CN1957939A - Using ABL and acetylated homolog to modulate reaction of vasculitis, and treating chronic vasculitis inflammatory disease - Google Patents
Using ABL and acetylated homolog to modulate reaction of vasculitis, and treating chronic vasculitis inflammatory disease Download PDFInfo
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- CN1957939A CN1957939A CN 200510119791 CN200510119791A CN1957939A CN 1957939 A CN1957939 A CN 1957939A CN 200510119791 CN200510119791 CN 200510119791 CN 200510119791 A CN200510119791 A CN 200510119791A CN 1957939 A CN1957939 A CN 1957939A
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Abstract
An application of the inulinin extracted from inula flower by chloroform and the three compounds (acetylbritannilacton (ABL), 1-0-ABL and 6-O2-ABL) extracted from said inulinin in preventing and treating the chronic vascular inflammatory diseases is disclosed.
Description
Technical field the present invention relates to the Chinese medicine preparation technical field
Background technology
The vascular inflammation disease is meant vessel wall thickening and the luminal stenosis cardiovascular disease due to vascular endothelial injury that a variety of causes brings out, smooth muscle cell proliferation, the apposition, comprises atherosclerosis, postangioplasty restenosis, hypertension etc.Present discovers, the pathology essence and the process of such disease are a kind of blood vessel chronic inflammatory reactions.Nuclear factor NF-kB activation and nuclear translocation, adhesion molecule (MCP-1, ICAM-1, VCAM-1) expression and iNOS, COX-2 are active raises, so cause that vascular endothelial cell activation, platelet aggregation, mononuclear cell are sticked, infiltration, macrophage activation and vascular smooth muscle cell proliferation.
Eurasian Flos Inulae is a kind of bronchitis and migrainous Chinese herbal medicine of being used for the treatment of, in order to determine effective ingredient wherein, we isolate three kinds of effective constituents A BL with anti-inflammatory and analgesic effect, 1-O-ABL, 1,6-O from the chloroform extract (inulin) of Eurasian Flos Inulae
2-ABL all is the sesquiterpene lactones chemical compound.Confirmed that now its antiinflammatory action is better than aspirin.Inulin has the effect of treatment of vascular diseases associated with inflammation, and its molecular mechanism is with inhibition inductive NF-kB activation of proinflammatory factor and nuclear translocation, (VCAM-1) expression is relevant with the active rising of iNOS, COX-2 for MCP-1, ICAM-1 for adhesion molecule.
Summary of the invention
From Eurasian Flos Inulae, separate and obtain three kinds of effective constituents A BL, 1-O-ABL, 1,6-O with anti-inflammatory and analgesic effect
2-ABL, and confirm that it has the obvious anti-inflammatory and anti effect and is better than aspirin.
The alcohol extraction of Eurasian Flos Inulae (10 kilograms) with 95% 3 times, petroleum ether, ethyl acetate, chloroform, n-butanol extraction concentrate, and gradient elution dodges the formula column chromatography, collects the chloroform part, obtains ABL; Collect petroleum ether: chloroform (10: 90) part obtains 1-O-ABL; Petroleum ether: chloroform (20: 80) part obtains 1,6-O
2-ABL.
With Eurasian Flos Inulae contain chloroform extract (inulin) or from inulin isolated chemical compound be used for prevention and treatment vascular inflammation disease.Separate three kinds of chemical compounds obtaining and be inulicin (acetylbritannilactone, ABL) and 1-O-ABL, 1,6-O
2-ABL, has modulation vasculitic cell (Monocytes respectively, endotheliocyte, smooth muscle cell) inflammatory response reaction, the effect of control animal chronic vasculitis inflammatory disease property disease, but three kinds of components are used dose-dependent inhibition vascular inflammation sexual cell NF-kB activation and nuclear translocation alone or in combination, adhesion molecule (MCP-1, ICAM-1, VCAM-1) activation of expression and iNOS and COX-2 gene, give the clothes animal with inulin (extract that contains three kinds of components) by effective dose, can treat chronic vasculitis inflammatory disease property disease.
Embodiment
With the research that experimentizes of Eurasian Flos Inulae extract, observe the effect of its modulation vascular inflammation reaction.Confirm with Monocytes, vascular endothelial cell and vascular smooth muscle cell at present: (1) inulin or three kinds of effective ingredient wherein induce the iNOS of generation and expression and the activation of COX-2 to have remarkable inhibitory action to inflammatory factor LPS; (2) inulin or three kinds of effective ingredient wherein can obviously be reduced the expression that inflammatory reaction triggers factor VCAM-1, ICAM-1 and MCP; (3) inulin or three kinds of effective ingredient wherein can suppress the nuclear translocation of NF-κ B and active with combining of DNA; (4) inulin or three kinds of effective ingredient wherein can suppress the activation of NF-κ B by the degraded that suppresses I-κ B; (5) inulin or three kinds of effective ingredient wherein can suppress sticking of vascular endothelial cell and mononuclear phagocyte, suppress the migration and the hypertrophy of vascular smooth muscle cell.
