CN111773212A - Application of daphnetin - Google Patents
Application of daphnetin Download PDFInfo
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- CN111773212A CN111773212A CN202010815902.6A CN202010815902A CN111773212A CN 111773212 A CN111773212 A CN 111773212A CN 202010815902 A CN202010815902 A CN 202010815902A CN 111773212 A CN111773212 A CN 111773212A
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- atopic dermatitis
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- ATEFPOUAMCWAQS-UHFFFAOYSA-N 7,8-dihydroxycoumarin Chemical compound C1=CC(=O)OC2=C(O)C(O)=CC=C21 ATEFPOUAMCWAQS-UHFFFAOYSA-N 0.000 title claims abstract description 76
- YBGKGTOOPNQOKH-UHFFFAOYSA-N daphnetin Natural products OC1=CC=CC2=C1OC(=O)C=C2O YBGKGTOOPNQOKH-UHFFFAOYSA-N 0.000 title claims abstract description 76
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Images
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
- A61K31/37—Coumarins, e.g. psoralen
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- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Abstract
The invention discloses an application of daphnetin. Experiments prove that the daphnetin can improve papules, crusts and the like at skin damage parts of mice with atopic dermatitis models, reduce the number of mast cells at the skin damage parts, and reduce the levels of IgE, IL-4, IL-13 and IL-6 in the blood serum of the mice with the atopic dermatitis models. Daphnetin may exert a therapeutic effect on atopic dermatitis by regulating the expression of mast cells and Th2 type cytokines to inhibit inflammation. Daphnetin has application prospect in the medicines for treating and preventing atopic dermatitis.
Description
Technical Field
The invention belongs to the technical field of medicines, relates to an application of daphnetin, and particularly relates to an application of daphnetin in medicines for treating and preventing atopic dermatitis.
Background
Atopic Dermatitis (AD) is a common chronic, recurrent, inflammatory skin disease. The disease occurs in all ages, with children being the most common, and about 10% to 20% and 1% to 3% of adults all over the world suffer from AD. Epidemiological studies find that the prevalence of AD in most countries of the world, particularly economically developed countries, has increased substantially over the last 30 years, with the prevalence of children reaching even as high as 10% -20% in europe and america; in China, the prevalence of atopic dermatitis has also been increasing for 20 years. The disease is generally clinically divided into 3 stages: infancy, childhood, adolescence and adulthood. After the age of 45, the patients with the disease are rare, and the patients who are stubborn can be cured by the age of 50-60. It is clinically characterized by extensive erythema, papules, desquamation, and persistent itching and dry skin, and patients often have a family history of "atopy". Frequent scratching results in thickening of the skin, lichenification and often immediate (type i) allergic reactions. Most of AD patients are adolescents and children, and currently, antihistamine drugs, hormone drugs, antibiotics and the like are mostly adopted, so that the side effect is large, and a plurality of adverse factors are generated on growth and development after long-term use, so that the search for medicines with small toxic and side effects and definite curative effect is imperative.
The traditional Chinese medicine considers that the skin disease is not only the pathological changes of the skin, but also the result of the general immune dysfunction, so the treatment is carried out by improving the general state and differentiating the symptoms. TCM gives play to the advantages of internal treatment, and usually has better effect when modified according to the disease condition. However, the clinical traditional Chinese medicine compound for treating AD of infants and children usually contains akebia stem, which is not suitable for long-term use and large-scale application due to the fact that akebia stem has bitter and cold properties to release heart and kidney qi and can cause renal failure, so that the application of traditional Chinese medicine in treating AD is limited.
