CN117357506A - Application of salvianolic acid A in treatment of calcified aortic valve diseases - Google Patents
Application of salvianolic acid A in treatment of calcified aortic valve diseases Download PDFInfo
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- CN117357506A CN117357506A CN202311166563.3A CN202311166563A CN117357506A CN 117357506 A CN117357506 A CN 117357506A CN 202311166563 A CN202311166563 A CN 202311166563A CN 117357506 A CN117357506 A CN 117357506A
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- salvianolic acid
- aortic valve
- calcified aortic
- valve diseases
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- YMGFTDKNIWPMGF-AGYDPFETSA-N 3-(3,4-dihydroxyphenyl)-2-[(e)-3-[2-[(e)-2-(3,4-dihydroxyphenyl)ethenyl]-3,4-dihydroxyphenyl]prop-2-enoyl]oxypropanoic acid Chemical compound C=1C=C(O)C(O)=C(\C=C\C=2C=C(O)C(O)=CC=2)C=1/C=C/C(=O)OC(C(=O)O)CC1=CC=C(O)C(O)=C1 YMGFTDKNIWPMGF-AGYDPFETSA-N 0.000 title claims abstract description 37
- YMGFTDKNIWPMGF-QHCPKHFHSA-N Salvianolic acid A Natural products OC(=O)[C@H](Cc1ccc(O)c(O)c1)OC(=O)C=Cc2ccc(O)c(O)c2C=Cc3ccc(O)c(O)c3 YMGFTDKNIWPMGF-QHCPKHFHSA-N 0.000 title claims abstract description 37
- 208000027896 Aortic valve disease Diseases 0.000 title claims abstract description 21
- 239000003814 drug Substances 0.000 claims description 20
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 244000132619 red sage Species 0.000 claims 1
- 210000001765 aortic valve Anatomy 0.000 abstract description 16
- 230000002308 calcification Effects 0.000 abstract description 11
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- 150000002632 lipids Chemical class 0.000 abstract description 7
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- 206010072810 Vascular wall hypertrophy Diseases 0.000 abstract description 3
- 210000003989 endothelium vascular Anatomy 0.000 abstract description 3
- 230000004060 metabolic process Effects 0.000 abstract description 3
- 230000001766 physiological effect Effects 0.000 abstract description 3
- 230000001105 regulatory effect Effects 0.000 abstract description 3
- 241000700159 Rattus Species 0.000 description 27
- 208000004434 Calcinosis Diseases 0.000 description 10
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 6
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 6
- 229960004844 lovastatin Drugs 0.000 description 6
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 6
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 6
- 229960002855 simvastatin Drugs 0.000 description 6
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 6
- 108010023302 HDL Cholesterol Proteins 0.000 description 4
- 108010028554 LDL Cholesterol Proteins 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
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- 101150037123 APOE gene Proteins 0.000 description 2
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 208000003017 Aortic Valve Stenosis Diseases 0.000 description 1
- 206010050559 Aortic valve calcification Diseases 0.000 description 1
- 108010025628 Apolipoproteins E Proteins 0.000 description 1
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- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 102000015775 Core Binding Factor Alpha 1 Subunit Human genes 0.000 description 1
- 108010024682 Core Binding Factor Alpha 1 Subunit Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
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- 241000124008 Mammalia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 241000304195 Salvia miltiorrhiza Species 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- 208000003959 Ventricular Outflow Obstruction Diseases 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
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- 210000000709 aorta Anatomy 0.000 description 1
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- 230000007423 decrease Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
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- 239000011159 matrix material Substances 0.000 description 1
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- 239000002504 physiological saline solution Substances 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/216—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- Health & Medical Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Cardiology (AREA)
- Alternative & Traditional Medicine (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
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- Mycology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to the technical field of aortic valve disease treatment, and discloses application of salvianolic acid A in treatment of calcified aortic valve disease, which can prevent vascular endothelium in an aortic valve from generating plaque, avoid intimal thickening and inhibit calcification; it also has effects in reducing blood lipid concentration, improving metabolism, and regulating physiological activity, and has no obvious effect on weight increase.
