CN1951380A - Medical usage of salvianolic acid B salt and total salvianolic acid - Google Patents
Medical usage of salvianolic acid B salt and total salvianolic acid Download PDFInfo
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- CN1951380A CN1951380A CN 200510031047 CN200510031047A CN1951380A CN 1951380 A CN1951380 A CN 1951380A CN 200510031047 CN200510031047 CN 200510031047 CN 200510031047 A CN200510031047 A CN 200510031047A CN 1951380 A CN1951380 A CN 1951380A
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Abstract
The invention ligatures the single ureter into mouse kidney fiber mode, watches the stomach treatment function on DS. Wherein, the 3D mouse is randomly divided into four groups as false surgery group, mode group, DS group and anode contrast chlorine group; after 7 days after feeding drug, killing the mouse, taking out the kidney, slicing with paraffin, colorizing with HE, watching in light lens; the experiment proves that the DS group and anode contrast group have similar kidney state and mode; but the DS group and anode contrast chlorine group have reduced expansion degree of nephric tubule epithelial cell, to reduce the foam generation, and the ill parts are distributed in sheets, whose range is less than 25% and different significance is lower than 0.05; using 293 cell to detect the effect of DS on the fiber cell increment, while the result proves that when DS density is 500mg/ml, it can restrain the 293 cell increment caused by vessel contract element II, similarly as the restrain function of DS on the mouse kidney filter process.
Description
Technical field
The present invention relates to extract in the Radix Salviae Miltiorrhizae active ingredient, more specifically refer to the purposes of the inhibition renal fibrosis of salvianolic acid B salt and Radix Salviae Miltiorrhizae total phenolic acids.
Background technology
Salvianolic acid B and its magnesium salt physicochemical data are molecular formula C
36H
28MgO
16Molecular weight 740.9154; [α] D
20+ 126.7 (C0.73, H
2O); (ε 1.92 * 10 for Uv λ max210
4), 286 (ε 1.35 * 10
4), 306 (ε 1.20 * 10
4); IR3400; 1700nm; 1608,1519; 1363; 1288cm
-1All there is absworption peak to pass through MS NMR.U.V IR and proves that its structure is:
1, salvianolic acid B Magnesium salt (MTB) is on hyperlipidemia animal model aortic article, pass through naked eyes, light microscopic, electron microscopic observation is to tangible anti-AS effect is arranged, the yellow speckle protuberance of the visible obviously minimizing of naked eyes, atherosis grading obviously reduces, and om observation foam cell number of plies under the inner membrance is less, and smooth muscle cell proliferation is lighter, it is lighter to show under the Electronic Speculum that endotheliocyte changes, foam cell is less, and shrinkage type smooth muscle cell proportion is bigger, does endoplasmic reticulum in the sliding myocyte, Golgi body, mitochondrion is less, and it is more to study carefully myofilament content, and cell differentiation is better;
2, MTB scalable blood fat reduces TC, TG, LDL, LP (a), rising HDL; Anti peroxidation of lipid, SOD activity improving;
3, MTB can improve NO, lowers the Endothelin blood plasma level, protects endotheliocyte, and organizes the expression of Bfgf (basic fibroblast growth factor) at arterial wall by suppressing atherosclerosis, the migration and the propagation of regulation and control smooth muscle cell, the process of intervening AS.
More than experiment all is that nifedipine is made positive control, acts on to be better than nifedipine.
1, MTB is to CCl
4Inductive rat chronic hepatic injury and hepatic fibrosis are formed with good inhibition effect.
(1) effectively suppress the liver connective tissue proliferation, reduce the liver collagen content, its effect is better than colchicine and crude drug in whole Radix Salviae Miltiorrhizae; (2) anti-hepatocyte injury, each dosage group of MTB all can significantly reduce Serum ALT, AST activity and the total bilirubin content that rat model increases by a relatively large margin, and high dose group significantly improves serum Alb content.Comprehensive function is in control drug (the Radix Salviae Miltiorrhizae group is not obvious to falling acting on of total bilirubin, and colchicine is not obvious to the effect of falling AST).(3) MTB dose-effect result shows that with middle dosage (the 12.5mg/Kg Mus is heavy) be good.
2, MTB has excellent curative to the inductive rat liver fibrosis of established DMN.
(1) significantly promotes the heavily absorption of collagen in the liver, reduce the deposition of hepatic tissue Hyp content and type i collagen; (2) promote the hepatocellular reparation of damage, improve serum Alb content, reduce Serum ALT, AST activity; (3) significantly reduce the rat ascites occurrence rate; (4) effect is better than colchicine and crude drug in whole Radix Salviae Miltiorrhizae; (5) the certain dose-effect relationship of tool, the effective dose interval is 12.5mg/kg/d～25mg/kg/d.