Daphnetin (Daphnetin, Dap.) is Daphnetin A extracted from daphne giraldii of Thymelaeaceae. Changbai Daphne odora is bitter and pungent in taste and warm in nature and enters heart, liver and lung meridians; it excels in relaxing muscles and tendons, activating collateral flow, promoting blood circulation, and removing blood stasis. Daphnetin is odorless and tasteless, is white or off-white powder, is slightly soluble in methanol, is slightly soluble in ethanol, and is insoluble in water. The chemical name is 7, 8-dihydroxycoumarin with the molecular formula of C9H6O4Structural formula is。
In the research process, the inventor finds that the daphnetin has the effect of treating and preventing atopic dermatitis.
Disclosure of Invention
The invention aims to provide application of daphnetin in medicines for treating and preventing atopic dermatitis.
The purpose of the invention is realized as follows:
daphnetin can protect the skin of atopic dermatitis patients, and promote the growth of part of new hair at skin lesion, and improve pimple and incrustation, and has the following structural formula:
daphnetin can protect atopic dermatitis patients from skin thickening, edema, inflammatory cell infiltration, etc.
Daphnetin inhibits mast cell number in skin lesions.
Daphnetin decreases IgE levels.
Daphnetin inhibits the expression of Th2 type cytokines IL-4, IL-6, IL-13.
Atopic dermatitis is atopic dermatitis, eczema, neurodermatitis or seborrheic dermatitis.
The dosage form of the medicine is oral dosage form or external dosage form.
The daphnetin dose is 3 times daily, 0.5-2g each time.
The dose of daphnetin is 3 times daily, 1g each time.
The invention has the advantages that:
1. the invention provides experimental research to prove that daphnetin can protect the skin of an atopic dermatitis model mouse, so that part of new hair grows from skin damage, and pimples and scabs are improved.
2. The invention provides application of daphnetin, namely application of daphnetin in preparing a medicament for treating atopic dermatitis, and the daphnetin can protect daphnetin of an atopic dermatitis model mouse and can effectively inhibit the conditions of skin thickening, edema, inflammatory cell infiltration and the like of the atopic dermatitis model mouse. The daphnetin has certain inhibitory effect on the number of mast cells at skin lesions after acting on atopic dermatitis model mice. Daphnetin can reduce IgE level and inhibit expression of Th2 type cytokines IL-4, IL-6 and IL-13.
Drawings
FIG. 1 is the appearance of skin lesions in mice;
FIG. 2 is the observation of pathological morphology of HE staining of dorsal skin lesion tissues of AD mice (200 ×);
FIG. 3 shows mast cell infiltration (200X) in skin lesion tissues of AD mice;
FIG. 4 shows the effect of daphnetin on the IgE expression level in the serum of AD mice;
note: # #: p < 0.01; *: p < 0.05; **: p < 0.01; ns: no significant difference exists;
FIG. 5 shows the effect of daphnetin on the expression level of cytokines in the serum of AD mice;
note: # # # # #: p < 0.0001; # #: p < 0.01; *: p < 0.05; **: p < 0.01; ***: p < 0.005;
***: p < 0.001; ns: there was no significant difference.
Detailed Description
The present invention is further illustrated but not limited in any way by the following examples, and any modifications made thereto are intended to fall within the scope of the present invention.
Application of daphnetin in preparing medicine for treating and preventing atopic dermatitis is provided.
Daphnetin can protect the skin of atopic dermatitis patients, and promote the growth of part of new hair at skin lesion, and improve pimple and incrustation, and has the following structural formula:
daphnetin can protect atopic dermatitis patients from skin thickening, edema, inflammatory cell infiltration, etc.
Daphnetin inhibits mast cell number in skin lesions.
Daphnetin decreases IgE levels.
Daphnetin inhibits the expression of Th2 type cytokines IL-4, IL-6, IL-13.
Atopic dermatitis is atopic dermatitis, eczema, neurodermatitis or seborrheic dermatitis.
The dosage form of the medicine is oral dosage form or external dosage form.
The daphnetin dose is 3 times daily, 0.5-2g each time.
The dose of daphnetin is 3 times daily, 1g each time.
