CN109939117B - The application of cycloastragalus in the preparation of medicine for treating psoriasis - Google Patents
The application of cycloastragalus in the preparation of medicine for treating psoriasis Download PDFInfo
- Publication number
- CN109939117B CN109939117B CN201910191294.3A CN201910191294A CN109939117B CN 109939117 B CN109939117 B CN 109939117B CN 201910191294 A CN201910191294 A CN 201910191294A CN 109939117 B CN109939117 B CN 109939117B
- Authority
- CN
- China
- Prior art keywords
- group
- mice
- cycloastragenol
- skin
- psoriasis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 201000004681 Psoriasis Diseases 0.000 title claims abstract description 22
- 239000003814 drug Substances 0.000 title claims abstract description 8
- 239000004480 active ingredient Substances 0.000 claims 1
- 229960002751 imiquimod Drugs 0.000 abstract description 18
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 abstract description 18
- 230000002757 inflammatory effect Effects 0.000 abstract description 11
- 231100000673 dose–response relationship Toxicity 0.000 abstract description 4
- 206010040867 Skin hypertrophy Diseases 0.000 abstract description 3
- 230000003902 lesion Effects 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 1
- 230000008595 infiltration Effects 0.000 abstract 1
- 238000001764 infiltration Methods 0.000 abstract 1
- 238000010172 mouse model Methods 0.000 abstract 1
- WENNXORDXYGDTP-UOUCMYEWSA-N cycloastragenol Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O)C4(C)C)[C@H]4[C@@H](O)C[C@H]3[C@]2(C)C[C@@H]1O WENNXORDXYGDTP-UOUCMYEWSA-N 0.000 description 42
- WENNXORDXYGDTP-UHFFFAOYSA-N cyclosiversigenin Natural products O1C(C(C)(O)C)CCC1(C)C1C2(C)CCC34CC4(CCC(O)C4(C)C)C4C(O)CC3C2(C)CC1O WENNXORDXYGDTP-UHFFFAOYSA-N 0.000 description 42
- 241000699670 Mus sp. Species 0.000 description 33
- 210000003491 skin Anatomy 0.000 description 20
- BOJKULTULYSRAS-OTESTREVSA-N Andrographolide Chemical compound C([C@H]1[C@]2(C)CC[C@@H](O)[C@]([C@H]2CCC1=C)(CO)C)\C=C1/[C@H](O)COC1=O BOJKULTULYSRAS-OTESTREVSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 102000003777 Interleukin-1 beta Human genes 0.000 description 4
- 108090000193 Interleukin-1 beta Proteins 0.000 description 4
- 108050003558 Interleukin-17 Proteins 0.000 description 4
- 102000013691 Interleukin-17 Human genes 0.000 description 4
- 102100030703 Interleukin-22 Human genes 0.000 description 4
- 108090001005 Interleukin-6 Proteins 0.000 description 4
- 102000004889 Interleukin-6 Human genes 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 108010074109 interleukin-22 Proteins 0.000 description 4
- 101000852980 Homo sapiens Interleukin-23 subunit alpha Proteins 0.000 description 3
- 102100036705 Interleukin-23 subunit alpha Human genes 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000011740 C57BL/6 mouse Methods 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 2
- 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- ASLUCFFROXVMFL-UHFFFAOYSA-N andrographolide Natural products CC1(CO)C(O)CCC2(C)C(CC=C3/C(O)OCC3=O)C(=C)CCC12 ASLUCFFROXVMFL-UHFFFAOYSA-N 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 230000008961 swelling Effects 0.000 description 2
- 230000008719 thickening Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000002886 autophagic effect Effects 0.000 description 1
- 230000007343 autophagic proteolysis Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000073 effect on psoriasis Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及环黄芪醇新用途，特别涉及环黄芪醇在制备治疗银屑病药物中的应用。环黄芪醇能有效改善病变皮肤部位的皮肤增厚和炎症因子浸润。对咪喹莫特诱导的银屑病模型小鼠，环黄芪醇能显著改善病变部位的皮肤增厚情况，同时剂量依赖性地降低病变部位皮肤中浸润的炎症因子水平。
The invention relates to a new use of cycloastragalus, in particular to the application of cycloastragalus in the preparation of medicines for treating psoriasis. Cycloastragali can effectively improve skin thickening and inflammatory factor infiltration in the lesioned skin. In imiquimod-induced psoriasis model mice, cycloastragali can significantly improve the skin thickening at the lesion site, and at the same time reduce the level of inflammatory factors infiltrated in the skin of the lesion site in a dose-dependent manner.