Description
Technical Field
The invention relates to the technical field of aortic valve disease treatment, in particular to application of salvianolic acid A in treatment of calcified aortic valve disease.
Background
Calcified heart valve disease is one of the most common heart valve diseases, mainly comprises Calcified Aortic Valve Diseases (CAVD), can cause heart cerebrovascular accidents, and is an important disease affecting the daily life quality and threatening life of the old, and comprises two types of aortic valve sclerosis (AVC) and calcified aortic valve stenosis (CAS) which can cause serious left ventricular outflow obstruction; calcification in turn leads to lesions in the aorta. When the aortic valve is calcified, the aortic valve is directly hardened, narrow, thick, inflexible and can not be completely closed, and the blood can flow reversely, so that the heart load is aggravated, and finally, the diseases such as myocardial ischemia, cerebral ischemia, heart failure, hypertension and the like can be caused.
Epidemiological studies have shown that aortic valve calcifications are found in advanced age, men, hypertension, lipid abnormalities, diabetes, etc. and in CAVD images. Epidemiological studies have shown that advanced age, men, hypertension, lipid abnormalities, diabetes and the like have a close relationship with the occurrence and development of CAVD. The pathogenesis is a complex and lengthy, active and adjustable process involving pathological processes such as abnormal lipid metabolism, inflammatory reaction, neovascularization, matrix remodeling and progressive calcification
Although use of Transcatheter Aortic Valve Implantation (TAVI) increases in high risk patients, mortality from CAVD decreases; however, the risk of surgical treatment is high, the cost is high, and part of patients cannot tolerate surgical operation due to advanced age and preoperative combination of other diseases, and meanwhile, the accessibility of surgical treatment on the whole world is different, so that the development of a drug treatment scheme capable of effectively delaying or preventing the progression of CAVD is not slow.
Disclosure of Invention
The invention aims to provide application of salvianolic acid A in treating calcified aortic valve diseases, so as to solve the problems in the background art.
In order to achieve the above purpose, the present invention provides the following technical solutions:
use of salvianolic acid a in the treatment of calcified aortic valve disorders.
The invention further provides the following scheme: salvianolic acid A is a compound extracted from dried root and rhizome of Salvia Miltiorrhiza Salvia miltiorrhiza bge of Labiatae; the chemical substance has accession number (CAS number) of 96574-01-5 and molecular formula of C 26 H 22 O 10 The molecular weight is 494.452, and the structural formula is:
the invention further provides the following scheme: the salvianolic acid A is used for preparing medicines for treating individual calcified aortic valve diseases, and the concentration of the effective components of the salvianolic acid A in the prepared medicines is 10-30 mu mol/L;
preferably, the individual is a mammal, including but not limited to, mice, rabbits, cats, dogs, pigs, cattle, sheep, horses, donkeys, camels;
preferably, the individual is a human.
The invention further provides the following scheme: the concentration of the effective components of the salvianolic acid A in the prepared medicine is 10 mu mol/L.
The invention further provides the following scheme: the concentration of the effective components of the salvianolic acid A in the prepared medicine is 20 mu mol/L.
The invention further provides the following scheme: the concentration of the effective component of the salvianolic acid A in the prepared medicine is 30 mu mol/L.
Compared with the prior art, the invention has the beneficial effects that:
the invention provides an application of a medicine prepared from salvianolic acid A in treating calcified aortic valve diseases, which can prevent vascular endothelium in the aortic valve from generating plaque, avoid intimal thickening and inhibit calcification; it also has effects in reducing blood lipid concentration, improving metabolism, and regulating physiological activity, and has no obvious effect on weight increase.
Detailed Description
Example 1
In the embodiment of the invention, the salvianolic acid A is used for treating calcified aortic valve diseases, and the concentration of the effective components of the salvianolic acid A in the prepared medicine is 10 mu mol/L.
