Application of berberine and doxorubicine mixed preparation in preparation of medicament against doxorubicine cardiac dysfunction or tumor

Abstract

The invention discloses application of a berberine and doxorubicine mixed preparation in preparation of a medicament against doxorubicine cardiac dysfunction or tumor. The molar concentration ratio of the berberine to the doxorubicine in the medicament is (0.625-4): 1, and the optimal ratio is 1:1. The medicament is an oral preparation or an injection preparation. The combined use of the berberine and the doxorubicine can lighten myocardial damage caused by the doxorubicine, also can play a role in inhibiting myocardial apoptosis caused by the doxorubicine, and does not weaken, even enhance the anti-tumor effect of the doxorubicine at the same time.

Description

technical field

[0001] The invention relates to berberine and doxorubicin, in particular to the application of a mixed preparation of berberine and doxorubicin in the preparation of anti-doxorubicin-induced cardiac dysfunction or anti-tumor drugs. Background technique

[0002] Doxorubicin is an anti-tumor drug widely used clinically. It has very significant curative effects on leukemia, lymphoma, breast cancer, lung cancer, etc., and is currently one of the most commonly used anti-tumor drugs in clinical practice. The main side effect of doxorubicin is myocardial toxicity, which can not only cause arrhythmia, but also induce progressive cardiomyopathy and congestive heart failure with the accumulation of doses. Since the 1980s, many new advances have been made in the research on the molecular mechanism of adriamycin cardiotoxicity. At present, most studies believe that it is possible that adriamycin can activate endogenous cardiomyopathy through oxidative stress pathways or ...

Examples

Embodiment 1

[0014] Example 1 Effect of berberine on cardiomyocyte injury induced by doxorubicin

[0015] One-day-old newborn SD suckling mice (provided by the Experimental Animal Center of Southern Medical University) were taken, and the apex of the heart was routinely digested with trypsin (Sigma, USA) to obtain cardiomyocytes according to the existing method.

[0016] Suspend the cells in DMEM (purchased from Gibico) containing 10% fetal bovine serum (purchased from Hyclone) and place at 37°C in 5% CO 2 In the incubator, incubate for 2 hours, and purify the obtained cardiomyocytes. According to 1×10 5 cells / mL were seeded in 96-well plates and cultured for 48 hours. 10 mg doxorubicin (DOX) (Sigma, USA) was dissolved in 5 mL of normal saline, and then diluted with DMEM (purchased from Gibico) medium to obtain a 10 μmol / L doxorubicin working solution. Berberine (Ber) (Sigma, USA) was dissolved in double-distilled water to 4.00 μmol / L working solution, and then diluted in DMEM to 1.00 μ...

Embodiment 2

[0027] Example 2 Effect of berberine on the viability of adriamycin-injured cardiomyocytes

[0028] The apical part of the apex of the SD suckling mouse was taken from 1-day-old newborn mice, and the cardiomyocytes were obtained by trypsinization. Suspend cells in DMEM containing 10% fetal bovine serum at 37°C, 5% CO 2 In the incubator, incubate for 2 hours, and purify the obtained cardiomyocytes. According to 1×10 5 cells / mL were seeded in 96-well plates and cultured for 48 hours. Dissolve doxorubicin injection (DOX) with 5 mL of normal saline, and then dilute with DMEM medium to 10 μmol / L doxorubicin working solution. Berberine (Ber) was dissolved in double distilled water to 4.00 μmol / L working solution, and then diluted to 1.00 μmol / L, 0.25 μmol / L, and 0.625 μmol / L working solution respectively. The purified cardiomyocytes were treated with the following drugs:

[0029] ①Control group: 200μL DMEM

[0030] ②Adriamycin (1 μmol / L) group: 180 μL DMEM+20 μL DOX

[0031] ...

Embodiment 3

[0042] Example 3 Observing the Effect of Berberine on Adriamycin-induced Myocardial Apoptosis

[0043] The apical part of the apex of the SD suckling mouse was taken from 1-day-old newborn mice, and the cardiomyocytes were obtained by trypsinization. Suspend the cells in DMEM (purchased from Gibico) containing 10% fetal bovine serum (purchased from Hyclone) and place at 37°C in 5% CO 2 In the incubator, incubate for 2 hours, and purify the obtained cardiomyocytes. According to 1×10 5 cells / mL were seeded in 96-well plates and cultured for 48 hours. Dissolve doxorubicin injection (DOX) with 5 mL of normal saline, and then dilute with DMEM medium to 10 μmol / L doxorubicin working solution. Berberine (Ber) was dissolved in double distilled water to 4.00 μmol / L working solution, and then diluted to 1.00 μmol / L, 0.25 μmol / L, and 0.625 μmol / L working solution respectively. After 48 hours of culture, cardiomyocytes were treated with the following drugs:

