CN117298079A - Application of plumbagin in preparation of medicine for treating atopic dermatitis - Google Patents
Application of plumbagin in preparation of medicine for treating atopic dermatitis Download PDFInfo
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- CN117298079A CN117298079A CN202311297819.4A CN202311297819A CN117298079A CN 117298079 A CN117298079 A CN 117298079A CN 202311297819 A CN202311297819 A CN 202311297819A CN 117298079 A CN117298079 A CN 117298079A
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- Prior art keywords
- plumbagin
- mice
- group
- skin
- atopic dermatitis
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- VCMMXZQDRFWYSE-UHFFFAOYSA-N plumbagin Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1O VCMMXZQDRFWYSE-UHFFFAOYSA-N 0.000 title claims abstract description 122
- ZMOIGGHUSNHCAB-UHFFFAOYSA-N Isoplumbagin Natural products C1=CC(O)=C2C(=O)C(C)=CC(=O)C2=C1 ZMOIGGHUSNHCAB-UHFFFAOYSA-N 0.000 title claims abstract description 61
- ALPCEXCHMFUSAN-UHFFFAOYSA-N beta-Dihydroplumbagin Natural products C1=CC=C2C(=O)C(C)CC(=O)C2=C1O ALPCEXCHMFUSAN-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 239000003814 drug Substances 0.000 title claims abstract description 33
- 206010012438 Dermatitis atopic Diseases 0.000 title claims abstract description 15
- 201000008937 atopic dermatitis Diseases 0.000 title claims abstract description 15
- 238000002360 preparation method Methods 0.000 title claims description 10
- 229940079593 drug Drugs 0.000 claims abstract description 16
- 210000001519 tissue Anatomy 0.000 claims description 21
- 102000003816 Interleukin-13 Human genes 0.000 claims description 16
- 108090000176 Interleukin-13 Proteins 0.000 claims description 16
- 108090000978 Interleukin-4 Proteins 0.000 claims description 16
- 108010002616 Interleukin-5 Proteins 0.000 claims description 16
- 210000003630 histaminocyte Anatomy 0.000 claims description 11
- 206010040882 skin lesion Diseases 0.000 claims description 11
- 231100000444 skin lesion Toxicity 0.000 claims description 11
- 210000005259 peripheral blood Anatomy 0.000 claims description 8
- 239000011886 peripheral blood Substances 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 210000002615 epidermis Anatomy 0.000 claims description 4
- 102000004127 Cytokines Human genes 0.000 claims description 3
- 108090000695 Cytokines Proteins 0.000 claims description 3
- 241000699670 Mus sp. Species 0.000 abstract description 49
- 230000000694 effects Effects 0.000 abstract description 20
- VYZAHLCBVHPDDF-UHFFFAOYSA-N Dinitrochlorobenzene Chemical compound [O-][N+](=O)C1=CC=C(Cl)C([N+]([O-])=O)=C1 VYZAHLCBVHPDDF-UHFFFAOYSA-N 0.000 abstract description 13
- 238000002474 experimental method Methods 0.000 abstract description 12
- 238000010186 staining Methods 0.000 abstract description 8
- 201000004624 Dermatitis Diseases 0.000 abstract description 6
- 238000002965 ELISA Methods 0.000 abstract description 4
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 abstract description 4
- 238000001514 detection method Methods 0.000 abstract description 3
- 230000037380 skin damage Effects 0.000 abstract description 3
- 238000010173 Alzheimer-disease mouse model Methods 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract 1
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- FPVRUILUEYSIMD-RPRRAYFGSA-N [(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(OC(C)=O)[C@@]1(C)C[C@@H]2O FPVRUILUEYSIMD-RPRRAYFGSA-N 0.000 description 3
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 238000011725 BALB/c mouse Methods 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 101100398282 Mus musculus Kit gene Proteins 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 210000004241 Th2 cell Anatomy 0.000 description 2
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- 230000001684 chronic effect Effects 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- WABPQHHGFIMREM-UHFFFAOYSA-N lead(0) Chemical compound [Pb] WABPQHHGFIMREM-UHFFFAOYSA-N 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
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- 208000024891 symptom Diseases 0.000 description 2
- 229950003937 tolonium Drugs 0.000 description 2
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- KZYAYVSWIPZDKL-UHFFFAOYSA-N 1,4-diamino-2,3-dichloroanthracene-9,10-dione Chemical group O=C1C2=CC=CC=C2C(=O)C2=C1C(N)=C(Cl)C(Cl)=C2N KZYAYVSWIPZDKL-UHFFFAOYSA-N 0.000 description 1
