CN103462957A - New application of isorhamnetin - Google Patents
New application of isorhamnetin Download PDFInfo
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- CN103462957A CN103462957A CN2012101871015A CN201210187101A CN103462957A CN 103462957 A CN103462957 A CN 103462957A CN 2012101871015 A CN2012101871015 A CN 2012101871015A CN 201210187101 A CN201210187101 A CN 201210187101A CN 103462957 A CN103462957 A CN 103462957A
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Abstract
The invention discloses a new application of isorhamnetin, and the new application means that isorhamnetin is taken as an active component for preparation of medicaments or health food for treating enteritis. Research results show that: isorhamnetin is capable of obviously improving symptoms such as body weight loss, bloody stools, colon shortening and tissue pathological damage and the like of ulcerative colitis mice, and inhibiting expression of colon tissue inflammatory cytokines TNF-alpha and IL-6. Therefore isorhamnetin can be taken as the active component expected to be developed as the medicaments or health food for treating enteritis, and especially is expected to be developed as medicaments or health food for treating ulcerative colitis.
Description
Technical field
The present invention relates to a kind of new purposes of isorhamnetin, specifically, relate to isorhamnetin in the medicine of preparation treatment enteritis or the application in health food, belong to technical field of Chinese medicines.
Background technology
Ulcerative colitis (Ulcerative colitis, UC) belong to inflammatory bowel (Inflammatory bowel disease, IBD), its cause of disease and pathogenesis it be not immediately clear, immune system abnormality is the intrinsic factor that cause inflammation and tissue injury, and closely related with factors such as heredity, environment, microorganisms.Clinical manifestation is mainly diarrhoea, stomachache, mucopurulent bloody stool and outbreak repeatedly.The visible mucosa hyperemia of colonoscopy, edema, rotten to the corn hemorrhage and ulcer.The sick data of Foreign Epidemic shows, primary disease can betide any age, is more common in the person between twenty and fifty in 20-40 year, send out the crowd well in 15-25 year in sickness rate be 50～1,00/,100,000.Along with growth in the living standard, the change of dietary structure, life style, be ascendant trend year by year at China's sickness rate in recent years.The primary disease course of disease is long, and outbreak, have a strong impact on patients ' life quality repeatedly, and in the extended patient, has 5～10% canceration occurs, and there is no so far clinically effective treatment measure, by World Health Organization (WHO), is classified as one of modern difficult treatment.
The Western medicine for the treatment of UC mainly contains aminosalicylic acids, glucocorticoids and immunosuppressant at present.Effect is all not bery desirable, and side effect is large, is difficult for life-time service.Sulfasalazine (SASP) is current clinical the most frequently used medicine, is applicable to moderate, slight and chronic UC patient.After oral, at intestinal degradation, be sulfapyridine and 5-aminosalicylic acid.The colon intestinal tissue is had to special affinity, play antiinflammatory action.The untoward reaction such as feeling sick appears in 10%～40% patient, dyspepsia, headache, leukopenia are arranged after oral SASP, the arthralgia of causing, erythra, albuminuria and pancreatitis etc. are occasionally arranged, most untoward reaction are all owing to the sulfapyridine part of SASP.
Because China's natural resources of Chinese medicinal materials is abundant, from natural plants, the new purposes of the native compound of the screening activated noval chemical compound of tool or known structure has become one of main path of new drug development.Therefore, the medicine of the treatment UC of this area, low toxicity efficient in the urgent need to finding from natural plants.
Isorhamnetin is the flavone compound of separating-purifying from the medicinal plants such as Semen Ginkgo, Fructus Hippophae, also extensively is present in flower, fruit and the leaf of other various plants.Large quantity research is found; isorhamnetin has protection cardiovascular (anti-myocardial ischemia, ischemia, allevating angina pectoris, arrhythmia, reduction serum cholesterol, promote that blood flow is unobstructed etc.), antioxidation, antitumor, antiinflammatory, antiviral, antiallergic and regulates the multiple biological activity such as immunologic function.But have no at present isorhamnetin and can be used as active component for the preparation of the medicine for the treatment of enteritis or the relevant report of health food.