[0044] ①Control group: 2...

technical field

[0001] The invention relates to berberine and doxorubicin, in particular to the application of a mixed preparation of berberine and doxorubicin in the preparation of anti-doxorubicin-induced cardiac dysfunction or anti-tumor drugs. Background technique

[0002] Doxorubicin is an anti-tumor drug widely used clinically. It has very significant curative effects on leukemia, lymphoma, breast cancer, lung cancer, etc., and is currently one of the most commonly used anti-tumor drugs in clinical practice. The main side effect of doxorubicin is myocardial toxicity, which can not only cause arrhythmia, but also induce progressive cardiomyopathy and congestive heart failure with the accumulation of doses. Since the 1980s, many new advances have been made in the research on the molecular mechanism of adriamycin cardiotoxicity. At present, most studies believe that it is possible that adriamycin can activate endogenous cardiomyopathy through oxidative stress pathways or ...

Examples

Embodiment 1

[0014] Example 1 Effect of berberine on cardiomyocyte injury induced by doxorubicin

[0015] One-day-old newborn SD suckling mice (provided by the Experimental Animal Center of Southern Medical University) were taken, and the apex of the heart was routinely digested with trypsin (Sigma, USA) to obtain cardiomyocytes according to the existing method.

[0016] Suspend the cells in DMEM (purchased from Gibico) containing 10% fetal bovine serum (purchased from Hyclone) and place at 37°C in 5% CO 2 In the incubator, incubate for 2 hours, and purify the obtained cardiomyocytes. According to 1×10 5 cells / mL were seeded in 96-well plates and cultured for 48 hours. 10 mg doxorubicin (DOX) (Sigma, USA) was dissolved in 5 mL of normal saline, and then diluted with DMEM (purchased from Gibico) medium to obtain a 10 μmol / L doxorubicin working solution. Berberine (Ber) (Sigma, USA) was dissolved in double-distilled water to 4.00 μmol / L working solution, and then diluted in DMEM to 1.00 μ...

Embodiment 2

[0027] Example 2 Effect of berberine on the viability of adriamycin-injured cardiomyocytes

[0028] The apical part of the apex of the SD suckling mouse was taken from 1-day-old newborn mice, and the cardiomyocytes were obtained by trypsinization. Suspend cells in DMEM containing 10% fetal bovine serum at 37°C, 5% CO 2 In the incubator, incubate for 2 hours, and purify the obtained cardiomyocytes. According to 1×10 5 cells / mL were seeded in 96-well plates and cultured for 48 hours. Dissolve doxorubicin injection (DOX) with 5 mL of normal saline, and then dilute with DMEM medium to 10 μmol / L doxorubicin working solution. Berberine (Ber) was dissolved in double distilled water to 4.00 μmol / L working solution, and then diluted to 1.00 μmol / L, 0.25 μmol / L, and 0.625 μmol / L working solution respectively. The purified cardiomyocytes were treated with the following drugs:

[0029] ①Control group: 200μL DMEM

[0030] ②Adriamycin (1 μmol / L) group: 180 μL DMEM+20 μL DOX

[0031] ...

Embodiment 3

[0042] Example 3 Observing the Effect of Berberine on Adriamycin-induced Myocardial Apoptosis

[0043] The apical part of the apex of the SD suckling mouse was taken from 1-day-old newborn mice, and the cardiomyocytes were obtained by trypsinization. Suspend the cells in DMEM (purchased from Gibico) containing 10% fetal bovine serum (purchased from Hyclone) and place at 37°C in 5% CO 2 In the incubator, incubate for 2 hours, and purify the obtained cardiomyocytes. According to 1×10 5 cells / mL were seeded in 96-well plates and cultured for 48 hours. Dissolve doxorubicin injection (DOX) with 5 mL of normal saline, and then dilute with DMEM medium to 10 μmol / L doxorubicin working solution. Berberine (Ber) was dissolved in double distilled water to 4.00 μmol / L working solution, and then diluted to 1.00 μmol / L, 0.25 μmol / L, and 0.625 μmol / L working solution respectively. After 48 hours of culture, cardiomyocytes were treated with the following drugs:

[0044] ①Control group: 2...

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