- 208000019300 CLIPPERS Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 101710112752 Cytotoxin Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 241000282373 Panthera pardus Species 0.000 description 1
- 206010058679 Skin oedema Diseases 0.000 description 1
- 208000033809 Suppuration Diseases 0.000 description 1
- 206010042674 Swelling Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 description 1
- -1 anthraquinone compound Chemical class 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000003855 cell nucleus Anatomy 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000007969 cellular immunity Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 208000021930 chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Diseases 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
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- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229940084954 dexamethasone 1 mg Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000002222 downregulating effect Effects 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 230000009610 hypersensitivity Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000021633 leukocyte mediated immunity Effects 0.000 description 1
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- 239000007788 liquid Substances 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- YGSFNCRAZOCNDJ-UHFFFAOYSA-N propan-2-one Chemical compound CC(C)=O.CC(C)=O YGSFNCRAZOCNDJ-UHFFFAOYSA-N 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000006748 scratching Methods 0.000 description 1
- 230000002393 scratching effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
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- 239000006228 supernatant Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- SWGJCIMEBVHMTA-UHFFFAOYSA-K trisodium;6-oxido-4-sulfo-5-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=C(S([O-])(=O)=O)C2=C1 SWGJCIMEBVHMTA-UHFFFAOYSA-K 0.000 description 1
- 230000005951 type IV hypersensitivity Effects 0.000 description 1
- 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/12—Ketones
- A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to the technical field of dermatitis drugs, and relates to a new application of plumbagin, in particular to an application of plumbagin in preparing a drug for treating atopic dermatitis. The therapeutic effect of plumbagin on a DNCB-induced AD mouse model is proved by experiments, and the plumbagin has a certain intervention effect on atopic dermatitis according to the results of the skin damage condition, HE staining, TB staining, ELISA detection and the like of the mice.
Description
Technical Field
The invention relates to the technical field of dermatitis drugs, and relates to a new application of plumbagin, in particular to an application of plumbagin in preparing a drug for treating atopic dermatitis.
Background
Atopic dermatitis (Atopic dermatitis, AD) is a chronic inflammatory skin disease, often accompanied by recurrent itching, redness, swelling, suppuration and other clinical symptoms. AD has a prevalence of about 10% in adults, but up to 20% in children. The pathogenesis of AD involves genetic, cell-mediated immune response alterations, igE (ImmunoglobulinE) -mediated hypersensitivity, inflammatory reactions, environmental factors, etc. AD is associated with an inflammatory response mediated by helper T cells in the acute onset phase, T cells are divided into two subgroups of Th1 and Th2, th1 secretes IL-4 and IL-5, and mainly mediates an immune response associated with cytotoxin and local inflammation, and is involved in cellular immunity and delayed type hypersensitivity inflammation, and Th2 cells produce high levels of IL-13 and mainly function to stimulate B cell proliferation and produce immunoglobulins to participate in humoral immunity. The mechanism of AD in the acute onset stage is that Th2 cells and eosinophils infiltrate the skin, B cell IgE is increased, mast cells are activated, the skin shows itching, erythema, blisters, even ulceration, crusting and the like, and when the AD is converted into chronic AD, dominant Th1 cells secrete IFN-gamma, IL-1 and the like to inhibit Th2 inflammatory reaction, and malignant circulation of itching and scratching is formed, so that the skin is thickened. Currently, most of the treatment of AD is carried out by cortisol, antihistamine and immunosuppressant, but these drugs have relatively large side effects after long-term administration and are relatively expensive to treat, so that a drug which has long-term safety and is effective should be sought.
