Effects of purified herbal extract of Salvia miltiorrhiza on ischemic rat myocardium after acute myocardial infarction
Introduction
Ischaemic heart diseases, especially acute myocardial infarction (MI), remain the leading cause of death in both developed and developing countries as seen over the past quarter century (Mochizuki et al., 1998, Zhu et al., 1998). Reduction of mortality rate and prevention of myocardial infarction are of utmost importance. Western drugs such as angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, angiotensin II receptor antagonists, etc. have been proven to have cardioprotective effects in both preclinical and clinical studies. However, there is a growing interest in the use of alternative medicine for long-term prevention of heart attack in high risk patients.
Salvia miltiorrhiza (SM) is an important Chinese natural herb used in the treatment of many diseases, especially ischemic cardiovascular diseases (Zhu and Zhu, 2002, Ji et al., 2003, Zhu et al., 2004, Ji et al., 2004). It is considered to possess ‘slightly cold’ and ‘bitter’ properties and enters the ‘heart’, ‘pericardium’, and ‘liver’ channels. Experiments using modern techniques showed that SM dilates coronary arteries, increases coronary blood flow and scavenges free radicals in patients with ischemic diseases, thus reducing cellular damage from ischemia (Anversa et al., 1993). Clinical trials have also indicated that SM is an effective medicine for angina pectoris, myocardial infarction and stroke (Zhu and Zhu, 2002, Ji et al., 2003, Zhu et al., 2004, Ji et al., 2004, Anversa et al., 1993 and Ji et al., 2000) To date, 20 major ingredients in SM have been identified (Ji et al., 2000). Purified SM used in the current study is an extract consisting of six active water-soluble ingredients from the 20 major ingredients of rude SM.
ACE inhibitors have been gradually introduced into the treatment of hypertension, congestive heart failure and myocardial infarction since the 1970s (Zhu et al., 1998, Linz et al., 1995, Zhu et al., 1996, Zhu et al., 1997). Experimental studies also showed that ACE inhibitors administered chronically before acute MI might limit myocardial infarct size, improve cardiac function and prevent cardiac hypertrophy (Zhu et al., 1998 and Stauss et al., 1994).
In our previous study, we demonstrated that SM reduced mortality and infarct size after MI in rats (Ji et al., 2003) SM was found to reduce oxidant stress from MI by increasing the activities of hepatic-antioxidant enzymes. In the present study, the effects of purified SM in comparison with Ramipril, a well-known ACE inhibitor, on ischemic myocardium in rats after experimental induced acute MI were investigated.
Section snippets
Animal model
Healthy male adult Wistar rats (4–6 months old) weighing from 230 to 250 g were obtained from the Laboratory Animal Center, National University of Singapore. The experiments were performed according to internationally accepted guidelines for care and use of laboratory animals. Myocardial infarction was induced by ligation of the left coronary artery (close to its origin from the aorta) of rats using a modified version (Stauss et al., 1994, Zhu et al., 2000) of the technique originally described
Cardiac antioxidant activity assays
SOD activity was assayed by an improved method of Marklund (Ji et al., 2003, Ji et al., 2004). Briefly, 1 mL cuvette contained 100 μL of 1 mol/L Tris-HCl-5 mmol/L EDTA, pH 8.2, and varying amounts of the enzyme sample (supernatant A) ranging from none in the control to 50 μL to provide more than 50% inhibition. Distilled H2O was added up to 980 μL. After 10 mins of incubation at room temperature, 20 μL of a 10 mmol/L pyrogallol solution prepared in 10 mmol/L HCl was added. The increase in
Thiobarbituric acid-reactive substances (TBARs) assays in the left ventricle
Heating tissues with thiobarbituric acid (TBA) in an acidic medium gives rise to the formation of a red 1:2 malonaldehyde: TBA adduct with absorption maximum at 532 nm. Here we used the method as we previously reported (Ji et al., 2003, Ji et al., 2004). Briefly, 0.2 mL of the homogenate which was set aside after spinning at 300 g for 10 min was used. 0.2 mL of 8.1% dodecyl sulfate sodium salt (SDS), 1.5 mL of 20% acetic acid (pH 3.5 adjusted by 10 N of NaOH), 0.02 μL of 2% BHT and 0.08 mL
In vitro experiment
Fig. 2 illustrates the effects of ascorbic acid, PSME and Ramipril (all at the same final concentration of 2 μg/mL) reacting with ABTS+ at 734 nm. 1 mM trolox was taken as the standard and calculated in terms of the trolox equivalent antioxidant activity (Whiteman et al., 2001). The result shows that the reduction of the radical cation as the inhibition of absorbance at 734 nm, PSME has a significantly higher TEAC value than Ramipril, and almost the same value as ascorbic acid.
Discussion
The results in this study demonstrated for the first time that PSME had similar cardioprotective effects as Ramipril, an ACE inhibitor, producing a higher survival rate and causing smaller infarct size compared to vehicle. Moreover, PSME showed antioxidant effects including higher TEAC value, greater inhibition of PR bleaching, prevention of DNA damage, inhibition of lipid peroxidation and preservation of SOD activity. But it has no direct effect on lowering blood pressure, unlike Ramipril.
Both
Acknowledgement
The current study was mainly supported by research grants from National Medical Research Council of Singapore (R-184-000-044-731 and R-184-000-066-213) and partially from Singapore CMM Corporation Pte. Ltd. The authors wish to thank Prof. George Webb for his valuable input and Miss Aw Yi Bing for her excellent technical assistance for a part of this study. Y.Z. Zhu is a recipient of a Lee Kuan Yew Research Fellowship.
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