Add dextran sulfate sodium (Dextran sulfate sodium in drinking water, DSS) freely drink directly to animal, cause the organizational structure of colonic mucosa to destroy and inflammatory cell infiltration, international ulcerative colitis modeling method (Gastroenterology, 1990,98:694-702; Digestive Disease and Science, 1993,38:1722-34).The lesions position that this kind of modeling method causes mainly concentrates on colon, also can involve small intestinal, the similar mankind's ulcerative colitis of its symptom (Yatrik M Sha, etal.Am J Physiol Gastrointest Liver Physiol.2007,292:G1114-1122), so be widely adopted at present (Chinese patent 00118309.5 " application of dimethyl silicone oil for treating ulcer colonitis ").
Summary of the invention
The new purposes that the purpose of this invention is to provide a kind of isorhamnetin, to give full play to the medical value of isorhamnetin in clinical.
A kind of new purposes of isorhamnetin of the present invention, refer to using isorhamnetin as active component for the preparation of the treatment enteritis medicine or health food.
As a kind of preferred version, a kind of new purposes of described isorhamnetin, refer to using isorhamnetin as active component for the preparation of the treatment enteritis or/and the medicine of colitis or health food.
As further preferred version, a kind of new purposes of described isorhamnetin, refer to using isorhamnetin as active component for the preparation of the treatment ulcerative colitis medicine or health food.
The purity of above-mentioned isorhamnetin is recommended > 50%, with 90% better, with 98% the best.
Above-mentioned medicine can be any pharmaceutically useful dosage form, comprising: tablet, sugar coated tablet, film coated tablet, enteric coated tablet, capsule, hard capsule, soft capsule, oral liquid, suck agent, granule, electuary, pill, powder, unguentum, sublimed preparation, suspensoid, powder, solution, injection, suppository, ointment, plaster, cream, spray, drop, patch etc.; The preferred oral dosage form, as: capsule, tablet, oral liquid, granule, pill, powder, sublimed preparation, unguentum etc.Described peroral dosage form can contain excipient commonly used, such as binding agent, filler, diluent, tablet agent, lubricant, disintegrating agent, coloring agent, flavoring agent and wetting agent, can carry out coating to tablet in case of necessity.Suitable filler comprises cellulose, mannitol, lactose and other similar filler; Suitable disintegrating agent comprises starch, polyvinylpyrrolidone and starch derivatives, for example sodium starch glycollate; Suitable lubricant comprises, for example magnesium stearate; The acceptable wetting agent of suitable medicine comprises sodium lauryl sulphate.
Experimental result shows, isorhamnetin can obviously improve the losing weight of ulcerative colitis mice, hemafecia, colon shortens and the symptom such as histopathology damage, can suppress the expression of the inflammatory cytokine TNF-α of colon and IL-6.Therefore, the isorhamnetin of usining is expected to be developed to medicine or the health food for the treatment of enteritis as active component, especially be expected to be developed to medicine or the health food for the treatment of ulcerative colitis.
The accompanying drawing explanation
Fig. 1 has embodied the impact of isorhamnetin on the ulcerative colitis Mouse Weight;
Fig. 2 has embodied the impact of isorhamnetin on ulcerative colitis mice hemafecia incidence rate;
Fig. 3 has embodied the impact of isorhamnetin on ulcerative colitis mice colon length;
The impact of isorhamnetin on ulcerative colitis mice colon pathology embodied in Fig. 4-5;
Fig. 6 has embodied the impact of isorhamnetin on the TNF-alpha expression of ulcerative colitis mice colon;
Fig. 7 has embodied the impact of isorhamnetin on the IL-6 expression of ulcerative colitis mice colon;
In figure: a means Normal group, and b means model control group, and c means positive controls, and d means the medication group.
The specific embodiment
Below in conjunction with embodiment to the present invention do further in detail, intactly explanation.
