Application of dihydromyricetin in preparation of medicines for inhibiting adriamycin cardiotoxicity

A technology for dihydromyricetin and cardiotoxicity, which is used in drug combinations, antitumor drugs, pharmaceutical formulations, etc.

Inactive Publication Date: 2013-09-25
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But so far there is no report on its protective effect on cardiotoxicity caused by doxorubicin

Method used

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  • Application of dihydromyricetin in preparation of medicines for inhibiting adriamycin cardiotoxicity
  • Application of dihydromyricetin in preparation of medicines for inhibiting adriamycin cardiotoxicity
  • Application of dihydromyricetin in preparation of medicines for inhibiting adriamycin cardiotoxicity

Examples

Experimental program
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Effect test

Embodiment 1

[0018] Rat primary cardiomyocytes were inoculated in a 96-well plate, and a blank control group, adriamycin (ADR) single use group and dihydromyricetin (DMY) pretreatment group were set up. Each group set 5 ADR concentration gradients, 2-fold dilution. Each concentration was replicated in triplicate. After the cells adhered to the wall, the dihydromyricetin (DMY) pretreatment group was added with DMY and cultured in the incubator for 24 hours. Then add different concentrations of ADR, continue to cultivate in the incubator for 48 hours, add 5 mg / ml MTT solution, and incubate for another 4 hours, then aspirate the liquid and add DMSO to completely dissolve formazan, then use a microplate reader to measure its concentration at 570 Absorbance was measured at nm. The results showed that after 0.5, 1, 2, 4 and 8 mM ADR, the growth of rat primary cardiomyocytes was inhibited in a dose-dependent manner, while DMY 25 and 50 mM pretreatment showed a significant reversal of the inhibi...

Embodiment 2

[0021] Forty-eight ICR male mice were randomly divided into 4 groups, including blank control group, doxorubicin model group and three DMY pretreatment groups with 12 each. The blank control group was given the same amount of normal saline; the doxorubicin model group was intragastrically administered with normal saline for four consecutive days, and 20 mg / kg doxorubicin was injected intraperitoneally on the fourth day. The DMY pretreatment group were given 125 mg / kg, 250 mg / kg, and 500 mg / kg DMY, respectively, for four consecutive days by intragastric administration, and 20 mg / kg doxorubicin was injected intraperitoneally 30 minutes after administration on the fourth day. The mice were weighed every day and the time of death was recorded. The results showed that the survival time of the mice in the 500 mg / kg dihydromyricetin pretreatment group was significantly longer than that of the model group, and the weight loss was significantly relieved than that of the model group. S...

Embodiment 3

[0023] Rat primary cardiomyocytes were pretreated with dihydromyricetin, and then collected 48 hours after ADR. JC-1 is a cationic dye that can accumulate in mitochondria in cells to form polymers and emit red fluorescence; when the mitochondrial membrane potential is damaged, JC-1 cannot be aggregated into mitochondria, but as a monomer The form of JC-1 exists in the cytoplasm, and at this time JC-1 emits green fluorescence. According to this characteristic, we used JC-1 staining combined with flow cytometry to measure the changes of mitochondrial membrane potential. The result is as image 3 As shown, 32.6±5.8% of the cardiomyocytes in the solvent control group showed green fluorescence, and after 2 mM ADR for 48 hours, 52.6±6.2% of the cardiomyocytes showed green fluorescence (that is, the membrane potential decreased), while after pretreatment with 50 mM dihydromyricetin , 35.5±7.8% of cardiomyocytes showed green fluorescence, and the mitochondrial membrane potential in...

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Abstract

The invention provides an application of a dihydromyricetin composition in preparation of medicines for inhibiting adriamycin cardiotoxicity. The composition is composed of dihydromyricetin and adriamycin; as shown by in vivo and in vitro experimental studies, the dihydromyricetin can inhibit cell apoptosis activated by the adriamycin and dependent to mitochondrial membrane potential so as to reduce lethality caused by adriamycin cardiotoxicity, and the composition provided by the invention has excellent protection effect on cardiotoxicity induced by adriamycin. The composition provided by the invention can be used for preventing and alleviating the cardiotoxicity educed by adriamycin and has clinical practicability.

Description

technical field [0001] The present invention relates to the combination of natural plant extract dihydromyricetin and antitumor drug doxorubicin, which can reduce the cardiotoxic effect caused by doxorubicin. This protective effect is achieved through the inhibition of doxorubicin-activated mitochondrial membrane potential-dependent apoptosis by dihydromyricetin. Background technique [0002] Adriamycin (ADR) is an anthracycline antitumor antibiotic with broad antitumor spectrum and strong antitumor effect. It is widely used in clinical treatment of acute lymphoblastic leukemia, acute myelogenous leukemia, breast cancer, Lung cancer, ovarian cancer, soft tissue sarcoma, osteogenic sarcoma, gastric cancer, liver cancer and other malignant tumors. However, like most antitumor drugs, ADR has many adverse reactions, the most serious being cardiotoxicity, which not only affects the quality of life of patients, but also severely limits the clinical application of ADR. The curren...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61K31/704A61P35/00A61P35/02A61P9/00
Inventor 何俏军杨波罗沛华翁勤洁杨晓春赵玉勤
Owner ZHEJIANG UNIV
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