3, MTB has certain promotion humoral immunity of organism function and cellular immune function effect.Can promote the phagocytic function of Turnover of Mouse Peritoneal Macrophages, improve the hemolysin content in the mice serum, the leukocyte that suppresses mice moves.Increase the quantity of mouse antibodies cellulation.
4, to the influence of external hepatic stellate cell function.The propagation that can significantly suppress HSC, the TGF β of inhibition activation HSC
1Autocrine and activation; Reduce the generation of original mRNA expression of I type forelimb and collagen protein, suppress TGF β
1The activation of MAPK in the signal transduction pathway.
5, MTB proves that by external, intravital test salvianolic acid B and its salt have the pulmonary fibrosis inhibitory action.
6, general pharmacology research: this product dosage be 3.8,7.5 and 15mg/kg irritate stomach the breathing of anesthesia Beagle dog and the function of blood circulation do not had tangible influence; This product dosage 15,30 and 60/kg irritate stomach does not all have influence to mice pole-jump test and Iruin behavior classification test.
Summary of the invention
The purpose of this invention is to provide a class has the inhibiting medicine of renal fibrosis (chemical compound), the chemical compound that the present invention relates to is salvianolic acid B and magnesium, ammonium, potassium salt (DS-1) salt and the Radix Salviae Miltiorrhizae total phenolic acids that wherein comprises it, comprises the medical usage of alkannic acid, rosmarinic acid, danshensu, salvianolic acid A etc.
Salvianolic acid B and magnesium salt are to cardiovascular effect and to hepatic injury, and a large amount of tests have been done in the effect of hepatic fibrosis.The present invention is to salvianolic acid B and its salt and Radix Salviae Miltiorrhizae total phenolic acids, comprise that alkannic acid, rosmarinic acid, danshensu, salvianolic acid A etc. carry out the inhibiting test of renal fibrosis, by external, intravital test, prove that salvianolic acid B and its salt have the renal fibrosis inhibitory action.
The present invention implements like this:
The chemical compound that the present invention relates to is magnesium, ammonium, potassium salt salt and Radix Salviae Miltiorrhizae total phenolic acids and its salt (DS-2) such as (DS-1) that salvianolic acid B salt and other salt comprise it.
Pharmacological testing:
One, in vitro tests
DS is to the influence of people's kidney fibroblast 293 propagation
1. experiment purpose
Estimate the external influence of DS to 293 cell proliferation
2. material and method
2.1 be subjected to reagent thing and reagent
DS is provided by Shanghai Pharmaceutical Inst., Chinese Academy of Sciences Natural Medicine Chemistry research department
Angiotensin II is available from Sigma company
2.2 cell culture
Human embryo kidney (HEK) fibrocyte 293, condition of culture are DMEM culture fluid (containing 10% calf serum), 37 ℃, and 5%CO
2Incubator is cultivated, and when treating that cell grows to 70% fusion, with about 0.25% trypsinization 2min, the cell of sucking-off certain volume moves in the new culture bottle, and adding has blood serum medium to continue to cultivate.
Make 2 * 10 with the DMEM culture fluid
5The cell suspension of cell/ml adds in 96 orifice plates by every hole 100 μ l, is used for cell proliferation rate and measures.
2.3 cell proliferating determining
The 293 cell trypsinizations of merging, centrifugal back makes 2 * 10 with DMEM culture fluid (containing 10% calf serum)
5The cell suspension of cell/ml adds in 96 orifice plates by every hole 100 μ l, at 37 ℃, and 5%CO
2Cultivated 24 hours, and removed the normal control group, every group all adds 10
-7Mol.L
-1Angiotensin II (AngII), sample sets adds the DS of variable concentrations simultaneously, continue to cultivate 24 hours,, every hole adds the MTT solution that is made into serum-free medium, and 37 ℃ of temperature were bathed 4 hours, making MTT be reduced to first replaces, the sucking-off supernatant adds 150 μ l dimethyl sulfoxines and makes first replace dissolving, measures absorbance value at 550nm.
2.4 data analysis and statistical method
The result represents that with mean ± SD the Bian Fang check compares.