Isorhamnetin source used in embodiment is for commercially available, and as Sigma chemical company, Chengdu Man Site bio tech ltd etc., the purity of specimen in use all meets medicinal standard.
Embodiment
1, experiment material
1.1 medical material
Isorhamnetin (CAS:480-19-3, molecular weight 316.26, HPLC purity >=98%, Chengdu Man Site bio tech ltd); Dextran sulfate sodium (molecular weight 35000～44000, produced by MP Biomedical LLC company for DSS, CAS:9011-18-1); Sulfasalazine (SASP, CAS:599-79-1, molecular weight 398.39, HPLC purity >=98%, produced by Sigma company).
1.2 laboratory animal
The C57BL/6 mice of body weight 20 ± 2g (8-10 week) is provided the animal quality certification number by Shanghai Univ. of Traditional Chinese Medicine's Experimental Animal Center: SYXK(Shanghai) 2009-0069.Be placed in conventional feeding environment, ad lib and drinking-water.
2, experimental technique
2.1 the foundation of Ulcerative Colitis Model
The C57BL/6 mice of selective body weight average one (20 ± 2g, 8-10 week), add DSS in distilled water and be made into 5%(w/v) solution, freely drink directly to mice.
2.2 grouping and medication
Normal group: 10, give normal diet.
Model control group: 10, give 5%DSS solution and freely drink 5 days, changed normal drinking water into since the 5th day, gavage gives continuous normal saline 7 days simultaneously.
Positive controls: 10, give 5%DSS solution and freely drink 5 days, changed normal drinking water into since the 5th day, gavage gives SASP(350mg/kg simultaneously) continuous 7 days.
The medication group: 10, give 5%DSS solution and freely drink 5 days, changed normal drinking water into since the 5th day, gavage gives isorhamnetin (50mg/kg) continuous 7 days simultaneously.
2.3 the assessment of enteritis
Experimental session records body weight change, symptom of diarrhea and hemafecia symptom every day.After experiment finishes, mice is put to death in anesthesia cervical vertebra dislocation, opens abdominal cavity, takes out colon, measures the colon length from the caecum to the rectum.And get colon and make tissue slice, carry out H& E dyeing.
Colon specimen pathological score: (1) inflammatory cell ooze out standards of grading: the minute quantity inflammatory cell is arranged in 0 minute-mucosa lamina propria, in 1 minute-mucosa lamina propria, there is the inflammatory cell in more inflammatory cell or mucosa lamina propria to increase, 2 minutes-inflammatory cell diffuses to Submucosa, and 3 minutes-holostrome all has inflammatory cell to ooze out; (2) tissue damage standards of grading: 0 minute-without mucosa injury, 1 minute-discrete mucosal epithelium is damaged, 2 minutes-top layer mucosal erosion, and 3 minutes-mucosa breakage is widely also expanded to the intestinal wall deep layer; By oozing out and tissue damage score addition of inflammatory cell, calculate histopathology scoring (1-6 divides).
2.4 fluorescence quantitative RT-RCR detects the TNF-α of colon and the expression of IL-6
In body, effect experiment is got colon after finishing, and with Trizol reagent, extracts the total RNA of colon also quantitatively, gets 3 μ gRNA and prepares cDNA by the M-MLV reverse transcription.Take cDNA as template, increased on ABI 7300 quantitative real time PCR Instruments.PCR reaction system: 2 * SYBR Premix Ex Taq(TakaRa, cat:DRR420A) 5 μ L, Forward Primer 0.4 μ L, Reverse Primer 0.4 μ L, 50 * ROX Reference Dye, 0.4 μ L, cDNA1 μ L, dH
2o 2.8 μ L, cumulative volume is 10 μ L.PCR response parameter: 95 ℃, 30s denaturation, 95 ℃, 5s degeneration, 60 ℃, 30s annealing, totally 40 circulations.Each amplification arranges β-actin internal reference.Primer sequence is as follows:
MTNF-α: positive-sense strand 5 '---CGTGGAACTGGCAGAAGAGG---3 ',
Antisense strand 5 '---AGACAGAAGAGCGTGGTGGC---3 ';
MIL-6: positive-sense strand 5 '---ACCACGGCCTTCCCTACTTC---3 ',
Antisense strand 5 '---CATTTCCACGATTTCCCAGA---3 ';
β-Actin: positive-sense strand 5 '---CAGCCTTCCTTCTTGGGTAT---3 ',
Antisense strand 5 '---GGTCTTTACGGATGTCAACG---3 '.
