Post-
myocardial infarction heart failure (post-MI HF) is one of the leading global causes of death, and current prevention and treatment methods still cannot avoid the increasing incidence.
Honokiol (HK) has previously been reported to improve
myocardial ischemia/
reperfusion injury and reverse myocardial
hypertrophy by activating
Sirt1 and
Sirt3. We suspect that HK may also have a
therapeutic effect on post-MI HF. In this study, we aimed to investigate the efficacy and mechanism of HK in the treatment of post-MI HF. We found that HK inhibited myocardial
reactive oxygen species (ROS) production, reduced myocardial
fibrosis, and improved cardiac function in mice after MI. HK also reduced the abnormality of mitochondrial membrane potential (
MMP) and apoptosis of cardiomyocytes caused by
peroxide in neonatal cardiomyocytes. RNAseq results revealed that HK restored the transcriptome changes to a certain extent and significantly enhanced the expression of mitochondrial inner membrane
uncoupling protein isoform 3 (Ucp3), a
protein that inhibits the production of mitochondrial ROS, protects cardiomyocytes, and relieves
heart failure after
myocardial infarction (MI). In cardiomyocytes with impaired Ucp3 expression, HK cannot protect against the damage caused by
peroxide. More importantly, in Ucp3 knockout mice, HK did not change the increase in the ROS level and cardiac function damage after MI. Taken together, our results suggest that HK can increase the expression of the cardioprotective
protein Ucp3 and maintain
MMP, thereby inhibiting the production of ROS after MI and ameliorating
heart failure.