3. result
The influence that the human embryo kidney (HEK) fibroblast 293 that DS is hatched Angiotensin II breeds, concrete outcome sees Table 1, adds 10 in culture medium
-7Mol.L
-1After AngII24 hour, absorbance obviously increases, and when simultaneously DS concentration is 500mg/ml, the propagation of 293 cells is had obvious inhibitory action (p＜0.05), but when DS concentration is 250mg/ml, to breeding no obvious suppression effect
Table 1 DS to the influence of inductive 293 cell proliferation of Ang II (X ± 9, n=10)
| Group | The OD value |
| Contrast Ang II group Ang II+DS (500mg/ml) Ang II+DS (250mg/ml) positive control losartan (10mg/ml) | 0.201±0.032 0.823±0.089 0.610±0.073 * 0.715±0.088 0.387±0.052 ** |
*P＜0.01,
*P＜0.05 VS Ang II group
4. brief summary
Experimental result shows the external proliferation function that can suppress by the human embryo kidney (HEK) fibroblast 293 of Ang II stimulation of DS.
Two. experiment in the body
1. experiment purpose
Whether observe DS inhibited to the kidney of rats fibrosis of one-sided ureter ligation.
2. laboratory animal
The SD rat is raised through animal institute of The 2nd Army Medical College 1 all adaptabilities before the experiment by providing by triumphant laboratory animal company limited.
3. experimental technique
The SD rat is divided into 4 groups at random, every group 10, comprise sham operated rats, model group, DS group and positive control losartan group, adopt etherization, abdominal incision separates the left side ureter, sew up abdominal part behind the ligation near-end, not ligation of sham operated rats ureter, the preceding 1 day DS group of performing the operation is irritated stomach with 10mg/kg, and the losartan group is irritated stomach with 1mg/kg, model group gives the equal volume normal saline, postoperative is respectively organized every day in 7 days and is all irritated stomach once, omnidistance ad lib and drinking-water, the anesthesia once more in the 7th day of operation back, win left kidney, 10% formalin fixed, paraffin embedding is cut into the 2mm section.The thick paraffin section of 2mm is done HE.Massn dyeing, observes the kidney ID then and become under light microscopic.
4. experimental result
1, histopathologic examination after the ligation of rats with left ureter, from stained as can be seen, the enlargement of model group rat ligation side kidney, color shoals, the capsule sexuality is arranged, occur matter class cellular infiltration between the diffusivity kidney under the light microscopic, interstitial edema, and be the atrophy of kitchen range shape with renal cells swelling, degeneration and part renal tubules in various degree, tubule obliteration and/or expansion, many kitchen ranges fibrosis appears in matter between kidney, and scope is greater than 50%, sham operated rats kidney size and form is normal, and color is dark red.DS group and positive controls kidney form and model group do not have obvious difference, but DS group and positive control losartan group renal cells swelling degree alleviate under the light microscopic, only minority renal cells generation cavity degeneration, the kidney ID becomes distribution in the form of sheets, scope＜25%, compare significant difference (P＜0.05) with model group
5. conclusion
DS has protective effect to obstructive kidney of rats interstitial fibrosis
Description of drawings
Experimental rat histopathologic examination finding in Fig. 1 body, wherein:
A. sham operated rats
B. model group: renal cells swelling, many kitchen ranges fibrosis appears in matter between kidney
C. (oral administration, 10mg/kg): the renal fibrosis focus obviously reduces salvianolic acid B salt group, alleviates
D. (oral administration, 1mg/kg): the renal fibrosis focus obviously reduces the losartan group, alleviates
Conclusion: salvianolic acid B salt group and losartan group oral administration have the obvious suppression effect to the kidney of rats fibrosis of one-sided ureter ligation.
The specific embodiment
Embodiment
Salvianolic acid B salt oral administration is to the Fibrotic inhibitory action of the kidney of rats of one-sided ureter ligation
40 of kunming mouses, male, about about 20 grams of body weight, available from the big Experimental Animal Center of two armies.To buy mice behind the laboratory and be divided into 4 groups at random, comprise sham operated rats, model group, salvianolic acid B salt group and positive control losartan group, adopt etherization, abdominal incision, separate the left side ureter, sew up abdominal part behind the ligation near-end, not ligation of sham operated rats ureter, the preceding 1 day salvianolic acid B salt group of performing the operation is irritated stomach with 10mg/kg, the losartan group is irritated stomach with 1mg/kg, and model group gives the equal volume normal saline, and postoperative is respectively organized every day in 7 days and all irritated stomach once, omnidistance ad lib and drinking-water, the anesthesia once more in the 7th day of operation back is won left kidney, 10% formalin fixed, paraffin embedding is cut into the 2mm section.The thick paraffin section of 2mm is done HE.Massn dyeing, observes the kidney ID then and become under light microscopic.
