Fargesin displayed similar chromatographic retention peak to
metoprolol in the cardiac muscle/cell membrane chromatography (CM/CMC) and β1
adrenergic receptor/cell membrane chromatography (β1AR/CMC) models. To provide more
biological information about
fargesin, we investigated the effects of
fargesin on
isoproterenol-(ISO-) induced cells injury in the high expression β1
adrenergic receptor/Chinese hamster ovary-S (β1AR/CHO-S) cells and occluding the left coronary artery- (LAD-) induced
myocardial ischemia/reperfusion (MI/R) injury in rats. The results in vitro showed that ISO-induced canonical cyclic
adenosine monophosphate (cAMP) and
protein kinase A (PKA) levels were decreased by
fargesin in β1AR/CHO-S cells.
Fargesin attenuated the serum
creatine kinase (CK),
lactate dehydrogenase (LDH), and improved histopathological changes of ischemic myocardium compared with the I/R rats. Similar results were obtained with
Evans Blue/TTC staining, in which
fargesin notably reduced
infarct size. Moreover, compared with the I/R group,
fargesin increased COX release and the activities of some endogenous antioxidative
enzymes including
superoxide dismutase (SOD),
catalase (CAT),
glutathione peroxidase (GSH-Px), but suppressed
malondialdehyde (MDA), and intracellular ROS release. Additionally,
terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay demonstrated
fargesin suppressed myocardial apoptosis, which may be related to inhibition of
caspase-3 activity. Taken together, these results provided substantial evidences that
fargesin as a potential β1AR antagonist through cAMP/PKA pathway could protect against
myocardial ischemia/
reperfusion injury in rats. The underlining mechanism may be related to inhibiting oxidative stress and myocardial apoptosis.