The plumbagin is an anthraquinone compound, the chemical name is 1, 4-diamino-2, 3-dichloro anthraquinone, and the molecular structural formula is as follows:
the prior art mainly focuses on the application of plumbagin in antitumor drugs, for example, chinese patent literature with publication number of CN103124563B and name of combined therapy for treating prostatic cancer discloses the application of plumbagin in preparing drugs for treating prostatic cancer, and the application of plumbagin in the aspect of atopic dermatitis is not reported.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide the application of the plumbagin in preparing the medicine for treating the atopic dermatitis 。
In order to solve the technical problems, the invention adopts the following technical scheme:
application of plumbagin in preparing medicine for treating atopic dermatitis is provided.
Preferably, the plumbagin is applied to the preparation of medicines for reducing the epidermis thickness of skin tissues.
Preferably, the plumbagin is applied to the preparation of medicines for inhibiting mast cells.
Preferably, the plumbagin is used for preparing medicines for inhibiting the expression of peripheral blood cytokines IgE, IL-4, IL-5 and IL-13.
Compared with the prior art, the invention has the beneficial effects that:
experiments prove that the plumbagin has a certain intervention effect on atopic dermatitis according to the treatment effect of the plumbagin on the AD mouse model induced by DNCB, the results of the skin damage condition, HE staining, TB staining, ELISA detection and the like of the mice.
Drawings
FIG. 1 is a graph showing the effect of plumbagin on the skin of the back of mice;
wherein, the A graph is a graph of the change condition of the back skin of the mouse; panel B is a plot of the score for back skin edema in mice;
FIG. 2 is a graph showing the effect of plumbagin on the back skin lesion tissue of mice in each group;
wherein, the A graph is a staining graph of skin tissue HE at the back of the mouse; panel B is a graph showing the effect of plumbagin on the thickness of the skin epidermis on the back of mice; panel C is a staining chart of plumbagin to the skin tissue TB on the back of the mice; panel D is a graph showing the effect of plumbagin on the number of skin mast cells on the back of mice;
FIG. 3 is a graph showing the effect of plumbagin on IgE, IL-4, IL-5, and IL-13 in the peripheral blood of dermatitis model mice;
FIG. 4 is a graph showing the effect of plumbagin on IL-4, IL-5, and IL-13 in skin homogenates of dermatitis model mice.
In the figure, # # P <0.001 compared to the normal group; p <0.01 compared to model group; * P <0.05; * P <0.001.
Detailed Description
The present invention will be described in detail with reference to the following examples, which are not intended to limit the scope of the invention in any way, but are intended to provide a comprehensive understanding of the invention to those skilled in the art.
1. Material
1. Animals: BALB/c mice (female, age 6-8 weeks), purchased from SPF (Beijing) laboratory animal technologies Co., ltd (SCXK [ Beijing ]2019-0010, beijing, china). Mice were kept in a living environment with controlled temperature (23 ℃ ±2 ℃) and humidity (55% ±5%) for 12 hours in a diurnal cycle, and provided laboratory diet and free drinking water. All experiments were performed with the animal ethics committee of Yunnan university of traditional Chinese medicine (approval number: R-062022087).
2. Medicine: plumbum Preparatium is from Chengdu plant standard pure biotechnology general purpose Co., ltd (product number: 220211), dexamethasone acetate (Dexamethasone acetate, dex) (product number: 909B 021) is from Beijing Soy Bao technology Co., ltd.
