CN111920808A - Application of alkaloid component in caulis et folium piperis longi in preparing medicine for treating ischemic heart disease - Google Patents
Application of alkaloid component in caulis et folium piperis longi in preparing medicine for treating ischemic heart disease Download PDFInfo
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- CN111920808A CN111920808A CN202010914268.1A CN202010914268A CN111920808A CN 111920808 A CN111920808 A CN 111920808A CN 202010914268 A CN202010914268 A CN 202010914268A CN 111920808 A CN111920808 A CN 111920808A
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- heart disease
- ischemic heart
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- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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Abstract
The invention discloses application of an alkaloid component in Chinese starjasmine stem in preparation of a medicament for treating ischemic heart disease. The inventor finds that the Chinese medicinal material pinecone contains alkaloid components, and further proves that the alkaloid named 3 alpha, 5 alpha-tetrahydroxycorticosteriol lactam (3 alpha, 5 alpha-tetrahydroxybenzodifoline lactam) can obviously reduce myocardial cell injury after myocardial ischemia, thereby playing a role in treating ischemic heart disease and providing a basis for developing anti-ischemic heart disease medicaments in the future.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to application of an alkaloid component in Chinese starjasmine stem in preparation of a medicine for treating ischemic heart disease.
Background
Ischemic heart diseases such as coronary heart disease, angina pectoris, acute myocardial infarction and arrhythmia become diseases with high morbidity and mortality in China. Ischemic heart disease is often accompanied by oxidative stress injury, necrosis, apoptosis, etc. of cardiac muscle cells, which all cause cardiac dysfunction. The Chinese medicine heart-nourishing rattan (copper diamond) is a classical national medicine of Yao nationality and Dai nationality and is used for treating palpitation in ancient times. The earlier researches of the invention find that the Chinese medicinal preparation contains alkaloid components in the Chinese medicinal preparation, and further prove that the alkaloid component named 3 alpha, 5 alpha-tetrahydroxycorticosteriol lactam (3 alpha, 5 alpha-tetrahydroxybenzodifoline lactam) can obviously reduce the myocardial cell injury after myocardial ischemia, thereby playing a role in treating the ischemic heart disease. The research of the component on the related pharmacology of the ischemic heart disease is not reported yet, and the invention can provide a basis for developing anti-ischemic heart disease drugs in the future.
Disclosure of Invention
The invention aims to provide application of an alkaloid component in a rattan to preparation of a medicine for treating ischemic heart disease.
The technical scheme of the invention is realized by the following modes: application of alkaloid component in caulis et folium piperis longi in preparing medicine for treating ischemic heart disease, wherein the alkaloid has chemical formula
The invention has the beneficial effects that: an alkaloid component named 3 alpha, 5 alpha-tetrahydroxycorticoid lactam (3 alpha, 5 alpha-tetrahydrodeoxycydifoline lactam) contained in the Chinese starjasmine can obviously reduce myocardial cell injury after myocardial ischemia, thereby playing a role in treating ischemic heart disease and providing a basis for developing anti-ischemic heart disease drugs in the future.
Detailed Description
The present invention is further illustrated by the following examples, which are not intended to be limiting in any way, and any modifications or alterations based on the teachings of the present invention are intended to fall within the scope of the present invention.
One alkaloid component in the grapevine can obviously relieve myocardial cell injury after myocardial ischemia, thereby playing a role in treating ischemic heart disease and being used for preparing a medicine for treating ischemic heart disease, wherein the alkaloid has the chemical formula as follows:
pharmacological tests:
(I) Effect on oxidative stress injury of rat H9c2 cardiomyocytes
1. Experimental methods
1.1 cell culture
H9c2 cardiomyocytes were cultured in vitro in DMEM (high glucose) + 10% FBS + 0.1% double antibody. And (3) placing the cells in the logarithmic growth phase on a 96-hole cell culture plate, culturing for 36h at constant temperature, and performing grouping treatment.
1.2 oxidative stress Damage model preparation
Taking H9c2 cardiomyocytes cultured for 24H, adding 100 mu mol.L into the culture medium-1H of (A) to (B)2O2And putting the mixture into an incubator at 37 ℃ for 2 hours of culture.
1.3 packet processing
1.3.1 blank group, taking H9c2 cardiomyocytes cultured for 24H, placing at 37 ℃ and 5% CO without any treatment2The cultivation was continued for 2h in the incubator.
1.3.2 oxidative stress injury model group: taking H9c2 cardiomyocytes cultured for 24H, adding 100 mu mol.L into the culture medium-1H of (A) to (B)2O2And putting the mixture into an incubator at 37 ℃ for 2 hours of culture.
1.3.3 administration group: the culture medium containing the alkaloid components (final concentration of 20, 60, 200 μ g/ml)-1) Acting for 2h, washing with PBS for 2 times, and changing with a solution containing 100 mumol·L-1H2O2The culture medium is prepared into different concentrations of alkaloid and positive medicine N-acetylcysteine (0.08 g/ml)-1) And putting the mixture into an incubator at 37 ℃ for closed culture for 2 hours.
1.4 index determination
1.4.1 cell viability assay Using the MTS method
1.4.2 Lactate Dehydrogenase (LDH) Activity assay: the cell culture supernatants of each group of samples were taken and the Lactate Dehydrogenase (LDH) activity was measured at 490nm according to the kit instructions.