Example 1:
1 materials of the experiment
1.1 animals
48 female BALB/c mice, SPF grade 6-8 weeks old, weight (20. + -.2) g, purchased from Schleksider laboratory animals Ltd, Hunan, animal license number [ SCXK (Hunan) 2016-. Adaptive feeding for 1 week, and feeding in clean animal room with no specific pathogen, air flow, temperature (23 + -2) ° C, humidity (55 + -5)%, light darkness per 12 hr as a circulation, and free food and water acquisition of mouse.
1.2 drugs and Primary Agents
Daphnetin, shanghai source leaf biotechnology limited; dexamethasone acetate, Zhejiang Xianju pharmaceutical products, batch number: 170512, respectively; 2, 4-dinitrochlorobenzene, Dodbett reagent, Inc., production batch No.: Z0016B 5; acetone, yunnan pharmaceutical industry limited company in the development area of the Yunnan Yanglin industry, production lot number: 20160325, respectively; olive oil, Shandong Lu Hua group Co., Ltd, production batch number: 20180803, respectively; sodium carboxymethylcellulose, shinyleaf fine chemical research institute in Tianjin, production lot number: 50116; elisa kit, dear, production lot number: 1218202.
1.3 Main experimental equipment and equipment
Full-wavelength multifunctional enzyme-labeling instrument, Beijie science and technology, model: plus 384; ultra low temperature refrigerator at-80 ℃, Thermo Forma company, usa, model: forma 902; low temperature high speed centrifuge, Eppendorf company, germany, model number: 5810R; electronic analytical balance, aohaus instruments ltd, model number: AR224 CN.
2 method of experiment
2.1 model replication, grouping and administration
BALB/c mice were adapted for 1 week and then used in the experiment, and were randomly divided into a blank control group, a model control group, a positive control group (dexamethasone acetate 2 mg/kg), daphnetin low, medium and high dose groups (25, 50, 100 mg/kg), 8 mice per group. 1 day before the experiment, all mice had their backs depilated (2 cm. times.2 cm) with electric clippers plus depilatory cream, exposing the skin; on the 1 st and 2 nd days of the experiment, except for the blank control group, the mice in other groups were smeared with 1% 2, 4-Dinitrochlorobenzene (DNCB) solution prepared by using an acetone-olive oil mixed solution as a solvent on the skin with depilated back, 100 uL of the solution was used once, no treatment was performed on the 3 rd to 6 th days, and on the 7 th day, 1 0.3% DNCB solution was smeared once every 1 day, 70 uL of the solution was used once, until the 28 th day. The unhaired skin on the back of the mice in the blank control group was applied with the acetone-olive oil mixed solution only, and the application time and volume were consistent with those of the model building group. The corresponding drugs were administered by gavage for 1 time/day and 28 days continuously from the 1 st day of the experiment.
2.2 sample selection and processing
After the last administration, fasting is carried out for 12 h, the abdominal aorta blood is collected from the anesthetized animals, the spleen and the thymus are dissected, the skin lesion tissue at the back molding position is cut into 2 parts, one part is placed in a refrigerator at the temperature of minus 80 ℃, and the other part is placed in 10% neutral formalin solution.
2.3 measurement index and method
(1) General observations in mice
Weighing and recording the weight of the mice every day; one day after each molding, the mice were observed for skin lesions on the back, including erythema (hemorrhage), erythema (pimple), exfoliation (scratch), scaling (dryness), etc., and recorded by photographing.
(2) General histopathological observations
Taking out the skin lesion tissue fixed in 10% neutral formalin solution, dehydrating, waxing, embedding, slicing, etc. to prepare pathological sections, and then carrying out HE staining.
(3) Mast cell infiltration number of skin lesion tissue
Paraffin section, dewaxing, Toluidine Blue (TB) staining, washing, drying, mounting, observing infiltration condition of Mast Cells (MC) in dermis of mouse skin tissue under a microscope, randomly selecting 8 visual fields in each group, photographing, mounting, and counting infiltration quantity of Mast cells.
