CN102872079A - Application of Houttuynoid C in drugs for restraining multiplication of liver fibroblasts - Google Patents
Application of Houttuynoid C in drugs for restraining multiplication of liver fibroblasts Download PDFInfo
- Publication number
- CN102872079A CN102872079A CN2012104175735A CN201210417573A CN102872079A CN 102872079 A CN102872079 A CN 102872079A CN 2012104175735 A CN2012104175735 A CN 2012104175735A CN 201210417573 A CN201210417573 A CN 201210417573A CN 102872079 A CN102872079 A CN 102872079A
- Authority
- CN
- China
- Prior art keywords
- houttuynoid
- liver
- drugs
- multiplication
- application
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an application of Houttuynoid C in drugs for restraining multiplication of liver fibroblasts. A pharmacological test proves that Houttuynoid C can obviously restrain the occurrence and development of liver fibrosis and can be applied to preparing anti-liver fibrosis drugs and drugs for preventing and treating cirrhosis of liver. The application of Houttuynoid C in drugs for restraining multiplication of liver fibroblasts disclosed by the invention is publicized for the first time. The skeleton type is brand new and has an unexpectedly strong inhibitory activity to the multiplication of liver fibroblasts; the possibility for other compounds to give any inspiration does not exist; the application has outstanding substantial characteristics and is obviously a significant progress to the restraint of the multiplication of liver fibroblasts.
Description
Technical field
The present invention relates to chemical compound can significantly suppress hepatic fibrosis through the pharmacological testing proof generation and development, more specifically refer to compound H outtuynoid C, it can be used in the preparation anti-hepatic fibrosis medicines.
Background technology
Hepatic fibrosis is chronic hepatic injury to the dynamic process of liver cirrhosis development, show as in a large number synthetic, secretion of extracellular matrix (ECM), and degraded is absolute or relative deficiency, makes ECM fill the air deposition in liver.It originates in hepatocyte (HC) necrosis, is that inflammatory reaction, fiber generate medium release thereupon, and hepatic stellate cell (FSC) activates, finally synthesizing and the obvious disequilibrium of degrading with liver connective tissue composition.Hepatic fibrosis is the common pathological process of multiple chronic hepatopathy, is the key factor that affects prognosis.
Between 20 years of past, the research of hepatic fibrosis makes significant progress, and confirms that hepatic fibrosis and liver cirrhosis to a certain degree all are reversible.Some Strategies of Anti-fibrosis Therapy methods have appearred in recent years successively, comprise chemical drugs, biological preparation, Chinese medicine and gene therapy etc., but desirable clinical treatment means still lack (Liu Ping. strengthen the research of effect of anti hepatic fibrosis mechanism. Chinese hepatopathy magazine, 2005,8(13): 561).The key of at present anti-treating the liver fiber is for the link relevant with hepatic stellate cell activator, mainly is: alleviate hepatic injury; Suppress stellate cell activator, reduce extracellular matrix and produce; The adjusting cytokine is disorderly, promotes the activated hepatic stellate cells apoptosis.
The compound H outtuynoid C that the present invention relates to is one and delivered (Chen in 2012, S. D. et al., 2012. Houttuynoid C_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.) New skeleton compound, this chemical compound has brand-new framework types, present purposes only relates to anti-herpes simplex virus activity (Chen, S. D. et al., 2012. Houttuynoid C_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.), belong to open first for the Houttuynoid C that the present invention relates in the purposes that preparation suppresses in the liver fibroblast proliferation medicine, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for the liver fibroblast proliferation, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for simultaneously anti-liver fibroblast proliferation and obviously have significant progress.
Summary of the invention
Compound H outtuynoid C proves that through pharmacological testing it can anti-hepatic fibrosis.
The structural formula of Houttuynoid C of the present invention is shown in formula I:
Formula I
The present invention suppresses the effect of liver fibroblast proliferation to Houttuynoid C and has carried out pharmacological testing.
Fibroblast proliferation and synthetic a large amount of extracellular matrixs (ECM) are the important steps that hepatic fibrosis occurs.The hepatic stellate cell (HSC) of activation has the fibroblast feature, and the NIH/3T3 cell is the active cell model commonly used of drugs anti-hepatic fibrosis.This research is observed the invention medicine to the impact of its propagation take the NIH/3T3 fibroblast as target cell.The result of the test of the inhibition cell proliferation that detects with mtt assay shows, medicine of the present invention has significant inhibitions activity to the cell proliferation of NIH/3T3.
Has effect of anti hepatic fibrosis according to pharmacological tests proof Houttuynoid C.
