CN1915236A - Application of woodruff glycoside in preparing medication for treating rheumatoid arthritis - Google Patents
Application of woodruff glycoside in preparing medication for treating rheumatoid arthritis Download PDFInfo
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- CN1915236A CN1915236A CN 200510019323 CN200510019323A CN1915236A CN 1915236 A CN1915236 A CN 1915236A CN 200510019323 CN200510019323 CN 200510019323 CN 200510019323 A CN200510019323 A CN 200510019323A CN 1915236 A CN1915236 A CN 1915236A
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Abstract
An application of the asperuloside in preparing the medicine for treating rheumatoid arthritis is disclosed.
Description
Technical field
The present invention relates to a kind of can be from the Cortex Eucommiae the new purposes, the particularly application in preparation treatment medicine for treating rheumatoid arthritis of isolating material-asperuloside.
Background technology
Its chemical structural formula of asperuloside (asperuloside) is as follows.
Asperuloside can separate from the Cortex Eucommiae (Eucommia ulmoides Oliver), Herba Galii Teneri plants such as (Tender Bedstraw), and asperuloside also can separate from other plant.Asperuloside is as a kind of material that has had, although definite molecular formula and structural formula are arranged, the activity of its research is not high, and the application in preparation treatment medicine for treating rheumatoid arthritis does not also appear in the newspapers as monomer.
RA is the abbreviation of Rheumatoid arthritis.
RA be a kind of be the chronic autoimmune disease of feature with the articular synovitis, still do not have at present the treatment good plan.The early lesion of RA is mainly at synovial membrane, because the stimulation of factors such as infection or wound, the synovial cell breeds rapidly, the synthetic various kinds of cell factor, and as interleukin 1 β (IL-1 β), tumor necrosis factor (TNF-α), interleukin-6 (IL-6) etc.Various cytokines are united mediation RA inflammation and tissue injury, and wherein comparatively outstanding with the effect of TNF-α, TNF-α can cause the tumor tissues hemorrhagic necrosis and have many-sided cytokine.In activeness RA, TNF-α participates in three kinds of main pathological processes: (1) activates vascular endothelial cell, strengthen the expression of endothelial cell adhesion molecule, and when arthritis, the leukocyte in the blood is pooled to articular cavity by interacting with adhesion molecule just.(2) stimulate connective tissue cell and polymorphonuclear cell to produce micromolecule inflammatory mediators such as prostaglandin.(3) by stimulating synovial cell, chondrocyte and osteoclast, it is synthetic to reduce glycoprotein, increases protein degradation, and produces collagenase and other neutral protease, discharges bone calcium etc., thereby causes the destruction and the osteoarthrosis dyskinesia of bone and cartilage.Therefore by suppressing the generation of TNF-α, be one of desirable approach of RA treatment thereby stop the hyper-proliferative of synovioblast.
The effect of IL-1 β is also comparatively outstanding in addition, and almost various nucleated cell can both produce IL-1 β, but most cells is not synthesized IL-1 β just often, is only just induced synthetic IL-1 β and IL-1 β precursor protein after activation.Lipopolysaccharide (LPS) is beta induced dose of effective I L-1, can the rapid induction various kinds of cell express IL-1 β.IL-1 β can stimulate synovioblast and capillary endothelial cell height propagation, constitutes RA characteristic pannus; Stimulate chondrocyte and osteoclast to produce multiple protein hydrolytic enzyme such as prostaglandin (PGE2) and collagenase; Activate neutrophilic granulocyte, discharge inflammatory mediators such as lysosomal enzyme, free radical, cause to cause arthritis adhesion and later stage joint deformity by disorganization such as articular cartilage, sclerotin.Therefore by suppressing the generation of IL-1 β; Thereby the hyper-proliferative that stops synovioblast is one of desirable approach of RA treatment.
Summary of the invention
The object of the present invention is to provide the new purposes of asperuloside, the application of asperuloside in preparation treatment medicine for treating rheumatoid arthritis.