(4) Serum total IgE and Th2 type cytokine expression
The Elisa method is used for measuring the content of total IgE and cytokines IL-6, IL-4 and IL-13 in serum.
2.4 statistical treatment
The data obtained were statistically analyzed using Graphpad prism 8.0.2 software, with data expressed as mean ± standard deviation, and using one-way anova and t-test analysis, values of P <0.05 indicating that the difference was statistically significant.
3 results of the experiment
3.1 Effect of daphnetin on skin lesion tissue in AD model mice
3.1.1 appearance of skin lesions in mice
The skin of the blank control group mouse is normal, and the tissue structure is basically normal; the skin of the mouse in the model control group can be changed by skin damage such as erythema, dryness, scale, pimple and incrustation; after 28 days of continuous administration, the skin of the back of the positive control group mice is smoother, and only a very small amount of scales can be seen; the daphnetin high-dose mice had a small amount of scales on the back, no obvious erythema, and some new hairs were grown on the skin lesions on the back of the individual animals at the end of the experiment, and the pimples and scabs of the middle-low dose mice were improved to some extent, and the results are shown in fig. 1.
3.1.2 general histopathology of mouse skin lesions
HE staining shows that the skin structure of the mice in the blank control group is complete and normal in shape, and no vasodilation and inflammatory cell infiltration are seen in the dermis; the skin structure of a tested region on the back of a mouse in a model control group is seriously damaged, hyperkeratosis is caused, the thick and thick spinous layer is obviously accompanied with focal spongiform edema, dermal blood vessels are dilated and congested and accompanied with a large amount of inflammatory cell infiltration, and the hair follicle structure is reduced; compared with a model control group, the positive control group mice have clear structures of all layers of the epidermis, the thickening of the epidermis is obviously reduced, the dermis does not have vasodilatation, inflammatory cells are obviously reduced compared with the model group, and hair follicle structures are obviously increased; the skin cornification degree of mice in the high and medium dose daphnetin groups is reduced, the acanthosis and focal spongiform edema are obviously reduced, the infiltration of inflammatory cells in the dermis is obviously reduced, the hair follicle structure is obviously increased, and the specific result is shown in figure 2. The daphnetin is suggested to be capable of effectively inhibiting the conditions of skin thickening, edema, inflammatory cell infiltration and the like of an AD model mouse.
3.2 Effect of daphnetin on mast cell infiltration in skin lesions of AD model mice
Toluidine blue staining showed only a small number of mast cells visible in the blank control; more mast cells were visible in the model control compared to the blank control; compared with a model control group, a small amount of mast cells can be seen at the skin lesion of the mice in the positive control group, and the number is obviously reduced; the number of mast cells at skin lesions of the AD model mice can be obviously reduced by high, medium and low daphnetin doses, wherein the number of the mast cells in a daphnetin high dose group is slightly higher than that in a positive control group, and the specific figure is shown in figure 3. The daphnetin has a certain inhibition effect on the number of mast cells at skin lesions after acting on AD model mice.
3.3 Effect of daphnetin on serum Total IgE and cytokine levels in AD model mice
Compared with a blank control group, the contents of total IgE and IL-4, IL-6 and IL-13 in the serum of the mouse in the model control group are obviously increased; compared with the model control group, each dose of daphnetin can obviously reduce the serum total IgE level and the contents of IL-4, IL-6 and IL-13, and the results are shown in a figure 4 and a figure 5; it is suggested that daphnetin can reduce IgE levels and inhibit the expression of Th2 type cytokines.
4. Conclusion
In the mouse AD model test, the dosage of daphnetin is 1 time per day, and the dosage is 25, 50 and 100 mg/kg each time. The dosage is converted into 1 time per day (calculated by adult weight 60 kg), 1.5, 3, 6 g each time. In consideration of taking, the recommended dose is 0.5-2g per 3 times a day. The most common dosage is 1g each time 3 times daily.
