Application of DYZ-9 in preparation of anti-cardiac hypertrophy product

A technology of DYZ-9, 1. DYZ-9 is applied in the application field of preparing anti-cardiac hypertrophy products, which can solve the problems of poor reversal of ventricular hypertrophy, no research report, etc., so as to improve the clinical cure rate and long-term survival. efficiency, mature preparation process, and the effect of saving health expenses

Active Publication Date: 2020-05-08
NANJING FIRST HOSPITAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

β-adrenoceptor blockers such as betaloc and atenolol have been widely used in the clinical treatment of heart failure and hypertension, but their effect on reversing ventricular hypertrophy is not good
However, the research on DYZ-9 in myocardial hypertrophy has not been reported

Method used

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  • Application of DYZ-9 in preparation of anti-cardiac hypertrophy product
  • Application of DYZ-9 in preparation of anti-cardiac hypertrophy product
  • Application of DYZ-9 in preparation of anti-cardiac hypertrophy product

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1: Establishment of an animal model of cardiac hypertrophy and testing the efficacy of DYZ-9 against cardiac hypertrophy

[0038] 1. Materials and methods

[0039] 1. Collection and preparation of specimens: (1) 8-week-old male ICR mice were selected, and the drug isoproterenol (ISO, 5 mg / kg / day) was pumped continuously subcutaneously, and DYZ-9 (1, 10 mg / kg / day) was given at the same time. / day) intraperitoneal injection once a day for a total of 2 weeks. (2) Divide all mice into 4 groups, i.e. control group (Control group, healthy mice without cardiac hypertrophy), isoproterenol group (ISO group), low dose DYZ-9 treatment group (DYZ-9 1mg / kg+ISO group), high-dose DYZ-9 treatment group (DYZ-9 10mg / kg+ISO group).

[0040] 2. The thickness of the left ventricle and the mass index of the left ventricle were measured by echocardiography; the heart and body weight were measured after the animals were sacrificed.

[0041] 3. Using hematoxylin-eosin (H&E) staining ...

Embodiment 2

[0051] Example 2: Establishment of hypertrophy model of isolated cardiomyocytes and research on the mechanism of action of DYZ-9 against cardiac hypertrophy

[0052] 1. Materials and methods

[0053] 1. The rat cardiomyocyte cell line (H9C2) was stimulated with ISO (10 μM) in vitro to establish a hypertrophy model of cardiomyocytes in vitro. Treatment group DYZ-9 (20 μM, 50 μM, 100 μM) was co-incubated with ISO for 24 hours.

[0054] 2. α-SMA immunofluorescence to observe the morphology of H9C2 cells.

[0055] 3. Real-time quantitative PCR method was used to detect the mRNA expression levels of ANP and BNP in H9C2 cells.

[0056] 4. Western blot detection of p-Akt, Akt, p-CREB, CREB protein expression levels.

[0057] 2. Experimental results

[0058] 1. Immunofluorescence α-SMA detection showed that ISO stimulation can significantly increase the volume of H9C2 cells, while DYZ-9 can reverse it ( Figure 4 A, B).

[0059] 2. Compared with the normal control group, ISO (10...

Embodiment 3

[0061] Example 3: Verification of the DYZ-9 target at the whole animal level

[0062] 1. Materials and methods

[0063] 8-week-old male ICR mice were selected, subcutaneously pumped into the drug isoproterenol and intraperitoneally injected with DYZ-9 (1, 10 mg / kg / day) once a day, and sacrificed for a total of 2 weeks. The mice were detected by Western blot p-Akt, Akt protein expression level.

[0064] 2. Experimental results

[0065] DYZ-9 treatment could significantly reverse the increase in the phosphorylation levels of Akt and CREB in mouse heart tissue caused by ISO ( Figure 7 A, B).

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Abstract

The invention discloses an application of DYZ-9 in preparation of an anti-cardiac hypertrophy product. Compared with the prior art, the DYZ-9 provided by the invention has the following advantages: (1) the DYZ-9 studied in the invention can be synthesized by known methods, has a mature preparation process, can provide a reliable compound source, and has the advantages of a reliable substance source, low production costs, a novel mechanism of action and good market prospects; (2) the DYZ-9 has the effects of inhibiting phosphorylation of AKT and adenosine cyclophosphate effector element bindingprotein caused by isoproterenol (ISO), reducing the levels of myocardial hypertrophy markers ANP and BNP and a cardiac weight index, and improving myocardial hypertrophy; and (3) the DYZ-9 contributes to the research and development of the novel anti-cardiac hypertrophy drug, can bring direct economic benefits, and the drug can reduce the possibility of forming heart failure and malignant arrhythmia caused by further deterioration of the myocardial hypertrophy, and can save a lot of health expenses from a long-term perspective.

Description

technical field [0001] The invention belongs to the technical field of medicines and relates to the application of DYZ-9 in the preparation of anti-cardiac hypertrophy products. Background technique [0002] As a traditional medicine, mahogany seeds have been verified by local residents in Southeast Asian countries for a long time, which proves that it may have certain anti-inflammatory effects. However, after it was introduced into the southern provinces of China, such as Hainan Province, it is currently only used as a street tree for ornamental purposes, and the value of its fruits has not been fully utilized. If it can be rationally developed and utilized, it will create huge value. In Indonesia, mahogany seeds are used as a traditional herbal medicine to treat hypertension, diabetes and other diseases, but there is a lack of systematic research on the exact active ingredients. [0003] DYZ-9 (swietenine), the molecular formula is C 32 h 40 o 9 , the structural formu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/366A61P9/00A61P9/04
CPCA61K31/366A61P9/00A61P9/04
Inventor 钱炜春丁竞竞刘寿柏陈峰储春燕李开俞尤嘉肖平喜王加程张天舒周琪骏
Owner NANJING FIRST HOSPITAL
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