Evaluation of the anti-myocardial ischemia effect of individual and combined extracts of Panax notoginseng and Carthamus tinctorius in rats

Ethnopharmacological relevance: The decoction of combined Panax notoginseng (Burk) F.H. Chen and Carthamus tinctorius L. has a history of use in traditional medicine for the prevention and treatment of cardiovascular diseases such as angina pectoris and myocardial infarction. Aim of the study: In this study, we investigated the effects of individual herbal extracts and combined extracts on anti-myocardial ischemia injuries in vivo, and determined the proper dosage of Panax notoginseng (EPN) combined with Carthamus tinctorius (ECT) that could strengthen their cardioprotective effects. Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. Material and Methods: SD rats were orally given individual EPN 50, 100 mg/kg, ECT 100,200 mg/kg, and different combinations between them. Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 24 h. Infarct area was determined with 2,3,5-triphenyltetrazolium chloride (TTC) staining. The biomarkers related to myocardial ischemia injury were determined. Simultaneously, hemodynamic parameters were monitored as left ventricular systolic pressure (LVSP), LV end-diastolic pressure (LVEDP) and maximal rate of increase and decrease of left ventricular pressure (dP/dt(max)). The oxidative stress indicators and inflammatory factors were also evaluated. Results: The results showed EPN or ECT significantly reduced infarct size, improved cardiac function, decreased levels of creatine kinase (CK) and lactate dehydrogenase (LDH) (all P < 0.05 vs. control). EPN or ECT alone also restrained the oxidative stress related to myocardial ischemia injury as evidenced by decreased malondialdehyde (MDA) and elevated superoxide dismutase (SOD) activity (all P < 0.05 vs. control). However, this cardio-protective effect was further strengthened by their combinations. Among all the combinations, EPN 50 mg/kg plus ECT 200 mg/kg showed predominant potential to reduce infarct size (22.21 +/- 1.72%, P < 0.05 vs. each single, respectively), preserve cardiac function (P < 0.05 vs. ECT 200 mg/kg for LVEDP and -dP/dt(max)) after myocardial ischemia injury in rats. This heart protection was confirmed with the lowered cardiac troponin I (cTnI) (P < 0.05 vs. ECT 200 mg/kg and EPN 50 mg/kg, respectively). Oxidative stress and inflammation are the two key factors in the pathogenesis of myocardial ischemia injury. In the present study, EPN 50 mg/kg plus ECT 200 mg/kg markedly increased SOD and GSH-Px activity (475.30 +/- 23.60 U/ml, P < 0.05 vs. each single, respectively), while elevated MDA level was significantly depressed. Meanwhile, the inflammatory cascade was inhibited as evidenced by decreased cytokines such as tumor necrosis factor-alpha (TNF-alpha), C-reactive protein (CRP) and interleukin-1 beta (IL-1 beta). Conclusion: These results demonstrated EPN, Ea and their combinations exhibited significant cardioprotective effects. The findings suggest EPN combined with ECT may be therapeutically more useful for ameliorating anti-myocardial ischemia injuries than individual herbal extract, and EPN 50 mg/kg plus ECT 200 mg/kg is the appropriate combination in the present research. The cardio-protective effect of this combination was achieved partially by decreasing oxidative stress and repressing inflammatory cascade. (C) 2012 Elsevier Ireland Ltd. All rights reserved.