The daphnetin provided by the invention can protect the skin of an AD model mouse, so that part of new hair grows from the skin lesion, and pimples and scabs are improved. Daphnetin can effectively inhibit skin thickening, edema, inflammatory cell infiltration and the like of AD model mice. The daphnetin has a certain inhibiting effect on the number of mast cells at skin lesions after acting on AD model mice. Daphnetin can reduce IgE level and inhibit expression of Th2 type cytokines IL-4, IL-6 and IL-13.
Claims (10)
2. the use of daphnetin according to claim 1, wherein daphnetin is capable of protecting the skin of atopic dermatitis patients by growing new hair from skin lesions and improving pimples and scabs.
3. The use of daphnetin according to claim 1, wherein daphnetin is capable of protecting skin thickening, edema and inflammatory cell infiltration in atopic dermatitis patients.
4. The use of daphnetin according to claim 1, wherein daphnetin inhibits mast cell number in lesions.
5. The use of daphnetin according to claim 1, wherein daphnetin reduces IgE levels.
6. The use of daphnetin according to claim 1, wherein daphnetin inhibits the expression of the Th2 type cytokines IL-4, IL-6, IL-13.
7. Daphnetin for use according to claim 1, wherein the atopic dermatitis is eczema, neurodermatitis or seborrheic dermatitis.
8. The use of daphnetin according to claim 1, wherein daphnetin is formulated for oral or topical administration.
9. The daphnetin application according to claim 1, wherein the daphnetin is applied in an amount of 0.5-2g per time and 3 times a day.
10. Daphnetin for use according to claim 1, wherein the daphnetin is administered in an amount of 1g 3 times a day.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101039689A (en) * | 2004-06-12 | 2007-09-19 | 西格纳姆生物科学公司 | Topical compositions and methods for epithelial-related conditions |
WO2009096695A2 (en) * | 2008-01-28 | 2009-08-06 | Alphacryptec Co., Ltd. | Cosmetic composition for alleviating pruritus or inflammation containing daphnetin |
WO2015102642A1 (en) * | 2014-01-03 | 2015-07-09 | Scioderm, Inc. | Allantoin compositions for treating inflammatory skin conditions |
CN105566269A (en) * | 2015-03-27 | 2016-05-11 | 北京大学 | Preparation and pharmacological effects of coumarin derivative and application of coumarin derivative to treatment on pruritus |
-
2020
- 2020-08-14 CN CN202010815902.6A patent/CN111773212A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101039689A (en) * | 2004-06-12 | 2007-09-19 | 西格纳姆生物科学公司 | Topical compositions and methods for epithelial-related conditions |
WO2009096695A2 (en) * | 2008-01-28 | 2009-08-06 | Alphacryptec Co., Ltd. | Cosmetic composition for alleviating pruritus or inflammation containing daphnetin |
WO2015102642A1 (en) * | 2014-01-03 | 2015-07-09 | Scioderm, Inc. | Allantoin compositions for treating inflammatory skin conditions |
CN105566269A (en) * | 2015-03-27 | 2016-05-11 | 北京大学 | Preparation and pharmacological effects of coumarin derivative and application of coumarin derivative to treatment on pruritus |
Non-Patent Citations (4)
Title |
---|
BEOM-GEUN JO,等: "A new flavonoid from Stellera chamaejasme L., stechamone, alleviated 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in a murine model", 《INT IMMUNOPHARMACOL》 * |
何荣安,等: "瑞香素对TNF-α刺激的HaCaT角质形成细胞炎症因子表达的影响", 《世界最新医学信息文摘》 * |
张祎,等: "民族药抗特应性皮炎活性研究进展", 《中华中医药杂志》 * |
武雪,等: "HPLC同时测定瑞香狼毒中瑞香素、伞形花内酯和东莨菪内酯的含量", 《中国现代应用药学》 * |
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