The Studies Of Pharmacologic Effect Of Combined Berberine With Doxorubicin

Doxorubicin is a very effective and often used anti-tumor drug. But its serious dose-dependent side effects largely limited the clinical useage. The aim of this study is to investigate whether berberine could protect against doxorubicin-induced cardiotoxicity and liver injury in mice, and to investigate whether combinate berberine with doxorubicin would generate synergistic anticancer effect.In animal study, forty healthy mice were randomly divited into four groups: control groups; doxorubicin-treated groups; berberine+doxorubicin-treated groups; berberine-treated groups. The mice were treated with drugs every two days, for7doses. In the fourteenth days, body weight and ECG changes were observed. At the end of the study, blood was drawn from the inner canthus, the activity of LDH、ALT and AST in the serum were tested. HE staining for histopathological analysis in the heart and liver were performed under the microscope. The result showed that a significant decline in body weight was observed in doxorubicin-treated groups, but doxorubicin-induced decline in body weight was reduced by pretreated with berberine. There was no change in the weight of berberine-treated mice. Compared with control group, prolongation of QRS duration and increased plasma LDH、ALT and AST activities were observed in doxorubicin-treated mice, and these changes were significantly prevented by pretreatment with berberine. Histopathological studies showed that doxorubicin caused structural injuries, such as vascular congestion, inflammatory cell infiltration, cell necrosis and fibrosis in the heart and liver. These histopathological changes were largely attenuated by berberine pretreatment, and berberine caused no histopathological change in berberine-treated groups. All these findings indicated that berberine had the cardioprotective and hepatoptotective on doxorubicin-induced heart and liver injury in mice.In this study, The3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay was used to detect the cell viability of A549, HeLa and HepG2cells after each cell line was treated with DOX, BER or a combination of DOX and BER for24h. The results showed that DOX exhibited dose-dependent inhibitory effects on A549. HepG2and HeLa cells, the IC50(μmol-L-1) of doxorubicin was3.1、9.2.16.7. Berberine also exhibited inhibitory effects which less than doxorubicin on A549. HepG2and HeLa cells, the IC50(μmol-L-1) of berberine was139.4、3587.8.159.5.In combination group, the IC50(μmol-L-1) of doxorubicin on A549and HeLa was1.7、1.9, and the IC50(μmol-L-1) of berberine on A549and HepG2was8.6、98.9. Isobologram illustration and combination index (CI) analyses revealed that the combination of doxorubicin and berberine generates synergistic effects in A549(CI=0.61)and HeLa (CI=0.73) cells. Apoptosis was evaluated by acridine orange staining. Results showed that the single and combined treatment with doxorubicin and berberine induced dose-dependent A549cell apoptosis. The apoptosis ration in combination group was higher than berberine-treated group and doxorubicin-treated group. These fndings indicated that cell apoptosis might be one of the mechanisms of combination of doxorubicin with berberine in inhibiting cell viability.