The acquisition of asperuloside:
The ethanol of at first using 5 times of Folium Eucommiae (Eucommia ulmoids Oliv.) medical material weight was with medical material reflux, extract, 3 times, each 1 hour; Centrifugal or the filtration with extracting solution then, it is 0.5g crude drug/ml that filtrate is evaporated to concentration at 55 ℃, filters, and gets supernatant; Supernatant is admixed silica gel, carry out silica gel column chromatography,, collect the acetone eluent, be evaporated to dried with ethyl acetate, acetone, methanol difference eluting; Get the acetone extract dissolve with ethanol, admix the silica gel of 3 times of amounts, separate with silica gel column chromatography dry back, and the isolating eluting solvent of silica gel chromatographic column is the chloroform of equal proportion weight: methanol: water mixed liquid, elution flow rate are 500 milliliters/hour.Thin layer chromatography is checked, merges same section, and recrystallization obtains asperuloside again, and the yield of asperuloside is 0.86%.
Perhaps, the ethanol of at first using 5 times of Folium Eucommiae (Eucommia ulmoids Oliv.) medical material weight was with medical material reflux, extract, 3 times, each 1 hour; Centrifugal or the filtration with extracting solution then, it is 0.5g crude drug/ml that filtrate is evaporated to concentration at 55 ℃, filters, and gets supernatant; Supernatant is carried out macroporous resin column chromatography,, collect 60% ethanol elution, be evaporated to dried with the ethanol, the water system eluting that contain ethanol percentage by weight 60%; Get the ethanol extraction dissolve with methanol, admix the silica gel of 3 times of amounts, separate with silica gel column chromatography dry back, and the isolating eluting solvent of silica gel chromatographic column is the chloroform of equal proportion weight: methyl alcohol mixed liquor, elution flow rate are 500 milliliters/hour.Thin layer chromatography is checked, merges same section, carries out the gel column chromatography purification again one time, and the methanol of equal proportion weight, water mixed liquid eluting obtain asperuloside, and the yield of asperuloside is 0.29%.
Asperuloside can also adopt additive method to obtain.
In the medicine for treating rheumatoid arthritis field, a lot of bibliographical information ingredients are arranged to synovial cell TNF secretion-α, PGE
2With the influence of IL-1 β, investigate the effect of Drug therapy RA with zooperal data.These documents have: [1] Ju Dahong, Jia Hongwei, Wu Hao, etc., cervus and cucumis polypeptide injection to the influence of the inductive autoimmune arthritis rat blood serum of C II TNF-α, IL-6 and C II antibody activity, Chinese TCM basis medical journal, 2003,9 (11): 17.[2] what Jinhua, beam Tsing-Hua University, Zhang Huaxian, etc. the swollen soup that disappears of, numbness to the influence of experimental arthritis rat plasma TNF-α, Hunan Medical University's journal, 2002,27 (5): 524.[3] Huang Qingchun, Zhang Shengpeng, Xu Qiuying, compound Salviae Miltiorrhizae is induced the influence of rat model synovial cell secretion and tumor necrosis factor, modern rehabilitation, 2001,5 (10): 54-55 to the II collagen type.[4] Zheng Zhigang, cytokine and detection method thereof and clinical meaning, Shaanxi medical test, 2001,16 (2): 59.[5] Zhou Jun, Fang Suping, Qi Yun, etc., GEGEN TANG to the influence of adjuvant arthritis rats joint fluid inflammatory mediator, Chinese experimental pharmacology of Chinese medical formulae magazine, 2001,7 (3): 29.[6] Ma Ji, Lu Bingjiu, Zhu Xiaoming, etc., the pharmacodynamic study of blood stasis dispelling granule therapy rheumatoid arthritis, Chinese medicine academic periodical, 2001,19 (6): 734.[7] Zhu Jiang, Xie Wenli, Jin Yuzhang, etc., Fructus Gardeniae to the influence of rheumatoid arthritis rat blood serum IL-1 β and TNF α, Chinese patent medicine, 2005,27 (7): 801.[8] Huang Qingchun, Zhang Shengpeng, Huang Weiyi, etc., the influence that FUFANG DANSHEN ZHUSHEYE is expressed CIA rat synovial cell IL-1 β mRNA, Anhui Chinese Medicine College journal, 2002,21 (5) .-39-41.
