State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, PR China.
J Ethnopharmacol. 2013 Feb 13;145(3):722-7. doi: 10.1016/j.jep.2012.11.036. Epub 2012 Dec 10.
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.
三七（Burk）F.H. Chen 和红花的煎剂在传统医学中有预防和治疗心绞痛和心肌梗死等心血管疾病的历史。
本研究旨在探讨单味草药提取物和联合提取物对体内抗心肌缺血损伤的作用，并确定增强其心脏保护作用的合适剂量。同时，评估它们的潜在抗氧化应激和抗炎作用。
SD 大鼠口服给予三七 50、100mg/kg、红花 100、200mg/kg 及两者不同组合。通过结扎左前降支冠状动脉 24 小时诱导心肌梗死。用 2,3,5-三苯基氯化四氮唑（TTC）染色确定梗死面积。测定与心肌缺血损伤相关的生物标志物。同时监测左心室收缩压（LVSP）、左心室舒张末期压（LVEDP）和左心室压力最大上升和下降速率（dP/dt(max)）等血流动力学参数。评估氧化应激指标和炎症因子。
结果表明，三七或红花可显著减小梗死面积，改善心功能，降低肌酸激酶（CK）和乳酸脱氢酶（LDH）水平（均 P<0.05 与对照组相比）。三七或红花单独也抑制与心肌缺血损伤相关的氧化应激，表现为丙二醛（MDA）降低和超氧化物歧化酶（SOD）活性升高（均 P<0.05 与对照组相比）。然而，它们的组合进一步增强了这种心脏保护作用。在所有组合中，三七 50mg/kg 加红花 200mg/kg 显示出降低梗死面积（22.21±1.72%，P<0.05 与单药组相比）、保护心功能（P<0.05 与红花 200mg/kg 相比，LVEDP 和-dP/dt(max)）的最大潜力大鼠心肌缺血损伤后。这种心脏保护作用得到了降低心肌肌钙蛋白 I（cTnI）的证实（P<0.05 与红花 200mg/kg 和三七 50mg/kg 相比，分别）。氧化应激和炎症是心肌缺血损伤发病机制中的两个关键因素。在本研究中，三七 50mg/kg 加红花 200mg/kg 显著增加 SOD 和 GSH-Px 活性（475.30±23.60U/ml，P<0.05 与单药组相比），同时升高 MDA 水平显著降低。同时，炎症级联反应受到抑制，肿瘤坏死因子-α（TNF-α）、C 反应蛋白（CRP）和白细胞介素-1β（IL-1β）等细胞因子减少。
这些结果表明三七、红花及其组合具有显著的心脏保护作用。研究结果表明，三七与红花联合应用可能比单味草药提取物更能有效改善抗心肌缺血损伤，本研究中三七 50mg/kg 加红花 200mg/kg 是合适的组合。该组合的心脏保护作用部分通过降低氧化应激和抑制炎症级联反应来实现。