3. Experimental reagent and consumable
The main reagents and consumables are as shown in Table 1:
| reagent(s) | Goods number | Source |
| DNCB | 97-00-7 | Sigma |
| 4% paraformaldehyde tissue fixing liquid | G1101 | Wuhan Seville Biotechnology Co.Ltd |
| IgEELISA kit | MM-0056M1 | Jiangsu enzyme free Utility Co Ltd |
| Xylene (P) | 100092683 | Sinopharm Group Chemical Reagent Co., Ltd. |
| Absolute ethyl alcohol | 10023418 | Sinopharm Group Chemical Reagent Co., Ltd. |
| HE dye liquor set | G1003 | Wuhan Seville Biotechnology Co.Ltd |
| Toluidine blue dye liquor | G1032 | Wuhan Seville Biotechnology Co.Ltd |
| Glacial acetic acid | G10000218 | Wuhan Seville Biotechnology Co.Ltd |
| MouseIL-4ELISA kit | MM-0165M1 | Jiangsu enzyme free Utility Co Ltd |
| MouseIL-5ELISA kit | MM-0164M1 | Jiangsu enzyme free Utility Co Ltd |
| MouseIL-13ELISA kit | MM-0173M1 | Jiangsu enzyme free Utility Co Ltd |
| PBS buffer | G0002 | Wuhan Seville Biotechnology Co.Ltd |
| 3% hydrogen peroxide | 10011208 | Sinopharm Group Chemical Reagent Co., Ltd. |
| Sodium carboxymethyl cellulose | 30036365 | Sinopharm Group Chemical Reagent Co., Ltd. |
| Acetone (acetone) | Oil Dian pharmaceutical Co Ltd | |
| Olive oil | Q/YHJL0108S | Sea-benefiting grain and oil industry Co.Ltd |
Table 1 reagents and consumables
4. Experimental solvent configuration
(1) Matrix solution
Acetone 500ml
Olive oil 100ml
(2) 1% DNCB solution
DNCB 200mg
Matrix solution 20mL
(3) 0.3% DNCB solution
DNCB 60mg
Matrix solution 20mL
(4)0.5％CMC-Na
CMC-Na 1g
Distilled water 200mL
(5) Dexamethasone (1 mg/kg)
Dexamethasone acetate 0.5mg
0.5％CMC-Na 10mL
5. Experimental instrument
The main laboratory instruments are as in table 2:
| instrument for measuring and controlling the intensity of light | Model number | Source |
| Enzyme label instrument | SpectraMax Plus384 | U.S. Mei Gu |
| -80 ℃ ultralow temperature refrigerator | Forma 902 | Thermo Forma in the United states |
| Low-temperature high-speed centrifugal machine | 5810R | Eppendorf, germany |
| Electronic analytical balance | AR224CN | Orhaus in the United states |
| Microscope | Axio Lab.A | German zeiss |
| Ultrapure water system | MILLI-Q/* | Millipore in the United states |
| High-pressure steam sterilizing pot | KG-SX-500 | Japanese tomykotyo |
| AS full-automatic dehydrator | EXCELSIOR | U.S. Thermo |
| Embedding machine | JB-P5 | Wuhanjunjie electronics Inc |
| Tissue spreading machine | KD-P | ZHEJIANG JINHUA KEDI INSTRUMENTAL EQUIPMENT Co.,Ltd. |
| E+ semi-automatic slicer | FINESS | U.S. Thermo |
| Freeze table | JB-L5 | Wuhanjunjie electronics Inc |
| Dyeing machine | Giotto | DIAPATH |
| Constant temperature shaking table | TS200B | Shanghai leopard test Equipment Co.Ltd |
| Vortex mixer | MX-S | SailoCzochralski in the United states |
| Palm centrifugal machine | Mini-6KS | HANGZHOU ALLSHENG INSTRUMENTS Co.,Ltd. |
| Refrigerator with a refrigerator body | BCD-260WDC | Chinese hal |
Table 2 laboratory apparatus
2. Experimental method
1. Grouping and adaptive feeding of laboratory animals
After 1 week of routine adaptive laboratory feeding of BALB/c mice, the mice were randomly divided into 6 groups of 8: the Normal group, the Model-Model group, the Dex-positive control group (dexamethasone 1 mg/kg), the Plu-H high-dose (100 mg/kg) group, the Plu-M medium-dose (50 mg/kg) group and the Plu-L low-dose (25 mg/kg) group of plumbagin, respectively.
AD animal model replication and administration
Early preparation: all the back skin of the mice was dehaired with a hair clipper at about (3 x 3) cm2 and dehaired with a dehairing paste 1 day before the formal experiment to smooth the skin surface without excessive hair.
Sensitization: on the 1 st to 2 nd days of the experiment, the backs of the mice in each group are uniformly coated with 150 mu L of DNCB solution with the concentration of 1% for sensitization, and the normal group is coated with matrix solution with the same volume for sensitization for 2 times.