Carry software with the pcr amplification instrument and carry out quantitative fluorescence analysis, and draw the Ct value.By calculating 2
-△ △ CTdraw relative expression's level of respectively organizing gene.
2.5 statistical analysis
All experimental datas all repeat 3 times, and result means with mean+SD, adopt SPSS 16.0 statistical softwares to adopt one way analysis of variance (One-way ANOVA) and LSD check to experimental data, and there is significance P<0.05 for difference statistically.
3, result
3.1 the therapeutical effect of isorhamnetin to ulcerative colitis
3.1.1 the impact on the ulcerative colitis Mouse Weight
Fig. 1 has embodied the impact of isorhamnetin on the ulcerative colitis Mouse Weight, as seen from Figure 1: the body weight of Normal group mice has increased by 2.7 ± 0.8%, the model group mice lost weight 6.8 ± 0.8%, the positive controls mice lost weight 0.7 ± 0.6%, medication group mice lost weight 2.4 ± 0.6%; Further illustrate the weight loss (P<0.01) that isorhamnetin can significantly suppress the ulcerative colitis mice that DSS causes.
3.1.2 the impact on ulcerative colitis mice hemafecia incidence rate
Fig. 2 has embodied the impact of isorhamnetin on ulcerative colitis mice hemafecia incidence rate, as seen from Figure 2: mice occurs without hemafecia Normal group, the hemafecia incidence rate of model group mice is 90 ± 0%, the hemafecia incidence rate of positive controls mice is 33.3 ± 5.8%, and the hemafecia incidence rate of medication group mice is 53.3 ± 5.8%; Further illustrate the hemafecia incidence rate (P<0.01) that isorhamnetin can significantly reduce the ulcerative colitis mice that DSS causes.
3.1.3 the impact on ulcerative colitis mice colon length
Fig. 3 has embodied the impact of isorhamnetin on ulcerative colitis mice colon length, as seen from Figure 3: the Normal group mice shortens and occurs without colon, the colon LVFS of model group mice is 37.7 ± 0.5%, the colon LVFS of positive controls mice is 24.1 ± 0.4%, and the colon LVFS of medication group mice is 31.3 ± 0.4%; Further illustrate the colon that isorhamnetin can significantly improve the ulcerative colitis mice that DSS causes and shorten symptom (P<0.05).
3.1.4 the impact on ulcerative colitis mice colon pathology
Fig. 4 has embodied the injury repairing effect of isorhamnetin to ulcerative colitis mice colon, as seen from Figure 4: the colon of model group mice is typical inflammation mucosa performance, visible mucosa, Submucosa be flesh layer massive inflammatory cells infiltrated even, organizational structure is disorderly, fracture, Submucosa is hemorrhage, edema, telangiectasis; The visible pathological changes of colon of positive controls mice and medication group mice alleviates, ulcer healing, and Submucosa is hemorrhage to be alleviated.
In addition, Fig. 5 has embodied colon specimen pathological score result, and the score of Normal group mice is 0, the score of model group mice is 5 ± 0.5%, and the score of positive controls mice is 2.5 ± 0.5%, and the score of medication group mice is 3.5 ± 0.5%, with model group, compare, difference has significance (P<0.05).
To sum up colon's pathological analysis result shows: isorhamnetin can alleviate the damage of colonic mucosa histopathology and inflammatory cell infiltration.
