Biochanin a Alleviated Doxorubicin‐Induced Cardiotoxicity but Did not Interfere With the Antitumor Effect of Doxorubicin

Doxorubicin (DOX)-induced cardiotoxicity (DIC) by the chemotherapeutic drug seriously affects the prognosis of patients with cancer. Therefore, it is significant to actively explore the underlying mechanisms of DIC and develop safe and effective adjuvant therapies to improve DIC. As a traditional Chinese medicine monomer, BCA can treat cardiovascular diseases. However, whether BCA is able to inhibit DOX-induced myocardial injury without affecting its anticancer effect is unclear. We divided tumor-bearing mice into four groups, constructed a heart failure model by administering DOX, and treated with BCA. Histopathological staining was performed (WGA, HE, IF, IHC, etc.), WB, qPCR, and serum detection of SOD and MDA. In vitro experiments, the effects of BCA and DOX in both kinds of cells were demonstrated by various experiments in primary cardiomyocytes and tumor cells panc02 of neonatal rats. The results showed that BCA could inhibit DOX-induced abnormal cardiac function in mice, improve heart failure, and inhibit the expression of ANP and BNP. It inhibited the level of myocardial oxidative stress and reduced the number of myocardial vacuolation and the degree of myocardial fibrosis in mice. BCA reduced DOX-induced oxidative stress in NRCMs. In terms of tumors, BCA cooperates with DOX to inhibit the occurrence and development of panc02 and reduce the body weight of tumors. It inhibited the expression of PCNA and promoted the expression of BAX. In vitro experiments, BCA cooperated with DOX to inhibit the proliferation and metastasis of panc02. To sum up, BCA can affect the occurrence and development of DOX-induced myocardial injury through multiple targets and pathways and does not interfere with the anti-tumor effect of DOX. This study seeks new drugs for DOX-induced myocardial injury and provides new ideas for the treatment of inhibiting DOX-induced myocardial injury and the research of related diseases.