Example two
In the embodiment of the invention, the salvianolic acid A is used for treating calcified aortic valve diseases, and the concentration of the effective components of the salvianolic acid A in the prepared medicine is 20 mu mol/L.
Example III
In the embodiment of the invention, the salvianolic acid A is used for treating calcified aortic valve diseases, and the concentration of the effective components of the salvianolic acid A in the prepared medicine is 30 mu mol/L.
Simvastatin was used in the comparative example, and 20. Mu. Mol/L of the active ingredient concentration in the prepared drug was used.
Lovastatin is selected as the second comparative example, and the concentration of the active ingredient in the prepared medicine is 20 mu mol/L.
In order to better illustrate the technical effects of the invention, it is illustrated by the following tests:
1. and (3) constructing a CAVD animal model by adopting gene intervention and diet intervention cooperation:
selecting male SD rats with the age of 2-3 months, the weight of 200+10g, dividing 140 rats into 7 groups, and weighing the average weight of each group, wherein the average weight is respectively a blank control group, a model control group, a first embodiment group, a second embodiment group, a third embodiment group, a first comparison example group and a second comparison example group; wherein, the rats in the blank control group are only fed with common feed, and the ApoE genes of the rats in the other 6 groups are knocked out, and are fed with high-fat and high-cholesterol feed (88% of basic feed, 9.8% of lard, 2% of cholesterol and 0.2% of bile salt are mixed, the total fat content is more than 12%), and the rats in the 7 groups are free to enter water and eat.
After 8 weeks, the rats in the control group, the first group, the second group, the third group, the first group and the second group were examined for the expression of OCN, OPN and ALP.Runx2 in the aortic valve, which indicates the establishment of the CAVD animal model.
Wherein, the method for constructing the animal model of knocking out the ApoE gene disclosed in Chinese patent and the short peptide thereof (publication No. 2020-10-09; publication No. CN 108690840B) are adopted to knock out the ApoE gene of the mouse.
2. The method comprises the steps of respectively carrying out gastric lavage on rats in a first group, a second group and a third group of examples to obtain 10mg/kg body mass/day of salvianolic acid A medicaments (wherein the effective component concentration of the salvianolic acid A in the three groups is respectively 10 mu mol/L, 20 mu mol/L and 30 mu mol/L), carrying out gastric lavage on rats in the first group to obtain 10mg/kg body mass/day of simvastatin medicaments (the effective component concentration of simvastatin is 20 mu mol/L), and carrying out gastric lavage on rats in the second group to obtain 10mg/kg body mass/day of lovastatin medicaments (the effective component concentration of lovastatin is 20 mu mol/L); the blank control group and the model control group were not treated; after continuous gastric lavage for 4 weeks, the patients are fasted and water is forbidden for 12 hours; the following tests were performed separately:
1) The average body weight of each group at 12 weeks of feed feeding (unit: g) And the weight change value Δm before feeding the feed (0 week) and after feeding the feed for 12 weeks was calculated and recorded in table 1 below.
2) The appearance and fecal status of each group of rats was observed and recorded in table 2 below.
3) Taking rat aortic valve, washing with physiological saline, slicing, preparing sample, and observing tissue morphology under an optical microscope; recording the number of rats with obvious intima thickening of the aortic valve lumen and hardening plaques, and calculating the thickening rate of the rats; simultaneously recording the number of rats with obvious calcification foci and calculating the calcification rate; recorded in table 3 below.
4) Blood was taken at the abdominal aortic valve and tested for Triglyceride (TG), total Cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) concentration (unit: mmmol/L); recorded in table 4 below.
Note that: all data are expressed as mean ± standard deviation (x ± s), SPSS16.0 statistical software is applied; the comparison of two pairs adopts t test, and P is less than 0.05, which is statistically significant.