Experiment confirm in the body, inulin or three kinds of effective ingredient wherein can significantly reduce the hyperplasia degree that endothelium strips off the postoperative tunica intima, reduce animal pattern Inflammatory Mediators---plasma C RP level, alleviate the vessel wall inflammation reaction, obviously the downward modulation inflammatory reaction triggers nuclear translocation and, inhibition damaged blood vessels VCAM-1, ICAM-1 active with combine of DNA and the expression of MCP-1 and the activation of iNOS and COX-2 of factor NF-κ B, and lesion degree is alleviated.
Confirm with RT-PCR, Western blot and immunohistochemical analysis, in Monocytes, vascular endothelial cell and vascular smooth muscle cell, ABL, 1-O-ABL and 1,6-O
2The expression of-ABL downward modulation VCAM-1, ICAM-1 and MCP, the expression and the activatory effective dosage ranges that suppress iNOS and COX-2 are 0.05～20 μ mol/L; Pharmacological action intensity is followed successively by 1,6-O
2-ABL＞1-O-ABL＞ABL; The different proportion combination of three kinds of compositions can produce synergism.These results compare (effective dose is 100 μ mol/L) with the anti-inflammatory drug aspirin of generally acknowledging at present, and the sesquiterpene lactones chemical compound is suppressing to be better than aspirin aspect inflammatory gene and the expression of adhesion molecule.In employed drug dose scope, measure cell viability with mtt assay and do not have significant change, ABL, 1-O-ABL and 1 under this dosage are described, 6-O
2The acellular toxic action of-ABL.
Analyze confirmation with analysis of Phosphorylation, co-immunoprecipitation and celluar localization, in Monocytes, vascular endothelial cell and vascular smooth muscle cell, ABL, 1-O-ABL and 1,6-O
2The effective dosage ranges that-ABL suppresses the degraded of I-κ B phosphorylation, NF-kB activation and nuclear translocation is 0.05～20 μ mol/L; Pharmacological action intensity is followed successively by 1,6-O
2-ABL＞1-O-ABL＞ABL; The different proportion combination of three kinds of chemical compounds can produce synergism.These results compare (effective dose is 100 μ mol/L) with the anti-inflammatory drug aspirin of generally acknowledging at present, and the sesquiterpene lactones chemical compound is better than aspirin at the degraded of inhibition I-κ B phosphorylation, NF-kB activation and nuclear translocation.In employed drug dose scope, measure cell viability with mtt assay and do not have significant change, ABL, 1-O-ABL and 1 under this dosage are described, 6-O
2The acellular toxic action of-ABL.
Analyze confirmation with gel shift rate change analysis, the super migration of gel, in Monocytes, vascular endothelial cell and vascular smooth muscle cell, ABL, 1-O-ABL and 1,6-O
2It is 0.05～20 μ mol/L that-ABL inhibition NF-kB activation reaches with the active effective dosage ranges of combining of DNA controlling element; Pharmacological action intensity is followed successively by 1,6-O
2-ABL＞1-O-ABL＞ABL; The different proportion combination of three kinds of chemical compounds can produce synergism.Compare (effective dose is 100 μ mol/L) with the anti-inflammatory drug aspirin of generally acknowledging at present, the effect of sesquiterpene lactones chemical compound is better than aspirin.In employed drug dose scope, measure cell viability with mtt assay and do not have significant change, ABL, 1-O-ABL and 1 under this dosage are described, 6-O
2The acellular toxic action of-ABL.
With cell adhesion analysis, cell plane/stride film to move analysis, analysis of cell proliferation confirmation, ABL, 1-O-ABL and 1,6-O
2-ABL suppresses the sticking of the inductive Monocytes of pro-inflammatory cytokine and endotheliocyte, smooth muscle cell sticks and the migration and the effective dosage ranges of breeding are 0.05～20 μ mol/L; Pharmacological action intensity is followed successively by 1,6-O
2-ABL＞1-O-ABL＞ABL; The different proportion combination of three kinds of chemical compounds can produce synergism.
ABL, 1-O-ABL and 1,6-O
2It is 0.05～20 μ mol/L to the toxic effective dosage ranges of endotheliocyte, Monocytes and smooth muscle cell that-ABL has the generation, the reduction lipid oxide that improve the endotheliocyte anti-oxidation function, reduce lipid oxide; Pharmacological action intensity is followed successively by 1,6-O
2-ABL＞1-O-ABL＞ABL.The different proportion combination of three kinds of chemical compounds can produce synergism.
