Chrysophanol attenuated isoproterenol-induced cardiac hypertrophy by inhibiting Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway.

Cardiac hypertrophy is a common pathological change found in various cardiovascular diseases. Although it has long been recognized as an important risk factor responsible for heart failure, there is still a lack of effective treatments in clinic. Chrysophanol is a natural compound with multiple biological activities and protective roles in the cardiovascular system. However, its potential effect on cardiac hypertrophy remains unclear. In the current study, we found that chrysophanol could protect against isoproterenol (ISO)-induced cardiac hypertrophy both in vitro and in vivo. Increase of cell surface and hypertrophic marker expression induced by ISO in neonatal rat cardiomyocytes was downregulated by chrysophanol. Moreover, chrysophanol ameliorated the abnormal changes of cardiac structure and function in rats subjected to ISO injection, as shown by echocardiography and morphometry measurements. Further mechanistical investigation demonstrated that chrysophanol inhibited phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) induced by ISO. Nuclear translocation of STAT3 and transcription of downstream genes promoted by ISO treatment were also remarkably suppressed by chrysophanol. Taken together, our findings revealed that chrysophanol attenuated ISO-induced cardiac hypertrophy by inhibiting JAK2/STAT3 signaling pathway. Chrysophanol may be a potential candidate compound for the prevention and treatment of hypertrophy-related cardiomyopathy.