Cardioprotective potential of Korean Red Ginseng extract on isoproterenol-induced cardiac injury in rats

Abstract

The present study was designed to investigate the cardioprotective effects of Korean Red Ginseng extract (KRG) on isoproterenol (ISO)-induced cardiac injury in rats, particularly in regards to electrocardiographic changes, hemodynamics, cardiac function, serum cardiac enzymes, components of the myocardial antioxidant defense system, as well as inflammatory markers and histopathological changes in heart tissue. ISO (150 mg/kg, subcutaneous, two doses administered at 24-hour intervals) treatment induced significant decreases in P waves and QRS complexes (p<0.01), as well as a significant increase in ST segments. Moreover, ISO-treated rats exhibited decreases in left-ventricular systolic pressure, maximal rate of developed left ventricular pressure (+dP/dtmax) and minimal rate of developed left ventricular pressure (-dP/dtmax), in addition to significant increases in lactate dehydrogenase, aspartate transaminase, alanine transaminase and creatine kinase activity. Heart rate, however, was not significantly altered. And the activities of superoxide dismutase, catalase and glutathione peroxidase were decreased, whereas the activity of malondialdehyde was increased in the ISO-treated group. ISO-treated group also showed increased caspase-3 level, release of inflammatory markers and neutrophil infiltration in heart tissue. KRG pretreatment (250 and 500 mg/kg, respectively) significantly ameliorated almost all of the parameters of heart failure and myocardial injury induced by ISO. The protective effect of KRG on ISO-induced cardiac injury was further confirmed by histopathological study. In this regard, ISO treatment induced fewer morphological changes in rats pretreated with 250 or 500 mg/kg of KRG. Compared with the control group, all indexes in rats administered KRG (500 mg/kg) alone were unaltered (p>0.05). Our results suggest that KRG significantly protects against cardiac injury and ISO-induced cardiac infarction by bolstering antioxidant action in myocardial tissue.

Keywords: Cardiac ischemia; Hemodynamics; Isoproterenol; Myocardial preservation; Panax ginseng.

Fig. 1.. Experimental protocol. All experimental groups began with a 3-day equilibration, and divided into the normal control (N/C) group, the Korean Red Ginseng extract (KRG) control, isoproterenol (ISO) control, 250 mg/kg KRG pretreatment and 500 mg/kg KRG pretreatment group. In KRG pretreated group, the animals were pretreated with 250 and 500 mg/kg of KRG for 7 d. And, ISO was injected subcutaneously to rats (150 mg/kg) daily for 2 consecutive days to induce experimental myocardial infarction.

Fig. 2.. Effect of Korean Red Ginseng extract (KRG) pretreatment on electrocardiographic pattern (A) normal control, (B) KRG control, (C) isoproterenol (ISO) control, (D) 250 mg/kg KRG+ISO, and (E) 500 mg/kg KRG+ISO. Arrows indicate the Q, R, S, and T waves in (A) and (C) panels, although it was not shown in (B, D, and E) panels. Electrocardiogram was recorded from limb leads II with recorder speed 50 ms/div in each group.

Fig. 3.. Effect of Korean Red Ginseng extract (KRG) on caspase-3. Cleaved caspase-3 was determined by Western blotting methods (A). Densitometric analysis of each protein was shown (B). Results are representative of three independent experiments. N/C, normal control; KRG control, isoproterenol (ISO) control, ISO injection only without KRG pretreatment; 250KRG+ISO, KRG pretreatment at the dose of 250 mg/kg for 7 d; 500KRG+ISO, KRG pretreatment at the dose of 500 mg/kg for 7 d. **p<0.01.

Fig. 4.. Effect of Korean Red Ginseng extract (KRG) pretreatment on tissue tumor necrosis factor-α (TNF-α) levels in isoproterenol (ISO)-induced myocardial infarction in rats. N/C, normal control; KRG control, ISO control, ISO injection only without KRG pretreatment; 250KRG+ISO, KRG pretreatment at the dose of 250 mg/kg for 7 d; 500KRG+ISO, KRG pretreatment at the dose of 500 mg/kg for 7 d. *p<0.05 and **p<0.01 as compared to ISO control group.

Fig. 5.. Effect of Korean Red Ginseng extract (KRG) pretreatment on myeloperoxidase (MPO) activity in the heart in isoproterenol (ISO)-induced myocardial infarction in rats. N/C, normal control; KRG control, ISO control, ISO injection only without KRG pretreatment; 250KRG+ISO, KRG pretreatment at the dose of 250 mg/kg for 7 d; 500KRG+ISO, KRG pretreatment at the dose of 500 mg/kg for 7 d. *p<0.05 and **p<0.01 as compared to ISO control group.

Fig. 6.. Effect of Korean Red Ginseng extract (KRG) pretreatment on histopathological changes. Photomicrograph of rat heart in (A) normal control showing normal limits with no edema and inflammatory cells, (B) KRG control showing also normal architecture, (C) isoproterenol (ISO) control showing areas of focal myonecrosis and edema with fibroblastic proliferation as indicated by arrow, (D) 250 mg/kg KRG+ISO showing decreased degree of necrosis, edema and less infiltration of inflammatory cells, and (E) 500 mg/kg KRG+ISO showing clear reversal of myocardial membrane damage in terms of decreased degree of necrosis and lesser infiltration of inflammatory cells. Heart tissues were stained with hematoxylin and eosin and visualized under light microscope at ×100 magnification. Scale bar, 50 μm.