A number of studies have shown that ischemic preconditioning is an innate protective strategy that markedly reduces ischemia-reperfusion (I/R) injury (35). the blood following oral administration and was shown to decrease MDA levels and increase the activity of SOD. In conclusion, the findings suggest that FCG, a combination of active ingredients in the DGSN decoction, can be absorbed into the blood and protect the myocardium from I/R injury. Keywords:ischemia-reperfusion cocktail, ferulic acid, cinnamic acid, glycyrrhizic acid == Introduction == Atractylenolide I Ischemic heart disease is one of the most common causes of mortality in the world (1). Following acute coronary occlusion with the threat of myocardial infarction, the current cardiological protocol for acute myocardial infarction is usually quick reperfusion. Although reperfusion is required to salvage ischemic tissue, it is associated with cellular damage due to the activation of deleterious signaling cascades (2). A number of studies have shown that ischemic preconditioning is an innate protective strategy that markedly reduces ischemia-reperfusion (I/R) RHOC injury (35). This, however, is not acceptable as a clinical tool due to practical difficulties associated with the local induction of cardiac ischemia, ethical reasons and the fact that this index ischemic episode is usually often unpredictable. Therefore, it is necessary to search for a novel approach, one that is usually more suitable for the clinical scenario. Pharmacological preconditioning can simulate ischemic preconditioning and markedly reduce injury from I/R. Furthermore, this method is usually associated with an easy execution. To date, numerous drugs that can prevent the myocardium from I/R injury (68) are available. Dang-gui-si-ni-tang (DGSN) decoction is usually a classical formula in Traditional Chinese Medicine that originated from a medical textbook known as the Treatise on Cold-Induced Febrile Diseases, which dates back to 200 C.E. DGSN is usually treatment for coronary heart disease. Studies have indicated that glycyrrhizic, ferulic and cinnamic acids are the active components in the DGSN decoction (911). In addition, the majority of these studies have reported that glycyrrhizic, cinnamic and ferulic acids have a protective effect against I/R injury. The protective mechanism of glycyrrhizic acid on I/R injury was found to be associated with its antioxidant (1214), anti-inflammatory (15) and anti-apoptosis effects (16), as well as its inhibition of lipid peroxide (17). Cinnamic acid exerts cytoprotection by acting as an antioxidant and anti-inflammatory agent (1820). Ferulic Atractylenolide I acid can also inhibit oxidative stress, inflammation Atractylenolide I (21) and cell apoptosis (22) and modulate mitochondrial function (23). These mechanisms are associated with the alleviation of I/R injury. Considering that glycyrrhizic, cinnamic and ferulic acids are major components of the DGSN decoction, which is used to treat coronary heart diseases (911), we hypothesized that different combinations of the active ingredients in the DGSN decoction may also have a similar therapeutic effect. The aims of this study were fourfold. Firstly, we aimed to verify whether glycyrrhizic, cinnamic and ferulic acids could be absorbed into the serum of rats following oral administration of the DGSN decoction. We then aimed to investigate the effects of pretreament with glycyrrhizic, cinnamic and ferulic acids and peoniflorin on superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the myocardium of a rat model of I/R injury, and to utilize anL16 (44) orthogonal experiment to find the optimal active combination. Thirdly, we aimed to investigate the protective effects of the optimal active combination pretreatment against myocardial I/R injury in rats, and, finally, to investigate whether the protective effects were associated with tumor necrosis factor- (TNF), interleukin (IL)-1, IL-6 and the nuclear factor-B (NF-B)p65 and peroxisome proliferator-activated (PPAR).