2. Results of the experiment
As shown in the following tables 1-1 and 1-2, compared with the normal group, the survival rate of the model group is obviously reduced, and the LDH leakage amount is obviously increased; 60 μ g/ml of alkaloid-1And positive drugs improve the cell survival rate, the difference is obvious, and the rest concentrations have no statistical significance. The results suggest that the alkaloid has protective effect on oxidative stress injury of cells.
Note that in comparison to the model set,**P<0.01,***P<0.001
(II) Effect on isolated perfused cardiac myocardial ischemia in rats
1. Experimental methods
1.1 grouping
SD rats are randomly divided into a blank group, a model group, a low-dose (1.44mg/kg) administration group, a medium-dose (4.8mg/kg) administration group and a high-dose (14.4mg/kg) administration group, wherein 6 rats in each group are subjected to intraperitoneal injection once a day, and the blank group and the model group are subjected to intraperitoneal injection of physiological saline with equal volume.
1.2 rat isolated perfusion heart model establishment
Rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (400mg/kg) and 500U-kg were intraperitoneally injected 10 minutes before thoracotomy-1Heparin according to (1). Fixing the heart in an isolated heart perfusion device from an aorta cannula after opening the chest to take the heart, perfusing the fixed heart with (K-H) buffer solution filled with saturated 95% O2And 5% CO2And maintained at 37 ℃. The heart was subjected to a 20 minute global cardiac arrest ischemia 20 minutes after perfusion was stabilized, followed by a 180 minute perfusate recovery. Cardiac effluent was collected for 1 minute at 180 minutes of reperfusion, and the heart was then removed for TTC staining.
1.3 Observation index
1.3.1 myocardial infarction area: taking off heart, freezing at-80 deg.C for 15min, and cutting heart into 2mm thick slices; placing the heart slices into a 1% TTC solution, placing the heart slices in a water bath at 37 ℃ and keeping out of the sun for dyeing for 15min, and fixing the dyed heart slices in a 10% formalin solution for 24 h; and (5) absorbing the formalin solution on the surface of the heart slice by using filter paper, weighing the formalin solution in sequence, and calculating the myocardial infarction range.
1.3.2 detection of serum enzymes: after collecting the heart effluent, using corresponding reagent kits to respectively determine and measure the content of Lactate Dehydrogenase (LDH).
2. Results of the experiment
2.1 measurement of myocardial infarction area
As shown in tables 1 to 3, the myocardial infarction area of the model group was significantly different (P <0.001) compared to the blank group, and the myocardial infarction area of the myocardial ischemia rats was significantly reduced (P <0.01) compared to the model group by the administration of the high dose group, and the results showed that: the alkaloid has remarkable protective effect on myocardial ischemia injury rat myocardium.
Note that as compared to the blank group,###P<0.001, compared to the model set,**P<0.01
2.2 measurement results of Lactate Dehydrogenase (LDH) content
As shown in tables 1-4, the LDH content in the model group was significantly increased compared to the blank group, and the LDH leakage was reduced in the high dose group compared to the model group (P <0.01, P <0.001) in both the administration groups, and the results showed that: the alkaloid has remarkable protective effect on myocardial ischemia injury rat myocardium.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN113480538A (en) * | 2021-08-23 | 2021-10-08 | 北京中医药大学 | Application of monoterpene indole alkaloid derivative |
CN113549071A (en) * | 2021-08-23 | 2021-10-26 | 北京中医药大学 | Monoterpene indole alkaloid compound and preparation method and application thereof |
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CN102000073A (en) * | 2009-09-01 | 2011-04-06 | 中国医学科学院药物研究所 | Application of coptisine in preventing and curing myocardial ischemic diseases |
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CN111592537A (en) * | 2019-11-13 | 2020-08-28 | 江西中医药大学 | Sinomenium majus indole alkaloid for reducing hyperuricemia and application thereof |
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Patent Citations (5)
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CN102000073A (en) * | 2009-09-01 | 2011-04-06 | 中国医学科学院药物研究所 | Application of coptisine in preventing and curing myocardial ischemic diseases |
WO2018148743A1 (en) * | 2017-02-13 | 2018-08-16 | East Carolina University | Modulation of ischemic cell bioenergetics |
CN107353319A (en) * | 2017-06-16 | 2017-11-17 | 江西中医药大学 | A kind of triterpenes components and preparation method and the application in Treating Ischemic Heart |
WO2019193540A1 (en) * | 2018-04-06 | 2019-10-10 | Glaxosmithkline Intellectual Property Development Limited | Heteroaryl derivatives of formula (i) as atf4 inhibitors |
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113480538A (en) * | 2021-08-23 | 2021-10-08 | 北京中医药大学 | Application of monoterpene indole alkaloid derivative |
CN113549071A (en) * | 2021-08-23 | 2021-10-26 | 北京中医药大学 | Monoterpene indole alkaloid compound and preparation method and application thereof |
CN113549071B (en) * | 2021-08-23 | 2023-10-31 | 北京中医药大学 | Monoterpene indole alkaloid compound, and preparation method and application thereof |
CN113480538B (en) * | 2021-08-23 | 2024-01-30 | 北京中医药大学 | Application of monoterpene indole alkaloid derivative |
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