Protection against Doxorubicin-Induced Cytotoxicity by Geniposide Involves AMPK Signaling Pathway.

Oxidative stress and cardiomyocyte apoptosis play critical roles in the development of doxorubicin- (DOX-) induced cardiotoxicity. Our previous study found that geniposide (GE) could inhibit cardiac oxidative stress and apoptosis of cardiomyocytes but its role in DOX-induced heart injury remains unknown. Our study is aimed at investigating whether GE could protect against DOX-induced heart injury. The mice were subjected to a single intraperitoneal injection of DOX (15 mg/kg) to induce cardiomyopathy model. To explore the protective effects, GE was orally given for 10 days. The morphological examination and biochemical analysis were used to evaluate the effects of GE. H9C2 cells were used to verify the protective role of GE in vitro. GE treatment alleviated heart dysfunction and attenuated cardiac oxidative stress and cell loss induced by DOX in vivo and in vitro. GE could activate AMP-activated protein kinase (AMPK) in vivo and in vitro. Moreover, inhibition of AMPK could abolish the protective effects of GE against DOX-induced oxidative stress and apoptosis. GE could protect against DOX-induced heart injury via activation of AMPK. GE has therapeutic potential for the treatment of DOX cardiotoxicity.