Get the asperuloside that the inventive method obtains, carry out the preparation of model preparation, medicine grouping, rat synovial cell cultivation and supernatant by the method that document [3] provides.
The method that provides by document [3] is investigated ingredient to synovial cell TNF secretion-α, PGE
2Influence.Investigate ingredient to the synovial cell being secreted the influence of IL-1 β by the method that document [8] provides.
The heavy dose of group of asperuloside (20mg/kg.d); Asperuloside small dose group (10mg/kg.d) is as follows with the experimental data of normal control, sodium chloride group:
The content of TNF-α in the table 1 synovial cell culture supernatant (x ± s, ng/ml)
| Group | TNF-α |
| The heavy dose of group of normal control sodium chloride asperuloside (20mg/kg.d) asperuloside small dose group (10mg/kg.d) | 0.35±0.052 0.71±0.136 * 0.42±0.036 *△ 0.45±0.025 |
Compare P＜0.05 with the normal control group; Compare with the sodium chloride group,
△P＜0.05
IL-1 β content in the table 2 synovial cell culture supernatant (x ± s, ng/ml)
| Group | IL-1β |
| The heavy dose of group of normal control sodium chloride asperuloside (20mg/kg.d) asperuloside small dose group (10mg/kg.d) | 0.15±0.043 0.46±0.155 * 0.21±0.056 *△ 0.25±0.016 *△ |
Compare P＜0.05 with the normal control group; Compare with the sodium chloride group,
△P＜0.05
The content of PGE2 in the table 3 synovial cell culture supernatant (x ± s, ng/ml)
| Group | PGE2 |
| The heavy dose of group of normal control sodium chloride asperuloside (20mg/kg.d) asperuloside small dose group (10mg/kg.d) | 8.21±1.32 33.51±15.12 * 12.30±1.46 *△ 15.71±0.34 *△ |
Compare P＜0.05 with the normal control group; Compare with the sodium chloride group,
△P＜0.05
The present invention adopts method that document 1,2,3,4,5,6,7,8 provides to investigate the asperuloside composition to synovial cell TNF secretion-α, PGE
2, IL-1 β influence.Similar trend is also arranged.
The present invention is human RA animal model with rat, adopts synovial cell's cultured method of former generation, has observed asperuloside to synovial cell TNF secretion-α, PGE
2With the influence of IL-1 β, the result shows that heavy dose of group, small dose group all can significantly be reduced TNF-α, PGE
2Content with IL-1 β, there is significant difference with the blank group, can not return to blank group of level, and there was no significant difference between three groups, this shows that asperuloside can suppress the generation of TNF-α, reduces the generation of IL-1 β, thereby inflammatory mediators such as minimizing PGE2 produce, reach and alleviate the destruction recovery joint movement function that causes bone and cartilage, performance treatment RA effect.
The specific embodiment
Embodiment 1, at first use 5 times of Folium Eucommiae (Eucommia ulmoids Oliv.) medical material weight ethanol with medical material reflux, extract, 3 times, each 1 hour; Centrifugal or the filtration with extracting solution then, it is 0.5g crude drug/ml that filtrate is evaporated to concentration at 55 ℃, filters, and gets supernatant; Supernatant is admixed silica gel, carry out silica gel column chromatography,, collect the acetone eluent, be evaporated to dried with ethyl acetate, acetone, methanol difference eluting; Get the acetone extract dissolve with ethanol, admix the silica gel of 3 times of amounts, separate with silica gel column chromatography dry back, and the isolating eluting solvent of silica gel chromatographic column is the chloroform of equal proportion weight: methanol: water mixed liquid, elution flow rate are 500 milliliters/hour.Thin layer chromatography is checked, merges same section, and recrystallization obtains asperuloside again, and the yield of asperuloside is 0.86%.