3.1.5 the impact on the TNF-alpha expression of ulcerative colitis mice colon
Fig. 6 has embodied the impact of isorhamnetin on the TNF-alpha expression of ulcerative colitis mice colon, and as seen from Figure 6: the model group mice TNF-of colon alpha expression is apparently higher than Normal group (P<0.001); After gavage gives SASP or isorhamnetin, the TNF-alpha expression of mice colon descends, and with model group, compares, and difference has significance (P<0.001), shows that isorhamnetin can significantly suppress the expression of TNF-α in inflammatory reaction that DSS causes.
3.1.6 the impact that the IL-6 of ulcerative colitis mice colon is expressed
Fig. 7 has embodied the impact of isorhamnetin on the IL-6 expression of ulcerative colitis mice colon, and as seen from Figure 7: the model group mice IL-6 of colon expresses apparently higher than Normal group (P<0.001); After gavage gives SASP or isorhamnetin, the IL-6 of mice colon expresses decline, with model group, compares, and difference has significance (P<0.01), shows that isorhamnetin can significantly suppress the expression of IL-6 in inflammatory reaction that DSS causes.
To sum up result of study shows, isorhamnetin can obviously improve the losing weight of ulcerative colitis mice, hemafecia, colon shortens and the symptom such as histopathology damage, can suppress the expression of the inflammatory cytokine TNF-α of colon and IL-6.Therefore, the isorhamnetin of usining is expected to be developed to medicine or the health food for the treatment of enteritis as active component, especially be expected to be developed to medicine or the health food for the treatment of ulcerative colitis.
Finally be necessary described herein: above embodiment is only for being described in more detail technical scheme of the present invention; can not be interpreted as limiting the scope of the invention, some nonessential improvement that those skilled in the art's foregoing according to the present invention is made and adjustment all belong to protection scope of the present invention.
Claims (6)
1. the new purposes of an isorhamnetin is characterized in that: using isorhamnetin as active component medicine or the health food for the preparation for the treatment of enteritis.
2. the new purposes of isorhamnetin according to claim 1 is characterized in that: using isorhamnetin as active component for the preparation of the treatment enteritis or/and the medicine of colitis or health food.
3. the new purposes of isorhamnetin according to claim 2 is characterized in that: using isorhamnetin as active component medicine or the health food for the preparation of the treatment ulcerative colitis.
4., according to the new purposes of the described isorhamnetin of any one in claims 1 to 3, it is characterized in that: the purity of described isorhamnetin 50%.
5. the new purposes of isorhamnetin according to claim 4, is characterized in that: the purity of described isorhamnetin > 90%.
6. the new purposes of isorhamnetin according to claim 5, is characterized in that: the purity of described isorhamnetin > 98%.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114159424A (en) * | 2021-08-25 | 2022-03-11 | 广州医科大学附属第一医院（广州呼吸中心） | Application of isorhamnetin in treating influenza |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20100138398A (en) * | 2009-06-25 | 2010-12-31 | 건국대학교 산학협력단 | Composition comprising 3-o-glucose-isorhamnetin as an effective ingredient for treatment and prevention of inflammatory diseases, immune diseases or cancers |
| CN102448455A (en) * | 2009-03-31 | 2012-05-09 | 雀巢产品技术援助有限公司 | Use of flavonoids to increase the bioavailability of hesperetin |
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- 2012-06-07 CN CN2012101871015A patent/CN103462957A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102448455A (en) * | 2009-03-31 | 2012-05-09 | 雀巢产品技术援助有限公司 | Use of flavonoids to increase the bioavailability of hesperetin |
| KR20100138398A (en) * | 2009-06-25 | 2010-12-31 | 건국대학교 산학협력단 | Composition comprising 3-o-glucose-isorhamnetin as an effective ingredient for treatment and prevention of inflammatory diseases, immune diseases or cancers |
Non-Patent Citations (1)
| Title |
|---|
| 杨云松，等: "糖苷类化合物体外生物转化的研究进展", 《中国生化药物杂志》, vol. 33, no. 6, 31 December 2012 (2012-12-31), pages 927 - 930 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114159424A (en) * | 2021-08-25 | 2022-03-11 | 广州医科大学附属第一医院（广州呼吸中心） | Application of isorhamnetin in treating influenza |
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