The Houttuynoid C that the present invention relates to belongs to open first in the purposes that preparation suppresses in the liver fibroblast proliferation medicine, because framework types belongs to brand-new framework types, and it suppresses active unexpectedly strong for the liver fibroblast proliferation, there is not the possibility that is provided any enlightenment by other chemical compounds, possess outstanding substantive distinguishing features, be used for simultaneously anti-liver fibroblast proliferation and obviously have significant progress.
The specific embodiment
The preparation method of compound H outtuynoid C involved in the present invention is referring to document (Chen, S. D. et al., 2012. Houttuynoid C_E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata. Organic Letters 14 (7), 1772 – 1775.).
The present invention is further detailed explanation by the following examples, but protection scope of the present invention is not subjected to any restriction of specific embodiment, but limited by claim.
Embodiment 1: the preparation of compound H outtuynoid C tablet involved in the present invention:
Get 20 and digest compound Houttuynoid C, add conventional adjuvant 180 grams of preparation tablet, mixing, conventional tablet machine are made 1000.
Embodiment 2: the preparation of compound H outtuynoid C capsule involved in the present invention:
Get 20 and digest compound Houttuynoid C, add conventional adjuvant such as starch 180 grams of preparation capsule, mixing is encapsulatedly made 1000.
Further specify its pharmaceutically active below by pharmacodynamic experiment.
Experimental example 1: medicine of the present invention is to the inhibitory action of fibroblast NIH/3T3 propagation
One, experimental technique:
The NIH/3T3 cell strain is available from drawing the Collection from ATCC(American Type Culture) Shanghai cell institute of Chinese Academy of Sciences cell bank.
With NIH/3T3 cell 0.25% trypsinization that merge the Asia of exponential phase, wash, centrifugal after, make 1 * 10 with DMEM culture fluid (containing 10%FCS)
4The cell suspension of cell/ml, Trypan Blue identify that survival rate greater than 95%, adds in 96 orifice plates by every hole 100 ul, at 37 ℃, 5%CO
2After cultivating synchronously processing of 24h, abandon supernatant, add DMEM culture fluid (containing 10%FCS) 200 ul that contain different diluted concentration medicines, cultivate 48h, every hole adds MTT solution and hatches 4h.Discard culture fluid, add 150 ulDMSO, vibrated 10 minutes, make dissolving crystallized, microplate reader 490 nm places read the OD value, and the result is with OD
490Expression.
Two, experimental result:
1, morphological observation
NIH/3T3 stretches before medication well, refractivity a little less than, directivity is arranged, be radial, the speed of cell proliferation is fast; And after adding medicine 24h, fibroblast decreased number, shape become irregular, and projection shortens, and cell arrangement is chaotic, and intracellular products increases.
Mtt assay detects medicine of the present invention to the inhibitory action of NIH/3T3 cell proliferation
Table 1:MTT method detects medicine of the present invention to the inhibitory action of NIH/3T3 propagation
Annotate: *, with cell negative control P＜0.05; * is with cell negative control P＜0.01
The result: medicine of the present invention has significant inhibitory action to the cell proliferation of fibroblast NIH/3T3 under the stimulation of 10% calf serum in the concentration range of 10 ug/ml-40 ug/ml.Show that vitro Drug of the present invention has remarkable inhibitory action to fibrocellular propagation.
Experimental example 2: medicine of the present invention is to transforming growth factor-beta
1(TGF-β
1) inhibitory action of the fibroblast proliferation of inducing
TGF-β
1Be to promote cell proliferation and collagenogenic strong active factors, in cell, add TGF-β
110ng/ml stimulates cellular proliferation, and the inhibitory action of the cell proliferation of TGF-β 1 being induced in detection of drugs is to analyze the mechanism of action of judging medicine of the present invention.
Table 2:MTT method detects medicine of the present invention is induced NIH/3T3 propagation to TGF inhibitory action
Annotate: * contrasts P＜0.05 with cell+TGF; * contrasts P＜0.01 with cell+TGF
The result: medicine of the present invention in two concentration intervals of 10-40ug/ml to fibroblast NIH/3T3 at TGF-β
1Induce under cell proliferation significant inhibitory action is arranged.Show that vitro Drug of the present invention may be by intervening the realization of TGF signal path to the inhibitory action of fibrocyte propagation.
Conclusion: Houttuynoid C has significant inhibitory action to the cell proliferation of fibroblast NIH/3T3 under the stimulation of 10% calf serum; Houttuynoid C to fibroblast NIH/3T3 at TGF-β
1Induce under cell proliferation significant inhibitory action is arranged.Houttuynoid C can be used for preparing anti-hepatic fibrosis medicines.
