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Panax quinquefoliumsaponin (PQS) alleviates hypoxia-reoxygenation injury of cardiomyocytes in vitroby inhibiting excessive endoplasmic reticulum stress (ERS)–related apoptosis. We hypothesized that inhibition of excessive ERS-related apoptosis contributes to cardioprotection in ventricular remodeling after acute myocardial infarction (AMI). Sprague-Dawley rats subjected to AMI were randomly treated with water, PQS (50 mgkg per day, 100 mgkg per day, or 200 mgkg per day), or taurine (300 mgkg per day), an ERS inhibitor, for 4 weeks. Left ventricular (LV) fractional shortening, ejection fraction, and structure were then evaluated using echocardiography. Myocardial infarct size was measured by Evans blue and 2,3,5-triphenyhetrazolium chloride staining. The hydroxyproline level was assayed using the colorimetric method. Cardiomyocyte apoptosis was detected using terminal deoxynucleotidyl transferase–mediated dUTP biotin nick end labeling. In addition, expression of ERS molecules in the noninfarcted myocardium was detected using Western blotting. We found that PQS treatment significantly reduced infarct size and LV dilation and improved LV ejection fraction and fractional shortening in rat hearts. Panax quinquefoliumsaponin treatment also decreased hydroxyproline level in noninfarcted myocardium. Panax quinquefoliumsaponin treatment significantly decreased expression of glucose regulating protein 78, calreticulin, CEBP homologous protein (CHOP), and Bax protein, as well as increased Bcl-2 protein expression in noninfarcted myocardium. Panax quinquefoliumsaponin treatment (200 mgkg per day) mimicked the results achieved from the taurine-treated rats. Expression of CHOP positively correlated with the apoptosis index of cardiomyocytes in the noninfarcted myocardium (r= 0.797, P< 0.01). Taken together, PQS treatment significantly improves AMI-induced LV remodeling, and this may be attributed to inhibiting CHOP-mediated ERS-related apoptosis.

Excessive endoplasmic reticulum stress (ERS) disrupts protein translation, protein folding, and calcium homeostasis and may contribute to ischemia-reperfusion injury. Saponins extracted from the stems and leaves of Panax quinquefolium(PQS) protect rat myocardium against ischemia-reperfusion injury, but it is not known if suppression of ERS contributes to cardioprotection. Neonatal rat cardiomyocytes were subjected to hypoxia-reoxygenation (H-R) in the presence of PQS or vehicle. Cell injury and apoptosis were assayed by trypan blue exclusion, lactate dehydrogenase activity, and flow cytometry. In addition, reverse transcriptase–polymerase chain reaction and Western blotting were used to examine mRNA and protein expression of the ERS-related proteins glucose-regulated protein 78, calreticulin, CCAATenhancer-binding protein homologous protein, and caspase-12, as well as the apoptosis-associated proteins Bax and Bcl-2. We confirmed that PQS protects cardiomyocytes from H-R–induced injury and apoptotic cell death. Furthermore, PQS suppressed H-R–induced excessive ERS, as evidenced by reduced caspase 12 activation and decreased glucose-regulated protein 78, calreticulin, and CCAATenhancer-binding protein homologous protein overexpression. These results indicated that PQS could alleviate H-R injury of cardiomyocytes, which would be probably related to inhibiting excessive ERS induced by H-R.