Description
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)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910191294.3A CN109939117B (en) | 2019-03-14 | 2019-03-14 | The application of cycloastragalus in the preparation of medicine for treating psoriasis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201910191294.3A CN109939117B (en) | 2019-03-14 | 2019-03-14 | The application of cycloastragalus in the preparation of medicine for treating psoriasis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109939117A CN109939117A (en) | 2019-06-28 |
| CN109939117B true CN109939117B (en) | 2021-06-15 |
Family
ID=67009831
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201910191294.3A Active CN109939117B (en) | 2019-03-14 | 2019-03-14 | The application of cycloastragalus in the preparation of medicine for treating psoriasis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109939117B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101116667A (en) * | 2006-08-01 | 2008-02-06 | 罗河生 | Medicine for treating and preventing immune abnormalism disease |
| CN102247397A (en) * | 2011-05-30 | 2011-11-23 | 浙江大学 | Application of astragaloside to preparation of drug |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108853404A (en) * | 2018-07-24 | 2018-11-23 | 近晟（上海）医药科技有限公司 | A kind of compound Chinese medicinal preparation and preparation method thereof for treating skin and mucous membrane disease |
-
2019
- 2019-03-14 CN CN201910191294.3A patent/CN109939117B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101116667A (en) * | 2006-08-01 | 2008-02-06 | 罗河生 | Medicine for treating and preventing immune abnormalism disease |
| CN102247397A (en) * | 2011-05-30 | 2011-11-23 | 浙江大学 | Application of astragaloside to preparation of drug |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109939117A (en) | 2019-06-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111265529B (en) | Application of protein tyrosine phosphatase SHP2 inhibitor in preparation of psoriasis medicine | |
| RU2671492C2 (en) | Compositions containing berberine or analogs thereof for treating rosacea or red face related skin disorders | |
| JP2006131623A (en) | Drug | |
| JP2021510159A (en) | Topical dermatological composition containing cerduratinib and its use | |
| CN103736030B (en) | Treat compound Chinese medicinal preparation of dysmenorrhoea and its production and use | |
| US20220233627A1 (en) | Compositions comprising plant extracts and oils and related methods of treatment and their preparation | |
| US11241465B2 (en) | Compositions and methods for skin treatments | |
| Halim et al. | A comparison study on the effectiveness of local honey and salicylate gel for treatment of minor recurrent aphtous stomatitis | |
| CN109939117B (en) | The application of cycloastragalus in the preparation of medicine for treating psoriasis | |
| CN104288168B (en) | Purposes of the cryptogenin in the medicine for preparing the disease for being used for treating and/or prevent microglia to mediate | |
| CN103099844B (en) | A kind of traditional Chinese medicine composition for treating infantile eczema | |
| CN112843113B (en) | A preparation for treating contact dermatitis | |
| ES2554332T3 (en) | Use of benzydamine in the treatment of p40 dependent diseases | |
| AU2015349153B2 (en) | Application of levalbuterol formulation in treatment of skin and mucous membrane traumatic ulcers | |
| KR101567735B1 (en) | Composition for preventing or improving or treating psoriasis comprising immunomodulating agent and glucosamine | |
| CN103893376B (en) | A kind of Chinese medicine composition for treating skin eczema bleb and preparation method thereof | |
| CN113995763B (en) | Application of phosphatidylethanolamine as an active ingredient in the preparation of medicines for treating psoriasis, medicines for treating psoriasis and preparation methods thereof | |
| CN117205223A (en) | Application of monogalactosyldiacylglycerogalactolipid in preparing drugs for treating psoriasis and pharmaceutical compositions thereof | |
| CN110327354B (en) | Application of diosgenin in treatment and prevention of psoriasis | |
| CN107998151B (en) | Compound rehabilitation liquid liniment and preparation method thereof | |
| Angadi et al. | MANAGEMENT OF EKA KUSHTA-A CASE STUDY | |
| CN117357540A (en) | Application of withanosine A in preparation of psoriasis prevention and treatment medicine | |
| CN118384153A (en) | Application of cimicifuga rhizome glycoside in preparing medicine for preventing and treating atopic dermatitis | |
| CN111249441A (en) | Application of small molecular oligopeptide in preparation of medicine for treating psoriasis | |
| CN100493606C (en) | Application of human lysozyme in preparation of medicine for treating pruritus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |