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Application of fuziline in preparation of medicine for preventing and/or treating diseases caused by myocardial cell apoptosis

A cardiomyocyte apoptosis and Fuziling technology, which is applied in cardiovascular system diseases, drug combinations, pharmaceutical formulations, etc., can solve death, endoplasmic reticulum stress-damaged cells, endoplasmic reticulum unfolded protein aggregation, calcium homeostasis disruption, etc. problem, achieve the effect of protecting cardiomyocytes and improving the survival rate

Inactive Publication Date: 2021-06-04
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, excessive ROS accumulation can cause aggregation of unfolded proteins in the endoplasmic reticulum, disrupt calcium homeostasis, and eventually lead to cell death due to endoplasmic reticulum stress damage

Method used

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  • Application of fuziline in preparation of medicine for preventing and/or treating diseases caused by myocardial cell apoptosis
  • Application of fuziline in preparation of medicine for preventing and/or treating diseases caused by myocardial cell apoptosis
  • Application of fuziline in preparation of medicine for preventing and/or treating diseases caused by myocardial cell apoptosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Effect of different structural types of alkaloids in aconite on cell survival in isoproterenol (ISO) injured cardiomyocyte model

[0029] Cell source and culture conditions:

[0030] H9c2 rat cardiomyocytes were derived from ATCC (American Type Culture Collection, Manassas, VA, USA), and the cells were cultured in high-sugar DMEM with 1% P / S (100unit / ml penicillin and 100mg / ml streptomycin) and 10 %FBS (fetal bovine serum) cultured in 5% CO 2 , 37°C and 95% humidity.

[0031]2. Source of monomeric compound:

[0032] Mesaconitine, Hypaconitine, Benzoylmesaconine, Benzoylhypaconine, Benzoylaconine and The purity of Fuziling (fuziline) is greater than 98%, purchased from Shanghai Ronghe Pharmaceutical Technology Development Co., Ltd., the structural formula is shown in the attached figure 1 .

[0033] 3. Monomer solution preparation:

[0034] Accurately weigh Mesaconitine, Hypaconitine, Benzoylmesaconine, Benzoylhypaconine, Benzoylhypaconine ( Benzoylaconi...

Embodiment 2

[0043] Example 2 Study on the Mechanism of Fuziling's Myocardial Protection

[0044] 1. Experimental method:

[0045] 1.1 Annexin-V-FLUOS double staining method to detect cardiomyocyte apoptosis

[0046] The H9c2 cells were inoculated into 6-well plates at a density of 1×105 cells / mL, and 1.5 mL was added to each well, and cultured for 24 hours. After the intervention of Fuziling, the cells and supernatant of each group were collected, centrifuged, washed once with pre-cooled PBS, and counted. Use the buffer provided in the kit to adjust the cell concentration to 2×105 cells / mL, take 500 μL of cell suspension, add 2 μL of Annexin-V-FITC binding solution and 2 μL of PI staining solution, pat gently to mix, and place in the incubator After staining in the dark for 15 minutes, detect in a flow cytometer at an excitation wavelength of 488nm and an emission wavelength of 525nm, repeat 3 times, record and perform statistical analysis.

[0047] 1.2 Detection of reactive oxygen spe...

Embodiment 3

[0055] Embodiment 3 The influence of the composition of Fuziling and other active substances on the survival rate of cardiomyocytes

[0056] 1. Experimental method:

[0057] H9c2 rat cardiomyocytes were seeded in a 96-well plate at a density of 6×104 / mL, and 100 μL was added to each well, and incubated for 24 hours. Fuziling (0.5 μM) and different concentrations (10, 50, 100 μM) of ginsenoside Rb1 and tanshinone IIA (purity greater than 98%, purchased from Shanghai Ronghe Pharmaceutical Technology Development Co., Ltd.; refer to Example 1 for the preparation method) were added in a 96-well plate. The rest of the methods were operated according to the MTT method in Example 1, and the cell survival rate of each group was calculated.

[0058] Experimental results:

[0059] As shown in Table 2, Fuziling (500 nM), ginsenoside Rb1 (100 μM) and tanshinone IIA (100 μM) can all significantly increase the survival rate of cardiomyocytes. Adding ginsenoside Rb1 or tanshinone IIA to F...

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Abstract

The invention discloses application of fuziline in preparation of a medicine for preventing and / or treating diseases caused by myocardial cell apoptosis. The invention discovers for the first time that fuziline has an effect of protecting myocardial cells, can inhibit the myocardial cell apoptosis caused by ISO by inhibiting the endoplasmic reticulum stress injury of the myocardial cells by reducing ROS generation, and can be used for preparing the medicine for preventing and / or treating the diseases caused by the myocardial cell apoptosis; and the invention also discovers that a composition of ginsenoside Rb1 and fuziline and a composition of tanshinone IIA and fuziline can obviously improve the survival rate of the myocardial cells compared with the single effect of fuziline. The fuziline disclosed by the invention can be widely applied to the field of medicines, and can provide a new medicine source for treatment of the diseases caused by the myocardial cell apoptosis.

Description

technical field [0001] The invention belongs to the field of biomedicine, and particularly relates to the application of Fuziling in the preparation of medicines for preventing and / or treating diseases caused by cardiomyocyte apoptosis. Background technique [0002] Chronic heart failure is a clinical syndrome in which myocardial damage caused by myocardial infarction, coronary heart disease, etc. leads to abnormal cardiac structure and function, resulting in decreased ventricular pumping or filling function. The number of chronic heart failure patients in my country has reached 4 million, and the mortality rate of hospitalized patients with heart failure is about 5.3%. The main pathophysiological mechanism of chronic heart failure is ventricular remodeling. The process of ventricular remodeling is often accompanied by massive apoptosis of follower cardiomyocytes. Studies have shown that the apoptotic index of cardiomyocytes in the myocardium of patients with severe myocar...

Claims

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Application Information

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IPC IPC(8): A61K31/439A61K31/704A61K31/58A61P9/00A61P9/10A61P9/12A61P9/04
CPCA61K31/439A61K31/704A61K31/58A61P9/00A61P9/10A61P9/12A61P9/04A61K2300/00
Inventor 戴毅樊采连唐曦阳运伟静姚新生
Owner JINAN UNIVERSITY
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