg, 50mg/kg) of Cycloastragenol (CAG), and an Andrographolide group (android, 10 mg/kg). The normal and model groups were dosed with equal amounts of PBS, and the remaining groups were gavaged once daily at 0.1ml per dose. In each group, except the normal group, an equivalent amount of imiquimod cream was applied evenly to the back skin of the mice each day. Thereafter, the body weights of the mice were recorded daily and scored. Mice were sacrificed on day 6. Results are expressed as mean ± standard deviation. *: p <0.05, x: p <0.01vsIMQ (Student's-t test).

Figure 2 photographs of mouse skin sacrificed on day 6 and HE detection results for imiquimod-induced psoriasis models with cycloastragenol. Mice were randomly divided into 6 groups, a normal group (Sham group), a model group (Imiquimod, IMQ group), a low, medium, and high dose group (12.5mg/kg, 25mg/kg, 50mg/kg) of Cycloastragenol (CAG), and an Andrographolide group (android, 10 mg/kg). The normal and model groups were dosed with equal amounts of PBS, and the remaining groups were gavaged once daily at 0.1ml per dose. In each group, except the normal group, an equivalent amount of imiquimod cream was applied evenly to the back skin of the mice each day. Thereafter, the body weights of the mice were recorded daily and scored. Mice were sacrificed on day 6 and the skin pathology sections were observed.

FIG. 3 RingEffect of astraganol on the level of inflammatory factor expression in mouse psoriasis model skin tissue induced by imiquimod. Mice were randomly divided into 6 groups, a normal group (Sham group), a model group (Imiquimod, IMQ group), a low, medium, and high dose group (12.5mg/kg, 25mg/kg, 50mg/kg) of Cycloastragenol (CAG), and an Andrographolide group (android, 10 mg/kg). The normal and model groups were dosed with equal amounts of PBS, and the remaining groups were gavaged once daily at 0.1ml per dose. In each group, except the normal group, an equivalent amount of imiquimod cream was applied evenly to the back skin of the mice each day. Thereafter, the body weights of the mice were recorded daily and scored. Mice were sacrificed on day 6 and the expression level of inflammatory factors in skin tissue of the mice was measured by q-PCR, wherein A is IL-1 β, B is IL-6, C is IL-17A, D is IL-22, and E is Il-23A. Results are expressed as mean ± standard deviation.^#：P<0.05，^##：P<0.01vsSham；*：P<0.05，**：P<0.01，***：P<0.001，****P<0.0001vsIMQ(Student’s-t test)。

Detailed Description

Example 1

1. Pharmacological experiment of cycloastragenol

Mouse psoriasis model induced by imiquimod^[1]

C57BL/6 female mice are taken, aged 6-8 weeks and 18-22 g, and are bred in an SPF animal room at 21 +/-2 ℃, and the mice are freely drunk by drinking water and are alternately eaten 12 hours day and night. After anesthetizing the mice with 1% sodium pentobarbital, the back hair of the mice was scraped off over an area of approximately 2cm by 2cm to expose the skin of the back. Two days later, mice were randomly divided into 6 groups, a normal group (Sham group), a model group (Imiquimod, IMQ group), a low, medium, and high dose group (12.5mg/kg, 25mg/kg, 50mg/kg) of Cycloastragenol (CAG), and an Andrographolide group (android, 10 mg/kg). The normal and model groups were dosed with equal amounts of PBS, and the remaining groups were gavaged once daily at 0.1ml per dose. In each group, except the normal group, an equivalent amount of imiquimod cream was applied evenly to the back skin of the mice each day.

The overall erythema and scaling status is scored according to Clinical Psoriasis Area and Severity Index (PASI) at 0-4: 0 min, none; 1 point, slight; 2 points, medium; grade 3, severe; 4 points, extremely severe.

Thereafter, the body weights of the mice were recorded daily and scored. Mice were sacrificed on day 6, and then the expression level of inflammatory factors in skin and serum was examined and pathological sections of skin were observed.

Model references:

[1]F.Shao,T.Tan,Y.Tan,Y.Sun,X.Wu,Q.Xu,Andrographolide alleviates imiquimod-induced psoriasis in mice via inducing autophagic proteolysis of MyD88,Biochemical Pharmacology,115(2016)94-103.

2. analysis of results of pharmacological experiments on cycloastragenol

1) Effect of Cycloastragenol on Imquimod-induced psoriasis model in mice

As shown in fig. 1, the PASI scores were significantly higher for the normal group (Sham group) compared to the model group (IMQ group); cycloastragenol (CAG)12.5mg/kg, 25mg/kg, 50mg/kg group was able to dose-dependently decrease the PASI score.

As shown in figure 2, compared with the normal group, the skin of the model group is obviously swollen, scales are generated, the administration of the cycloastragenol can obviously eliminate the swelling and reduce the scales, and the HE dyeing result shows that the cycloastragenol can obviously inhibit the thickening of the epidermis.

As shown in FIG. 3, the expression levels of the inflammatory factors IL-1 β, IL-6, IL-17A, IL-22 and IL-23A in the skin of the model group were significantly increased as compared with the normal group; the cycloastragenol can reduce the expression level of inflammatory factors in a dose-dependent manner after administration.

Claims (1)

1. Use of cycloastragenol as the sole active ingredient in the preparation of a medicament for the treatment of psoriasis.

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