The saponin of red ginseng protects the cardiac myocytes against ischemic injury in vitro and in vivo.

Steamed root of Panax ginseng C.A. Mayer, known as "red ginseng", differs from other ginseng preparations in terms of its saponin components and content, as some partly deglycosylated saponins are produced as artifacts during the steaming process. However, whether saponins derived from red ginseng (SRG) can have a protective effect on cardiomyocytes remains unknown. The present study aimed to explore the effect of SRG on myocardial ischemia in vitro and in vivo. MTT assays revealed that SRG pretreatment significantly increased the viability of cardiomyocytes injured by Na(2)S(2)O(4) hypoxia in vitro. This effect was almost completely abolished by glibenclamide, a blocker of the ATP-sensitive potassium channel, but the cardioprotective activity of SRG was not influenced by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. SRG also significantly reduced the Na(2)S(2)O(4)-induced increase in intracellular calcium, as shown by Fluo-3/AM probes with flow cytometry. Adult rat heart ischemia, which was induced by ligation of the left anterior descending coronary artery, was employed for the in vivo analysis. SRG pretreatment reduced infarct size and resulted in a higher left ventricle (LV) developed pressure, LV (+)dP/dt(max) and LV systolic pressure and lower LV (-)dP/dt(max) and LV end diastolic pressure after 24h of ischemia. Moreover, SRG significantly reduced the level of cardiac Troponin I (cTnI) in the serum, which suggests that cTnI, a protein component of the troponin regulatory complex involved in cardiac contractility, contributes to the SRG-mediated recovery of cardiac systolic function. In conclusion, this study is the first to provide evidence and a mechanistic analysis of the cardioprotective effects of SRG. SRG significantly attenuated myocardial ischemic injury by improving cardiac systole function, partly by reducing cTnI secretion and improving cardiac diastolic function. Also, SRG attenuated the Ca(2+) overload in cardiomyocytes and modulated the K(ATP), but not PI3K, signaling pathway; taken together, these mechanisms synergistically reduced infarct size.

Li HX ，Han SY ，Ma X ，Zhang K ，Wang L ，Ma ZZ ，Tu PF ... -  《-》

Protective effects of purified safflower extract on myocardial ischemia in vivo and in vitro.

Han SY ，Li HX ，Ma X ，Zhang K ，Ma ZZ ，Tu PF ... -  《-》

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

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. 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 cardio-protective effects. Meanwhile, their potential anti-oxidative stress and anti-inflammation effect were assessed. SD rats were orally given individual EPN 50, 100mg/kg, ECT 100, 200mg/kg, and different combinations between them. Myocardial infarction was produced by occlusion of the left anterior descending coronary artery for 24h. 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. 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 50mg/kg plus ECT 200mg/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 200mg/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 200mg/kg and EPN 50mg/kg, respectively). Oxidative stress and inflammation are the two key factors in the pathogenesis of myocardial ischemia injury. In the present study, EPN 50mg/kg plus ECT 200mg/kg markedly increased SOD and GSH-Px activity (475.30±23.60U/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-α (TNF-α), C-reactive protein (CRP) and interleukin-1β (IL-1β). These results demonstrated EPN, ECT and their combinations exhibited significant cardio-protective 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 50mg/kg plus ECT 200mg/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.

Han SY ，Li HX ，Ma X ，Zhang K ，Ma ZZ ，Jiang Y ，Tu PF ... -  《-》

Extracts from Astragalus membranaceus limit myocardial cell death and improve cardiac function in a rat model of myocardial ischemia.

The root of Astragalus membranaceus, known as "huang-qi", is one of the most widely used Chinese herbal medicines for the prevention and treatment of myocardial ischemic diseases. However, the mechanisms governing its therapeutic effects are largely unknown. The aims of the present study were to investigate the cardioprotective effect of the root extract of Astragalu membranaceus (EAM) in myocardial ischemia and to explore its underlying mechanisms in ROS-mediated signaling cascade in vivo and in vitro. The saponins in EAM were analyzed using HPLC. The tests for the cardioprotective effects of EAM and its mechanisms were performed in vivo and in vitro. In vivo, the rat model of persistent myocardial ischemia was produced by occlusion of the left anterior descending (LAD) coronary artery. In vitro, the cardiomyocyte model of oxidative stress was mimicked by the direct free radical donor, H2O2. In vivo, the increased myocardial infarct size and the increased serum levels of lactate dehydrogenase (LDH), creatine kinase isoform MB (CK-MB), and cardiac troponin (cTnI) were significantly decreased by pre-treatment with EAM. Moreover, cardiac function, as assessed by±dP/dt, left ventricular developed pressure (LVDP), and left ventricular end-diastolic pressure (LVEDP), was dramatically improved. An oxidative stress biomarker, malondialdehyde (MDA), was reduced, and the antioxidant enzyme superoxide dismutase (SOD) was induced. In vitro, H2O2-triggered myocardial cell death and cytoplasm Ca(2+) overload were blocked by treatment with EAM. Furthermore, the KATP channel blocker (5-HD, glibenclamide) blocked the anti-apoptotic protective effect of EAM on cardiomyocytes injured by H2O2. The cardioprotection of EAM was manifested as a protection of tissue structure and as a decrease in serum markers of ischemic injury. The mechanisms underlying the EAM-mediated protective effects may involve improving cardiac function, attenuating the oxidative injury via a decrease in MDA, a maintenance in SOD, and a reduction in free radical-induced myocardial cell injury. Additionally, EAM enhanced the myocardial cell viability via arresting the influx of Ca(2+) to block cell death and opening mitochondrial KATP channels to reduce cell apoptosis.

Ma X ，Zhang K ，Li H ，Han S ，Ma Z ，Tu P ... -  《-》

Panax notoginseng saponins inhibit ischemia-induced apoptosis by activating PI3K/Akt pathway in cardiomyocytes.

Chen S ，Liu J ，Liu X ，Fu Y ，Zhang M ，Lin Q ，Zhu J ，Mai L ，Shan Z ，Yu X ，Yang M ，Lin S ... -  《-》