The result
From stained (Fig. 1) as can be seen, the enlargement of model group rat ligation side kidney, color shoals, and the capsule sexuality is arranged, matter class cellular infiltration between the diffusivity kidney appears under the light microscopic, interstitial edema, and be the atrophy of kitchen range shape, tubule obliteration and/or expansion with renal cells swelling, degeneration and part renal tubules in various degree, many kitchen ranges fibrosis appears in matter between kidney, scope is greater than 50%, and sham operated rats kidney size and form is normal, and color is dark red.Salvianolic acid B salt group and positive controls kidney form and model group do not have obvious difference, but salvianolic acid B salt group and positive control losartan group renal cells swelling degree alleviate under the light microscopic, only minority renal cells generation cavity degeneration, the kidney ID becomes distribution in the form of sheets, scope＜25%, compare significant difference (P＜0.05) with model group.
Claims (5)
1. the medical usage of salvianolic acid B salt and Radix Salviae Miltiorrhizae total phenolic acids is in the preparation prevention.Use in the medicine of the disease that treatment is caused by renal fibrosis.
2. the medical usage of salvianolic acid B salt according to claim 1 and Radix Salviae Miltiorrhizae total phenolic acids is characterized in that salvianolic acid B salt uses in the medicine of the disease that preparation prevention, treatment are caused by renal fibrosis.
3. the medical usage of salvianolic acid B salt according to claim 1 and Radix Salviae Miltiorrhizae total phenolic acids is characterized in that salvianolic acid B salt comprises in the medicine of the disease that magnesium, ammonium, potassium salt (DS-1) salt preparation prevention, treatment are caused by renal fibrosis to use.
4. the medical usage of salvianolic acid B salt according to claim 1 and Radix Salviae Miltiorrhizae total phenolic acids is characterized in that Radix Salviae Miltiorrhizae total phenolic acids uses in the medicine of the disease that preparation prevention, treatment are caused by renal fibrosis.
5. the medical usage of salvianolic acid B salt according to claim 1 and Radix Salviae Miltiorrhizae total phenolic acids way, it is characterized in that Radix Salviae Miltiorrhizae total phenolic acids comprise alkannic acid, rosmarinic acid, danshensu, salvianolic acid A the disease that preparation prevention, treatment are caused by renal fibrosis comprise it medicine in use.
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|---|---|---|---|
| CN 200510031047 CN1951380A (en) | 2005-10-21 | 2005-10-21 | Medical usage of salvianolic acid B salt and total salvianolic acid |
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|---|---|---|---|
| CN 200510031047 CN1951380A (en) | 2005-10-21 | 2005-10-21 | Medical usage of salvianolic acid B salt and total salvianolic acid |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102614164A (en) * | 2012-03-27 | 2012-08-01 | 上海中医药大学附属曙光医院 | Application of salvianolic acid A in pharmacy |
| CN104434899A (en) * | 2013-09-24 | 2015-03-25 | 天士力制药集团股份有限公司 | Application of danshinolic acid L in preparing medicament for treating or preventing hepatic fibrosis and renal fibrosis |
| CN108949677A (en) * | 2018-07-05 | 2018-12-07 | 浙江大学 | Martynoside C and salviandic acid A are promoting Marrow Mesenchymal Stem Cells In Vitro proliferation and are inhibiting the application in replicative senescence |
| CN111035636A (en) * | 2020-01-14 | 2020-04-21 | 南京中医药大学 | Composition for preventing and treating diabetic nephropathy and application thereof |
-
2005
- 2005-10-21 CN CN 200510031047 patent/CN1951380A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102614164A (en) * | 2012-03-27 | 2012-08-01 | 上海中医药大学附属曙光医院 | Application of salvianolic acid A in pharmacy |
| CN104434899A (en) * | 2013-09-24 | 2015-03-25 | 天士力制药集团股份有限公司 | Application of danshinolic acid L in preparing medicament for treating or preventing hepatic fibrosis and renal fibrosis |
| CN108949677A (en) * | 2018-07-05 | 2018-12-07 | 浙江大学 | Martynoside C and salviandic acid A are promoting Marrow Mesenchymal Stem Cells In Vitro proliferation and are inhibiting the application in replicative senescence |
| CN108949677B (en) * | 2018-07-05 | 2021-11-30 | 浙江大学 | Application of rehmannia root glycoside C and salvianolic acid A in promoting proliferation of mesenchymal stem cells cultured in vitro and inhibiting replicative senescence |
| CN111035636A (en) * | 2020-01-14 | 2020-04-21 | 南京中医药大学 | Composition for preventing and treating diabetic nephropathy and application thereof |
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Open date: 20070425 |