Claims (1)
1.Houttuynoid the application of C in suppressing liver fibroblast proliferation medicine, described compound H outtuynoid C-structure as
Formula IShown in:
Formula I.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104175735A CN102872079A (en) | 2012-10-27 | 2012-10-27 | Application of Houttuynoid C in drugs for restraining multiplication of liver fibroblasts |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104175735A CN102872079A (en) | 2012-10-27 | 2012-10-27 | Application of Houttuynoid C in drugs for restraining multiplication of liver fibroblasts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102872079A true CN102872079A (en) | 2013-01-16 |
Family
ID=47473750
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012104175735A Pending CN102872079A (en) | 2012-10-27 | 2012-10-27 | Application of Houttuynoid C in drugs for restraining multiplication of liver fibroblasts |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102872079A (en) |
-
2012
- 2012-10-27 CN CN2012104175735A patent/CN102872079A/en active Pending
Non-Patent Citations (3)
| Title |
|---|
| 《Organic Letters》 20120313 Shao-Dan Chen等 Houttuynoids A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata 1772-1775 1 第14卷, 第7期 * |
| SHAO-DAN CHEN等: "Houttuynoids A-E, Anti-Herpes Simplex Virus Active Flavonoids with Novel Skeletons from Houttuynia cordata", 《ORGANIC LETTERS》 * |
| 张硕等: "4 种黄酮类化合物对CCl4致小鼠肝纤维化的防治作用", 《华西药学杂志》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104095859A (en) | Application of O-(piperidinyl) ethyl derivative of Cleistanone in preparing drugs for resisting liver fibrosis | |
| CN104095857A (en) | Application of diethylamine derivative of Cleistanine in preparation of anti-hepatic fibrosis medicines | |
| CN102872114A (en) | Application of Houttuynoid E in medicament for suppressing liver fibroblast proliferation | |
| CN103356533A (en) | Application of Sarcaboside A in medicine for inhibiting liver fibroblast proliferation | |
| CN103251614A (en) | Application of Aspeverin in preparation of medicines for inhibiting liver fibroblast proliferation | |
| CN102885808A (en) | Application of Aphanamixoid A to inhibition of liver fibroblast proliferation drug | |
| CN103356523A (en) | Application of Sarcaboside B in preparation of medicines for inhibiting liver fibroblast proliferation | |
| CN102861054B (en) | Application of Houttuynoid D in medicine for inhibiting liver fibroblast proliferation | |
| CN102872009A (en) | Application of Eryngiolide A in drugs for inhibiting liver fibroblast cell proliferation | |
| CN102872079A (en) | Application of Houttuynoid C in drugs for restraining multiplication of liver fibroblasts | |
| CN103446132B (en) | Lycojaponicumin A suppresses the application in liver fibroblast proliferation drug in preparation | |
| CN103446131B (en) | Lycojaponicumin B suppresses the application in liver fibroblast proliferation drug in preparation | |
| CN102872107A (en) | Application of Houttuynoid A in medicine for suppressing liver fibroblast proliferation | |
| CN102872136A (en) | Application of Houttuynoid B in drug for suppressing liver fibroblast proliferation | |
| CN103393697B (en) | Application of Chukrasone A on medicament for inhibiting proliferation of hepatic fibroblast | |
| CN103463074B (en) | Application of Lycojaponicumin C in preparation of liver fibroblast proliferation inhibition drug | |
| CN103463011B (en) | Fluevirosines A suppresses the application in liver fibroblast proliferation drug in preparation | |
| CN103372005A (en) | Application of Chukrasone B in preparation of medicines for inhibiting liver fibroblast proliferation | |
| CN103536600B (en) | Phyllanthoid A suppresses the application in liver fibroblast proliferation drug in preparation | |
| CN103479647A (en) | Application of Kadcoccitones A to in preparation of medicament for inhibiting liver fibroblast proliferation | |
| CN103446090B (en) | Incarviatone A suppresses the application in liver fibroblast proliferation drug in preparation | |
| CN106420706A (en) | Application of linderolide H to preparation of medicines for inhibiting liver fibroblast proliferation | |
| CN102895240A (en) | Application of Gypensapogenin A to medicament for inhibiting liver fibroblast proliferation | |
| CN103127149A (en) | Application of Gypensapogenin B in medicines inhibiting liver fibroblast proliferation | |
| CN103315990A (en) | Application of Nardoaristolones A in preparation of medicine used for inhibiting proliferation of fibroblast of liver |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20130116 |