TABLE 1 analysis of rat body weight changes
As can be seen from table 1: the rats in the blank control group are fed with common feed, the weight change value of the common feed is smaller, and the other 6 groups are fed with high-fat high-cholesterol feed, the weight change values are not different, and no obvious difference exists; it can thus be derived that: salvianolic acid A has no obvious effect on the weight gain of rats.
Table 2 rat appearance and stool analysis table
As can be seen from table 2: salvianolic acid A, simvastatin and lovastatin can improve metabolism of rats and regulate physiological activity.
TABLE 3 rat aortic valve tissue morphology analysis Table
As can be seen from table 3: the inner walls of the aortic valve lumens of all rats in the blank control group are smooth, and no calcification phenomenon exists; in the model control group, 90% of the rat aortic valve lumens have a plurality of protruding hardened plaques, the intima is thickened obviously, and 85% of the rat aortic valve lumens have a plurality of flaky calcification foci; 70% -85% of rats in the first group, the second group and the third group have no obvious plaque in the aortic valve lumen, slightly thickened intima, no obvious calcification foci and unsmooth inner wall of the lumen; 55% -65% of rats in the first and second groups had no apparent plaque in the aortic valve lumen, slightly thickened intima, no apparent calcification foci, and no smooth lumen wall.
It can be derived that: the salvianolic acid A, simvastatin and lovastatin can prevent plaque of vascular endothelium in rat aortic valve, avoid intimal thickening, and inhibit calcification.
TABLE 4 analysis of blood lipid changes in rats
As can be seen from table 4: compared with a blank control group, TC and HDL-C, LDL-C in the model control group are obviously increased; TG does not vary much; no significant difference in TG was found in the examples one, two, three, one, two, and two relative to the model control group; and TC and HDL-C, LDL-C are obviously reduced.
It can be derived that: salvianolic acid A, simvastatin and lovastatin can reduce blood lipid concentration, and have blood lipid regulating effect.
The foregoing description is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical solution of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.
Claims (6)
1. Use of salvianolic acid a in the treatment of calcified aortic valve disorders.
2. The use of salvianolic acid a according to claim 1 for treating calcified aortic valve diseases, wherein salvianolic acid a is a compound extracted from dried root and rhizome of the labiate plant danshen Salvia miltiorrhiza bge; the chemical substance accession number is 96574-01-5, and the molecular formula is C 26 H 22 O 10 The molecular weight is 494.452, and the structural formula is:
3. the use of salvianolic acid a according to claim 1 for treating calcified aortic valve diseases, wherein the salvianolic acid a is used for preparing a medicament for treating individual calcified aortic valve diseases, and the concentration of the effective components of the salvianolic acid a in the prepared medicament is 10-30 mu mol/L.
4. The use of salvianolic acid a according to claim 1 for treating calcified aortic valve diseases, wherein the concentration of the effective component of the salvianolic acid a in the prepared medicament is 10 μmol/L.
5. The use of salvianolic acid a according to claim 1 for treating calcified aortic valve diseases, wherein the concentration of the effective component of the salvianolic acid a in the prepared medicament is 20 μmol/L.
6. The use of salvianolic acid a according to claim 1 for treating calcified aortic valve diseases, wherein the concentration of the effective component of the salvianolic acid a in the prepared medicament is 30 mu mol/L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311166563.3A CN117357506A (en) | 2023-09-11 | 2023-09-11 | Application of salvianolic acid A in treatment of calcified aortic valve diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311166563.3A CN117357506A (en) | 2023-09-11 | 2023-09-11 | Application of salvianolic acid A in treatment of calcified aortic valve diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117357506A true CN117357506A (en) | 2024-01-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311166563.3A Pending CN117357506A (en) | 2023-09-11 | 2023-09-11 | Application of salvianolic acid A in treatment of calcified aortic valve diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117357506A (en) |
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2023
- 2023-09-11 CN CN202311166563.3A patent/CN117357506A/en active Pending
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