Excitation: on the 8 th to 21 th days of the experiment, 0.4% DNCB is externally coated for excitation, the excitation volume is 100 mu L, the normal group mice are coated with an equal volume of matrix solution, and the total excitation is 8 times.
Drug administration intervention: on the 1 st to 21 th days of the experiment, each group of mice is respectively orally interfered by the corresponding medicine, and the normal group and the model group are orally administrated with 0.5% CMC-Na water solution for 1 time/d, and the time is 21 days continuously until the experiment is ended.
Drawing materials: on experiment day 22, mice were anesthetized, blood was taken, and the back skin of the mice was dissected and stored in different ways for subsequent experiments.
3. Index detection
3.1 Effect of plumbagin on the appearance of skin lesions in AD mice
The skin inflammation of the mice was evaluated according to the scoring criteria shown in Table 3, including the observed signs of skin lesions such as edema (pimple), erythema (hemorrhage), scaling (dryness), scaling (scratch), etc., the final score of the severity of skin lesions of the mice was the sum of 4 symptom scores, the score range was 0-12 points, and the photographs were taken.
TABLE 3 skin injury scoring criteria
3.2 determination of the general histopathological changes of the skin lesions of AD mice by plumbagin (HE staining)
(1) And (5) preparing paraffin sections.
Killing the mice, taking the back tissues of the mice, placing the back tissues of the mice in a 4% paraformaldehyde solution for more than 24 hours, taking out the solution, placing the solution in a dehydration box for washing, dehydrating the back tissues of the mice by using ethanol with different concentrations after washing, immersing the tissues in xylene for transparent treatment, immersing the tissues in wax, embedding and slicing the tissues after treatment, and finally spreading, slicing and baking the tissues.
(2) HE staining
Paraffin sections were dewaxed to water and stained with hematoxylin (staining nuclei); differentiation and bluing; and (3) staining with eosin, removing water from the slice, finally observing the slice under an optical microscope, enabling cell nuclei to be blue, enabling cytoplasm to be red, and collecting images and analyzing.
3.3 Effect of plumbagin on the infiltration of damaged mast cells in AD mice
(1) And (5) preparing paraffin sections.
And 3.3.2.
(2) TB staining
After staining the tissue sections with toluidine blue, transparent sealing is carried out, the mast cells are observed under an optical microscope to be purple-red, the background is light blue, and the images are collected and analyzed.
3.4 Effect of plumbagin on total IgE and IL-4, IL-5, IL-13 in the peripheral blood of AD mice
On day 22 of the experiment, the anesthetized mice were taken from peripheral blood, allowed to stand at room temperature for 30min, then centrifuged at 3000r/min at 4℃for 10min in a centrifuge, and the supernatant was taken and stored in a-80℃refrigerator for freezing. The ELISA kit is adopted, the OD value is determined strictly according to the instruction of the mouse kit, the concentration is calculated, and the expression level of each factor in the serum of each group of mice is compared.
3.5 Effect of plumbagin on IL-4, IL-5, IL-13 in skin homogenates of AD model mice
The OD values were determined using ELISA kits, strictly following the mouse kit instructions, and the concentrations were calculated and the levels of expression of each factor in the skin homogenates of each group of mice were compared.
3.6 statistics
Statistical analysis was performed on the resulting data using Graphpad prism 8.0.2 software, the data were expressed as mean ± standard deviation (x±s) or percent (%), and using analysis of variance (ANOVA), P <0.05 indicated that the difference was statistically significant.
3. Experimental results
1. Influence of plumbagin on appearance of skin injury of AD mice
As shown in FIG. 1 (A), the back skin of the mice in the normal group is not obviously changed, the back skin of the mice in the model group is obviously dry, skin-lifting, red swelling and the like compared with the back skin of the mice in the normal group, the inflammation of the back skin of the mice in the high, medium and low-dose groups of the plumbagin is improved compared with the back skin of the mice in the model group, and the mice in the model group are optimized in high dose and the medium and low dose are inferior. As can be seen from fig. 1 (B), the skin score of the normal mice is not significantly changed, the skin score of the model mice is gradually increased, and gradually decreased after reaching the peak on 13 days, compared with the model mice, the skin score of the mice is decreased compared with the model mice after other drugs are administered, wherein the effect of the plumbagin high dose group and the positive drug group is obvious, which indicates that the plumbagin has a certain intervention effect on the AD mice induced by DNCB.
