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 PDF

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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
alkaloid
alpha
treating ischemic
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CN111920808B (en
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权赫秀
张普照
邵峰
韩英
杨小琪
朱穆峰
李传峰
唐芳瑞
谢永艳
王曾涛
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Jiangxi University of Traditional Chinese Medicine
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/4353Heterocyclic 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
    • A61K31/4375Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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

Application of alkaloid component in caulis et folium piperis longi in preparing medicine for treating ischemic heart disease
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
Figure BDA0002664440850000011
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:
Figure BDA0002664440850000021
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.
Tables 1-1 for H2O2Results in the Effect of H9c2 on myocardial cell survival
Figure BDA0002664440850000031
Figure BDA0002664440850000032
Figure BDA0002664440850000041
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.
TABLE 1-3 Effect on myocardial ischemic infarct size
Figure BDA0002664440850000051
Figure BDA0002664440850000052
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.
TABLE 1-4 Effect on LDH content in rats with myocardial ischemia injury
Figure BDA0002664440850000054
Figure BDA0002664440850000053
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.

Claims (1)

1. The application of an alkaloid component in the caulis et folium piperis longi in the preparation of drugs for treating ischemic heart disease is characterized in that the alkaloid has the chemical formula
Figure FDA0002664440840000011
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Cited By (2)

* Cited by examiner, † Cited by third party
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

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WO2019193540A1 (en) * 2018-04-06 2019-10-10 Glaxosmithkline Intellectual Property Development Limited Heteroaryl derivatives of formula (i) as atf4 inhibitors
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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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)

* Cited by examiner, † Cited by third party
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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