With rat or ApoE-/-mice prepares endothelium and strips off model or Atherosclerosis Model, the dosage of pressing ABL0.7-15mg/kg/ days behind the 21d, is got blood, vascular tissue respectively, observing effect with inulin emulsion gastric infusion 3,7,14.The result confirms, inulin can significantly reduce the hyperplasia degree (I/M ratio reduces by 50%) that endothelium strips off the back tunica intima, reduce the animal pattern Inflammatory Mediators---plasma C RP level (reducing by 60%), alleviate the vessel wall inflammation reaction, obviously the downward modulation inflammatory reaction triggers the expression (downward modulation 50%) of factor VCAM-1, ICAM-1 and MCP, suppress NF-kB activation and nuclear translocation, lesion degree is alleviated.Effect obviously is better than the positive drug losartan and blood vessel is logical.The ordinary circumstance of animal is good, no obvious toxic and side effects and body weight change.
The above-mentioned inulin that experiment showed, all can be brought into play anti-angiogenic inflammatory effect with external in animal body, safely and effectively the treatment of vascular diseases associated with inflammation.Inulin can be prepared into emulsion, drop pill and tablet form, can also be prepared into slow releasing agent or injection as medicine, nutriment and food additive development and use, using dosage draws in can the result by cell research or obtains by body weight and surface area conversion.
Accompanying drawing is the ABL molecular structure.
Claims (4)
1. with a certain amount of inulin or effective constituents A BL, 1-O-ABL and 1,6-O
2-ABL uses the reaction of effective modulation vascular inflammation alone or in combination, suppresses vascellum endometrial hyperplasia, the method for protection tunica intima function and treatment of vascular diseases associated with inflammation.
2. stating employed three kinds of drug doses and portfolio ratio in 1.
3. use a certain amount of ABL, 1-O-ABL or 1,6-O
2-ABL uses alone or in combination and can suppress the vasculitic cell activation; The method that suppresses NF-κ B nuclear translocation and adhesion molecule (MCP-1, ICAM-1, VCAM-1) and iNOS and COX-2 gene expression.
4. stating employed three kinds of drug doses and portfolio ratio in 3.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284835B (en) * | 2008-06-05 | 2010-06-16 | 中国人民解放军第二军医大学 | Dimeric sesquiterpene lactone compounds, preparation method and applications thereof |
| CN101284833B (en) * | 2008-06-05 | 2010-06-16 | 中国人民解放军第二军医大学 | Compound bi-inulicin 4, preparation method and applications thereof |
| CN101830875A (en) * | 2010-06-13 | 2010-09-15 | 上海交通大学 | Anti-inflammatory compound inula lineariifolia lactone A and preparation method and application thereof |
| CN102406637A (en) * | 2011-11-15 | 2012-04-11 | 中国人民解放军第二军医大学 | Application of japonicone A in preparation of tumor necrosis factor (TNF) inhibitor drugs |
| CN102727486A (en) * | 2012-06-21 | 2012-10-17 | 中国人民解放军第二军医大学 | Application of Inula lineariifolia lactone A in preparation of medicine for treating myocarditis |
| CN112618538A (en) * | 2020-12-18 | 2021-04-09 | 西北农林科技大学 | Preparation method of 1, 6-O, O-diacetyl inula flower lactone and application of inula flower lactone in preparation of anti-Alzheimer's disease drugs |
-
2005
- 2005-11-06 CN CN 200510119791 patent/CN1957939A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101284835B (en) * | 2008-06-05 | 2010-06-16 | 中国人民解放军第二军医大学 | Dimeric sesquiterpene lactone compounds, preparation method and applications thereof |
| CN101284833B (en) * | 2008-06-05 | 2010-06-16 | 中国人民解放军第二军医大学 | Compound bi-inulicin 4, preparation method and applications thereof |
| CN101830875A (en) * | 2010-06-13 | 2010-09-15 | 上海交通大学 | Anti-inflammatory compound inula lineariifolia lactone A and preparation method and application thereof |
| CN102406637A (en) * | 2011-11-15 | 2012-04-11 | 中国人民解放军第二军医大学 | Application of japonicone A in preparation of tumor necrosis factor (TNF) inhibitor drugs |
| CN102727486A (en) * | 2012-06-21 | 2012-10-17 | 中国人民解放军第二军医大学 | Application of Inula lineariifolia lactone A in preparation of medicine for treating myocarditis |
| CN102727486B (en) * | 2012-06-21 | 2013-12-25 | 中国人民解放军第二军医大学 | Application of Inula lineariifolia lactone A in preparation of medicine for treating myocarditis |
| CN112618538A (en) * | 2020-12-18 | 2021-04-09 | 西北农林科技大学 | Preparation method of 1, 6-O, O-diacetyl inula flower lactone and application of inula flower lactone in preparation of anti-Alzheimer's disease drugs |
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