2. Influence of Plumbum Preparatium on Back skin lesion tissue of mice of each group
2.1 pathological Effect of plumbagin on skin lesions tissue
As shown in fig. 2 (a) and 2 (B), the skin epidermis of the mice in the normal group was normal, and the cells in each layer were not significantly changed, and the appearance was dry and smooth. The skin thickness of the skin damage tissue of the mice in the model group is obviously increased, which shows that the AD model is successfully copied, compared with the model group, the skin thickness of the plumbagin high, medium and low dose groups and the positive control group is reduced, the local inflammatory cell infiltration condition is also reduced to different degrees, wherein the plumbagin high dose group is optimal.
2.2 determination of the number of skin-damaged mast cells in mice of each group
As shown in fig. 2 (C) and 2 (D), the normal group had normal mast cell numbers, the model group mice had significantly increased mast cell numbers, and the mast cell infiltration was significantly decreased in the high, medium, low dose and positive control groups of plumbagin, compared to the model group, and the mast cell infiltration was decreased, wherein the high dose of plumbagin was optimal.
ELISA method for detecting IgE, IL-4, IL-5 and IL-13 expression level in peripheral blood of mice of each group
As shown in FIG. 3, the IgE, IL-4, IL-5, and IL-13 levels were significantly elevated in the peripheral blood of the mice in the model group compared to the normal group; compared with the model group, the positive medicine group and the plumbagin high, medium and low dosage groups have certain down regulation effect on the expression of IgE, IL-4, IL-5 and IL-13. Compared with the model group, the expression level of the positive medicine group and the high-dose group of plumbagin is lower and similar, and the low-dose group of plumbagin is next; for the expression of IL-4, the positive medicine group and the plumbagin high-medium dosage group have lower and similar expression, and the plumbagin low-dosage group is the second; for the expression of IL-5 and IL-13, positive medicine group, plumbagin high dose group, plumbagin medium dose group and plumbagin low dose group are sequentially from low to high. The results show that the high, medium and low doses of plumbagin have an inhibitory effect on the expression of DNCB-induced AD-like mouse peripheral blood cytokines IgE, IL-4, IL-5 and IL-13.
ELISA method for detecting expression level of IL-4, IL-5 and IL-13 in skin lesion tissue of mice in each group
As shown in FIG. 4, the expression levels of IL-4, IL-5, and IL-13 were significantly increased in the homogenates of the skin lesions of mice in the model group compared to the normal group; compared with the model group, the positive group and the plumbagin high, medium and low dose groups have obvious down-regulation trend on each factor in the skin injury tissue homogenate of the mice. Compared with the model group, the high-dose group of the plumbagin has the best down-regulation effect on IL-4; for IL-5 expression, both positive and drug groups inhibited its expression, with the high dose group of plumbagin down-regulating effect being best; for the expression of IL-13, the down-regulation effect is that the positive medicine group and the medicine group are in high-low dosage from high to low in sequence. Therefore, the high, medium and low doses of plumbagin have obvious inhibition effect on the expression of cytokines IL-4, IL-5 and IL-13 in the skin lesion tissue homogenate of the AD-like mouse model induced by DNCB, and are dose-dependent.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (4)
1. Application of plumbagin in preparing medicine for treating atopic dermatitis is provided.
2. Use of plumbagin according to claim 1 for the preparation of a medicament for the treatment of atopic dermatitis, characterized in that: the plumbagin is applied to the preparation of medicines for reducing the thickness of the epidermis of the skin lesion tissue.
3. Use of plumbagin according to claim 1 for the preparation of a medicament for the treatment of atopic dermatitis, characterized in that: the application of the plumbagin in preparing the medicine for inhibiting the mast cells.
4. Use of plumbagin according to claim 1 for the preparation of a medicament for the treatment of atopic dermatitis, characterized in that: the plumbagin is applied to the preparation of medicines for inhibiting the expression of peripheral blood cytokines IgE, IL-4, IL-5 and IL-13.
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