Embodiment 2, at first use 5 times of Folium Eucommiae (Eucommia ulmoids Oliv.) medical material weight ethanol with medical material reflux, extract, 3 times, each 1 hour; Centrifugal or the filtration with extracting solution then, it is 0.5g crude drug/ml that filtrate is evaporated to concentration at 55 ℃, filters, and gets supernatant; Supernatant is carried out macroporous resin column chromatography,, collect 60% ethanol elution, be evaporated to dried with the ethanol, the water system eluting that contain ethanol percentage by weight 60%; Get the ethanol extraction dissolve with methanol, admix the silica gel of 3 times of amounts, separate with silica gel column chromatography dry back, and the isolating eluting solvent of silica gel chromatographic column is the chloroform of equal proportion weight: methyl alcohol mixed liquor, elution flow rate are 500 milliliters/hour.Thin layer chromatography is checked, merges same section, carries out the gel column chromatography purification again one time, and the methanol of equal proportion weight, water mixed liquid eluting obtain asperuloside, and the yield of asperuloside is 0.29%.
Embodiment 3, get asperuloside 200 grams that obtain by the method for embodiment 1, low-substituted hydroxypropyl cellulose 20 grams, PEG6000 20 grams, microcrystalline Cellulose 210 grams, PVP 50 grams, lactose 440 grams, after magnesium stearate 60 gram pulverize separately are even, mix being pressed into 1000.
Therapeutic Method: rheumatoid patient takes twice every day, each 1-2 sheet.The 7-21 days course of treatment.
Embodiment 4, get asperuloside 100 grams that obtain by the method for embodiment 2, low-substituted hydroxypropyl cellulose 20 grams, crospolyvinylpyrrolidone 30 grams, microcrystalline Cellulose 100 grams, sucrose 650 grams after magnesium stearate 50 gram pulverize separately are even, mix being pressed into 1000.
Therapeutic Method: rheumatoid patient takes twice every day, each 2-4 sheet.The 7-21 days course of treatment.
Claims (1)
1, the application of asperuloside in preparation treatment medicine for treating rheumatoid arthritis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2005100193236A CN100425243C (en) | 2005-08-19 | 2005-08-19 | Application of woodruff glycoside in preparing medication for treating rheumatoid arthritis |
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| CNB2005100193236A CN100425243C (en) | 2005-08-19 | 2005-08-19 | Application of woodruff glycoside in preparing medication for treating rheumatoid arthritis |
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| CN1915236A true CN1915236A (en) | 2007-02-21 |
| CN100425243C CN100425243C (en) | 2008-10-15 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012518A (en) * | 2012-12-14 | 2013-04-03 | 湘西自治州奥瑞克医药化工有限责任公司 | Production process for simultaneously extracting asperuloside and chlorogenic acid from folium cortex eucommiae |
| CN107198696A (en) * | 2017-06-22 | 2017-09-26 | 南方医科大学 | Application of the woodruff thuja acid in treatment kidney fibrosis medicine is prepared |
| CN115247211A (en) * | 2022-08-17 | 2022-10-28 | 山东省科学院生物研究所 | Method for screening refreshing medicine and application of asperuloside in refreshing |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2579255B2 (en) * | 1991-06-18 | 1997-02-05 | 日立造船株式会社 | Angiotensin converting enzyme activity inhibitor from Tochu leaf extract |
| CN1219425A (en) * | 1998-11-13 | 1999-06-16 | 郝玉凤 | Medicine for curing rheumatic and rheumatoid arthritis and its preparation method |
| CN1181870C (en) * | 2002-10-22 | 2004-12-29 | 高泉 | Decoction of traditional Chinese drug for curing rheumatoid arthritis |
-
2005
- 2005-08-19 CN CNB2005100193236A patent/CN100425243C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103012518A (en) * | 2012-12-14 | 2013-04-03 | 湘西自治州奥瑞克医药化工有限责任公司 | Production process for simultaneously extracting asperuloside and chlorogenic acid from folium cortex eucommiae |
| CN107198696A (en) * | 2017-06-22 | 2017-09-26 | 南方医科大学 | Application of the woodruff thuja acid in treatment kidney fibrosis medicine is prepared |
| CN107198696B (en) * | 2017-06-22 | 2020-05-29 | 南方医科大学 | Application of asperuloside in preparation of medicine for treating renal fibrosis |
| CN115247211A (en) * | 2022-08-17 | 2022-10-28 | 山东省科学院生物研究所 | Method for screening refreshing medicine and application of asperuloside in refreshing |
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| CN100425243C (en) | 2008-10-15 |
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